@article {pmid35050941, year = {2022}, author = {Beran, A and Sharma, S and Ghazaleh, S and Lee-Smith, W and Aziz, M and Kamal, F and Acharya, A and Adler, DG}, title = {Predictors of Fecal Microbiota Transplant Failure in Clostridioides difficile Infection: An Updated Meta-analysis.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000001667}, pmid = {35050941}, issn = {1539-2031}, abstract = {INTRODUCTION AND AIM: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent/refractory Clostridioides difficile infection (CDI) with a 10% to 20% risk of recurrence after a single FMT. In this meta-analysis, we aimed to evaluate the predictors of FMT failure.<br><br>METHODS: A comprehensive search of MEDLINE, Embase, Cochrane, and Web of Science databases through July 2021 was performed. All studies that evaluated risk factors associated with FMT failure in a multivariate model were included. We calculated pooled odds ratios with 95% confidence intervals for risk factors reported in ≥3 studies using a random-effects model.<br><br>RESULTS: Twenty studies involving 4327 patients (63.6% females) with recurrent/refractory CDI who underwent FMT were included. FMT failed in 705 patients (16.3%) with 2 to 3 months of follow-up in most studies. A total of 12 different risk factors were reported in a multivariate model in ≥3 studies. Meta-analysis showed that advanced age, severe CDI, inflammatory bowel disease, peri-FMT use of non-CDI antibiotics, prior CDI-related hospitalizations, inpatient status, and poor quality of bowel preparation were significant predictors of FMT failure. Charlson Comorbidity Index, female gender, immunosuppressed status, patient-directed donor, and number of CDI recurrences were not associated with FMT failure.<br><br>CONCLUSIONS: Adequate bowel preparation at the time of FMT and optimizing antibiotic stewardship practices in the peri-FMT period can improve the success of FMT. Patients with nonmodifiable risk factors should be counseled about the risk of FMT failure. Our results may help develop a risk stratification model to predict FMT failure in CDI patients.}, }
@article {pmid35046924, year = {2021}, author = {Qiao, Y and Zhang, Z and Zhai, Y and Yan, X and Zhou, W and Liu, H and Guan, L and Peng, L}, title = {Apigenin Alleviates Obesity-Associated Metabolic Syndrome by Regulating the Composition of the Gut Microbiome.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {805827}, doi = {10.3389/fmicb.2021.805827}, pmid = {35046924}, issn = {1664-302X}, abstract = {The gut microbiota, often viewed as a "digestive organ," can influence the development of obesity and related metabolic disorders. Diet is significantly important in shaping the structure and modulating the function of the gut microbiota. Apigenin (Api) widely exists in fruits and vegetables as a naturally occurring flavonoid and has anti-obesogenic, anti-inflammatory, and anti-carcinogenic properties. Its low bioavailability means it has enough time to interact with the intestine thus becomes a potential substrate for the gut intestine; thus, contributing to gut health. Here, we show that Api reduces whole-body weight, low-grade inflammation, and insulin resistance in high-fat diet (HFD)-induced obese mice. Our results reflect that Api supplementation can substantially improve intestinal dysbiosis triggered by HFD and restores gut barrier damage by alleviating metabolic endotoxemia. Augmentation of Akkermansia and Incertae_Sedis along with reduction of Faecalibaculum and Dubosiella at the genus level potentially mediated the protective effects of Api on metabolic syndrome. Furthermore, we show that the impact of Api on the reduction of body weight and the modification of gut microbiota could be transferred from Api-administered mice to HFD-feeding mice via horizontal fecal microbiota transplantation. Taken together, our data highlight the prebiotic role of Api and show its contribution to the restraint of gut dysbiosis and metabolic deterioration associated with obesity in mice.}, }
@article {pmid35045605, year = {2022}, author = {Kang, SH and Gweon, TG and Hwang, H and Baeg, MK}, title = {A Case of Ischemic Colitis Complicated by Clostridioides Difficile Infection Treated with Fecal Microbiota Transplantation.}, journal = {Clinical endoscopy}, volume = {}, number = {}, pages = {}, doi = {10.5946/ce.2021.199}, pmid = {35045605}, issn = {2234-2400}, abstract = {Ischemic colitis is an inflammatory condition of the colon that results from insufficient blood supply commonly caused by enterocolitis, vessel occlusion, or shock. In contrast, pseudomembranous colitis is a clinical manifestation of Clostridioides difficile infection (CDI). Ischemic colitis caused by CDI has rarely been reported. Fecal microbiota transplantation (FMT) is an efficient treatment for refractory or fulminant CDI, and the indications for its use have recently expanded. However, performing FMT in patients with ischemic colitis is challenging because of the risk of perforation. Here, we have presented a case of ischemic colitis caused by CDI that was successfully treated with FMT via sigmoidoscopy.}, }
@article {pmid33798737, year = {2021}, author = {Li, X and Khan, I and Xia, W and Huang, G and Liu, L and Law, BYK and Yin, L and Liao, W and Leong, W and Han, R and Wong, VKW and Xia, C and Guo, X and Hsiao, WLW}, title = {Icariin enhances youth-like features by attenuating the declined gut microbiota in the aged mice.}, journal = {Pharmacological research}, volume = {168}, number = {}, pages = {105587}, doi = {10.1016/j.phrs.2021.105587}, pmid = {33798737}, issn = {1096-1186}, mesh = {Aging/*drug effects ; Animals ; Fecal Microbiota Transplantation ; Flavonoids/*pharmacology ; Gastrointestinal Microbiome/*drug effects/physiology ; Goblet Cells/drug effects ; Intestines/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Tight Junctions/drug effects ; }, abstract = {We previously reported the neuroprotective effects of icariin in rat cortical neurons. Here, we present a study on icariin's anti-aging effect in 24-month aged mice by treating them with a single daily dose of 100 mg/kg of icariin for 15 consecutive days. Icariin treatment improved motor coordination and learning skills while lowered oxidative stress biomarkers in the serum, brain, kidney, and liver of the aged mice. In addition, icariin improved the intestinal integrity of the aged mice by upregulating tight junction adhesion molecules and the Paneth and goblet cells, along with the reduction of iNOS and pro-inflammatory cytokines (IL-1β, TNF-α, IL-2 and IL-6, and IL-12). Icariin treatments also significantly upregulated aging-related signaling molecules, Sirt 1, 3 &amp; 6, Pot1α, BUB1b, FOXO1, Ep300, ANXA3, Calb1, SNAP25, and BDNF in old mice. Through gut microbiota (GM) analysis, we observed icariin-associated improvements in GM composition of aged mice by reinstating bacteria found in the young mice, while suppressing some bacteria found in the untreated old mice. To clarify whether icariin's anti-aging effect is rooted in the GM, we performed fecal microbiota transfer (FMT) from icariin-treated old mice to the old mice. FMT-recipients exhibited similar improvements in the rotarod score and age-related biomarkers as observed in the icariin-treated old mice. Equal or better improvement on the youth-like features was noticed when aged mice were FMT with feces from young mice. Our study shows that both direct treatments with icariin and fecal transplant from the icariin-treated aged mice produce similar anti-aging phenotypes in the aged mice. We prove that GM plays a pivotal role in the healing abilities of icariin. Icariin has the potentials to be developed as a medicine for the wellness of the aged adults.}, }
@article {pmid35045306, year = {2022}, author = {Huang, G and Wang, L and Li, J and Hou, R and Wang, M and Wang, Z and Qu, Q and Zhou, W and Nie, Y and Hu, Y and Ma, Y and Yan, L and Wei, H and Wei, F}, title = {Seasonal shift of the gut microbiome synchronizes host peripheral circadian rhythm for physiological adaptation to a low-fat diet in the giant panda.}, journal = {Cell reports}, volume = {38}, number = {3}, pages = {110203}, doi = {10.1016/j.celrep.2021.110203}, pmid = {35045306}, issn = {2211-1247}, abstract = {Characteristics of the gut microbiome vary synchronously with changes in host diet. However, the underlying effects of these fluctuations remain unclear. Here, we performed fecal microbiota transplantation (FMT) of diet-specific feces from an endangered mammal (the giant panda) into a germ-free mouse model. We demonstrated that the butyrate-producing bacterium Clostridium butyricum was more abundant during shoot-eating season than during the leaf-eating season, congruent with the significant increase in host body mass. Following season-specific FMT, the microbiota of the mouse model resembled that of the donor, and mice transplanted with the microbiota from the shoot-eating season grew faster and stored more fat. Mechanistic investigations revealed that butyrate extended the upregulation of hepatic circadian gene Per2, subsequently increasing phospholipid biosynthesis. Validation experiments further confirmed this causal relationship. This study demonstrated that seasonal shifts in the gut microbiome affect growth performance, facilitating a deeper understanding of host-microbe interactions in wild mammals.}, }
@article {pmid35040380, year = {2022}, author = {Wang, Y and Cui, B and Zhang, F}, title = {Refractory ulcerative colitis stabilized by interval washed microbiota transplantation: less is more.}, journal = {Current medical research and opinion}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/03007995.2022.2030563}, pmid = {35040380}, issn = {1473-4877}, abstract = {Ulcerative colitis (UC) is an autoimmune inflammatory disorder characterized by a relapsing and remitting course. The gut microbiota is implicated in the pathogenesis of UC. Fecal microbiota transplant (FMT) has been reported as a rescue therapy for refractory UC. The newly improved methodology of FMT was recently coined as washed microbiota transplantation (WMT) based on the automatic purification system and washing process. Colonic transendoscopic enteral tubing (TET) is a novel delivery of WMT within the whole colon. In this case, the patient with refractory UC underwent two different strategies of fresh FMT. The prior strategy conducted daily FMT through the percutaneous endoscopic cecostomy (PEC) tube for 60 days. The latter performed WMT every 3-35 months by colonic TET or gastroscopy. The patient was effectively responsive to both strategies. The repeated interval WMTs induced the long-term clinical remission for the patient. The case encouraged the physicians to consider repeated interval WMTs into practice as a long-term treatment strategy for refractory UC. Moreover, we hope more physicians and researchers would be inspired to study clinical strategies, such as optimizing the frequency and interval of WMTs and the related delivering strategy.}, }
@article {pmid35040302, year = {2021}, author = {Larussa, T and Abenavoli, L and Fabiano, G and Mancuso, MA and Polimeni, N and Dumitrascu, DL and Luzza, F}, title = {Gut microbiota in inflammatory bowel disease: a target for therapy not to be missed.}, journal = {Minerva gastroenterology}, volume = {67}, number = {4}, pages = {357-368}, doi = {10.23736/S2724-5985.21.02907-7}, pmid = {35040302}, issn = {2724-5365}, abstract = {In the last years, the gut microbiota achieved great importance, since several studies demonstrated its correlation with the immune system and with the maintenance of intestinal homeostasis, as well as with the regulation of the integrity of the epithelium and the intestinal motility. An imbalance in microbial species promotes a dysbiosis, which has been associated with chronic diseases such as metabolic syndrome, inflammatory diseases, and some behavior disorders. The association with gut microbiota and dysbiosis has been demonstrated mostly in inflammatory bowel disease (IBD). Several studies investigated the application of antibiotics, prebiotics, probiotics, and fecal microbiota transplantation in the treatment strategies for IBD. In this review, we discuss the recent findings on the potential role of the gut microbiota manipulation, with particular attention to bacterial microbiota, which could be implicated for a successful IBD therapeutic approach.}, }
@article {pmid35037353, year = {2022}, author = {Benech, N and Legendre, P and Radoszycki, L and Varriale, P and Sokol, H}, title = {Patient knowledge of gut microbiota and acceptability of fecal microbiota transplantation in various diseases.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {}, number = {}, pages = {e14320}, doi = {10.1111/nmo.14320}, pmid = {35037353}, issn = {1365-2982}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is now evaluated in various diseases. However, large-scale population treatment may encounter feasibility issues in terms of acceptance. We aim to evaluate patient knowledge of gut microbiota and the acceptability of FMT in various diseases.<br><br>METHODS: Patients of Carenity's French online community were invited by email to participate in a questionnaire. The following parameters were assessed: patient's principal illness and duration, demographic data, therapeutics, dietary habits, knowledge of gut microbiota, probiotics and FMT, and its acceptability.<br><br>KEY RESULTS: In total, 877 patients participated in the online questionnaire: 156 with inflammatory bowel disease (17.8%), 127 with rheumatoid arthritis (14.5%), 222 with ankylosing spondylitis (25.3%), 52 with lupus (5.9%), 64 with psoriasis (7.3%), 61 with obesity (7%), and 195 with type 2 diabetes (22.2%). Characteristics of participating patients were similar to those of the entire cohort (n = 23084). Overall, 47.1% (n = 413/877) of patients knew what the microbiota is with no difference among diseases. Knowledge was reported to be developed by patients themselves (203/413; 49.2%) without involving a healthcare professional. If proposed by a healthcare professional, 37.2% (326/877) reported being interested or very interested in undergoing FMT. Factors associated with good acceptability of FMT were the male sex (OR: 1.63, CI95% [1.14 to 2.32]), previous knowledge of FMT (OR: 4.16, CI95% [2.92 to 5.96]), and previous knowledge of gut microbiota (OR: 1.54, CI95% [1.05 to 2.24]).<br><br>CONCLUSION AND INFERENCES: Knowledge of gut microbiota is still limited in patients' communities and mainly developed by patients themselves, impacting FMT acceptability.}, }
@article {pmid34508776, year = {2021}, author = {van de Guchte, M and Mondot, S and Doré, J}, title = {Dynamic Properties of the Intestinal Ecosystem Call for Combination Therapies, Targeting Inflammation and Microbiota, in Ulcerative Colitis.}, journal = {Gastroenterology}, volume = {161}, number = {6}, pages = {1969-1981.e12}, doi = {10.1053/j.gastro.2021.08.057}, pmid = {34508776}, issn = {1528-0012}, mesh = {Anti-Inflammatory Agents/adverse effects/*therapeutic use ; Bacteria/*drug effects/genetics/immunology ; Case-Control Studies ; *Cellular Microenvironment ; Colitis, Ulcerative/immunology/microbiology/*therapy ; Combined Modality Therapy ; Dysbiosis ; *Fecal Microbiota Transplantation/adverse effects ; Gastrointestinal Microbiome/*drug effects ; Host-Pathogen Interactions ; Humans ; Immunity, Innate/*drug effects ; Inflammation Mediators/*antagonists &amp; inhibitors/metabolism ; Intestines/*drug effects/metabolism/microbiology ; Models, Biological ; Remission Induction ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND &amp; AIMS: Intestinal microbiota-host interactions play a major role in health and disease. This has been documented at the microbiota level ("dysbiosis" in chronic immune-mediated diseases) and through the study of specific bacteria-host interactions but rarely at the level of intestinal ecosystem dynamics. However, understanding the behavior of this ecosystem may be key to the successful treatment of disease. We recently postulated that health and disease represent alternative stable states of the intestinal ecosystem (different configurations that can exist under identical external conditions), which would require adapted strategies in disease treatment. Here, we examine if alternative stable states indeed exist in this ecosystem and if they could affect remission from ulcerative colitis (UC).<br><br>METHODS: We analyzed data from a study on pediatric UC. The data reflect current treatment practice following the recruitment of treatment-naive patients with new-onset disease. Patients received personalized anti-inflammatory treatments over a period of 1 year. Stool samples at 0, 4, 12, and 52 weeks allowed an estimation of microbiota status (through 16S ribosomal RNA gene sequencing) and host inflammatory status (through the measurement of fecal calprotectin levels).<br><br>RESULTS: We identify 4 microbiota states and 4 host states. Longitudinal data show that the improvement of inflammatory status is accompanied by an improvement of microbiota status. However, they also provide strong indications that both improvements are retarded or blocked by alternative states barriers.<br><br>CONCLUSIONS: Our observations strongly suggest that inflammation suppression should be combined with microbiota management where possible to improve the efficacy of UC treatment.}, }
@article {pmid35031549, year = {2022}, author = {Messaoudene, M and Pidgeon, R and Richard, C and Ponce, M and Diop, K and Benlaifaoui, M and Nolin-Lapalme, A and Cauchois, F and Malo, J and Belkaid, W and Isnard, S and Fradet, Y and Dridi, L and Velin, D and Oster, P and Raoult, D and Ghiringhelli, F and Boidot, R and Chevrier, S and Kysela, DT and Brun, YV and Falcone, EL and Pilon, G and Plaza Onate, F and Gitton-Quent, O and Le Chatelier, E and Durand, S and Kroemer, G and Elkrief, A and Marette, A and Castagner, B and Routy, B}, title = {A natural polyphenol exerts antitumor activity and circumvents anti-PD-1 resistance through effects on the gut microbiota.}, journal = {Cancer discovery}, volume = {}, number = {}, pages = {}, doi = {10.1158/2159-8290.CD-21-0808}, pmid = {35031549}, issn = {2159-8290}, abstract = {Several approaches to manipulate the gut microbiome for improving the activity of cancer immune checkpoint inhibitors (ICI) are currently under evaluation. Here, we show that oral supplementation with the polyphenol-rich berry camu-camu (CC, Myrciaria dubia) in mice shifted gut microbial composition, which translated into antitumor activity and a stronger anti-PD-1 response. We identified castalagin, an ellagitannin, as the active compound in CC. Oral administration of castalagin enriched for bacteria associated with efficient immunotherapeutic responses (Ruminococcaceae and Alistipes) and improved the CD8+/Foxp3+CD4+ ratio within the tumor microenvironment. Moreover, castalagin induced metabolic changes, resulting in an increase in taurine conjugated bile acids. Oral supplementation of castalagin following fecal microbiota transplantation from ICI-refractory patients into mice supported anti-PD-1 activity. Finally, we found that castalagin binds to Ruminococcus bromii and promoted an anticancer response. Altogether, our results identify castalagin as a polyphenol that acts as a prebiotic to circumvent anti-PD-1 resistance.}, }
@article {pmid35028606, year = {2021}, author = {Blake, SJ and James, J and Ryan, FJ and Caparros-Martin, J and Eden, GL and Tee, YC and Salamon, JR and Benson, SC and Tumes, DJ and Sribnaia, A and Stevens, NE and Finnie, JW and Kobayashi, H and White, DL and Wesselingh, SL and O'Gara, F and Lynn, MA and Lynn, DJ}, title = {The immunotoxicity, but not anti-tumor efficacy, of anti-CD40 and anti-CD137 immunotherapies is dependent on the gut microbiota.}, journal = {Cell reports. Medicine}, volume = {2}, number = {12}, pages = {100464}, doi = {10.1016/j.xcrm.2021.100464}, pmid = {35028606}, issn = {2666-3791}, abstract = {Immune agonist antibodies (IAAs) are promising immunotherapies that target co-stimulatory receptors to induce potent anti-tumor immune responses, particularly when combined with checkpoint inhibitors. Unfortunately, their clinical translation is hampered by serious dose-limiting, immune-mediated toxicities, including high-grade and sometimes fatal liver damage, cytokine release syndrome (CRS), and colitis. We show that the immunotoxicity, induced by the IAAs anti-CD40 and anti-CD137, is dependent on the gut microbiota. Germ-free or antibiotic-treated mice have significantly reduced colitis, CRS, and liver damage following IAA treatment compared with conventional mice or germ-free mice recolonized via fecal microbiota transplant. MyD88 signaling is required for IAA-induced CRS and for anti-CD137-induced, but not anti-CD40-induced, liver damage. Importantly, antibiotic treatment does not impair IAA anti-tumor efficacy, alone or in combination with anti-PD1. Our results suggest that microbiota-targeted therapies could overcome the toxicity induced by IAAs without impairing their anti-tumor activity.}, }
@article {pmid34941392, year = {2021}, author = {Spencer, CN and McQuade, JL and Gopalakrishnan, V and McCulloch, JA and Vetizou, M and Cogdill, AP and Khan, MAW and Zhang, X and White, MG and Peterson, CB and Wong, MC and Morad, G and Rodgers, T and Badger, JH and Helmink, BA and Andrews, MC and Rodrigues, RR and Morgun, A and Kim, YS and Roszik, J and Hoffman, KL and Zheng, J and Zhou, Y and Medik, YB and Kahn, LM and Johnson, S and Hudgens, CW and Wani, K and Gaudreau, PO and Harris, AL and Jamal, MA and Baruch, EN and Perez-Guijarro, E and Day, CP and Merlino, G and Pazdrak, B and Lochmann, BS and Szczepaniak-Sloane, RA and Arora, R and Anderson, J and Zobniw, CM and Posada, E and Sirmans, E and Simon, J and Haydu, LE and Burton, EM and Wang, L and Dang, M and Clise-Dwyer, K and Schneider, S and Chapman, T and Anang, NAS and Duncan, S and Toker, J and Malke, JC and Glitza, IC and Amaria, RN and Tawbi, HA and Diab, A and Wong, MK and Patel, SP and Woodman, SE and Davies, MA and Ross, MI and Gershenwald, JE and Lee, JE and Hwu, P and Jensen, V and Samuels, Y and Straussman, R and Ajami, NJ and Nelson, KC and Nezi, L and Petrosino, JF and Futreal, PA and Lazar, AJ and Hu, J and Jenq, RR and Tetzlaff, MT and Yan, Y and Garrett, WS and Huttenhower, C and Sharma, P and Watowich, SS and Allison, JP and Cohen, L and Trinchieri, G and Daniel, CR and Wargo, JA}, title = {Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response.}, journal = {Science (New York, N.Y.)}, volume = {374}, number = {6575}, pages = {1632-1640}, doi = {10.1126/science.aaz7015}, pmid = {34941392}, issn = {1095-9203}, support = {R01 CA219896/CA/NCI NIH HHS/United States ; T32 CA009599/CA/NCI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; F32 CA260769/CA/NCI NIH HHS/United States ; R01 AI143886/AI/NIAID NIH HHS/United States ; P30 CA013696/CA/NCI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; R01 AI109294/AI/NIAID NIH HHS/United States ; R01 AI133822/AI/NIAID NIH HHS/United States ; P50 CA221703/CA/NCI NIH HHS/United States ; U54 CA224070/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cohort Studies ; *Dietary Fiber ; Fatty Acids, Volatile/analysis ; Fecal Microbiota Transplantation ; Feces/chemistry/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; Immunotherapy ; Male ; Melanoma/immunology/microbiology/*therapy ; Melanoma, Experimental/immunology/microbiology/therapy ; Mice ; Mice, Inbred C57BL ; *Probiotics ; Progression-Free Survival ; T-Lymphocytes ; }, abstract = {[Figure: see text].}, }
@article {pmid35024588, year = {2022}, author = {Wang, Y and Tang, J and Lv, Q and Tan, Y and Dong, X and Liu, H and Zhao, N and He, Z and Kou, Y and Tan, Y and Liu, XA and Wang, L and Liu, YY and Dai, L}, title = {Establishment and resilience of transplanted gut microbiota in aged mice.}, journal = {iScience}, volume = {25}, number = {1}, pages = {103654}, doi = {10.1016/j.isci.2021.103654}, pmid = {35024588}, issn = {2589-0042}, abstract = {The maintenance of healthy and resilient gut microbiota is critical for the life quality and healthspan of the elderly. Fecal microbiota transplantation (FMT) has been increasingly used to restore healthy gut microbiota. We systemically studied the establishment and resilience of transplanted microbiota after autologous versus heterologous FMT in aged recipients. Gut microbiota of aged mice (20 months old) failed to restore their original diversity and composition over 8 weeks via spontaneous recovery after antibiotics treatment; in contrast, FMT using either autologous or heterologous (2 months old from a different vendor) donors facilitated the recovery successfully, established donor-like microbiota states, and affected host gene expression profile. Furthermore, the transplanted microbiota established by heterologous FMT is not resilient during chemical-induced colonic inflammation, in contrast to that of autologous FMT. Our findings highlighted the need to monitor the long-term stability of transplanted gut microbiota and to perform multiple FMT when necessary.}, }
@article {pmid35023946, year = {2022}, author = {Azimirad, M and Jo, Y and Kim, MS and Jeong, M and Shahrokh, S and Asadzadeh Aghdaei, H and Zali, MR and Lee, S and Yadegar, A and Shin, JH}, title = {Alterations and Prediction of Functional Profiles of Gut Microbiota After Fecal Microbiota Transplantation for Iranian Recurrent Clostridioides difficile Infection with Underlying Inflammatory Bowel Disease: A Pilot Study.}, journal = {Journal of inflammation research}, volume = {15}, number = {}, pages = {105-116}, doi = {10.2147/JIR.S338212}, pmid = {35023946}, issn = {1178-7031}, abstract = {Background and Purpose: Fecal microbiota transplantation (FMT) has emerged for the therapeutic treatment of recurrent Clostridioides difficile infection (rCDI) with concurrent inflammatory bowel disease (IBD). As the first Iranian population cohort, we examined how gut microbiota and their functional profiles change in Iranian rCDI patients with underlying IBD before and after FMT.<br><br>Patients and Methods: FMT was performed to eight IBD patients via colonoscopy. Profiles of gut microbiota from donors and recipients were investigated using 16S rRNA gene sequence analysis.<br><br>Results: Patients experienced no IBD flare-ups or other adverse effects, and all recovered to full health. Moreover, all rCDI patients lacked the Bacteroidetes present in donor samples. After FMT, the proportion of Bacteroidetes increased until a normal range was achieved. More specifically, the relative abundance of Prevotella was found to increase significantly following FMT. Prevotella was also found to correlate negatively with inflammation metrics, suggesting that Prevotella may be a key factor for resolving CDI and IBD. Gut microbiota diversity was found to increase following FMT, while dysbiosis decreased. However, the similarity of microbial communities of host and recipients did not increase, and wide variation in the extent of donor stool engraftment indicated that the gut bacterial communities of recipients do not shift towards those of donors.<br><br>Conclusion: FMT leads to significant alterations of the community structure of gut bacteria in rCDI patients with IBD. The change in relative abundance of Proteobacteria and bacterial diversity indicated that FMT promotes recovery from intestinal permeability and inflammation in rCDI patients. Moreover, strong negative correlation between Prevotella and inflammation index, and decreased dysbiosis index advocate that the improvement of CDI is possibly due to gut microbiome alteration. Collectively, our findings show that FMT would be a promising therapy to help reprogram the gut microbiome of Iranian rCDI patients with IBD.}, }
@article {pmid33443023, year = {2021}, author = {Zhang, C and Xiong, B and Chen, L and Ge, W and Yin, S and Feng, Y and Sun, Z and Sun, Q and Zhao, Y and Shen, W and Zhang, H}, title = {Rescue of male fertility following faecal microbiota transplantation from alginate oligosaccharide-dosed mice.}, journal = {Gut}, volume = {70}, number = {11}, pages = {2213-2215}, pmid = {33443023}, issn = {1468-3288}, mesh = {Alginates ; Animals ; *Fecal Microbiota Transplantation ; Fertility ; *Gastrointestinal Microbiome ; Male ; Mice ; Oligosaccharides ; }, }
@article {pmid35017486, year = {2022}, author = {Hu, H and Shao, W and Liu, Q and Liu, N and Wang, Q and Xu, J and Zhang, X and Weng, Z and Lu, Q and Jiao, L and Chen, C and Sun, H and Jiang, Z and Zhang, X and Gu, A}, title = {Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion.}, journal = {Nature communications}, volume = {13}, number = {1}, pages = {252}, pmid = {35017486}, issn = {2041-1723}, support = {81770626//National Natural Science Foundation of China (National Science Foundation of China)/ ; 91839102//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81770625//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81573174//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82070654//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Cholesterol gallstone disease is a worldwide common disease. Cholesterol supersaturation in gallbladder bile is the prerequisite for its pathogenesis, while the mechanism is not completely understood. In this study, we find enrichment of gut microbiota (especially Desulfovibrionales) in patients with gallstone disease. Fecal transplantation of gut microbiota from gallstone patients to gallstone-resistant strain of mice can induce gallstone formation. Carrying Desulfovibrionales is associated with enhanced cecal secondary bile acids production and increase of bile acid hydrophobicity facilitating intestinal cholesterol absorption. Meanwhile, the metabolic product of Desulfovibrionales, H2S increase and is shown to induce hepatic FXR and inhibit CYP7A1 expression. Mice carrying Desulfovibrionales present induction of hepatic expression of cholesterol transporters Abcg5/g8 to promote biliary secretion of cholesterol as well. Our study demonstrates the role of gut microbiota, Desulfovibrionales, as an environmental regulator contributing to gallstone formation through its influence on bile acid and cholesterol metabolism.}, }
@article {pmid34245901, year = {2021}, author = {Reigadas, E and van Prehn, J and Falcone, M and Fitzpatrick, F and Vehreschild, MJGT and Kuijper, EJ and Bouza, E and , }, title = {How to: prophylactic interventions for prevention of Clostridioides difficile infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {27}, number = {12}, pages = {1777-1783}, doi = {10.1016/j.cmi.2021.06.037}, pmid = {34245901}, issn = {1469-0691}, mesh = {*Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile ; *Clostridium Infections/prevention &amp; control/therapy ; *Fecal Microbiota Transplantation ; Humans ; Recurrence ; }, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) remains the leading cause of healthcare-associated diarrhoea, despite existing guidelines for infection control measures and antimicrobial stewardship. The high associated health and economic burden of CDI calls for novel strategies to prevent the development and spread of CDI in susceptible patients.<br><br>OBJECTIVES: We aim to review CDI prophylactic treatment strategies and their implementation in clinical practice.<br><br>SOURCES: We searched PubMed, Embase, Emcare, Web of Science, and the COCHRANE Library databases to identify prophylactic interventions aimed at prevention of CDI. The search was restricted to articles published in English since 2012.<br><br>CONTENT: A toxin-based vaccine candidate is currently being investigated in a phase III clinical trial. However, a recent attempt to develop a toxin-based vaccine has failed. Conventional probiotics have not yet proved to be an effective strategy for prevention of CDI. New promising microbiota-based interventions that bind and inactivate concomitantly administered antibiotics, such as ribaxamase and DAV-132, have been developed. Prophylaxis of CDI with C. difficile antibiotics should not be performed routinely and should be considered only for secondary prophylaxis in very selected patients who are at the highest imminent risk for recurrent CDI (R-CDI) after a thorough evaluation. Faecal microbiota transplantation (FMT) has proved to be a very effective treatment for patients with multiple recurrences. Bezlotoxumab provides protection against R-CDI, mainly in patients with primary episodes and a high risk of relapse.<br><br>IMPLICATIONS: There are no proven effective, evidenced-based prophylaxis options for primary CDI. As for secondary prevention, FMT is considered the option of choice in patients with multiple recurrences. Bezlotoxumab can be added to standard treatment for patients at high risk for R-CDI. The most promising strategies are those aimed at reducing changes in intestinal microbiota and development of a new effective non-toxin-based vaccine.}, }
@article {pmid33514598, year = {2021}, author = {Arnoriaga-Rodríguez, M and Mayneris-Perxachs, J and Contreras-Rodríguez, O and Burokas, A and Ortega-Sanchez, JA and Blasco, G and Coll, C and Biarnés, C and Castells-Nobau, A and Puig, J and Garre-Olmo, J and Ramos, R and Pedraza, S and Brugada, R and Vilanova, JC and Serena, J and Barretina, J and Gich, J and Pérez-Brocal, V and Moya, A and Fernández-Real, X and Ramio-Torrentà, L and Pamplona, R and Sol, J and Jové, M and Ricart, W and Portero-Otin, M and Maldonado, R and Fernández-Real, JM}, title = {Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways.}, journal = {Gut}, volume = {70}, number = {12}, pages = {2283-2296}, pmid = {33514598}, issn = {1468-3288}, mesh = {Adult ; Aged ; Amino Acids, Aromatic/*metabolism ; Animals ; Carbon/*metabolism ; Cross-Sectional Studies ; Fatty Liver/microbiology ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; *Inhibition, Psychological ; Male ; Mice ; Middle Aged ; Obesity/*complications ; Phenotype ; Transcriptome ; }, abstract = {BACKGROUND: Inhibitory control (IC) is critical to keep long-term goals in everyday life. Bidirectional relationships between IC deficits and obesity are behind unhealthy eating and physical exercise habits.<br><br>METHODS: We studied gut microbiome composition and functionality, and plasma and faecal metabolomics in association with cognitive tests evaluating inhibitory control (Stroop test) and brain structure in a discovery (n=156), both cross-sectionally and longitudinally, and in an independent replication cohort (n=970). Faecal microbiota transplantation (FMT) in mice evaluated the impact on reversal learning and medial prefrontal cortex (mPFC) transcriptomics.<br><br>RESULTS: An interplay among IC, brain structure (in humans) and mPFC transcriptomics (in mice), plasma/faecal metabolomics and the gut metagenome was found. Obesity-dependent alterations in one-carbon metabolism, tryptophan and histidine pathways were associated with IC in the two independent cohorts. Bacterial functions linked to one-carbon metabolism (thyX,dut, exodeoxyribonuclease V), and the anterior cingulate cortex volume were associated with IC, cross-sectionally and longitudinally. FMT from individuals with obesity led to alterations in mice reversal learning. In an independent FMT experiment, human donor's bacterial functions related to IC deficits were associated with mPFC expression of one-carbon metabolism-related genes of recipient's mice.<br><br>CONCLUSION: These results highlight the importance of targeting obesity-related impulsive behaviour through the induction of gut microbiota shifts.}, }
@article {pmid35014601, year = {2022}, author = {Singh, P and Alm, EJ and Kelley, JM and Cheng, V and Smith, M and Kassam, Z and Nee, J and Iturrino, J and Lembo, A}, title = {Effect of antibiotic pretreatment on bacterial engraftment after Fecal Microbiota Transplant (FMT) in IBS-D.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2020067}, doi = {10.1080/19490976.2021.2020067}, pmid = {35014601}, issn = {1949-0984}, abstract = {Fecal microbiota transplantation (FMT) is an attractive strategy to correct microbial dysbiosis in diarrhea-predominant irritable bowel syndrome (IBS-D). Although the mechanism of FMT is thought to be bacterial engraftment, the best approach to achieve engraftment after FMT in IBS-D (and other diseases) is not clear. We evaluated the effect of FMT (with or without pretreatment with antibiotics) on gut microbiome and symptoms in patients with IBS-D. In this randomized, placebo-controlled, single-center study, 44 patients with IBS-D with a least moderate severity (IBS severity scoring system, i.e., IBS-SSS, ≥175) were randomly assigned to one of four groups: single-dose oral FMT alone, single-dose oral FMT following a 7-day pretreatment course of Ciprofloxacin and Metronidazole (CM-FMT) or Rifaximin (R-FMT), or Placebo FMT. Primary endpoint was engraftment post-FMT and secondary endpoints were changes in IBS-SSS, and IBS-quality of life (IBS-QOL) at week 10. Median engraftment was significantly different among the three FMT groups (P = .013). Engraftment post-FMT was significantly higher in the FMT alone arm (15.5%) compared to that in R-FMT group (5%, P = .04) and CM-FMT group (2.4%, P = .002). The mean change in IBS-SSS and IBS-QOL from baseline were not significantly different among the four groups or between the three FMT groups combined vs. placebo at week 10. In summary, antibiotic pretreatment significantly reduced bacterial engraftment after FMT in patients with IBS-D.}, }
@article {pmid35011199, year = {2021}, author = {Chen, S and Luo, S and Yan, C}, title = {Gut Microbiota Implications for Health and Welfare in Farm Animals: A Review.}, journal = {Animals : an open access journal from MDPI}, volume = {12}, number = {1}, pages = {}, doi = {10.3390/ani12010093}, pmid = {35011199}, issn = {2076-2615}, support = {2019A1515110598//the Joint Fund of Basic and Applied Basic Research Fund of Guangdong Province/ ; 2019B030301010//the Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding/ ; }, abstract = {In the past few decades, farm animal health and welfare have been paid increasing concern worldwide. Farm animal health and welfare are generally assessed by the measurements of physical health, immune response, behavior, and physiological indicators. The gut microbiota has been reported to have a great influence on host phenotypes, possibly via the immune processes, neural functions, and endocrine pathways, thereby influencing host phenotypes. However, there are few reviews regarding farm animals' health and welfare status concerning the gut microbiota. In this point of view, (1) we reviewed recent studies showing that gut microbiota (higher alpha diversity, beneficial composition, and positive functions) effectively influenced health characteristics, immunity, behaviors, and stress response in farm animals (such as pigs, chickens, and cows), which would provide a novel approach to measure and evaluate the health status and welfare of farm animals. In addition, fecal microbiota transplantation (FMT) as one of the methods can modulate the recipient individual's gut microbiota to realize the expected phenotype. Further, (2) we highlighted the application of FMT on the improvement of the production performance, the reduction in disease and abnormal behavior, as well as the attenuation of stress in farm animals. It is concluded that the gut microbiota can be scientifically used to assess and improve the welfare of farm animals. Moreover, FMT may be a helpful strategy to reduce abnormal behavior and improve stress adaption, as well as the treatment of disease for farm animals. This review suggests that gut microbiota is a promising field to evaluate and improve animal welfare.}, }
@article {pmid35011044, year = {2021}, author = {Iatcu, CO and Steen, A and Covasa, M}, title = {Gut Microbiota and Complications of Type-2 Diabetes.}, journal = {Nutrients}, volume = {14}, number = {1}, pages = {}, doi = {10.3390/nu14010166}, pmid = {35011044}, issn = {2072-6643}, support = {120/16.09.2016.//European Regional Development Fund through Competitiveness Operational Program/ ; }, abstract = {The gut microbiota has been linked to the emergence of obesity, metabolic syndrome and the onset of type 2 diabetes through decreased glucose tolerance and insulin resistance. Uncontrolled diabetes can lead to serious health consequences such as impaired kidney function, blindness, stroke, myocardial infarction and lower limb amputation. Despite a variety of treatments currently available, cases of diabetes and resulting complications are on the rise. One promising new approach to diabetes focuses on modulating the gut microbiota with probiotics, prebiotics, synbiotics and fecal microbial transplantation. Differences in gut microbiota composition have been observed in preclinical animal models as well as patients with type 2 diabetes and complications such as diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, cerebrovascular disease, coronary heart disease and peripheral artery disease compared to healthy controls. Severity of gut microbiota dysbiosis was associated with disease severity and restoration with probiotic administration in animal models and human patients has been associated with improvement of symptoms and disease progression. Characterizing the gut microbiota dysbiosis in different diseases and determining a causal relationship between the gut microbiota and disease can be beneficial in formulating therapeutic interventions for type 2 diabetes and associated complications. In this review, we present the most important findings regarding the role of the gut microbiota in type 2 diabetes and chronic complications as well as their underlying mechanisms.}, }
@article {pmid35010223, year = {2021}, author = {Liu, P and Zhou, W and Xu, W and Peng, Y and Yan, Y and Lu, L and Mi, J and Zeng, X and Cao, Y}, title = {The Main Anthocyanin Monomer from Lycium ruthenicum Murray Fruit Mediates Obesity via Modulating the Gut Microbiota and Improving the Intestinal Barrier.}, journal = {Foods (Basel, Switzerland)}, volume = {11}, number = {1}, pages = {}, doi = {10.3390/foods11010098}, pmid = {35010223}, issn = {2304-8158}, support = {2019BFG02026//Research and Development Project funded by Ningxia Hui Autonomous Region of China/ ; PAPD//Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; }, abstract = {Anthocyanins have been shown to exert certain antiobesity properties, but the specific relationship between anthocyanin-induced beneficial effects and the gut microbiota remains unclear. Petunidin-3-O-[rhamnopyranosyl-(trans-p-coumaroyl)]-5-O-(β-D-glucopyranoside) (P3G) is the main anthocyanin monomer from the fruit of Lycium ruthenicum Murray. Therefore, in this study, we investigated the antiobesity and remodeling effects of P3G on gut microbiota through a high-fat diet (HFD)-induced obesity mouse model and a fecal microbiota transplantation experiment. P3G was found to reduce body weight gain, fat accumulation, and liver steatosis in HFD-induced obese mice. Moreover, supplementation with P3G alleviated the HFD-induced imbalance in gut microbiota composition, and transferring the P3G-regulated gut microbiota to recipient mice provided comparable protection against obesity. This is the first time evidence is provided that P3G has an antiobesity effect by changing the intestinal microbiota. Our present data highlight a link between P3G intervention and enhancement in gut barrier integrity. This may be a promising option for obesity prevention.}, }
@article {pmid35008915, year = {2022}, author = {Sevcikova, A and Izoldova, N and Stevurkova, V and Kasperova, B and Chovanec, M and Ciernikova, S and Mego, M}, title = {The Impact of the Microbiome on Resistance to Cancer Treatment with Chemotherapeutic Agents and Immunotherapy.}, journal = {International journal of molecular sciences}, volume = {23}, number = {1}, pages = {}, doi = {10.3390/ijms23010488}, pmid = {35008915}, issn = {1422-0067}, support = {APVV-19-0411, APVV-20-0158//Slovak Research and Development Agency/ ; 1/0327/19, 2/0069/22//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; }, abstract = {Understanding the mechanisms of resistance to therapy in human cancer cells has become a multifaceted limiting factor to achieving optimal cures in cancer patients. Besides genetic and epigenetic alterations, enhanced DNA damage repair activity, deregulation of cell death, overexpression of transmembrane transporters, and complex interactions within the tumor microenvironment, other mechanisms of cancer treatment resistance have been recently proposed. In this review, we will summarize the preclinical and clinical studies highlighting the critical role of the microbiome in the efficacy of cancer treatment, concerning mainly chemotherapy and immunotherapy with immune checkpoint inhibitors. In addition to involvement in drug metabolism and immune surveillance, the production of microbiota-derived metabolites might represent the link between gut/intratumoral bacteria and response to anticancer therapies. Importantly, an emerging trend of using microbiota modulation by probiotics and fecal microbiota transplantation (FMT) to overcome cancer treatment resistance will be also discussed.}, }
@article {pmid34718953, year = {2022}, author = {Bhattacharjee, A and Dubey, S and Sharma, S}, title = {Storage of soil microbiome for application in sustainable agriculture: prospects and challenges.}, journal = {Environmental science and pollution research international}, volume = {29}, number = {3}, pages = {3171-3183}, pmid = {34718953}, issn = {1614-7499}, support = {BT/PR27680/BCE/8/1434/2018//Department of Biotechnology , Ministry of Science and Technology/ ; PDF/2018/001905//Science and Engineering Research Board/ ; fellowship//Indian Institute of Technology Delhi/ ; }, mesh = {Agriculture ; *Microbiota ; *Soil ; Soil Microbiology ; }, abstract = {Soil microbiome is a dynamic micro-ecosystem driving and fine-tuning several biological processes in the global macro-ecosystems. Its tremendous potential towards mediating sustainability in the ecosystem necessitates the urgent need to store it optimally and efficiently as "next-generation biologicals" for future applications via soil transplantation. The challenge, therefore, is to devise a strategy for the storage of soil microbiome such that its "functionality" is preserved for later application. This review discusses the current endeavours made towards storage of the soil microbiome. The methods for assessing the integrity of soil microbiome by targeting the structural diversity and functional potential of the preserved microbiomes have also been discussed. Further, the success stories related to the storage of fecal microbiome for application in transplants have also been highlighted. This is done primarily with the objective of learning lessons, and parallel application of the knowledge gained, in bringing about improvement in the research domain of soil microbiome storage. Subsequently, the limitations of current techniques of preservation have also been delineated. Further, the open questions in the area have been critically discussed. In conclusion, possible alternatives for storage, comprehensive analyses of the composition of the stored microbiome and their potential have been presented.}, }
@article {pmid35004750, year = {2021}, author = {Wang, H and Wang, H and Sun, Y and Ren, Z and Zhu, W and Li, A and Cui, G}, title = {Potential Associations Between Microbiome and COVID-19.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {785496}, doi = {10.3389/fmed.2021.785496}, pmid = {35004750}, issn = {2296-858X}, abstract = {The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has plunged the world into a major crisis. The disease is characterized by strong infectivity, high morbidity, and high mortality. It is still spreading in some countries. Microbiota and their metabolites affect human physiological health and diseases by participating in host digestion and nutrition, promoting metabolic function, and regulating the immune system. Studies have shown that human microecology is associated with many diseases, including COVID-19. In this research, we first reviewed the microbial characteristics of COVID-19 from the aspects of gut microbiome, lung microbime, and oral microbiome. We found that significant changes take place in both the gut microbiome and airway microbiome in patients with COVID-19 and are characterized by an increase in conditional pathogenic bacteria and a decrease in beneficial bacteria. Then, we summarized the possible microecological mechanisms involved in the progression of COVID-19. Intestinal microecological disorders in individuals may be involved in the occurrence and development of COVID-19 in the host through interaction with ACE2, mitochondria, and the lung-gut axis. In addition, fecal bacteria transplantation (FMT), prebiotics, and probiotics may play a positive role in the treatment of COVID-19 and reduce the fatal consequences of the disease.}, }
@article {pmid35003127, year = {2021}, author = {Yuan, B and Lu, XJ and Wu, Q}, title = {Gut Microbiota and Acute Central Nervous System Injury: A New Target for Therapeutic Intervention.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {800796}, doi = {10.3389/fimmu.2021.800796}, pmid = {35003127}, issn = {1664-3224}, abstract = {Acute central nervous system (CNS) injuries, including stroke, traumatic brain injury (TBI), and spinal cord injury (SCI), are the common causes of death or lifelong disabilities. Research into the role of the gut microbiota in modulating CNS function has been rapidly increasing in the past few decades, particularly in animal models. Growing preclinical and clinical evidence suggests that gut microbiota is involved in the modulation of multiple cellular and molecular mechanisms fundamental to the progression of acute CNS injury-induced pathophysiological processes. The altered composition of gut microbiota after acute CNS injury damages the equilibrium of the bidirectional gut-brain axis, aggravating secondary brain injury, cognitive impairments, and motor dysfunctions, which leads to poor prognosis by triggering pro-inflammatory responses in both peripheral circulation and CNS. This review summarizes the studies concerning gut microbiota and acute CNS injuries. Experimental models identify a bidirectional communication between the gut and CNS in post-injury gut dysbiosis, intestinal lymphatic tissue-mediated neuroinflammation, and bacterial-metabolite-associated neurotransmission. Additionally, fecal microbiota transplantation, probiotics, and prebiotics manipulating the gut microbiota can be used as effective therapeutic agents to alleviate secondary brain injury and facilitate functional outcomes. The role of gut microbiota in acute CNS injury would be an exciting frontier in clinical and experimental medicine.}, }
@article {pmid35000023, year = {2022}, author = {Suchman, K and Luo, Y and Grinspan, A}, title = {Fecal Microbiota Transplant for Clostridioides Difficile Infection Is Safe and Efficacious in an Immunocompromised Cohort.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {35000023}, issn = {1573-2568}, abstract = {BACKGROUND: Immunocompromised patients are particularly vulnerable to Clostridioides difficile infection (CDI), hospitalizations and recurrences. Studies have shown that fecal microbiota transplant (FMT) is safe and effective in immunocompromised patients.<br><br>AIMS: To examine the outcomes of FMT for CDI in a diverse cohort of immunocompromised patients stratified by medication class.<br><br>METHODS: We performed a retrospective, long-term follow-up study of FMT in immunocompromised patients, including those undergoing chemotherapy, with inflammatory bowel disease (IBD) on immunomodulators, prior solid organ transplant on immunosuppressants, on chronic steroids 20 mg/day or higher for a minimum of three months, or HIV positive. Primary outcomes included adjusted primary cure rate within 8 weeks, as well as rates of non-response, recurrences, relapses and adverse events. Secondary outcomes included adjusted overall cure rate. Primary cure rate was defined as patients not requiring repeat CDI treatment within 8 weeks after index FMT, and overall cure rate was defined as resolution of CDI symptoms after index FMT or second FMT.<br><br>RESULTS: Our cohort included 77 immunosuppressed patients (53.2% female, median age 39.1 years, range 7-95 years). The majority of our cohort were IBD patients on biologics (62.3%). Adjusting for colectomies and deaths, our primary and overall cure rates were 85.1% and 86.5%, respectively. Twelve patients received FMT for severe or fulminant CDI with a 3-month survival rate of 91.7%. 11.7% of patients experienced serious adverse events following FMT.<br><br>CONCLUSIONS: Our study supports the efficacy and safety of FMT in immunocompromised patients, though future research is needed to further ascertain the potential effects of immunosuppression on FMT outcomes.}, }
@article {pmid34873153, year = {2021}, author = {Gao, A and Su, J and Liu, R and Zhao, S and Li, W and Xu, X and Li, D and Shi, J and Gu, B and Zhang, J and Li, Q and Wang, X and Zhang, Y and Xu, Y and Lu, J and Ning, G and Hong, J and Bi, Y and Gu, W and Wang, J and Wang, W}, title = {Sexual dimorphism in glucose metabolism is shaped by androgen-driven gut microbiome.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {7080}, pmid = {34873153}, issn = {2041-1723}, mesh = {3T3-L1 Cells ; Androgens/*pharmacology ; Animals ; Anti-Bacterial Agents/pharmacology ; Cell Line ; Dihydrotestosterone/pharmacology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects/genetics/physiology ; Glucose/*metabolism ; Glutamic Acid/blood ; Glutamine/blood ; Hep G2 Cells ; Homeostasis/*drug effects ; Humans ; Insulin Resistance/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Orchiectomy ; Sex Factors ; }, abstract = {Males are generally more susceptible to impaired glucose metabolism and type 2 diabetes (T2D) than females. However, the underlying mechanisms remain to be determined. Here, we revealed that gut microbiome depletion abolished sexual dimorphism in glucose metabolism. The transfer of male donor microbiota into antibiotics-treated female mice led the recipients to be more insulin resistant. Depleting androgen via castration changed the gut microbiome of male mice to be more similar to that of females and improved glucose metabolism, while reintroducing dihydrotestosterone (DHT) reversed these alterations. More importantly, the effects of androgen on glucose metabolism were largely abolished when the gut microbiome was depleted. Next, we demonstrated that androgen modulated circulating glutamine and glutamine/glutamate (Gln/Glu) ratio partially depending on the gut microbiome, and glutamine supplementation increases insulin sensitivity in vitro. Our study identifies the effects of androgen in deteriorating glucose homeostasis partially by modulating the gut microbiome and circulating glutamine and Gln/Glu ratio, thereby contributing to the difference in glucose metabolism between the two sexes.}, }
@article {pmid34864063, year = {2022}, author = {Pradhan, S and Ray, P and Aich, P}, title = {Microbiota transplantation from younger to older mice could restore lost immunity to effectively clear salmonella infection in Th2-biased BALB/c mice.}, journal = {Life sciences}, volume = {288}, number = {}, pages = {120201}, doi = {10.1016/j.lfs.2021.120201}, pmid = {34864063}, issn = {1879-0631}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bacteria/*growth &amp; development ; Cecum/*transplantation ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Homeostasis ; Immunity, Innate ; Male ; Metabolome ; Metagenomics ; Mice ; Mice, Inbred BALB C ; Salmonella/drug effects/genetics/*immunology/metabolism ; Salmonella Infections/immunology/metabolism/microbiology/*therapy ; Th2 Cells/*immunology ; }, abstract = {AIMS: The composition, overtly abundance, and diversity of gut microbiota, play a significant role in maintaining physiological homeostasis with age. Reports revealed that the gut microbial profile might be correlated with immunity and metabolism. It is, therefore, tantamount to know if an older individual can achieve the immunity and metabolic profile of a younger individual by receiving the gut microbiome of a younger individual. In the current report, we have studied the effects of cecal microbiota transplantation (CMT) from younger to older mice.<br><br>MATERIALS AND METHODS: In this study, older BALB/c mice (23 weeks) received CMT from younger BALB/c mice (3 weeks).<br><br>KEY FINDINGS: CMT recipient mice showed altered expressions of immune and tight junction protein genes in the colon of mice, while the non-CMT recipient mice did not. Older mice were treated with AVNM to make them compatible with CMT. Further data from metabolite studies revealed that AVNM treatment mainly affected the aromatic amino acid biosynthesis pathway while CMT mostly affected the metabolism of different carbohydrates. We repeated the analysis in C57BL/6 mice without any significant effects of CMT.<br><br>SIGNIFICANCE: Results revealed that mice who received CMT showed more efficient restoration of gut microbiota than non-CMT recipient mice. CMT caused the alleviation of Salmonella infection and efficient recovery of the cecal index in the mice following antibiotics treatment.}, }
@article {pmid34838850, year = {2022}, author = {Chen, L and Li, R and Wang, Z and Zhang, Z and Wang, J and Qiao, Y and Huang, Y and Liu, W}, title = {Lactate-utilizing bacteria ameliorates DSS-induced colitis in mice.}, journal = {Life sciences}, volume = {288}, number = {}, pages = {120179}, doi = {10.1016/j.lfs.2021.120179}, pmid = {34838850}, issn = {1879-0631}, mesh = {Adult ; Animals ; Bacteria/*growth &amp; development ; Colitis/chemically induced/microbiology/pathology/*prevention &amp; control ; Dextran Sulfate/*toxicity ; Dysbiosis/chemically induced/microbiology/pathology/prevention &amp; control ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Female ; Humans ; Lactic Acid/*metabolism ; Male ; Mice, Inbred C57BL ; Probiotics/*administration &amp; dosage ; Young Adult ; }, abstract = {Inflammatory bowel diseases (IBD) stem from alterations in the intestinal immune system and microbial dysbiosis, but the precise interactions between bacteria and IBD remain obscure. The commensal microbiota have a profound impact on human health and diseases. Here, we developed a selective culture medium for lactate-utilizing bacteria (LUB) that function as candidate probiotics to ameliorate IBD using a mouse model. Firstly, LUB, including Megasphaera, were enriched from human faeces using a selective medium with lactate. LUB efficiently attenuated the pathology of colitis induced by dextran sulphate sodium (DSS). Next, LUB administration counteracted the dysbiosis associated with the intestinal inflammatory process, and elevated the proportion of Escherichia-Shigella in intestines. Moreover, E. coli isolated from healthy faeces downstream recapitulated lactate-utilizing bacterial community to ameliorate the severity of DSS-induced acute colitis. In conclusion, our finding revealed that LUB were sufficient to exert inflammatory protection against colitis in mice, highlighting a novel therapeutic strategy to use LUB as potentially curable probiotics for therapeutic manipulation for IBD.}, }
@article {pmid33870869, year = {2021}, author = {Wuethrich, I and W Pelzer, B and Khodamoradi, Y and Vehreschild, MJGT}, title = {The role of the human gut microbiota in colonization and infection with multidrug-resistant bacteria.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-13}, pmid = {33870869}, issn = {1949-0984}, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects ; Bacterial Infections/*immunology/*microbiology/*therapy/virology ; Bacteriophages ; Biological Therapy ; *Drug Resistance, Multiple, Bacterial ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Host Microbial Interactions ; Humans ; *Immunity ; Prebiotics ; Probiotics ; Vaccines ; }, abstract = {About 100 years ago, the first antibiotic drug was introduced into health care. Since then, antibiotics have made an outstanding impact on human medicine. However, our society increasingly suffers from collateral damage exerted by these highly effective drugs. The rise of resistant pathogen strains, combined with a reduction of microbiota diversity upon antibiotic treatment, has become a significant obstacle in the fight against invasive infections worldwide.Alternative and complementary strategies to classical "Fleming antibiotics" comprise microbiota-based treatments such as fecal microbiota transfer and administration of probiotics, live-biotherapeutics, prebiotics, and postbiotics. Other promising interventions, whose efficacy may also be influenced by the human microbiota, are phages and vaccines. They will facilitate antimicrobial stewardship, to date the only globally applied antibiotic resistance mitigation strategy.In this review, we present the available evidence on these nontraditional interventions, highlight their interaction with the human microbiota, and discuss their clinical applicability.}, }
@article {pmid33563544, year = {2021}, author = {Liwinski, T and Leshem, A and Elinav, E}, title = {Breakthroughs and Bottlenecks in Microbiome Research.}, journal = {Trends in molecular medicine}, volume = {27}, number = {4}, pages = {298-301}, doi = {10.1016/j.molmed.2021.01.003}, pmid = {33563544}, issn = {1471-499X}, mesh = {Diet ; Fecal Microbiota Transplantation ; Host Microbial Interactions ; Humans ; Metagenomics/methods ; *Microbiota/drug effects/genetics/immunology ; Phage Therapy ; Precision Medicine/trends ; Probiotics ; }, abstract = {Over the past 15 years, the research community has witnessed unprecedented progress in microbiome research. We review this increasing knowledge and first attempts of its clinical application, and also limitations and challenges faced by the research community, in mechanistically understanding host-microbiome interactions and integrating these insights into clinical practice.}, }
@article {pmid33303563, year = {2021}, author = {Haifer, C and Saikal, A and Paramsothy, R and Kaakoush, NO and Leong, RW and Borody, TJ and Kamm, MA and Paramsothy, S}, title = {Response to faecal microbiota transplantation in ulcerative colitis is not sustained long term following induction therapy.}, journal = {Gut}, volume = {70}, number = {11}, pages = {2210-2211}, doi = {10.1136/gutjnl-2020-323581}, pmid = {33303563}, issn = {1468-3288}, mesh = {*Colitis, Ulcerative/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Induction Chemotherapy ; }, }
@article {pmid34992678, year = {2021}, author = {Sandhu, A and Chopra, T}, title = {Fecal microbiota transplantation for recurrent Clostridioides difficile, safety, and pitfalls.}, journal = {Therapeutic advances in gastroenterology}, volume = {14}, number = {}, pages = {17562848211053105}, doi = {10.1177/17562848211053105}, pmid = {34992678}, issn = {1756-283X}, abstract = {Clostridioides difficile infection (CDI) is one of the leading causes of hospital-acquired infection attributing to substantial morbidity, mortality, and healthcare cost. Recurrent CDI (rCDI) is common and occurs after effective treatment of first episode. Treatment of rCDI is based on accurate diagnoses, due to difficulty in distinguishing between colonization of C. difficile spores or CDI; coronavirus disease 2019 (COVID-19) added to the complexity of diagnoses as both entities can co-occur. It is difficult to eradicate rCDI, and there remains a critical gap regarding treatment of rCDI. The treatment goal of rCDI is to reestablish normal microbiota. Fecal microbiota transplantation (FMT) is suggested as a treatment for second episode of rCDI. Based on the collective evidence of all randomized controlled trials, FMT was reported more efficacious compared with vancomycin or fidaxomicin; however, these trials had limited number of patients and all patients were pre-treated with vancomycin prior to FMT. Furthermore, when comparing various routes of instillation and types of preparation of fecal microbiota, no difference was observed in cure rate. Despite the success rate of FMT, there remains a concern for transmission of infectious agents, such as Gram negative bacteremia or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), adverse events (diarrhea and abdominal pain), and reports of new diagnoses (inflammatory bowel disease, weight gain and irritable bowel syndrome). To lessen the risk of transmissible infections, donor screening should be performed, which includes screening for medical comorbidities and infectious pathogens in blood and feces. Scheduling complexities and reimbursement places an additional roadblock for using FMT. Microbiome-based therapies are being developed to eliminate the logistical challenges related to FMT. Large prospective and placebo-controlled studies are needed to evaluate the efficacy and long-term safety of FMT, so its use can be justified in clinical practice.}, }
@article {pmid34992606, year = {2021}, author = {Lai, J and Zhang, P and Jiang, J and Mou, T and Li, Y and Xi, C and Wu, L and Gao, X and Zhang, D and Chen, Y and Huang, H and Li, H and Cai, X and Li, M and Zheng, P and Hu, S}, title = {New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {789647}, doi = {10.3389/fimmu.2021.789647}, pmid = {34992606}, issn = {1664-3224}, abstract = {Tetratricopeptide repeat and ankyrin repeat containing 1 (TRANK1) is a robust risk gene of bipolar disorder (BD). However, little is known on the role of TRANK1 in the pathogenesis of BD and whether the gut microbiota is capable of regulating TRANK1 expression. In this study, we first investigated the serum mRNA level of TRANK1 in medication-free patients with a depressive episode of BD, then a mice model was constructed by fecal microbiota transplantation (FMT) to explore the effects of gut microbiota on brain TRANK1 expression and neuroinflammation, which was further verified by in vitro Lipopolysaccharide (LPS) treatment in BV-2 microglial cells and neurons. 22 patients with a depressive episode and 28 healthy individuals were recruited. Serum level of TRANK1 mRNA was higher in depressed patients than that of healthy controls. Mice harboring 'BD microbiota' following FMT presented depression-like phenotype. mRNA levels of inflammatory cytokines and TRANK1 were elevated in mice hippocampus and prefrontal cortex. In vitro, LPS treatment activated the secretion of pro-inflammatory factors in BV-2 cells, which was capable of upregulating the neuronal expression of TRANK1 mRNA. Moreover, primary cortical neurons transfected with plasmid Cytomegalovirus DNA (pcDNA3.1(+)) vector encoding human TRANK1 showed decreased dendritic spine density. Together, these findings add new evidence to the microbiota-gut-brain regulation in BD, indicating that microbiota is possibly involved in the neuropathogenesis of BD by modulating the expression of TRANK1.}, }
@article {pmid34846698, year = {2021}, author = {Wu, LH and Ye, ZN and Peng, P and Xie, WR and Xu, JT and Zhang, XY and Xia, HH and He, XX}, title = {Efficacy and Safety of Washed Microbiota Transplantation to Treat Patients with Mild-to-Severe COVID-19 and Suspected of Having Gut Microbiota Dysbiosis: Study Protocol for a Randomized Controlled Trial.}, journal = {Current medical science}, volume = {41}, number = {6}, pages = {1087-1095}, pmid = {34846698}, issn = {2523-899X}, mesh = {Adult ; Aged ; COVID-19/complications/*microbiology/*therapy ; China ; Clinical Protocols ; Dysbiosis/etiology/*microbiology/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; *Gastrointestinal Microbiome ; Humans ; Living Donors ; Male ; Middle Aged ; Prospective Studies ; *SARS-CoV-2 ; Safety ; Single-Blind Method ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: Coronavirus disease 2019 (COVID-19) is often accompanied by gastrointestinal symptoms, which are related to gut microbiota dysbiosis (GMD). Whether washed microbiota transplantation (WMT) is an effective treatment for COVID-19 patients suspected of having GMD by restoring the gut microbiota is unknown. This study is designed to explore the efficacy and safety of WMT in COVID-19 patients suspected of having GMD.<br><br>METHODS: This is a randomized, multicenter, single-blind prospective study. COVID-19 patients suspected of having GMD will be randomly divided to receive routine treatment only or to receive routine treatment and WMT. The frequency of WMT will be once a day for three consecutive days. Laboratory and imaging examinations will be performed at admission, 1 and 2 weeks after treatment, and on the day of discharge. Then a telephone follow-up will be conducted at 1st week, 2nd week, and 6th month after discharge. The clinical efficacy and safety of WMT in COVD-19 patients suspected of having GMD and the effects of WMT on the organ function, homeostasis, inflammatory response, intestinal mucosal barrier function, and immunity of the patients will be evaluated.<br><br>RESULTS: By following the proposed protocol, WMT is expected to be efficacious and safe for the treatment of COVID-19 patients suspected of having GMD, and the therapeutic effect is expected to be associated with improvement of the intestinal mucosal barrier function, inflammatory response, and immunity.<br><br>CONCLUSION: The findings from this study may offer a new approach for the prevention and treatment of COVID-19 patients suspected of having GMD.}, }
@article {pmid34580480, year = {2021}, author = {Wolter, M and Grant, ET and Boudaud, M and Steimle, A and Pereira, GV and Martens, EC and Desai, MS}, title = {Leveraging diet to engineer the gut microbiome.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {18}, number = {12}, pages = {885-902}, pmid = {34580480}, issn = {1759-5053}, mesh = {Autoimmune Diseases/immunology/*microbiology/physiopathology/*therapy ; Combined Modality Therapy ; Diet/*methods ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology/*physiology ; Humans ; Prebiotics ; Primary Prevention/methods ; Probiotics/therapeutic use ; }, abstract = {Autoimmune diseases, including inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, have distinct clinical presentations but share underlying patterns of gut microbiome perturbation and intestinal barrier dysfunction. Their potentially common microbial drivers advocate for treatment strategies aimed at restoring appropriate microbiome function, but individual variation in host factors makes a uniform approach unlikely. In this Perspective, we consolidate knowledge on diet-microbiome interactions in local inflammation, gut microbiota imbalance and host immune dysregulation. By understanding and incorporating the effects of individual dietary components on microbial metabolic output and host physiology, we examine the potential for diet-based therapies for autoimmune disease prevention and treatment. We also discuss tools targeting the gut microbiome, such as faecal microbiota transplantation, probiotics and orthogonal niche engineering, which could be optimized using custom dietary interventions. These approaches highlight paths towards leveraging diet for precise engineering of the gut microbiome at a time of increasing autoimmune disease.}, }
@article {pmid34508775, year = {2022}, author = {Lau, HC and Ng, SC and Yu, J}, title = {Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?.}, journal = {Gastroenterology}, volume = {162}, number = {1}, pages = {9-16}, pmid = {34508775}, issn = {1528-0012}, mesh = {COVID-19/etiology/*microbiology/therapy ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; Probiotics/therapeutic use ; *SARS-CoV-2 ; Severity of Illness Index ; }, }
@article {pmid34482269, year = {2021}, author = {Farshbafnadi, M and Agah, E and Rezaei, N}, title = {The second brain: The connection between gut microbiota composition and multiple sclerosis.}, journal = {Journal of neuroimmunology}, volume = {360}, number = {}, pages = {577700}, doi = {10.1016/j.jneuroim.2021.577700}, pmid = {34482269}, issn = {1872-8421}, mesh = {Animals ; *Brain-Gut Axis/immunology/physiology ; Disease Models, Animal ; Dysbiosis/*complications/physiopathology/therapy ; Encephalomyelitis, Autoimmune, Experimental/*microbiology/physiopathology ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred Strains ; Mice, Transgenic ; Multiple Sclerosis/etiology/*microbiology/physiopathology/therapy ; Neurodegenerative Diseases/etiology/immunology/microbiology ; Probiotics ; Rats ; Vitamin D/therapeutic use ; }, abstract = {Gut microbiota composition may affect the central nervous system (CNS) and immune function. Several studies have recently examined the possible link between gut microbiota composition and multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Most of these studies agree that patients with MS suffer from dysbiosis. Moreover, an altered proportion of certain phyla of bacteria was detected in the digestive tracts of these patients compared to healthy individuals. This review article gathers information from research papers that have examined the relationship between gut microbiota composition and MS and its possible mechanisms.}, }
@article {pmid33769200, year = {2021}, author = {Glenny, EM and Fouladi, F and Thomas, SA and Bulik-Sullivan, EC and Tang, Q and Djukic, Z and Trillo-Ordonez, YS and A Fodor, A and Tarantino, LM and M Bulik, C and M Carroll, I}, title = {Gut microbial communities from patients with anorexia nervosa do not influence body weight in recipient germ-free mice.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-15}, pmid = {33769200}, issn = {1949-0984}, support = {R01 MH119084/MH/NIMH NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; R01 MH105684/MH/NIMH NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; R01 MH118278/MH/NIMH NIH HHS/United States ; R01 MH120170/MH/NIMH NIH HHS/United States ; T32 DK007686/DK/NIDDK NIH HHS/United States ; P30 DK056350/DK/NIDDK NIH HHS/United States ; T32 DK007737/DK/NIDDK NIH HHS/United States ; U01 MH109528/MH/NIMH NIH HHS/United States ; }, mesh = {Adiposity ; Adult ; Animals ; Anorexia Nervosa/*microbiology ; Bacteria/*growth &amp; development ; *Body Weight ; Cecum/physiology ; Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Germ-Free Life ; Humans ; Male ; Mice ; Organ Size ; }, abstract = {Anorexia nervosa (AN) is a psychiatric disorder that presents with profound weight dysregulation, metabolic disturbances, and an abnormal composition of gut microbial communities. As the intestinal microbiota can influence host metabolism, the impact of enteric microbial communities from patients with AN on host weight and adiposity was investigated. Germ-free (GF) mice were colonized with fecal microbiotas from either patients with AN (n = 4) prior to inpatient treatment (AN T1, n = 50 recipient mice), the same 4 patients following clinical renourishment (AN T2, n = 53 recipient mice), or age- and sex-matched non-AN controls (n = 4 human donors; non-AN, n = 50 recipient mice). Biological and fecal microbiota data were analyzed with linear mixed-effects models. Body weight did not differ significantly between AN recipient mice (T1 and T2) and non-AN recipient mice following 4 weeks of colonization. Enteric microbiotas from recipient mice colonized with AN T1 and AN T2 fecal microbiotas were more similar to each other compared with enteric microbiotas from non-AN recipient mice. Specific bacterial families in the Actinobacteria, Bacteroidetes, and Firmicutes phyla were significantly associated with body weight, fat mass, and cecum weight irrespective of the donor group. These data suggest that body weight, fat mass, and cecum weight of colonized GF mice are associated with human fecal microbes and independent of donor AN status, although additional analyses with larger cohorts are warranted.}, }
@article {pmid33691599, year = {2021}, author = {Meng, Q and Ma, M and Zhang, W and Bi, Y and Cheng, P and Yu, X and Fu, Y and Chao, Y and Ji, T and Li, J and Chen, Q and Zhang, Q and Li, Y and Shan, J and Bian, H}, title = {The gut microbiota during the progression of atherosclerosis in the perimenopausal period shows specific compositional changes and significant correlations with circulating lipid metabolites.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-27}, pmid = {33691599}, issn = {1949-0984}, mesh = {Animals ; Atherosclerosis/*microbiology/*physiopathology ; Bacteria/growth &amp; development ; Diet, High-Fat ; Disease Progression ; Estradiol/administration &amp; dosage ; Estrogen Replacement Therapy ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; *Lipid Metabolism ; Lipids/blood ; Metabolomics ; Mice ; Mice, Inbred C57BL ; Ovariectomy ; *Perimenopause ; }, abstract = {Atherosclerosis (AS) is exacerbated in the perimenopausal period, which significantly increases the incidence rate of cardiovascular disease. The disruption of the gut microbiota has been associated with AS or menopause, but the specific changes of AS-associated gut microbiota in the perimenopausal period remain largely unknown. As lipid abnormalities are mainly responsible for AS, the relationship between lipid metabolism abnormalities and gut microbiota disruptions during menopause is rarely reported hitherto. In the present study, ApoE-/- mice fed with a high-fat diet (HFD) were subjected to ovariectomy and supplemented with estrogen. The ovariectomized HFD-fed ApoE-/- mice underwent significant AS damage, hepatic lipid damage, hyperlipidemia, and changes of lipid metabolism- and transport-related enzymes. There was significantly higher abundance of some lipid metabolites in the plasma of ovariectomized HFD-fed ApoE-/- mice than in non-ovariectomized ones, including cholesterol esters, triglycerides, phospholipids, and other types of lipids (free fatty acids, acylcarnitine, sphingomyelins, and ceramides). The administration of estrogen significantly reduced the contents of most lipid metabolites. The diversity and composition of gut microbiota evidently changed in ovariectomized HFD-fed ApoE-/- mice, compared to HFD-fed ApoE-/- mice without ovariectomy. In contrast, with estrogen supplementation, the diversity and composition of gut microbiota were restored to approach that of non-ovariectomized HFD-fed ApoE-/- mice, and the relative abundances of some bacteria were even like those of C57BL/6 mice fed with a normal diet. On the other hand, the transplantation of feces from C57BL/6 mice fed with normal diet to ovariectomized HFD-fed ApoE-/- mice was sufficient to correct the hyperlipidemia and AS damage, and to reverse the characteristics changing of lipid metabolomics in ovariectomized HFD-fed ApoE-/- mice. These phenomena were also been observed after transplantation of feces from estrogen-treated ovariectomized HFD-fed ApoE-/- mice to ovariectomized HFD-fed ApoE-/- mice. Moreover, the gut microbiota and lipid metabolites were significantly correlated, demonstrating that the changes of serum lipids may be associated with the gut microbiota disruptions in the perimenopausal period. In conclusion, the gut microbiota during the progression of AS in the perimenopausal period showed specific compositional changes and significant correlations with circulating lipid metabolites. Estrogen supplementation may exert beneficial effects on gut bacteria and lipid metabolism.}, }
@article {pmid34990844, year = {2022}, author = {Aaldijk, E and Vermeiren, Y}, title = {The role of serotonin within the microbiota-gut-brain axis in the development of Alzheimer's disease: a narrative review.}, journal = {Ageing research reviews}, volume = {}, number = {}, pages = {101556}, doi = {10.1016/j.arr.2021.101556}, pmid = {34990844}, issn = {1872-9649}, abstract = {Alzheimer's disease (AD) is the most common cause of dementia, accounting for more than 50 million patients worldwide. Current evidence suggests the exact mechanism behind this devastating disease to be of multifactorial origin, which seriously complicates the quest for an effective disease-modifying therapy, as well as impedes the search for strategic preventative measures. Of interest, preclinical studies point to serotonergic alterations, either induced via selective serotonin reuptake inhibitors or serotonin receptor (ant)agonists, in mitigating AD brain neuropathology next to its clinical symptoms, the latter being supported by a handful of human intervention trials. Additionally, a substantial amount of preclinical trials highlight the potential of diet, fecal microbiota transplantations, as well as pre- and probiotics in modulating the brain's serotonergic neurotransmitter system, starting from the gut. Whether such interventions could truly prevent, reverse or slow down AD progression likewise, should be initially tested in preclinical studies with AD mouse models, including sufficient analytical measurements both in gut and brain. Thereafter, its potential therapeutic effect could be confirmed in rigorously randomized controlled trials in humans, preferentially across the Alzheimer's continuum, but especially from the prodromal up to the mild stages, where both high adherence to such therapies, as well as sufficient room for noticeable enhancement are feasible still. In the end, such studies might aid in the development of a comprehensive approach to tackle this complex multifactorial disease, since serotonin and its derivatives across the microbiota-gut-brain axis might serve as possible biomarkers of disease progression, next to forming a valuable target in AD drug development. In this narrative review, the available evidence concerning the orchestrating role of serotonin within the microbiota-gut-brain axis in the development of AD is summarized and discussed, and general considerations for future studies are highlighted.}, }
@article {pmid34987741, year = {2021}, author = {Spindelboeck, W and Halwachs, B and Bayer, N and Huber-Krassnitzer, B and Schulz, E and Uhl, B and Gaksch, L and Hatzl, S and Bachmayr, V and Kleissl, L and Kump, P and Deutsch, A and Stary, G and Greinix, H and Gorkiewicz, G and Högenauer, C and Neumeister, P}, title = {Antibiotic use and ileocolonic immune cells in patients receiving fecal microbiota transplantation for refractory intestinal GvHD: a prospective cohort study.}, journal = {Therapeutic advances in hematology}, volume = {12}, number = {}, pages = {20406207211058333}, doi = {10.1177/20406207211058333}, pmid = {34987741}, issn = {2040-6207}, abstract = {Introduction: Treatment-refractory, acute graft-versus-host disease (GvHD) of the lower gastrointestinal tract (GI) after allogeneic hematopoietic stem cell transplantation is life threatening and lacks effective treatment options. While fecal microbiota transplantation (FMT) was shown to ameliorate GI-GvHD, its mechanisms of action and the factors influencing the treatment response in humans remain unclear.The objective of this study is to assess response to FMT treatment, factors influencing response, and to study the mucosal immune cell composition in treatment-refractory GI-GvHD.<br><br>Methods: Consecutive patients with treatment-refractory GI-GvHD were treated with up to six endoscopically applied FMTs.<br><br>Results: We observed the response to FMT in four out of nine patients with severe, treatment refractory GI-GvHD, associated with a significant survival benefit (p = 0.017). The concomitant use of broad-spectrum antibiotics was the main factor associated with FMT failure (p = 0.048). In addition, antibiotic administration hindered the establishment of donor microbiota after FMT. Unlike in non-responders, the microbiota characteristics (e.g. α- and β-diversity, abundance of anaerobe butyrate-producers) in responders were more significantly similar to those of FMT donors. During active refractory GI-GvHD, an increased infiltrate of T cells, mainly Th17 and CD8+ T cells, was observed in the ileocolonic mucosa of patients, while the number of immunomodulatory cells such as regulatory T-cells and type 3 innate lymphoid cells decreased. After FMT, a change in immune cell patterns was induced, depending on the clinical response.<br><br>Conclusion: This study increases the knowledge about the crucial effects of antibiotics in patients given FMT for treatment refractory GI-GvHD and defines the characteristic alterations of ileocolonic mucosal immune cells in this setting.}, }
@article {pmid34986765, year = {2022}, author = {D'Amico, F and Barone, M and Tavella, T and Rampelli, S and Brigidi, P and Turroni, S}, title = {Host microbiomes in tumor precision medicine: how far are we?.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0929867329666220105121754}, pmid = {34986765}, issn = {1875-533X}, abstract = {The human gut microbiome has received a crescendo of attention in recent years, due to the countless influences on human pathophysiology, including cancer. Research on cancer and anticancer therapy is constantly looking for new hints to improve the response to therapy while reducing the risk of relapse. In this scenario, the gut microbiome and the plethora of microbial-derived metabolites are considered a new opening in the development of innovative anticancer treatments for a better prognosis. This narrative review summarizes the current knowledge on the role of the gut microbiome in the onset and progression of cancer, as well as in response to chemo-immunotherapy. Recent findings regarding the tumor microbiome and its implications for clinical practice are also commented on. Current microbiome-based intervention strategies (i.e., prebiotics, probiotics, live biotherapeutics and fecal microbiota transplantation) are then discussed, along with key shortcomings, including a lack of long-term safety information in patients who are already severely compromised by standard treatments. The implementation of bioinformatic tools applied to microbiomics and other omics data, such as machine learning, has an enormous potential to push research in the field, enabling the prediction of health risk and therapeutic outcomes, for a truly personalized precision medicine.}, }
@article {pmid34544375, year = {2021}, author = {Koo, H and Morrow, CD}, title = {Incongruence between dominant commensal donor microbes in recipient feces post fecal transplant and response to anti-PD-1 immunotherapy.}, journal = {BMC microbiology}, volume = {21}, number = {1}, pages = {251}, pmid = {34544375}, issn = {1471-2180}, mesh = {Clostridium Infections/*prevention &amp; control ; Fecal Microbiota Transplantation/*methods/standards ; Feces/*microbiology ; Gastrointestinal Microbiome/*genetics/*physiology ; Humans ; Immunotherapy/*adverse effects ; Longitudinal Studies ; Melanoma/immunology/therapy ; *Symbiosis ; }, abstract = {BACKGROUND: To understand inter-individual variability of fecal microbe transplantation (FMT) to enhance anti-PD-1 immunotherapy (IT) for melanoma, we analyzed the data sets from two recent publications with a microbial strain-tracking tool to determine if donor strains were dominant in the recipient feces following FMT.<br><br>RESULTS: Analysis of the Baruch et al. data set found that the presence of commensal donor microbes in recipient feces post-FMT did not correlate with the patient response to IT. From the Davar et al., data set, we found 4 patients that responded to IT had donor's related strain post-FMT, while 2 patients that did not respond to the IT also had donor's strain post-FMT. Importantly, we identified no donor microbes in the feces in one recipient post-FMT that responded to IT. Furthermore, in depth analysis from two patients who responded to IT revealed both donor and recipient strains at different times post-FMT. Colonization of the gastrointestinal tract niches is important for the interaction with the host immune system. Using a separate data set, we show that mucosa from the cecum, transverse colon, and sigmoid colon share strains, providing a large reservoir of niches containing recipient microbes.<br><br>CONCLUSIONS: We demonstrated using strain-tracking analysis individual variation with the respect to the presence of fecal dominant donor microbes in the recipient following FMT that did not correlate with the response to anti-PD-1 immunotherapy. The inter-individual differences of FMT to enhance IT might be explained by the variability of the donor microbes to occupy and outcompete recipient microbes for the gastrointestinal niches. The result from our study supports the use of new approaches to clear the niches in the gastrointestinal tract to promote donor colonization to reduce inter-individual variability of IT for melanoma and potentially other cancers.}, }
@article {pmid34392792, year = {2021}, author = {Han, X and Wang, Y and Zhang, P and Zhu, M and Li, L and Mao, X and Sha, X and Li, L}, title = {Kazak faecal microbiota transplantation induces short-chain fatty acids that promote glucagon-like peptide-1 secretion by regulating gut microbiota in db/db mice.}, journal = {Pharmaceutical biology}, volume = {59}, number = {1}, pages = {1077-1087}, pmid = {34392792}, issn = {1744-5116}, mesh = {Animals ; Bacteroides/isolation &amp; purification ; Diabetes Mellitus, Experimental/physiopathology/*therapy ; Diabetes Mellitus, Type 2/physiopathology/*therapy ; Fatty Acids, Volatile/*metabolism ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Glucagon-Like Peptide 1/metabolism ; Glucose Tolerance Test ; Glycolipids/metabolism ; Humans ; Mice ; RNA, Ribosomal, 16S ; Receptors, G-Protein-Coupled/metabolism ; }, abstract = {CONTEXT: Faecal microbiota transplantation (FMT) from Kazak individuals with normal glucose tolerance (KNGT) significantly reduces plasma glycolipid levels in type 2 diabetes mellitus db/db mice. However, the mechanism behind this effect has not been reported.<br><br>OBJECTIVE: To study the mechanism of improved glycolipid disorders in db/db mice by FMT from a KNGT donor.<br><br>MATERIALS AND METHODS: The normal diet group consisted of db/m mice orally administered 0.2 mL phosphate buffer saline (PBS) (db/m + PBS). For the db/db + PBS (Vehicle) and db/db + KNGT (FMT intervention group) groups, db/db mice received oral 0.2 mL PBS or faecal microorganisms from a KNGT donor, respectively. All mice were treated daily for 0, 6 or 10 weeks. Faecal DNA samples were sequenced and quantified using 16S rRNA gene sequencing and RT-qPCR, respectively. Short-chain fatty acid (SCFA) levels in the mouse faeces were determined by gas chromatography. G protein-coupled receptor 43 (GPR43) and glucagon-like peptide-1 (GLP-1) expression levels were determined.<br><br>RESULTS: FMT intervention significantly increased the relative abundance of Bacteroides uniformis (0.038%, p < 0.05). Clostridium levels (LogSQ) were increased (p < 0.01), while Mucispirillum schaedleri levels (LogSQ) were decreased (p < 0.01). Acetate and butyrate levels in the faeces were significantly increased (acetate; butyrate: 22.68 ± 1.82 mmol/L; 4.13 ± 1.09 mmol/L, p < 0.05). GPR43 mRNA expression and GLP-1 protein expression increased in colon tissue (p < 0.05).<br><br>DISCUSSION AND CONCLUSIONS: Mechanistically, FMT-KNGT could improve glycolipid disorders by changing the bacterial composition responsible for producing SCFAs and activating the GPR43/GLP-1 pathway.}, }
@article {pmid34985651, year = {2022}, author = {Szychowiak, P and Villageois-Tran, K and Patrier, J and Timsit, JF and Ruppé, É}, title = {The role of the microbiota in the management of intensive care patients.}, journal = {Annals of intensive care}, volume = {12}, number = {1}, pages = {3}, pmid = {34985651}, issn = {2110-5820}, abstract = {The composition of the gut microbiota is highly dynamic and changes according to various conditions. The gut microbiota mainly includes difficult-to-cultivate anaerobic bacteria, hence knowledge about its composition has significantly arisen from culture-independent methods based on next-generation sequencing (NGS) such as 16S profiling and shotgun metagenomics. The gut microbiota of patients hospitalized in intensive care units (ICU) undergoes many alterations because of critical illness, antibiotics, and other ICU-specific medications. It is then characterized by lower richness and diversity, and dominated by opportunistic pathogens such as Clostridioides difficile and multidrug-resistant bacteria. These alterations are associated with an increased risk of infectious complications or death. Specifically, at the time of writing, it appears possible to identify distinct microbiota patterns associated with severity or infectivity in COVID-19 patients, paving the way for the potential use of dysbiosis markers to predict patient outcomes. Correcting the microbiota disturbances to avoid their consequences is now possible. Fecal microbiota transplantation is recommended in recurrent C. difficile infections and microbiota-protecting treatments such as antibiotic inactivators are currently being developed. The growing interest in the microbiota and microbiota-associated therapies suggests that the control of the dysbiosis could be a key factor in the management of critically ill patients. The present narrative review aims to provide a synthetic overview of microbiota, from healthy individuals to critically ill patients. After an introduction to the different techniques used for studying the microbiota, we review the determinants involved in the alteration of the microbiota in ICU patients and the latter's consequences. Last, we assess the means to prevent or correct microbiota alteration.}, }
@article {pmid34985325, year = {2022}, author = {Sorboni, SG and Moghaddam, HS and Jafarzadeh-Esfehani, R and Soleimanpour, S}, title = {A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders.}, journal = {Clinical microbiology reviews}, volume = {}, number = {}, pages = {e0033820}, doi = {10.1128/CMR.00338-20}, pmid = {34985325}, issn = {1098-6618}, abstract = {The human body is full of an extensive number of commensal microbes, consisting of bacteria, viruses, and fungi, collectively termed the human microbiome. The initial acquisition of microbiota occurs from both the external and maternal environments, and the vast majority of them colonize the gastrointestinal tract (GIT). These microbial communities play a central role in the maturation and development of the immune system, the central nervous system, and the GIT system and are also responsible for essential metabolic pathways. Various factors, including host genetic predisposition, environmental factors, lifestyle, diet, antibiotic or nonantibiotic drug use, etc., affect the composition of the gut microbiota. Recent publications have highlighted that an imbalance in the gut microflora, known as dysbiosis, is associated with the onset and progression of neurological disorders. Moreover, characterization of the microbiome-host cross talk pathways provides insight into novel therapeutic strategies. Novel preclinical and clinical research on interventions related to the gut microbiome for treating neurological conditions, including autism spectrum disorders, Parkinson's disease, schizophrenia, multiple sclerosis, Alzheimer's disease, epilepsy, and stroke, hold significant promise. This review aims to present a comprehensive overview of the potential involvement of the human gut microbiome in the pathogenesis of neurological disorders, with a particular emphasis on the potential of microbe-based therapies and/or diagnostic microbial biomarkers. This review also discusses the potential health benefits of the administration of probiotics, prebiotics, postbiotics, and synbiotics and fecal microbiota transplantation in neurological disorders.}, }
@article {pmid34980687, year = {2022}, author = {Gweon, TG and Lee, YJ and Kim, KO and Yim, SK and Soh, JS and Kim, SY and Park, JJ and Shin, SY and Lee, TH and Choi, CH and Cho, YS and Yong, D and Chung, JW and Lee, KJ and Lee, OY and Choi, MG and Choi, M and , }, title = {Clinical Practice Guidelines for Fecal Microbiota Transplantation in Korea.}, journal = {Journal of neurogastroenterology and motility}, volume = {28}, number = {1}, pages = {28-42}, doi = {10.5056/jnm21221}, pmid = {34980687}, issn = {2093-0879}, abstract = {Fecal microbiota transplantation (FMT) is a highly efficacious and safe modality for the treatment of recurrent or refractory Clostridioides difficile infection (CDI), with overall success rates of 90%. Thus, FMT has been widely used for 10 years. The incidence and clinical characteristics of CDI, the main indication for FMT, differ between countries. To date, several guidelines have been published. However, most of them were published in Western countries and therefore cannot represent the Korean national healthcare systems. One of the barriers to performing FMT is a lack of national guidelines. Accordingly, multidisciplinary experts in this field have developed practical guidelines for FMT. The purpose of these guidelines is to aid physicians performing FMT, which can be adapted to treat CDI and other conditions.}, }
@article {pmid34980222, year = {2022}, author = {Chen, Y and Liu, Y and Wang, Y and Chen, X and Wang, C and Chen, X and Yuan, X and Liu, L and Yang, J and Zhou, X}, title = {Prevotellaceae produces butyrate to alleviate PD-1/PD-L1 inhibitor-related cardiotoxicity via PPARα-CYP4X1 axis in colonic macrophages.}, journal = {Journal of experimental &amp; clinical cancer research : CR}, volume = {41}, number = {1}, pages = {1}, pmid = {34980222}, issn = {1756-9966}, abstract = {BACKGROUND: Immune checkpoint inhibitor-related cardiotoxicity is one of the most lethal adverse effects, and thus, the identification of underlying mechanisms for developing strategies to overcome it has clinical importance. This study aimed to investigate whether microbiota-host interactions contribute to PD-1/PD-L1 inhibitor-related cardiotoxicity.<br><br>METHODS: A mouse model of immune checkpoint inhibitor-related cardiotoxicity was constructed by PD-1/PD-L1 inhibitor BMS-1 (5 and 10 mg/kg), and cardiomyocyte apoptosis and cardiotoxicity were determined by hematoxylin and eosin, Masson's trichome and TUNEL assays. 16S rRNA sequencing was used to define the gut microbiota composition. Gut microbiota metabolites short-chain fatty acids (SCFAs) were determined by HPLC. The serum levels of myocardial enzymes (creatine kinase, aspartate transaminase, creatine kinase-MB and lactate dehydrogenase) and the production of M1 factors (TNF-α and IL-1β) were measured by ELISA. The colonic macrophage phenotype was measured by mmunofluorescence and qPCR. The expression of Claudin-1, Occludin, ZO-1 and p-p65 was measured by western blot. The gene expression of peroxisome proliferator-activated receptor α (PPARα) and cytochrome P450 (CYP) 4X1 was determined using qPCR. Statistical analyses were performed using Student's t-test for two-group comparisons, and one-way ANOVA followed by Student-Newman-Keul test for multiple-group comparisons.<br><br>RESULTS: We observed intestinal barrier injury and gut microbiota dysbiosis characterized by Prevotellaceae and Rikenellaceae genus depletion and Escherichia-Shigella and Ruminococcaceae genus enrichment, accompanied by low butyrate production and M1-like polarization of colonic macrophages in BMS-1 (5 and 10 mg/kg)-induced cardiotoxicity. Fecal microbiota transplantation mirrored the effect of BMS-1 on cardiomyocyte apoptosis and cardiotoxicity, while macrophage depletion and neutralization of TNF-α and IL-1β greatly attenuated BMS-1-induced cardiotoxicity. Importantly, Prevotella loescheii recolonization and butyrate supplementation alleviated PD-1/PD-L1 inhibitor-related cardiotoxicity. Mechanistically, gut microbiota dysbiosis promoted M1-like polarization of colonic macrophages and the production of proinflammatory factors TNF-α and IL-1β through downregulation of PPARα-CYP4X1 axis.<br><br>CONCLUSIONS: Intestinal barrier dysfunction amplifies PD-1/PD-L1 inhibitor-related cardiotoxicity by upregulating proinflammatory factors TNF-α and IL-1β in colonic macrophages via downregulation of butyrate-PPARα-CYP4X1 axis. Thus, targeting gut microbiota to polarize colonic macrophages away from the M1-like phenotype could provide a potential therapeutic strategy for PD-1/PD-L1 inhibitor-related cardiotoxicity.}, }
@article {pmid34977119, year = {2021}, author = {Pan, B and Liu, X and Shi, J and Chen, Y and Xu, Z and Shi, D and Ruan, G and Wang, F and Huang, Y and Xu, C}, title = {A Meta-Analysis of Microbial Therapy Against Metabolic Syndrome: Evidence From Randomized Controlled Trials.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {775216}, doi = {10.3389/fnut.2021.775216}, pmid = {34977119}, issn = {2296-861X}, abstract = {Background and aims: Metabolic syndrome (MetS), accompanied with significant intestinal dysbiosis, causes a great public health burden to human society. Here, we carried out a meta-analysis to qualify randomized controlled trials (RCTs) and to systematically evaluate the effect of microbial therapy on MetS. Methods and results: Forty-two RCTs were eligible for this meta-analysis after searching the PubMed, Cochrane, and Embase databases. Pooled estimates demonstrated that treatment with microbial therapy significantly reduced the waist circumference (WC) (SMD = -0.26, 95% CI -0.49, -0.03), fasting blood glucose (FBG) (SMD = -0.35, 95% CI -0.52, -0.18), total cholesterol (TC) (SMD = -0.36, 95% CI -0.55, -0.17), low-density lipoprotein cholesterol (LDL-C) (SMD = -0.42, 95% CI -0.61, -0.22), and triacylglycerol (TG)(SMD = -0.38, 95% CI -0.55, -0.20), but increased the high-density lipoprotein cholesterol (HDL-C) (SMD = 0.28, 95% CI.03, 0.52). Sensitivity analysis indicated that after eliminating one study utilizing Bifidobacteriumlactis, results became statistically significant in diastolic blood pressure (DBP) (SMD = -0.24, 95% CI -0.41, -0.07) and in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (SMD = -0.28, 95% CI -0.54, -0.03), while the body mass index (BMI) showed significant difference after eliminating one study utilizing oat bran (SMD = -0.16, 95% CI -0.31, -0.01). There was still no significant effect in systolic blood pressure (SBP) and in hemoglobin A1c (HbA1c%). Conclusion: In patients with MetS, the conditioning with microbial therapy notably improves FBG, TC, TG, HDL-C, LDL-C, WC, BMI (except for the study using oat bran), HOMA-IR, and DBP (except for the Study using Bifidobacteriumlactis), however, with no effect in SBP and in HbA1c%.}, }
@article {pmid34976874, year = {2021}, author = {Li, S and Wei, J and Chen, T}, title = {Editorial: Gut Microbiota in the Occurrence, Development and Treatment of Gut-Brain Disorders.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {808454}, doi = {10.3389/fcimb.2021.808454}, pmid = {34976874}, issn = {2235-2988}, }
@article {pmid34975748, year = {2021}, author = {Ye, X and Liu, Y and Hu, J and Gao, Y and Ma, Y and Wen, D}, title = {Chlorogenic Acid-Induced Gut Microbiota Improves Metabolic Endotoxemia.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {762691}, doi = {10.3389/fendo.2021.762691}, pmid = {34975748}, issn = {1664-2392}, abstract = {Background: Coffee can regulate glucose homeostasis but the underlying mechanism is unclear. This study investigated the preventive and therapeutic effects of chlorogenic acid (CGA), a polyphenol that is found in coffee, on obesity and obesity-related metabolic endotoxemia.<br><br>Method: Male 4-week-old C57BL/6 mice were fed either normal chow or a high-fat diet or 20 weeks and half the mice in each group were gavaged with CGA. Oral glucose tolerance tests (OGTTs) and insulin tolerance tests (ITTs) were performed. Markers of inflammation and intestinal barrier function were assayed. The composition of the gut microbiota was analyzed by 16S rRNA high-throughput pyrosequencing. The role of CGA-altered microbiota in metabolic endotoxemia was verified by fecal microbiota transplantation.<br><br>Results: CGA protected against HFD-induced weight gain, decreased the relative weight of subcutaneous and visceral adipose, improved intestinal barrier integrity, and prevented glucose metabolic disorders and endotoxemia (P <0.05). CGA significantly changed the composition of the gut microbiota and increased the abundance of short chain fatty acid (SCFA)-producers (e.g., Dubosiella, Romboutsia, Mucispirillum, and Faecalibaculum) and Akkermansia, which can protect the intestinal barrier. In addition, mice with the CGA-altered microbiota had decreased body weight and fat content and inhibited metabolic endotoxemia.<br><br>Conclusion: CGA-induced changes in the gut microbiota played an important role in the inhibition of metabolic endotoxemia in HFD-fed mice.}, }
@article {pmid34970262, year = {2021}, author = {Gao, G and Ma, T and Zhang, T and Jin, H and Li, Y and Kwok, LY and Zhang, H and Sun, Z}, title = {Adjunctive Probiotic Lactobacillus rhamnosus Probio-M9 Administration Enhances the Effect of Anti-PD-1 Antitumor Therapy via Restoring Antibiotic-Disrupted Gut Microbiota.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {772532}, pmid = {34970262}, issn = {1664-3224}, abstract = {Emerging evidence supports that the efficacy of immune checkpoint blockade (ICB) therapy is associated with the host's gut microbiota, as prior antibiotic intake often leads to poor outcome and low responsiveness toward ICB treatment. Therefore, we hypothesized that the efficacy of ICB therapy like anti-programmed cell death protein-1 (PD-1) treatment required an intact host gut microbiota, and it was established that probiotics could enhance the recovery of gut microbiota disruption by external stimuli. Thus, the present study aimed to evaluate the effect of the probiotics, Lactobacillus rhamnosus Probio-M9, on recovering antibiotic-disrupted gut microbiota and its impact on the outcome of ICB therapy in tumor-bearing mice. We first disrupted the mouse microbiota by antibiotics and then remediated the gut microbiota by probiotics or naturally. Tumor transplantation was then performed, followed by anti-PD-1-based antitumor therapy. Changes in the fecal metagenomes and the tumor suppression effect were monitored during different stages of the experiment. Our results showed that Probio-M9 synergized with ICB therapy, significantly improving tumor inhibition compared with groups not receiving the probiotic treatment (P < 0.05 at most time points). The synergistic effect was accompanied by effective restoration of antibiotic-disrupted fecal microbiome that was characterized by a drastically reduced Shannon diversity value and shifted composition of dominating taxa. Moreover, probiotic administration significantly increased the relative abundance of beneficial bacteria (e.g., Bifidobacterium pseudolongum, Parabacteroides distasonis, and some Bacteroides species; 0.0001 < P < 0.05). The gut microbiome changes were accompanied by mild reshaping of the functional metagenomes characterized by enrichment in sugar degradation and vitamin and amino acid synthesis pathways. Collectively, this study supported that probiotic administration could enhance the efficacy and responsiveness of anti-PD-1-based immunotherapy, and Probio-M9 could be a potential candidate of microbe-based synergistic tumor therapeutics. The preclinical data obtained here would support the design of future human clinical trials for further consolidating the current findings and for safety assessment of probiotic adjunctive treatment in ICB therapy.}, }
@article {pmid34590904, year = {2021}, author = {Vuyyuru, SK and Kedia, S and Kalaivani, M and Sahu, P and Kante, B and Kumar, P and Ranjan, MK and Makharia, G and Ananthakrishnan, A and Ahuja, V}, title = {Efficacy and safety of fecal transplantation versus targeted therapies in ulcerative colitis: network meta-analysis.}, journal = {Future microbiology}, volume = {16}, number = {}, pages = {1215-1227}, doi = {10.2217/fmb-2020-0242}, pmid = {34590904}, issn = {1746-0921}, mesh = {Adalimumab/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; *Colitis, Ulcerative/therapy ; *Fecal Microbiota Transplantation ; Humans ; Network Meta-Analysis ; Randomized Controlled Trials as Topic ; }, abstract = {Aim: We conducted this network meta-analysis to compare the efficacy and safety of targeted pharmacotherapies and fecal microbial transplantation (FMT). Patients &amp; methods: Nineteen studies were included and there was only one head-to-head randomized controlled trial (adalimumab vs vedolizumab). Results: All interventions, including FMT, were superior to a placebo in inducing clinical remission (except adalimumab - odds ratio 1.66; 95% CI: 0.97-2.85), clinical response and endoscopic remission. FMT was comparable with other agents in achieving all efficacy outcomes. Infliximab was ranked highest in inducing clinical remission (surface under the cumulative ranking, 0.8). There was no difference in safety outcomes between FMT and other targeted therapies. Conclusion: FMT is as efficacious and as safe as other targeted therapies in inducing clinical remission, clinical response and endoscopic remission. Further studies to assess the long-term benefits are needed in order to reach a definitive conclusion.}, }
@article {pmid34363822, year = {2021}, author = {Zheng, W and Duan, M and Jia, J and Song, S and Ai, C}, title = {Low-molecular alginate improved diet-induced obesity and metabolic syndrome through modulating the gut microbiota in BALB/c mice.}, journal = {International journal of biological macromolecules}, volume = {187}, number = {}, pages = {811-820}, doi = {10.1016/j.ijbiomac.2021.08.003}, pmid = {34363822}, issn = {1879-0003}, mesh = {Adiposity ; *Alginates ; Animal Feed ; Animals ; Bacteria/*metabolism ; Biomarkers/blood ; Diet, High-Fat ; Disease Models, Animal ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Inflammation Mediators/metabolism ; Lipids/blood ; Male ; Metabolic Syndrome/blood/*diet therapy/microbiology ; Mice, Inbred BALB C ; Molecular Weight ; Obesity/blood/*diet therapy/microbiology ; *Prebiotics ; Weight Gain ; }, abstract = {Alginate is the most abundant polysaccharide in brown seaweed, which is widely used as a food additive, but its high viscosity and gel property limit its applications in foods as a functional ingredient. In this study, low-molecular alginate from Laminaria japonica (L-LJA) was prepared, and its effect on obesity and metabolic syndrome was analyzed in high-fat diet (HFD)-fed mice. L-LJA reduced weight gain, fat accumulation in the liver and epididymal adipose tissue, lipid abnormality and inflammation in HFD-fed mice accompanied with the improvement of gut microbiota. L-LJA modulated the structure of gut microbiota, increased some Bacteroidales members, and reduced some Clostridiales members in mice, which were positively correlated with the improvement of physiological status. Fecal transplant from L-LJA-fed mice reduced fat accumulation in body tissues and lipid abnormality in the serum and liver and increased short chain fatty acids production in HFD-fed mice, confirming that L-LJA-induced gut microbiota alteration played an important role in its bioactivity. L-LJA has better solubility and can be utilized in food systems in high dose, implying that it can be developed as a prebiotic agent to increase both economic value and nutritive value of alginate.}, }
@article {pmid34224741, year = {2021}, author = {Khoruts, A}, title = {Can FMT Cause or Prevent CRC? Maybe, But There Is More to Consider.}, journal = {Gastroenterology}, volume = {161}, number = {4}, pages = {1103-1105}, doi = {10.1053/j.gastro.2021.06.074}, pmid = {34224741}, issn = {1528-0012}, mesh = {*Clostridioides difficile ; *Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid34966755, year = {2021}, author = {Hu, Y and Ye, Z and Wu, M and She, Y and Li, L and Xu, Y and Qin, K and Hu, Z and Yang, M and Lu, F and Ye, Q}, title = {The Communication Between Intestinal Microbiota and Ulcerative Colitis: An Exploration of Pathogenesis, Animal Models, and Potential Therapeutic Strategies.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {766126}, doi = {10.3389/fmed.2021.766126}, pmid = {34966755}, issn = {2296-858X}, abstract = {Ulcerative Colitis (UC) is a chronic inflammatory bowel disease. The prolonged course of UC and the lack of effective treatment management make it difficult to cure, affecting the health and life safety of patients. Although UC has received more attention, the etiology and pathogenesis of UC are still unclear. Therefore, it is urgent to establish an updated and comprehensive understanding of UC and explore effective treatment strategies. Notably, sufficient evidence shows that the intestinal microbiota plays an important role in the pathogenesis of UC, and the treating method aimed at improving the balance of the intestinal microbiota exhibits a therapeutic potential for UC. This article reviews the relationship between the genetic, immunological and microbial risk factors with UC. At the same time, the UC animal models related to intestinal microbiota dysbiosis induced by chemical drugs were evaluated. Finally, the potential value of the therapeutic strategies for restoring intestinal microbial homeostasis and treating UC were also investigated. Comprehensively, this study may help to carry out preclinical research, treatment theory and methods, and health management strategy of UC, and provide some theoretical basis for TCM in the treatment of UC.}, }
@article {pmid34965174, year = {2022}, author = {Hiippala, K and Khan, I and Ronkainen, A and Boulund, F and Vähä-Mäkilä, H and Suutarinen, M and Seifert, M and Engstrand, L and Satokari, R}, title = {Novel strain of Pseudoruminococcus massiliensis possesses traits important in gut adaptation and host-microbe interactions.}, journal = {Gut microbes}, volume = {14}, number = {1}, pages = {2013761}, doi = {10.1080/19490976.2021.2013761}, pmid = {34965174}, issn = {1949-0984}, abstract = {Fecal microbiota transplantation (FMT) is an efficient treatment for recurrent Clostridioides difficile infection and currently investigated as a treatment for other intestinal and systemic diseases. Better understanding of the species potentially transferred in FMT is needed. We isolated from a healthy fecal donor a novel strain E10-96H of Pseudoruminococcus massiliensis, a recently described strictly anaerobic species currently represented only by the type strain. The whole genome sequence of E10-96H had over 98% similarity with the type strain. E10-96H carries 20 glycoside hydrolase encoding genes, degrades starch in vitro and thus may contribute to fiber degradation, cross-feeding of other species and butyrate production in the intestinal ecosystem. The strain carries pilus-like structures, harbors pilin genes in its genome and adheres to enterocytes in vitro but does not provoke a proinflammatory response. P. massiliensis seems to have commensal behavior with the host epithelium, and its role in intestinal ecology should be studied further.}, }
@article {pmid34963452, year = {2021}, author = {Lin, H and Guo, Q and Wen, Z and Tan, S and Chen, J and Lin, L and Chen, P and He, J and Wen, J and Chen, Y}, title = {The multiple effects of fecal microbiota transplantation on diarrhea-predominant irritable bowel syndrome (IBS-D) patients with anxiety and depression behaviors.}, journal = {Microbial cell factories}, volume = {20}, number = {1}, pages = {233}, pmid = {34963452}, issn = {1475-2859}, support = {No. 81770529//National Natural Science Foundation of China/ ; No. 82070543//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Anxiety and depression are complications in Irritable bowel syndrome (IBS) patients. In this study, we recruited 18 IBS patients with mild-modest anxiety and depression behaviors, and after the screening, we defined the FMT treatment group (n = 9) and the control group (n = 9). The IBS symptom severity scale (IBS-SSS), Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D), Irritable Bowel Syndrome Quality of Life (IBS-QOL) and Bristol stool scale (BSS) were evaluated one week before FMT (baseline), one-week-, one-month-, two-month-, and three-month-following FMT. Meanwhile, we determined the SCFAs in the patient's feces and serum and continued the metagenomic analysis of the microorganisms in the patient's feces.<br><br>RESULTS: The results showed that the patient's anxiety and depression behavior gradually improved with FMT treatment. Moreover, the illness and quality of life had also been relieved significantly. The content of isovaleric acid and valeric acid was significantly reduced in the FMT group compared to the Col group. Metagenomic analysis showed that FMT treatment decreased the abundance of Faecalibacterium, Eubacterium and Escherichia. From KEGG functional analysis, we confirmed that the top five abundant pathways were "bacterial chemotaxis, "flagellar assembly", "glycine, serine and threonine metabolism", "apoptosis", and "bacterial invasion of epithelial cells".<br><br>CONCLUSIONS: FMT treatment can effectively alleviate the anxiety and depression behaviors of IBS-D patients and reduce the IBS-SSS score, indicating that FMT can improve patients' symptoms. The high throughput sequencing results show that Bifidobacterium and Escherichia play the most critical role in the formation and recovery of IBS-D patients. The GC/MS data indicated that faeces isovaleric acid and valeric acid might be more suitable as a metabolic indicator of IBS-D remission. Trial registration ChiCTR, ChiCTR1900024924, Registered 3 August 2019, https://www.chictr.org.cn/showproj.aspx?proj=41676 .}, }
@article {pmid34898421, year = {2021}, author = {Tu, T and Zhao, C}, title = {Treating autism spectrum disorder by intervening with gut microbiota.}, journal = {Journal of medical microbiology}, volume = {70}, number = {12}, pages = {}, doi = {10.1099/jmm.0.001469}, pmid = {34898421}, issn = {1473-5644}, mesh = {*Autism Spectrum Disorder/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Diseases/therapy ; *Gastrointestinal Microbiome ; Humans ; *Probiotics/therapeutic use ; }, abstract = {Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders with a high prevalence in childhood. The gut microbiota can affect human cognition and moods and has a strong correlation with ASD. Microbiota transplantation, including faecal microbiota transplantation (FMT), probiotics, breastfeeding, formula feeding, gluten-free and casein-free (GFCF) diet and ketogenic diet therapy, may provide satisfying effects for ASD and its related various symptoms. For instance, FMT can improve the core symptoms of ASD and gastrointestinal symptoms. Probiotics, breastfeeding and formula feeding, and GFCF diet can improve gastrointestinal symptoms. The core symptom score still needs to be confirmed by large-scale clinical randomized controlled studies. It is recommended to use a ketogenic diet to treat patients with epilepsy in ASD. At present, the unresolved problems include which of gut the microbiota are beneficial, which of the microorganisms are harmful, how to safely and effectively implant beneficial bacteria into the human body, and how to extract and eliminate harmful microorganisms before transplantation. In future studies, large sample and randomized controlled clinical studies are needed to confirm the mechanism of intestinal microorganisms in the treatment of ASD and the method of microbial transplantation.}, }
@article {pmid34962114, year = {2021}, author = {Jang, S and Kim, Y and Lee, C and Kwon, B and Noh, J and Jee, JJ and Yoon, SS and Koh, H and Park, S}, title = {The Effect of Formula-based Nutritional Treatment on Colitis in a Murine Model.}, journal = {Journal of Korean medical science}, volume = {36}, number = {50}, pages = {e342}, doi = {10.3346/jkms.2021.36.e342}, pmid = {34962114}, issn = {1598-6357}, support = {//Korea Health Industry Development Institute/Korea ; }, abstract = {BACKGROUND: Exclusive enteral nutrition (EEN) induces remission in pediatric Crohn's disease (CD). The exact mechanism of EEN therapy in CD is unknown, but alteration of the intestinal microflora after EEN is thought to affect mucosal healing. To determine the link between EEN therapy and therapeutic efficacy in CD, we established a murine model of dextran sulfate sodium (DSS)-induced colitis and applied EEN therapy.<br><br>METHODS: Eight-week-old C57BL/6 mice were administered DSS for 4 days to induce colitis, and either normal chow (NC) or EEN was administered for the following 4 days. The mice were grouped according to the feeding pattern after DSS administration: DSS/NC and DSS/EEN groups. The clinical course was confirmed via daily observation of the weight and stool. Fecal samples were collected and 16sRNA sequencing was used. The mice were sacrificed to confirm colonic histopathology.<br><br>RESULTS: Weight reduction and increase in disease activity were observed as the day progressed for 4 days after DSS administration. There was significant weight recovery and improvement in disease activity in the EEN group compared to that in the NC group. Verrucomicrobia and Proteobacteria abundances tended to increase and Bacteroidetes abundance decreased in the EEN group. In the EEN group, significant changes in the β-diversity of the microbiota were observed. In the analysis of microbiome species, abundances of Akkermansia muciniphila, Clostridium cocleatum, mucin-degrading bacteria, Flintibacter butyricus, and Parabacteroides goldsteinii, which are beneficial microbiota, were significantly increased in the EEN group compared to those in the NC group. More abundant mucins were confirmed in the colonic histopathology of the EEN group. These microbial and histopathological differences suggested that EEN might improve colitis symptoms in a murine colitis model by promoting mucin recycling and subsequently inducing the healing effect of the gut barrier.<br><br>CONCLUSION: EEN showed clinical efficacy in a murine model of colitis. Based on the increase in mucin-degrading bacteria and the pathological increase in mucin production after EEN administration, it can be observed that mucin plays an important role in the therapeutic effect of EEN.}, }
@article {pmid34960049, year = {2021}, author = {Chernikova, MA and Flores, GD and Kilroy, E and Labus, JS and Mayer, EA and Aziz-Zadeh, L}, title = {The Brain-Gut-Microbiome System: Pathways and Implications for Autism Spectrum Disorder.}, journal = {Nutrients}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/nu13124497}, pmid = {34960049}, issn = {2072-6643}, support = {AR170062//United States Department of Defense/ ; }, abstract = {Gastrointestinal dysfunction is one of the most prevalent physiological symptoms of autism spectrum disorder (ASD). A growing body of largely preclinical research suggests that dysbiotic gut microbiota may modulate brain function and social behavior, yet little is known about the mechanisms that underlie these relationships and how they may influence the pathogenesis or severity of ASD. While various genetic and environmental risk factors have been implicated in ASD, this review aims to provide an overview of studies elucidating the mechanisms by which gut microbiota, associated metabolites, and the brain interact to influence behavior and ASD development, in at least a subgroup of individuals with gastrointestinal problems. Specifically, we review the brain-gut-microbiome system and discuss findings from current animal and human studies as they relate to social-behavioral and neurological impairments in ASD, microbiota-targeted therapies (i.e., probiotics, fecal microbiota transplantation) in ASD, and how microbiota may influence the brain at molecular, structural, and functional levels, with a particular interest in social and emotion-related brain networks. A deeper understanding of microbiome-brain-behavior interactions has the potential to inform new therapies aimed at modulating this system and alleviating both behavioral and physiological symptomatology in individuals with ASD.}, }
@article {pmid34959977, year = {2021}, author = {Sobocki, BK and Kaźmierczak-Siedlecka, K and Folwarski, M and Hawryłkowicz, V and Makarewicz, W and Stachowska, E}, title = {Pancreatic Cancer and Gut Microbiome-Related Aspects: A Comprehensive Review and Dietary Recommendations.}, journal = {Nutrients}, volume = {13}, number = {12}, pages = {}, doi = {10.3390/nu13124425}, pmid = {34959977}, issn = {2072-6643}, abstract = {Gut microbiota plays a significant role in the human body providing many beneficial effects on the host. However, its dysbiotic alterations may affect the tumorigenic pathway and then trigger the development of pancreatic cancer. This dysbiosis can also modulate the aggressiveness of the tumor, influencing the microenvironment. Because pancreatic cancer is still one of the most lethal cancers worldwide with surgery as the only method that influences prognosis and has curative potential, there is a need to search for other strategies which will enhance the efficiency of standard therapy and improve patients' quality of life. The administration of prebiotics, probiotics, next-generation probiotics (Faecalibacterium prausnitzii, Akkermansia muciniphila), synbiotics, postbiotics, and fecal microbiota transplantation through multiple mechanisms affects the composition of the gut microbiota and may restore its balance. Despite limited data, some studies indicate that the aforementioned methods may allow to achieve better effect of pancreatic cancer treatment and improve therapeutic strategies for pancreatic cancer patients.}, }
@article {pmid34959505, year = {2021}, author = {Pane, S and Ristori, MV and Gardini, S and Russo, A and Del Chierico, F and Putignani, L}, title = {Clinical Parasitology and Parasitome Maps as Old and New Tools to Improve Clinical Microbiomics.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {12}, pages = {}, doi = {10.3390/pathogens10121550}, pmid = {34959505}, issn = {2076-0817}, support = {Ricerca Corrente 2020 and 2021//Italian Ministry of Health/ ; }, abstract = {A growing body of evidence shows that dysbiotic gut microbiota may correlate with a wide range of disorders; hence, the clinical use of microbiota maps and fecal microbiota transplantation (FMT) can be exploited in the clinic of some infectious diseases. Through direct or indirect ecological and functional competition, FMT may stimulate decolonization of pathogens or opportunistic pathogens, modulating immune response and colonic inflammation, and restoring intestinal homeostasis, which reduces host damage. Herein, we discuss how diagnostic parasitology may contribute to designing clinical metagenomic pipelines and FMT programs, especially in pediatric subjects. The consequences of more specialized diagnostics in the context of gut microbiota communities may improve the clinical parasitology and extend its applications to the prevention and treatment of several communicable and even noncommunicable disorders.}, }
@article {pmid33825149, year = {2021}, author = {Liang, Y and Cui, L and Gao, J and Zhu, M and Zhang, Y and Zhang, HL}, title = {Gut Microbial Metabolites in Parkinson's Disease: Implications of Mitochondrial Dysfunction in the Pathogenesis and Treatment.}, journal = {Molecular neurobiology}, volume = {58}, number = {8}, pages = {3745-3758}, pmid = {33825149}, issn = {1559-1182}, support = {81974194//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Brain/*metabolism ; Brain-Gut Axis/*physiology ; Dysbiosis/genetics/metabolism/therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Mitochondria/genetics/*metabolism ; Parkinson Disease/genetics/*metabolism/*therapy ; Probiotics/therapeutic use ; Treatment Outcome ; Ubiquitin-Protein Ligases/genetics/metabolism ; }, abstract = {The search for therapeutic targets for Parkinson's disease (PD) is hindered by the incomplete understanding of the pathophysiology of the disease. Mitochondrial dysfunction is an area with high potential. The neurobiological signaling connections between the gut microbiome and the central nervous system are incompletely understood. Multiple lines of evidence suggest that the gut microbiota participates in the pathogenesis of PD. Gut microbial dysbiosis may contribute to the loss of dopaminergic neurons through mitochondrial dysfunction. The intervention of gut microbial metabolites via the microbiota-gut-brain axis may serve as a promising therapeutic strategy for PD. In this narrative review, we summarize the potential roles of gut microbial dysbiosis in PD, with emphasis on microbial metabolites and mitochondrial function. We then review the possible ways in which microbial metabolites affect the central nervous system, as well as the impact of microbial metabolites on mitochondrial dysfunction. We finally discuss the possibility of gut microbiota as a therapeutic target for PD.}, }
@article {pmid34957088, year = {2021}, author = {Bi, C and Xiao, G and Liu, C and Yan, J and Chen, J and Si, W and Zhang, J and Liu, Z}, title = {Molecular Immune Mechanism of Intestinal Microbiota and Their Metabolites in the Occurrence and Development of Liver Cancer.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {702414}, doi = {10.3389/fcell.2021.702414}, pmid = {34957088}, issn = {2296-634X}, abstract = {Intestinal microorganisms are closely associated with immunity, metabolism, and inflammation, and play an important role in health and diseases such as inflammatory bowel disease, diabetes, cardiovascular disease, Parkinson's disease, and cancer. Liver cancer is one of the most fatal cancers in humans. Most of liver cancers are slowly transformed from viral hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease. However, the relationship between intestinal microbiota and their metabolites, including short-chain fatty acids, bile acids, indoles, and ethanol, and liver cancer remains unclear. Here, we summarize the molecular immune mechanism of intestinal microbiota and their metabolites in the occurrence and development of liver cancer and reveal the important role of the microbiota-gut-liver axis in liver cancer. In addition, we describe how the intestinal flora can be balanced by antibiotics, probiotics, postbiotics, and fecal bacteria transplantation to improve the treatment of liver cancer. This review describes the immunomolecular mechanism of intestinal microbiota and their metabolites in the occurrence and development of hepatic cancer and provides theoretical evidence support for future clinical practice.}, }
@article {pmid34956503, year = {2021}, author = {Zhao, D and Ye, C and Zhang, S and Lv, X and Yang, B}, title = {Analysis of risk factors for early clinical recurrence of inflammatory bowel disease after fecal microbiota transplantation.}, journal = {American journal of translational research}, volume = {13}, number = {11}, pages = {12875-12886}, pmid = {34956503}, issn = {1943-8141}, abstract = {OBJECTIVE: To explore the risk factors for early clinical recurrence of inflammatory bowel disease (IBD) after fecal microbiota transplantation (FMT).<br><br>METHODS: A retrospective study was conducted on 192 patients with IBD who received FMT treatment in the Colorectal Disease Specialty/Intestinal Microecology Treatment Center of the Tenth People's Hospital Affiliated to Tongji University from February 2017 to June 2020. Univariate and multivariate logistic regression models were used to analyze the risk factors for early recurrence of inflammation. Feces from all participants were collected to extract the total bacterial genomic DNA. The V6-8 regions of the bacterial 16S rDNA gene were amplified by polymerase chain reaction (PCR), the PCR products were detected by the denaturing gradient gel electrophoresis (DGGE) method, and the intestinal flora was analyzed by DNA fingerprinting. Stool samples from all patients were tested for 9 bacteria, white blood cells (WBC) and platelet (PLT) counts, as well as the erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) level.<br><br>RESULTS: Of the 192 patients, 15 cases had inflammation recurrence during FMT and within one week after treatment, including 11 cases of ulcerative colitis (UC) and 4 cases of Crohn's disease (CD), with a total recurrence rate of 7.8%. High Mayo inflammatory activity score, Mayo endoscopic sub-item score (MES) =3 points, CRP>10 mg/L, anemia, albumin <30 g/L, absolute value of peripheral blood lymphocytes (PBL) <500/mm3, and intolerance to enteral full nutrition were independent risk factors for recurrence during and after FMT in UC patients (P<0.05). Albumin <30 g/L and simultaneous use of immunosuppressive agents were associated with disease recurrence during and after FMT in CD patients. WBC, PLT, and CRP were all negatively correlated with Enterococcus (EC), and ESR was positively correlated with Saccharomyces boulardii (SB) (P<0.01).<br><br>CONCLUSION: The low recurrence rate of IBD after FMT indicates the safety of FMT, but this procedure should be cautiously used in patients with severe intestinal barrier dysfunction and/or severe intestinal dysfunction.}, }
@article {pmid34955896, year = {2021}, author = {Zhao, Z and Guo, Z and Yin, Z and Qiu, Y and Zhou, B}, title = {Gut Microbiota Was Involved in the Process of Liver Injury During Intra-Abdominal Hypertension.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {790182}, doi = {10.3389/fphys.2021.790182}, pmid = {34955896}, issn = {1664-042X}, abstract = {Background: Intestinal damage caused by intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) can lead to the ectopic gut microbiota, which can contribute to liver injury via portal veins. Therefore, it is speculated that gut microbiota disorder caused by IAH/ACS may result in liver injury. The relationship between gut microbiota and IAH/ACS-related liver injury was investigated in this study. Methods: A model of IAH was established in rats, and 16S rRNA sequencing was analyzed for gut microbiota in the feces of rats. The elimination of gut microbiota was completed by antibiotics gavage, and fecal microbiota transplantation (FMT) was used to change the composition of gut microbiota in rats. Results: In addition to the traditional cause of liver blood vessel compression, liver injury caused by IAH was also associated with gut microbiota dysbiosis. Gut microbiota clearance can relieve liver injury caused by IAH, while FMT from IAH-intervened rats can aggravate IAH-related liver injury. Conclusion: The gut microbiota was one of the most important factors contributing to the IAH-related liver injury, and the JNK/p38 signaling pathway was activated in this process.}, }
@article {pmid34955437, year = {2021}, author = {Aira, A and Arajol, C and Casals-Pascual, C and González-Suárez, B and Martí, S and Domínguez, MÁ and Guardiola, J and Soriano, Á and , }, title = {Recommendations for stool donor selection for fecal microbiota transplant. Consensus document endorsed by the Catalan Society of Digestology, Catalan Society of Infectious diseases and Clinical Microbiology and the GEMBIOTA group from Spanish Society of Infectious Diseases and Clinical Microbiology.}, journal = {Enfermedades infecciosas y microbiologia clinica (English ed.)}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.eimce.2021.12.001}, pmid = {34955437}, issn = {2529-993X}, abstract = {Fecal microbiota transplantation (FMT) is an effective and safe treatment to treat recurrent Clostridioides difficile infection. It is essential to make every effort to perform FMT rigorously and based on scientific knowledge. Selection of the fecal microbiota donor is a key point of the process to ensure recipient safety. It is necessary to have protocols of action that allow clinicians to act with the maximum guarantees and to minimise the risks of the procedure. For this reason, a multidisciplinary working group has been set up in Cataluña with the aim of establishing recommendations for the selection of the fecal microbiota donor.}, }
@article {pmid34950432, year = {2021}, author = {Shaikh, DH and Patel, H and Munshi, R and Sun, H and Mehershahi, S and Baiomi, A and Alemam, A and Pirzada, U and Nawaz, I and Naher, K and Hanumanthu, S and Nayudu, S}, title = {Patients with Clostridium difficile infection and prior appendectomy may be prone to worse outcomes.}, journal = {World journal of gastrointestinal surgery}, volume = {13}, number = {11}, pages = {1436-1447}, pmid = {34950432}, issn = {1948-9366}, abstract = {BACKGROUND: Clostridium difficile infection (CDI) occurs due to a dysbiosis in the colon. The appendix is considered a 'safe house' for gut microbiota and may help repopulate gut flora of patients with CDI.<br><br>AIM: To study the impact of prior appendectomy on the severity and outcomes of CDI.<br><br>METHODS: We retrospectively reviewed data of 1580 patients with CDI, admitted to our hospital between 2008 to 2018. Patients were grouped based on the presence or absence of the appendix. The primary aim was to (1) assess all-cause mortality and (2) the severity of CDI. Severity was defined as per the Infectious Diseases Society of America criteria. Logistic regression, and propensity score analysis using inverse probability of treatment weights (IPTW) was performed.<br><br>RESULTS: Of the 1580 patients, 12.5% had a history of appendectomy. There was no statistical difference in mortality between patients with a prior appendectomy or without (13.7% vs 14%, P = 0.877). However, a history of appendectomy affected the severity of CDI [odds ratio (OR) = 1.32, 95% confidence interval: 1.01-1.75]. On IPTW, this association remained significant (OR = 1.59, P < 0.05). On multivariable analysis of secondary outcomes, prior appendectomy was also associated with toxic megacolon (OR = 5.37, P < 0.05) and colectomy (OR = 2.77, P < 0.05).<br><br>CONCLUSION: Prior appendectomy may affect the severity of CDI, development of toxic megacolon and the eventual need for colectomy. Since treatment of CDI is governed by its severity, stronger antibiotic regimens or earlier use of fecal microbiota transplant may be a viable option for patients with prior appendectomy.}, }
@article {pmid34950418, year = {2021}, author = {Xu, B and Qin, W and Xu, Y and Yang, W and Chen, Y and Huang, J and Zhao, J and Ma, L}, title = {Dietary Quercetin Supplementation Attenuates Diarrhea and Intestinal Damage by Regulating Gut Microbiota in Weanling Piglets.}, journal = {Oxidative medicine and cellular longevity}, volume = {2021}, number = {}, pages = {6221012}, pmid = {34950418}, issn = {1942-0994}, abstract = {Antioxidant polyphenols from plants are potential dietary supplementation to alleviate early weaning-induced intestinal disorders in piglets. Recent evidences showed polyphenol quercetin could reshape gut microbiota when it functioned as anti-inflammation or antioxidation agents in rodent models. However, the effect of dietary quercetin supplementation on intestinal disorders and gut microbiota of weanling piglets, along with the role of gut microbiota in this effect, both remain unclear. Here, we determined the quercetin's effect on attenuating diarrhea, intestinal damage, and redox imbalance, as well as the role of gut microbiota by transferring the quercetin-treated fecal microbiota to the recipient piglets. The results showed that dietary quercetin supplementation decreased piglets' fecal scores improved intestinal damage by increasing tight junction protein occludin, villus height, and villus height/crypt depth ratio but decreased crypt depth and intestinal epithelial apoptosis (TUNEL staining). Quercetin also increased antioxidant capacity indices, including total antioxidant capacity, catalase, and glutathione/oxidized glutathione disulfide but decreased oxidative metabolite malondialdehyde in the jejunum tissue. Fecal microbiota transplantation (FMT) from quercetin-treated piglets had comparable effects on improving intestinal damage and antioxidative capacity than dietary quercetin supplementation. Further analysis of gut microbiota using 16S rDNA sequencing showed that dietary quercetin supplementation or FMT shifted the structure and increased the diversity of gut microbiota. Especially, anaerobic trait and carbohydrate metabolism functions of gut microbiota were enriched after dietary quercetin supplementation and FMT, which may owe to the increased antioxidative capacity of intestine. Quercetin increased the relative abundances of Fibrobacteres, Akkermansia muciniphila, Clostridium butyricum, Clostridium celatum, and Prevotella copri but decreased the relative abundances of Proteobacteria, Lactobacillus coleohominis, and Ruminococcus bromii. Besides, quercetin-shifted bacteria and carbohydrate metabolites short chain fatty acids were significantly related to the indices of antioxidant capacity and intestinal integrity. Overall, dietary quercetin supplementation attenuated diarrhea and intestinal damage by enhancing the antioxidant capacity and regulating gut microbial structure and metabolism in piglets.}, }
@article {pmid34949194, year = {2021}, author = {Wu, Y and Zhang, Y and Xie, B and Abdelgawad, A and Chen, X and Han, M and Shang, Y and Yuan, S and Zhang, J}, title = {RhANP attenuates endotoxin-derived cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota-brain axis.}, journal = {Journal of neuroinflammation}, volume = {18}, number = {1}, pages = {300}, pmid = {34949194}, issn = {1742-2094}, support = {82071480//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Atrial natriuretic peptide (ANP) secreted from atrial myocytes is shown to possess anti-inflammatory, anti-oxidant and immunomodulatory effects. The aim of this study is to assess the effect of ANP on bacterial lipopolysaccharide (LPS)-induced endotoxemia-derived neuroinflammation and cognitive impairment.<br><br>METHODS: LPS (5 mg/kg) was given intraperitoneally to mice. Recombinant human ANP (rhANP) (1.0 mg/kg) was injected intravenously 24 h before and/or 10 min after LPS injection. Subdiaphragmatic vagotomy (SDV) was performed 14 days before LPS injection or 28 days before fecal microbiota transplantation (FMT). ANA-12 (0.5 mg/kg) was administrated intraperitoneally 30 min prior to rhANP treatment.<br><br>RESULTS: LPS (5.0 mg/kg) induced remarkable splenomegaly and an increase in the plasma cytokines at 24 h after LPS injection. There were positive correlations between spleen weight and plasma cytokines levels. LPS also led to increased protein levels of ionized calcium-binding adaptor molecule (iba)-1, cytokines and inducible nitric oxide synthase (iNOS) in the hippocampus. LPS impaired the natural and learned behavior, as demonstrated by an increase in the latency to eat the food in the buried food test and a decrease in the number of entries and duration in the novel arm in the Y maze test. Combined prophylactic and therapeutic treatment with rhANP reversed LPS-induced splenomegaly, hippocampal and peripheral inflammation as well as cognitive impairment. However, rhANP could not further enhance the protective effects of SDV on hippocampal and peripheral inflammation. We further found that PGF mice transplanted with fecal bacteria from rhANP-treated endotoxemia mice alleviated the decreased protein levels of hippocampal polyclonal phosphorylated tyrosine kinase receptor B (p-TrkB), brain-derived neurotrophic factor (BDNF) and cognitive impairment, which was abolished by SDV. Moreover, TrkB/BDNF signaling inhibitor ANA-12 abolished the improving effects of rhANP on LPS-induced cognitive impairment.<br><br>CONCLUSIONS: Our results suggest that rhANP could mitigate LPS-induced hippocampal inflammation and cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota-brain axis.}, }
@article {pmid34946163, year = {2021}, author = {Kosaka, S and Nadatani, Y and Higashimori, A and Otani, K and Fujimoto, K and Nagata, Y and Ominami, M and Fukunaga, S and Hosomi, S and Kamata, N and Tanaka, F and Nagami, Y and Taira, K and Imoto, S and Uematsu, S and Watanabe, T and Fujiwara, Y}, title = {Ovariectomy-Induced Dysbiosis May Have a Minor Effect on Bone in Mice.}, journal = {Microorganisms}, volume = {9}, number = {12}, pages = {}, doi = {10.3390/microorganisms9122563}, pmid = {34946163}, issn = {2076-2607}, support = {17K15962//JSPS KAKENHI/ ; }, abstract = {We determined the bone mineral density (BMD) and the expression of serum bone formation marker (procollagen type I N-terminal propeptide: PINP) and bone resorption marker (C-terminal telopeptide of collagen: CTX) by ELISA to evaluate ovariectomy-induced osteoporosis in ovariectomized (OVX) mice. The intestinal microbiota of the mice was assessed using 16S rRNA gene sequencing. OVX mice exhibited a lower BMD of 87% with higher serum levels of CTX and PINP compared to sham-operated (sham) mice. The cecum microbiome of OVX mice showed lower bacterial diversity than that of sham mice. TNFα mRNA levels in the colon were 1.6 times higher, and zonula occludens-1 mRNA and protein expression were lower in OVX mice than in sham mice, suggesting that ovariectomy induced inflammation and increased intestinal permeability. Next, we used antibiotic treatment followed by fecal microbiota transplantation (FMT) to remodel the gut microbiota in the OVX mice. A decrease in PINP was observed in antibiotic-treated mice, while there was no change in BMD or CTX between mice with and without antibiotic treatment. Oral transplantation of the luminal cecal content of OVX or sham mice to antibiotic-treated mice did not affect the BMD or PINP and CTX expression. Additionally, transplantation of the luminal contents of OVX or sham mice to antibiotic-treated OVX mice had similar effects on BMD, PINP, and CTX. In conclusion, although ovariectomy induces dysbiosis in the colon, the changes in the gut microbiota may only have a minor role in ovariectomy-induced osteoporosis.}, }
@article {pmid34946139, year = {2021}, author = {Broecker, F and Moelling, K}, title = {The Roles of the Virome in Cancer.}, journal = {Microorganisms}, volume = {9}, number = {12}, pages = {}, doi = {10.3390/microorganisms9122538}, pmid = {34946139}, issn = {2076-2607}, abstract = {Viral infections as well as changes in the composition of the intestinal microbiota and virome have been linked to cancer. Moreover, the success of cancer immunotherapy with checkpoint inhibitors has been correlated with the intestinal microbial composition of patients. The transfer of feces-which contain mainly bacteria and their viruses (phages)-from immunotherapy responders to non-responders, known as fecal microbiota transplantation (FMT), has been shown to be able to convert some non-responders to responders. Since phages may also increase the response to immunotherapy, for example by inducing T cells cross-reacting with cancer antigens, modulating phage populations may provide a new avenue to improve immunotherapy responsiveness. In this review, we summarize the current knowledge on the human virome and its links to cancer, and discuss the potential utility of bacteriophages in increasing the responder rate for cancer immunotherapy.}, }
@article {pmid34945118, year = {2021}, author = {Popa, D and Neamtu, B and Mihalache, M and Boicean, A and Banciu, A and Banciu, DD and Moga, DFC and Birlutiu, V}, title = {Fecal Microbiota Transplant in Severe and Non-Severe Clostridioides difficile Infection. Is There a Role of FMT in Primary Severe CDI?.}, journal = {Journal of clinical medicine}, volume = {10}, number = {24}, pages = {}, doi = {10.3390/jcm10245822}, pmid = {34945118}, issn = {2077-0383}, support = {LBUS-IRG-2021-07//Lucian Blaga University of Sibiu &amp; Hasso Plattner Foundation/ ; }, abstract = {BACKGROUND: Faecal microbiota transplant (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) with cure rates ranging between 85 and 92%. The FMT role for primary Clostridioides difficile infection (CDI) has yet to be settled because of limited data and small-sample studies presented in the current literature. Our study goals were to report the risk factors and the risk of recurrence after FMT for each CDI episode (first, second, and third) and to explore if there is a role of FMT in primary severe CDI.<br><br>METHODS: We conducted a retrospective study to analyze the clinical characteristics and the outcomes of 96 FMT patients with a prior 10 day course of antibiotic treatment in the medical records, of which 71 patients with recurrent CDI and 25 patients with a primary CDI.<br><br>RESULTS: The overall primary cure rate in our study was 88.5% and the primary cure rate for the severe forms was 85.7%. The data analysis revealed 5.25%, 15.15%, and 27.3% FMT recurrence rates for primary, secondary, and tertiary severe CDI. The risk of recurrence was significantly associated with FMT after the second and the third CDI severe episodes (p < 0.05), but not with FMT after the first severe CDI episode.<br><br>CONCLUSIONS: This study brings new data in supporting the FMT role in CDI treatment, including the primary severe CDI, however, further prospective and controlled studies on larger cohorts should be performed in this respect.}, }
@article {pmid34764444, year = {2021}, author = {Rolling, T and Zhai, B and Gjonbalaj, M and Tosini, N and Yasuma-Mitobe, K and Fontana, E and Amoretti, LA and Wright, RJ and Ponce, DM and Perales, MA and Xavier, JB and van den Brink, MRM and Markey, KA and Peled, JU and Taur, Y and Hohl, TM}, title = {Haematopoietic cell transplantation outcomes are linked to intestinal mycobiota dynamics and an expansion of Candida parapsilosis complex species.}, journal = {Nature microbiology}, volume = {6}, number = {12}, pages = {1505-1515}, pmid = {34764444}, issn = {2058-5276}, support = {U01 AI124275/AI/NIAID NIH HHS/United States ; R01 AI093808/AI/NIAID NIH HHS/United States ; R21 AI156157/AI/NIAID NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/classification/genetics/isolation &amp; purification ; Biodiversity ; Candida parapsilosis/genetics/*growth &amp; development/physiology ; Dysbiosis/immunology/microbiology ; Feces/microbiology ; Fungi/classification/genetics/isolation &amp; purification ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation ; Humans ; Intestines/immunology/microbiology ; Prospective Studies ; Transplantation, Homologous ; Treatment Outcome ; }, abstract = {Allogeneic haematopoietic cell transplantation (allo-HCT) induces profound shifts in the intestinal bacterial microbiota. The dynamics of intestinal fungi and their impact on clinical outcomes during allo-HCT are not fully understood. Here we combined parallel high-throughput fungal ITS1 amplicon sequencing, bacterial 16S amplicon sequencing and fungal cultures of 1,279 faecal samples from a cohort of 156 patients undergoing allo-HCT to reveal potential trans-kingdom dynamics and their association with patient outcomes. We saw that the overall density and the biodiversity of intestinal fungi were stable during allo-HCT but the species composition changed drastically from day to day. We identified a subset of patients with fungal dysbiosis defined by culture positivity (n = 53) and stable expansion of Candida parapsilosis complex species (n = 19). They presented with distinct trans-kingdom microbiota profiles, characterized by a decreased intestinal bacterial biomass. These patients had worse overall survival and higher transplant-related mortality independent of candidaemia. This expands our understanding of the clinical significance of the mycobiota and suggests that targeting fungal dysbiosis may help to improve long-term patient survival.}, }
@article {pmid33493658, year = {2021}, author = {Fang, Y and Zhang, J and Zhu, S and He, M and Ma, S and Jia, Q and Sun, Q and Song, L and Wang, Y and Duan, L}, title = {Berberine ameliorates ovariectomy-induced anxiety-like behaviors by enrichment in equol generating gut microbiota.}, journal = {Pharmacological research}, volume = {165}, number = {}, pages = {105439}, doi = {10.1016/j.phrs.2021.105439}, pmid = {33493658}, issn = {1096-1186}, mesh = {Animals ; Anxiety/*drug therapy/etiology/*metabolism ; Berberine/pharmacology/*therapeutic use ; Equol/*metabolism ; Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Microbiome/*drug effects/physiology ; Ovariectomy/*adverse effects ; Rats ; Rats, Sprague-Dawley ; }, abstract = {The gut microbiota is recognized as a promising therapeutic target for anxiety. Berberine (BBR) has shown efficacy in the treatment of diseases such as postmenopausal osteoporosis, obesity, and type 2 diabetes through regulating the gut microbiota. However, the effects of BBR on postmenopausal anxiety are still unclear. The purpose of the study is to test whether BBR ameliorates anxiety by modulating intestinal microbiota under estrogen-deficient conditions. Experimental anxiety was established in specific pathogen-free (SPF) ovariectomized (OVX) rats, which were then treated with BBR for 4 weeks before undergoing behavioral tests. Open field and elevated plus maze tests demonstrated that BBR treatment significantly ameliorated anxiety-like behaviors of OVX rats compared with vehicle-treated counterparts. Moreover, as demonstrated by 16S rRNA sequencing and liquid chromatography/mass spectrometry (LC/MS) analysis, BBR-treated OVX rats harbored a higher abundance of beneficial gut microbes, such as Bacteroides, Bifidobacterium, Lactobacillus, and Akkermansia, and exhibited increased equol generation. Notably, gavage feeding of BBR had no significant anti-anxiety effects on germ-free (GF) rats that underwent ovariectomy, whereas GF rats transplanted with fecal microbiota from SPF rats substantially phenocopied the donor rats in terms of anxiety-like symptoms and isoflavone levels. This study indicates that the gut microbiota is critical in the treatment of ovariectomy-aggravated anxiety, and that BBR modulation of the gut microbiota is a promising therapeutic strategy for treating postmenopausal symptoms of anxiety.}, }
@article {pmid34938813, year = {2021}, author = {Wang, S and Chen, H and Wen, X and Mu, J and Sun, M and Song, X and Liu, B and Chen, J and Fan, X}, title = {The Efficacy of Fecal Microbiota Transplantation in Experimental Autoimmune Encephalomyelitis: Transcriptome and Gut Microbiota Profiling.}, journal = {Journal of immunology research}, volume = {2021}, number = {}, pages = {4400428}, doi = {10.1155/2021/4400428}, pmid = {34938813}, issn = {2314-7156}, abstract = {Objective: To study the protective effect of fecal microbiota transplantation (FMT) on experimental autoimmune encephalomyelitis (EAE) and reveal its potential intestinal microflora-dependent mechanism through analyses of the intestinal microbiota and spinal cord transcriptome in mice.<br><br>Method: We measured the severity of disease by clinical EAE scores and H&amp;E staining. Gut microbiota alteration in the gut and differentially expressed genes (DEGs) in the spinal cord were analyzed through 16S rRNA and transcriptome sequencing. Finally, we analyzed associations between the relative abundance of intestinal microbiota constituents and DEGs.<br><br>Results: We observed that clinical EAE scores were lower in the EAE+FMT group than in the EAE group. Meanwhile, mice in the EAE+FMT group also had a lower number of infiltrating cells. The results of 16S rRNA sequence analysis showed that FMT increased the relative abundance of Firmicutes and Proteobacteria and reduced the abundance of Bacteroides and Actinobacteria. Meanwhile, FMT could modulate gut microbiota balance, especially via increasing the relative abundance of g_Adlercreutzia, g_Sutterella, g_Prevotella_9, and g_Tyzzerella_3 and decreasing the relative abundance of g_Turicibacter. Next, we analyzed the transcriptome of mouse spinal cord tissue and found that 1476 genes were differentially expressed between the EAE and FMT groups. The analysis of these genes showed that FMT mainly participated in the inflammatory response. Correlation analysis between gut microbes and transcriptome revealed that the relative abundance of Adlercreutzia was correlated with the expression of inflammation-related genes negatively, including Casp6, IL1RL2 (IL-36R), IL-17RA, TNF, CCL3, CCR5, and CCL8, and correlated with the expression of neuroprotection-related genes positively, including Snap25, Edil3, Nrn1, Cpeb3, and Gpr37.<br><br>Conclusion: Altogether, FMT may selectively regulate gene expression to improve inflammation and maintain the stability of the intestinal environment in a gut microbiota-dependent manner.}, }
@article {pmid34933877, year = {2021}, author = {Hofmeister, M and Clement, F and Patten, S and Li, J and Dowsett, LE and Farkas, B and Mastikhina, L and Egunsola, O and Diaz, R and Cooke, NCA and Taylor, VH}, title = {The effect of interventions targeting gut microbiota on depressive symptoms: a systematic review and meta-analysis.}, journal = {CMAJ open}, volume = {9}, number = {4}, pages = {E1195-E1204}, doi = {10.9778/cmajo.20200283}, pmid = {34933877}, issn = {2291-0026}, abstract = {BACKGROUND: Despite their popularity, the efficacy of interventions targeting gut microbiota to improve depressive symptoms is unknown. Our objective is to summarize the effect of microbiome-targeting interventions on depressive symptoms.<br><br>METHODS: We conducted a systematic review and meta-analysis. We searched MEDLINE, Embase, PsycINFO, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews and the Cochrane Controlled Register of Trials from inception to Mar. 5, 2021. We included studies that evaluated probiotic, prebiotic, synbiotic, paraprobiotic or fecal microbiota transplant interventions in an adult population (age ≥ 18 yr) with an inactive or placebo comparator (defined by the absence of active intervention). Studies must have measured depressive symptoms with a validated scale, and used a randomized controlled trial study design. We conducted a random effects meta-analysis of change scores, using standardized mean difference as the measure of effect.<br><br>RESULTS: Sixty-two studies formed the final data set, with 50 included in the meta-analysis. Probiotic, prebiotic, and synbiotic interventions on depressive symptoms showed statistically significant benefits. In the single studies evaluating each of fecal microbiota transplant and paraprobiotic interventions, neither showed a statistically significant benefit.<br><br>INTERPRETATION: Despite promising findings of benefit of probiotic, prebiotic and synbiotic interventions for depressive symptoms in study populations, there is not yet strong enough evidence to favour inclusion of these interventions in treatment guidelines for depression. Critical questions about species administered, dosage and timing relative to other antidepressant medications remain to be answered.<br><br>STUDY REGISTRATION: PROSPERO no. 143178.}, }
@article {pmid34588655, year = {2021}, author = {Hofer, U}, title = {Faecal phage transplant to the rescue?.}, journal = {Nature reviews. Microbiology}, volume = {19}, number = {12}, pages = {744}, pmid = {34588655}, issn = {1740-1534}, mesh = {*Bacteriophages/genetics ; Fecal Microbiota Transplantation ; Feces ; }, }
@article {pmid33633259, year = {2021}, author = {Sasaki, K and Sasaki, D and Sasaki, K and Nishidono, Y and Yamamori, A and Tanaka, K and Kondo, A}, title = {Growth stimulation of Bifidobacterium from human colon using daikenchuto in an in vitro model of human intestinal microbiota.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {4580}, pmid = {33633259}, issn = {2045-2322}, mesh = {Bifidobacterium/*drug effects/growth &amp; development/isolation &amp; purification ; Colon/*microbiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/genetics ; Humans ; In Vitro Techniques ; Panax ; Plant Extracts/*pharmacology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, RNA/methods ; Zanthoxylum ; Zingiberaceae ; }, abstract = {Daikenchuto (DKT) is a Japanese traditional herbal (Kampo) medicine containing ginseng, processed ginger, and Japanese or Chinese pepper. We aimed to determine how DKT affects human colonic microbiota. An in vitro microbiota model was established using fecal inocula collected from nine healthy volunteers, and each model was found to retain operational taxonomic units similar to the ones in the original human fecal samples. DKT was added to the in vitro microbiota model culture at a concentration of 0.5% by weight. Next-generation sequencing of bacterial 16S rRNA gene revealed a significant increase in the relative abundance of bacteria related to the Bifidobacterium genus in the model after incubation with DKT. In pure cultures, DKT significantly promoted the growth of Bifidobacterium adolescentis, but not that of Fusobacterium nucleatum or Escherichia coli. Additionally, in pure cultures, B. adolescentis transformed ginsenoside Rc to Rd, which was then probably utilized for its growth. Our study reveals the in vitro bifidogenic effect of DKT that likely contributes to its beneficial effects on the human colon.}, }
@article {pmid34931881, year = {2021}, author = {Chen, X and Wu, Q and Gao, X and Wang, H and Zhu, J and Xia, G and He, Y and Song, W and Xu, K}, title = {Gut Microbial Dysbiosis Associated with Type 2 Diabetes Aggravates Acute Ischemic Stroke.}, journal = {mSystems}, volume = {6}, number = {6}, pages = {e0130421}, doi = {10.1128/msystems.01304-21}, pmid = {34931881}, issn = {2379-5077}, support = {201904010091//Science and Technology Program of Guangzhou/ ; 2018M630967//China Postdoctoral Science Foundation/ ; NSFC31800415//National Natural Science Foundation of China (NSFC)/ ; NSFC82022044//National Natural Science Foundation of China (NSFC)/ ; }, abstract = {Type 2 diabetes (T2D) is an independent risk factor for acute ischemic stroke (AIS), but the underlying mechanisms remain elusive. Because the gut microbiota plays a causal role in both T2D and AIS, we wondered whether gut dysbiosis in T2D aggravates stroke progression. We recruited 35 T2D, 90 AIS, 60 AIS with T2D (AIS_T2D) patients, and 55 healthy controls and found that AIS and T2D had an additive effect on AIS_T2D patient gut dysbiosis by exhibiting the largest difference from the heathy controls. In addition, we found that the degree of gut dysbiosis associated with T2D was positively correlated with the National Institutes of Health Stroke Scale (NIHSS), modified Rankin score (mRS), and Essen stroke risk score in patients with AIS, including AIS and AIS_T2D patients. Compared with mice colonized with gut microbiota from healthy controls poststroke modeling, germfree (GF) mice colonized with gut microbiota from T2D patients showed exacerbated cerebral injury and impaired gut barrier function. Specifically, exacerbated brain injury and gut barrier dysfunction in T2D-treated GF mice were significantly associated with a reduction in short-chain fatty acid (SCFA)-producing bacteria. Our study showed that T2D and AIS have an additive effect on AIS_T2D patient gut microbiota dysbiosis. T2D-associated gut microbiota dysbiosis is associated with stroke severity in AIS patients and aggravates stroke progression in mice. IMPORTANCE We demonstrated an additive effect of type 2 diabetes (T2D) and acute ischemic stroke (AIS) on AIS with T2D (AIS_T2D) patient gut microbiota dysbiosis, and gut dysbiosis associated with T2D was positively correlated with stroke severity in AIS patients. Through animal experiments, we found that cerebral injury was exacerbated by fecal microbiota transplantation from T2D patients compared with that from healthy controls, which was associated with a reduction in short-chain fatty acid (SCFA)-producing bacteria. This study provided a novel view that links T2D and AIS through gut microbial dysbiosis.}, }
@article {pmid34931478, year = {2021}, author = {Mashiah, J and Karady, T and Fliss-Isakov, N and Sprecher, E and Slodownik, D and Artzi, O and Samuelov, L and Ellenbogen, E and Godneva, A and Segal, E and Maharshak, N}, title = {Clinical efficacy of fecal microbial transplantation treatment in adults with moderate-to-severe atopic dermatitis.}, journal = {Immunity, inflammation and disease}, volume = {}, number = {}, pages = {}, doi = {10.1002/iid3.570}, pmid = {34931478}, issn = {2050-4527}, abstract = {BACKGROUND: Atopic dermatitis (AD) is a remitting relapsing chronic eczematous pruritic disease. Several studies suggest that gut microbiota may influence AD by immune system regulation.<br><br>METHODS: We performed the first in-human efficacy and safety assessment of fecal microbiota transplantation (FMT) for AD adult patients. All patients received 2 placebo transplantations followed by 4 FMTs each 2 weeks apart. AD severity and fecal microbiome profile were evaluated by the Scoring Atopic Dermatitis Score (SCORAD), the weekly frequency of topical corticosteroids usage, and gut microbiota metagenomic analysis, at the study beginning, before every FMT, and 1-8 months after the last FMT.<br><br>RESULTS: Nine patients completed the study protocol. There was no significant change in the SCORAD score following the two placebo transplants. The average SCORAD score significantly decreased from baseline at Weeks 4-12 (before and 2 weeks after 4 times of FMT) (59.2 ± 34.9%, Wilcoxon p = .011), 50% and 75% decrease was achieved by 7 (77%) and 4 (44%) patients, respectively. At Week 18 (8 weeks after the last FMT) the average SCORAD score decreased from baseline at Week 4 (85.5 ± 8.4%, Wilcoxon p = .018), 50% and 75% decrease was achieved by 7 (77%) and 6 (66.7%) patients respectively. Weekly topical corticosteroids usage was diminished during the study and follow-up period as well. Two patients had a quick relapse and were switched to a different treatment. Two patients developed exacerbations alleviated after an additional fifth FMT. Metagenomic analysis of the fecal microbiota of patients and donors showed bacterial strains transmission from donors to patients. No adverse events were recorded during the study and follow-up period.<br><br>CONCLUSIONS: FMT may be a safe and effective therapeutic intervention for AD patients, associated with transfer of specific microbial species from the donors to the patients. Further studies are required to reconfirm these results.}, }
@article {pmid34926663, year = {2021}, author = {Zhang, Y and Xue, X and Su, S and Zhou, H and Jin, Y and Shi, Y and Lin, J and Wang, J and Li, X and Yang, G and Philpott, JR and Liang, J}, title = {Patients and physicians' attitudes change on fecal microbiota transplantation for inflammatory bowel disease over the past 3 years.}, journal = {Annals of translational medicine}, volume = {9}, number = {21}, pages = {1619}, doi = {10.21037/atm-21-3683}, pmid = {34926663}, issn = {2305-5839}, abstract = {Background: In the past 3 years, increasing data and experience has become available regarding fecal microbiota transplantation (FMT) for the treatment of inflammatory bowel disease (IBD). However, how this increase in knowledge has impacted the attitudes of patients and physicians is largely unknown. This study aimed to investigate the change of patients' and physicians' attitudes towards FMT for IBD treatment.<br><br>Methods: Questionnaires for patient and physician attitude on FMT for IBD were pilot-tested and developed. Patients and physicians from the same groups completed the questionnaires in 2016 and 2019, separately. The attitudes towards efficacy, adverse events, and methodological features of FMT in 2016 were compared with those in 2019.<br><br>Results: A total of 1,255 questionnaires from 486 patients and 769 physicians were collected. Over the 3 years, an increased number of patients had heard of FMT and had similarly positive opinions towards using FMT for IBD therapy. Additionally, patients retained the tendency to overestimate the efficacy. The physicians' perceptions became closer to the findings reported in recent studies in 2019 compared with 2016. However, only a minority of patients and physicians understood the frequency required of FMT courses for induction of clinical remission. In particular, both patients and physicians underestimated the risk of mild adverse events and IBD flare.<br><br>Conclusions: Patients are receptive towards FMT as therapy for IBD but opportunity remains to improve understanding of benefit and potential risks. Physicians also demonstrated knowledge gaps in use of this therapy. Aligning patient preference and physician knowledge gap will lead to better education and facilitate the development of decision-making guidelines.}, }
@article {pmid34925385, year = {2021}, author = {Pan, Q and Guo, F and Huang, Y and Li, A and Chen, S and Chen, J and Liu, HF and Pan, Q}, title = {Gut Microbiota Dysbiosis in Systemic Lupus Erythematosus: Novel Insights into Mechanisms and Promising Therapeutic Strategies.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {799788}, doi = {10.3389/fimmu.2021.799788}, pmid = {34925385}, issn = {1664-3224}, abstract = {Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that was traditionally thought to be closely related to genetic and environmental risk factors. Although treatment options for SLE with hormones, immunosuppressants, and biologic drugs are now available, the rates of clinical response and functional remission of these drugs are still not satisfactory. Currently, emerging evidence suggests that gut microbiota dysbiosis may play crucial roles in the occurrence and development of SLE, and manipulation of targeting the gut microbiota holds great promises for the successful treatment of SLE. The possible mechanisms of gut microbiota dysbiosis in SLE have not yet been well identified to date, although they may include molecular mimicry, impaired intestinal barrier function and leaky gut, bacterial biofilms, intestinal specific pathogen infection, gender bias, intestinal epithelial cells autophagy, and extracellular vesicles and microRNAs. Potential therapies for modulating gut microbiota in SLE include oral antibiotic therapy, fecal microbiota transplantation, glucocorticoid therapy, regulation of intestinal epithelial cells autophagy, extracellular vesicle-derived miRNA therapy, mesenchymal stem cell therapy, and vaccination. This review summarizes novel insights into the mechanisms of microbiota dysbiosis in SLE and promising therapeutic strategies, which may help improve our understanding of the pathogenesis of SLE and provide novel therapies for SLE.}, }
@article {pmid34923901, year = {2021}, author = {Guo, Q and Lin, H and Chen, P and Tan, S and Wen, Z and Lin, L and He, J and Wen, J and Lu, S}, title = {Dynamic changes of intestinal flora in patients with irritable bowel syndrome combined with anxiety and depression after oral administration of enterobacteria capsules.}, journal = {Bioengineered}, volume = {}, number = {}, pages = {}, doi = {10.1080/21655979.2021.1999374}, pmid = {34923901}, issn = {2165-5987}, abstract = {This study investigated the clinical characteristics and dynamic changes of intestinal bacterial community to evaluate the curative effect of fecal microbiota transplantation (FMT) on irritable bowel syndrome with predominant diarrhea (IBS-D) comorbid with anxiety and depression. Total two treatments were designed in randomize-controlled trial includes oral FMT capsules with 1 week (A1), 8 weeks (A2), and 12 weeks (A3), as well as oral empty capsules with 1 week (B1), 8 weeks (B2), and 12 weeks (B3) as control for comparation. The positive therapeutic effects occurred in FMT colonized patient with IBS-D comorbid psychological disorder, demonstrated at alleviated IBS-D severity (IBS-SSS score from 291.11 reduced to 144.44), altered stool type (from 6 changed to 4), reduced anxiety and depression scores (from 18.33 to 8.39 and from 22.33 to 17.78) after FMT treated 12 weeks. The FMT therapy improved bacterial alpha diversity and the majority bacterial community predominant by Bacteroidetes and Firmicutes, and the relative abundance (RA) was higher after FMT treated 12 weeks (50.61% and 45.52%) than control (47.62% and 38.96%). In short, FMT therapy has great potential for IBS-D patients combined with anxiety and depression by alleviated clinical symptoms and restore the intestinal micro-ecology.[Figure: see text].}, }
@article {pmid34922582, year = {2021}, author = {He, Y and Du, W and Xiao, S and Zeng, B and She, X and Liu, D and Du, H and Li, L and Li, F and Ai, Q and He, J and Song, C and Wei, H and Zhao, X and Yu, J}, title = {Colonization of fecal microbiota from patients with neonatal necrotizing enterocolitis exacerbates intestinal injury in germfree mice subjected to necrotizing enterocolitis-induction protocol via alterations in butyrate and regulatory T cells.}, journal = {Journal of translational medicine}, volume = {19}, number = {1}, pages = {510}, pmid = {34922582}, issn = {1479-5876}, support = {82001602//National Natural Science Foundation of China/ ; 81971431//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Necrotizing enterocolitis (NEC) remains a life-threatening disease in neonates. Numerous studies have shown a correlation between the intestinal microbiota and NEC, but the causal link remains unclear. This study aimed to demonstrate the causal role of gut microbiota in NEC and explore potential mechanisms involved.<br><br>METHODS: Eighty-one fecal samples from patients with NEC and eighty-one matched controls (matched to the NEC infants by gestational age, birth weight, date of birth, mode of delivery and feeding patterns) were collected. To explore if altered gut microbiota contributes to the pathogenesis of NEC, fecal microbiota transplantation (FMT) was carried out in germ-free (GF) mice prior to a NEC-induction protocol that included exposure to hypoxia and cold stress. Butyric acid was also administered to demonstrate its role in NEC. The fecal microbiota from patients and mice were analyzed by 16S rRNA gene sequencing analysis. Short chain fatty acid (SCFA) levels were measured by gas chromatography-mass spectrometry (GC-MS). The ontogeny of T cells and regulatory T cells (Tregs) in lamina propria mononuclear cells (LPMC) from the ileum of patients and mice were isolated and analyzed by flow cytometry.The transcription of inflammatory cytokines was quantified by qRT-PCR.<br><br>RESULTS: NEC patients had increased Proteobacteria and decreased Firmicutes and Bacteroidetes compared to fecal control samples, and the level of butyric acid in the NEC group was lower than the control group. FMT in GF mice with samples from NEC patients achieved a higher histological injury scores when compared to mice that received FMT with control samples. Alterations in microbiota and butyrate levels were maintained in mice following FMT. The ratio of Treg/CD4+T (Thelper) cells was reduced in both NEC patients and mice modeling NEC following FMT.<br><br>CONCLUSIONS: The microbiota was found to have NEC and the microbial butyrate-Treg axis was identified as a potential mechanism for the observed effects.}, }
@article {pmid34920070, year = {2021}, author = {Zhang, L and Wang, Y and Wu, F and Wang, X and Feng, Y and Wang, Y}, title = {MDG, an Ophiopogon japonicus polysaccharide, inhibits non-alcoholic fatty liver disease by regulating the abundance of Akkermansia muciniphila.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ijbiomac.2021.12.036}, pmid = {34920070}, issn = {1879-0003}, abstract = {MDG, a polysaccharide derived from Ophiopogon japonicus, displays a protective effect against obesity and non-alcoholic fatty liver disease (NAFLD). However, there is no definitive evidence proving the specific mechanism of MDG against NAFLD. The results showed MDG supplementation ameliorated lipid accumulation, liver steatosis, and chronic inflammation in high-fat diet-induced NAFLD mice. Besides, MDG increased the abundance and diversity of microbial communities in the gut. These effects were mediated by the colonization of fecal microbiota. Further investigation revealed that Akkermansia muciniphila levels correlated negatively with NAFLD development, and lipid metabolism-related signaling might be the key regulator. Our study suggested that MDG treatment could inhibit obesity and the NAFLD process by modulating lipid-related pathways via altering the structure and diversity of gut microbiota. In addition, Akkermansia miniciphila might be a promising candidate in future research into NAFLD.}, }
@article {pmid34918995, year = {2021}, author = {Qi, L and Huang, X and He, C and Ji, D and Li, F}, title = {Steroid-resistant intestinal aGVHD and refractory CMV and EBV infections complicated by haplo-HSCT were successfully rescued by FMT and CTL infusion.}, journal = {The Journal of international medical research}, volume = {49}, number = {12}, pages = {3000605211063292}, doi = {10.1177/03000605211063292}, pmid = {34918995}, issn = {1473-2300}, abstract = {Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) produces similar survival outcomes as HLA-matched sibling donor allogeneic HCST in younger patients with acquired severe aplastic anemia (SAA). This study reported a 29-years-old man with SAA and intracranial hemorrhage who underwent haplo-HSCT with a modified BU/CY + ATG conditioning regimen. Neutrophil and platelet engraftment were both achieved on day 14 after HSCT. The patient developed grade IV acute graft-versus-host disease (aGVHD) on day 20 and acquired cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections on day 47. After the failure of methylprednisolone, basiliximab, ruxolitinib, and antiviral treatment, the patient was diagnosed with steroid-resistant grade IV aGVHD and refractory CMV and EBV infections. We performed fecal microbiota transplantation and infused CMV- and EBV-specific cytotoxic T lymphocytes. After that the stool volume and frequency gradually decreased, and viral DNA was undetectable on day 80. This report provides helpful clinical experience for treating steroid-resistant aGVHD and refractory viral infections.}, }
@article {pmid34918486, year = {2021}, author = {Wang, Y and Xie, Z}, title = {Exploring the role of gut microbiome in male reproduction.}, journal = {Andrology}, volume = {}, number = {}, pages = {}, doi = {10.1111/andr.13143}, pmid = {34918486}, issn = {2047-2927}, abstract = {BACKGROUND: The impact of the gut microbiome on the organism has become a growing research focus with the development of 16S rRNA sequencing. However, the effect of the gut microbiome in male reproduction has yet to be investigated.<br><br>OBJECTIVE: To overview on possible mechanisms by which gut microbiome could affect male reproduction and therapeutic opportunities related to the gut microbiome METHODS: Authors searched PubMed/MEDLINE, EMBASE, Web of Science, Cochrane Library for medical subject headings terms and free text words referred to "male infertility" "testis" "gut microbiome" "insulin resistance" "erectile dysfunction" "therapy" "sex hormones" "Genital Diseases." until Dec 2nd 2021.<br><br>RESULTS: Evidence suggests that immune system activation caused by the gut microbiome translocation not only leads to testicular and epididymal inflammation but can also induce insulin resistance together with gastrointestinal hormones such as leptin and ghrelin, which in turn affects the secretion of various sex hormones such as LH, FSH, and T to regulate spermatogenesis. In addition, the gut microbiome can influence spermatogenesis by controlling and metabolizing androgens as well as affecting the blood-testis barrier. It also promotes vascular inflammation by raising trimethylamine-N-oxide (TMAO) levels in the blood, which causes erectile dysfunction. Testicular microbiome and gut microbiome can interact to influence male reproductive function. This study discusses therapeutic options such as probiotics, prebiotics, and fecal microbiota transplantation, as well as the challenges and opportunities behind ongoing research, and emphasizes the need for additional research in the future to demonstrate the links and underlying mechanisms between gut microbiome and male reproduction. Therapeutic options such as probiotic, prebiotics and fecal microbiota transplantation are potential treatments for male infertility.<br><br>DISCUSSION AND CONCLUSION: Gut microbiota may have a causal role in male reproduction health, therapeutic strategies such as supplementation with appropriate probiotics could be undertaken as a complementary treatment. In the future, additional research is needed to demonstrate the links and underlying mechanisms between gut microbiome and male reproduction. This article is protected by copyright. All rights reserved.}, }
@article {pmid34531862, year = {2021}, author = {Islam, SMS and Ryu, HM and Sayeed, HM and Byun, HO and Jung, JY and Kim, HA and Suh, CH and Sohn, S}, title = {Eubacterium rectale Attenuates HSV-1 Induced Systemic Inflammation in Mice by Inhibiting CD83.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {712312}, pmid = {34531862}, issn = {1664-3224}, mesh = {Administration, Oral ; Adult ; Animals ; Antigens, CD/biosynthesis/genetics ; Bacteria/classification/isolation &amp; purification ; Behcet Syndrome/drug therapy/microbiology/*therapy ; Butyrates/metabolism/therapeutic use ; Colchicine/therapeutic use ; Combined Modality Therapy ; Dendritic Cells/immunology ; Disease Models, Animal ; Down-Regulation/drug effects ; *Eubacterium ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Herpes Simplex/immunology/microbiology/therapy ; Herpesvirus 1, Human/*pathogenicity ; Humans ; Immunoglobulins/biosynthesis/genetics ; Inflammation/drug therapy/*therapy ; Interleukin-17/blood ; Killer Cells, Natural/immunology ; Male ; Membrane Glycoproteins/*antagonists &amp; inhibitors/biosynthesis/genetics ; Metagenome ; Mice ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Random Allocation ; Ribotyping ; Severity of Illness Index ; }, abstract = {The purpose of this study was to determine whether administration of the microorganism Eubacterium rectale (E. rectale) could regulate dendritic cell (DC) activation and systemic inflammation in herpes simplex virus type 1-induced Behçet's disease (BD). E. rectale, butyrate-producing bacteria, was administered to BD mice. Peripheral blood leukocytes (PBL) and lymph node cells were isolated and analyzed by flow cytometry. 16S rRNA metagenomic analysis was performed in the feces of mice to determine the differences in the composition of the microbial population between normal and BD mice. Serum cytokine levels were measured by enzyme-linked immunosorbent assay. The frequency of DC activation marker CD83 positive cells was significantly increased in PBL of BD mice. Frequencies of CD83+ cells were also significantly increased in patients with active BD. 16S rRNA metagenomic analysis revealed different gut microbiota composition between normal and BD mice. The administration of E. rectale to BD mice reduced the frequency of CD83+ cells and significantly increased the frequency of NK1.1+ cells with the improvement of symptoms. The co-administration of colchicine and E. rectale also significantly reduced the frequency of CD83+ cells. Differences in gut microbiota were observed between normal mice and BD mice, and the administration of E. rectale downregulated the frequency of CD83, which was associated with BD deterioration. These data indicate that E. rectale could be a new therapeutic adjuvant for BD management.}, }
@article {pmid34512631, year = {2021}, author = {Bozward, AG and Ronca, V and Osei-Bordom, D and Oo, YH}, title = {Gut-Liver Immune Traffic: Deciphering Immune-Pathogenesis to Underpin Translational Therapy.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {711217}, pmid = {34512631}, issn = {1664-3224}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Antibodies, Monoclonal, Humanized/therapeutic use ; Bile Acids and Salts/physiology ; Cholangitis, Sclerosing/drug therapy/*etiology/immunology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Inflammatory Bowel Diseases/etiology ; Intestinal Mucosa/*immunology ; Liver/*immunology ; Liver Cirrhosis, Biliary/etiology ; Receptors, Cytoplasmic and Nuclear/physiology ; T-Lymphocytes, Regulatory/immunology ; Vancomycin/pharmacology ; }, abstract = {The tight relationship between the gut and liver on embryological, anatomical and physiological levels inspired the concept of a gut-liver axis as a central element in the pathogenesis of gut-liver axis diseases. This axis refers to the reciprocal regulation between these two organs causing an integrated system of immune homeostasis or tolerance breakdown guided by the microbiota, the diet, genetic background, and environmental factors. Continuous exposure of gut microbiome, various hormones, drugs and toxins, or metabolites from the diet through the portal vein adapt the liver to maintain its tolerogenic state. This is orchestrated by the combined effort of immune cells network: behaving as a sinusoidal and biliary firewall, along with a regulatory network of immune cells including, regulatory T cells and tolerogenic dendritic cells (DC). In addition, downregulation of costimulatory molecules on hepatic sinusoids, hepatocytes and biliary epithelial cells as well as regulating the bile acids chain also play a part in hepatic immune homeostasis. Recent evidence also demonstrated the link between changes in the gut microbiome and liver resident immune cells in the progression of cirrhosis and the tight correlation among primary sclerosing cholangitis (PSC) and also checkpoint induced liver and gut injury. In this review, we will summarize the most recent evidence of the bidirectional relationship among the gut and the liver and how it contributes to liver disease, focusing mainly on PSC and checkpoint induced hepatitis and colitis. We will also focus on completed therapeutic options and on potential targets for future treatment linking with immunology and describe the future direction of this research, taking advantage of modern technologies.}, }
@article {pmid33674230, year = {2021}, author = {Zhou, CB and Zhou, YL and Fang, JY}, title = {Gut Microbiota in Cancer Immune Response and Immunotherapy.}, journal = {Trends in cancer}, volume = {7}, number = {7}, pages = {647-660}, doi = {10.1016/j.trecan.2021.01.010}, pmid = {33674230}, issn = {2405-8025}, mesh = {Adaptive Immunity ; Animals ; Anti-Bacterial Agents/adverse effects ; Combined Modality Therapy/methods ; Disease Models, Animal ; Disease-Free Survival ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*immunology ; Host Microbial Interactions/drug effects/*immunology ; Humans ; Immune Checkpoint Inhibitors/*administration &amp; dosage/adverse effects ; Immunotherapy/methods ; Mice ; Neoplasm Recurrence, Local/*epidemiology/immunology/prevention &amp; control ; Neoplasms/immunology/microbiology/mortality/*therapy ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; Prognosis ; Progression-Free Survival ; }, abstract = {The gastrointestinal tract (GIT) is the largest immune organ and maintains systemic immune homeostasis in the presence of bacterial challenge. Immune elimination and immune escape are hallmarks of cancer, both of which can be partly bacteria dependent in shaping immunity by mediating host immunomodulation. In addition, host immunity regulates the microbiome by altering bacteria-associated signaling to influence tumor surveillance. Cancer immunotherapy, including immune checkpoint blockade (ICB), appears to have heterogeneous therapeutic effects in different individuals, partially attributed to the microbiota. Thus, the microbiome signature can predict clinical outcomes, prognosis, and immunotherapy responses. In this review, we summarize the intricate crosstalk among the gut microbiome, cancer immune response, and immunotherapy. Interactive modulation of the host microbiota provides new therapeutic strategies to promote anticancer therapy efficacy and/or reduce toxicity.}, }
@article {pmid34912583, year = {2021}, author = {Hollingshead, C and Ciricillo, J and Kammeyer, J}, title = {Ethical Implications of the Fecal Microbiota Transplantation: Disclosure of a False-Positive HIV Test.}, journal = {Case reports in infectious diseases}, volume = {2021}, number = {}, pages = {6696542}, doi = {10.1155/2021/6696542}, pmid = {34912583}, issn = {2090-6625}, abstract = {Fecal microbiota transplantation (FMT) has gained popularity as an effective therapeutic option for Clostridioides difficile infection (CDI). Since its FDA recognition as a treatment modality for recurrent CDI in 2013, screening protocols for FMT donor stool have been in flux. However, extensive health questionnaires, in combination with serological and stool assays, have become mainstays in the donor screening process, although ethical implications are yet to be thoroughly considered. Herein, we present the case of a family member found to have a false-positive HIV test during the donor screening process and discuss potential ethical ramifications associated with FMT stool donation.}, }
@article {pmid34912328, year = {2021}, author = {Liang, M and Liwen, Z and Jianguo, S and Juan, D and Fei, D and Yin, Z and Changping, W and Jianping, C}, title = {Fecal Microbiota Transplantation Controls Progression of Experimental Autoimmune Hepatitis in Mice by Modulating the TFR/TFH Immune Imbalance and Intestinal Microbiota Composition.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {728723}, doi = {10.3389/fimmu.2021.728723}, pmid = {34912328}, issn = {1664-3224}, abstract = {Intestinal microbiota (IM) dysbiosis contributes to the development of autoimmune hepatitis (AIH). This study aimed to investigate the potential effect of fecal microbiota transplantation (FMT) in a murine model of experimental AIH (EAH), a condition more similar to that of AIH patients. Changes in the enteric microbiome were determined in AIH patients and EAH mice. Moreover, we established an experimental model of secondary EAH mice harboring dysbiosis (ABx) to analyze the effects of therapeutic FMT administration on follicular regulatory T (TFR) and helper T (TFH) cell imbalances and IM composition in vivo. Alterations of the IM composition and bacterial translocation occurred in AIH patients compared to nonalcoholic fatty liver disease patients and healthy controls (HCs). Therapeutic FMT significantly attenuated liver injury and bacterial translocation and improved the imbalance between splenic TFR cells and TFH cells in ABx EAH mice. Furthermore, therapeutic FMT also partially reversed the increasing trend in serum liver enzymes (ALT and AST) of CXCR5-/-EAH mice on the 28th day. Finally, therapeutic FMT could effectively restore antibiotic-induced IM dysbiosis in EAH mice. Taken together, our findings demonstrated that FMT was capable of controlling hepatitis progression in EAH mice, and the associated mechanism might be involved in the regulation of the TFR/TFH immune imbalance and the restoration of IM composition.}, }
@article {pmid34262150, year = {2021}, author = {Lee, KA and Luong, MK and Shaw, H and Nathan, P and Bataille, V and Spector, TD}, title = {The gut microbiome: what the oncologist ought to know.}, journal = {British journal of cancer}, volume = {125}, number = {9}, pages = {1197-1209}, pmid = {34262150}, issn = {1532-1827}, mesh = {Bacteria/*classification/genetics/immunology ; Diet Therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Neoplasms/immunology/*microbiology/therapy ; Precision Medicine ; Probiotics ; Tumor Microenvironment ; }, abstract = {The gut microbiome (GM) has been implicated in a vast number of human pathologies and has become a focus of oncology research over the past 5 years. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation and protection against pathogens. Strong evidence is emerging to support the effects of the GM on the development of some malignancies but also on responses to cancer therapies, most notably, immune checkpoint inhibition. Tools for manipulating the GM including dietary modification, probiotics and faecal microbiota transfer (FMT) are in development. Current understandings of the many complex interrelationships between the GM, cancer, the immune system, nutrition and medication are ultimately based on a combination of short-term clinical trials and observational studies, paired with an ever-evolving understanding of cancer biology. The next generation of personalised cancer therapies focusses on molecular and phenotypic heterogeneity, tumour evolution and immune status; it is distinctly possible that the GM will become an increasingly central focus amongst them. The aim of this review is to provide clinicians with an overview of microbiome science and our current understanding of the role the GM plays in cancer.}, }
@article {pmid34904826, year = {2021}, author = {Zhao, Y and Chen, X and Shen, J and Xu, A and Wang, Y and Meng, Q and Xu, P}, title = {Black Tea Alleviates Particulate Matter-Induced Lung Injury via the Gut-Lung Axis in Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.1c06796}, pmid = {34904826}, issn = {1520-5118}, abstract = {Black tea, as the most consumed kind of tea, is shown to have beneficial effects on human health. However, its impact on particulate matter (PM) induced lung injury and the mechanisms involved have been sparsely addressed. Here, we show that PM-exposed mice exhibited oxidative stress and inflammation in the lungs, which was significantly alleviated by a daily intake of black tea infusion (TI) in a concentration-dependent manner. Interestingly, both the ethanol-soluble fraction (ES) and the ethanol precipitate fraction (EP) exhibited better effects than those of TI; moreover, EP tended to have stronger protection than ES in some indicators, implying that EP played a dominant role in the prevention effects. Furthermore, fecal microbiota transplantation (FMT) revealed that the gut microbiota was differentially reshaped by TI and its fractions were able to directly alleviate the injury induced by PMs. These results indicate that daily intake of black tea and its fractions, especially EP, may alleviate particulate matter-induced lung injury via the gut-lung axis in mice. In addition, the Lachnospiraceae_NK4A136_group could be the core gut microbe contributing to the protection of EP and thus should be further studied in the future.}, }
@article {pmid34896161, year = {2021}, author = {de Souza, JB and Brelaz-de-Castro, MCA and Cavalcanti, IMF}, title = {Strategies for the treatment of colorectal cancer caused by gut microbiota.}, journal = {Life sciences}, volume = {}, number = {}, pages = {120202}, doi = {10.1016/j.lfs.2021.120202}, pmid = {34896161}, issn = {1879-0631}, abstract = {Colorectal cancer (CRC), also named as colon and rectal or bowel cancer, is one of the leading neoplasia diagnosed in the world. Genetic sequencing studies of microorganisms from the intestinal microbiota of patients with CRC revealed that changes in its composition occur with the development of the disease, which can play a fundamental role in its development, being mediated by the production of metabolites and toxins that damage enterocytes. Some microorganisms are frequently reported in the literature as the main agents of this process, such as the bacteria Fusobacterium nucleatum, Escherichia coli and Bacteroides fragilis. Thus, understanding the mechanisms and function of each microorganism in CRC is essential for the development of treatment tools that focus on the gut microbiota. This review verifies current research aimed at evaluating the microorganisms present in the microbiota that can influence the development of CRC, as well as possible forms of treatment that can prevent the initiation and/or spread of this disease. Due to the incidence of CRC, alternatives have been launched considering factors beyond those already known in the disease development, such as diet, fecal microbiota transplantation, use of probiotics and antibiotics, which have been widely studied for this purpose. However, despite being promising, the studies that focus on the development of new therapeutic approaches targeting the microorganisms that cause CRC still need to be improved and better developed, involving new techniques to elucidate the effectiveness and safety of these new methods.}, }
@article {pmid34384521, year = {2021}, author = {Greathouse, KL and Johnson, AJ}, title = {Does caloric restriction prime the microbiome for pathogenic bacteria?.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {8}, pages = {1209-1211}, doi = {10.1016/j.chom.2021.07.009}, pmid = {34384521}, issn = {1934-6069}, mesh = {Animals ; Bacteria/*pathogenicity ; *Caloric Restriction ; Clostridioides difficile ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Mice ; Obesity/microbiology ; Weight Loss ; }, abstract = {A recent study in Nature finds significant shifts in the gut microbiome of post-menopausal women on severe calorie restriction concomitant with weight loss. Microbiota transplantation to germ-free mice display a similar weight loss, along with a bloom in C. difficile, unlocking clues to microbial metabolic alteration in weight loss.}, }
@article {pmid34230217, year = {2022}, author = {Biliński, J and Winter, K and Jasiński, M and Szczęś, A and Bilinska, N and Mullish, BH and Małecka-Panas, E and Basak, GW}, title = {Rapid resolution of COVID-19 after faecal microbiota transplantation.}, journal = {Gut}, volume = {71}, number = {1}, pages = {230-232}, doi = {10.1136/gutjnl-2021-325010}, pmid = {34230217}, issn = {1468-3288}, mesh = {Aged, 80 and over ; COVID-19/complications/diagnosis/*therapy ; Clostridium Infections/complications/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Male ; Young Adult ; }, }
@article {pmid34130227, year = {2021}, author = {Wardill, HR and van der Aa, SAR and da Silva Ferreira, AR and Havinga, R and Tissing, WJE and Harmsen, HJM}, title = {Antibiotic-induced disruption of the microbiome exacerbates chemotherapy-induced diarrhoea and can be mitigated with autologous faecal microbiota transplantation.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {153}, number = {}, pages = {27-39}, doi = {10.1016/j.ejca.2021.05.015}, pmid = {34130227}, issn = {1879-0852}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects ; Diarrhea/*chemically induced ; Fecal Microbiota Transplantation ; Humans ; Microbiota ; Rats ; }, abstract = {BACKGROUND: Chemotherapy is well documented to disrupt the gut microbiome, leading to poor treatment outcomes and a heightened risk of adverse toxicity. Although strong associations exist between its composition and gastrointestinal toxicity, its causal contribution remains unclear. Our inability to move beyond association has limited the development and implementation of microbial-based therapeutics in chemotherapy adjuncts with no clear rationale of how and when to deliver them.<br><br>METHODS/RESULTS: Here, we investigate the impact of augmenting the gut microbiome on gastrointestinal toxicity caused by the chemotherapeutic agent, methotrexate (MTX). Faecal microbiome transplantation (FMT) delivered after MTX had no appreciable impact on gastrointestinal toxicity. In contrast, disruption of the microbiome with antibiotics administered before chemotherapy exacerbated gastrointestinal toxicity, impairing mucosal recovery (P < 0.0001) whilst increasing diarrhoea severity (P = 0.0007) and treatment-related mortality (P = 0.0045). Importantly, these detrimental effects were reversed when the microbiome was restored using autologous FMT (P = 0.03), a phenomenon dictated by the uptake and subsequent expansion of Muribaculaceae.<br><br>CONCLUSIONS: These are the first data to show that clinically impactful symptoms of gastrointestinal toxicity are dictated by the microbiome and provide a clear rationale for how and when to target the microbiome to mitigate the acute and chronic complications caused by disruption of the gastrointestinal microenvironment. Translation of this new knowledge should focus on stabilising and strengthening the gut microbiome before chemotherapy and developing new microbial approaches to accelerate recovery of the mucosa. By controlling the depth and duration of mucosal injury, secondary consequences of gastrointestinal toxicity may be avoided.}, }
@article {pmid33856024, year = {2021}, author = {Wang, Q and Luo, Y and Ray Chaudhuri, K and Reynolds, R and Tan, EK and Pettersson, S}, title = {The role of gut dysbiosis in Parkinson's disease: mechanistic insights and therapeutic options.}, journal = {Brain : a journal of neurology}, volume = {144}, number = {9}, pages = {2571-2593}, doi = {10.1093/brain/awab156}, pmid = {33856024}, issn = {1460-2156}, mesh = {Brain-Gut Axis/drug effects/*physiology ; Dysbiosis/immunology/*metabolism/*therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Parkinson Disease/immunology/*metabolism/*therapy ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; }, abstract = {Parkinson's disease is a common neurodegenerative disorder in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alterations in the gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson's disease by regulating neuroinflammation, barrier function and neurotransmitter activity. There is bidirectional communication between the enteric nervous system and the CNS, and the microbiota-gut-brain axis may provide a pathway for the transmission of α-synuclein. We highlight recent discoveries about alterations to the gut microbiota in Parkinson's disease and focus on current mechanistic insights into the microbiota-gut-brain axis in disease pathophysiology. Moreover, we discuss the interactions between the production and transmission of α-synuclein and gut inflammation and neuroinflammation. In addition, we draw attention to diet modification, the use of probiotics and prebiotics and faecal microbiota transplantation as potential therapeutic approaches that may lead to a new treatment paradigm for Parkinson's disease.}, }
@article {pmid33644835, year = {2021}, author = {Wu, C and Shang, H and Jiang, X and Wang, X and Wei, H}, title = {Application of germ-free NOD-scid IL2rgnull mice as a humanized model for tumor microbiome precision medicine.}, journal = {Science China. Life sciences}, volume = {64}, number = {4}, pages = {644-647}, pmid = {33644835}, issn = {1869-1889}, mesh = {Animals ; *Disease Models, Animal ; Fecal Microbiota Transplantation/methods ; Germ-Free Life/*immunology ; Humans ; Immunotherapy/methods ; Interleukin Receptor Common gamma Subunit/deficiency/genetics/*immunology ; Mice ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Mice, Transgenic ; Microbiota/*immunology ; Neoplasms/*immunology/microbiology/therapy ; Precision Medicine/*methods ; }, }
@article {pmid34900994, year = {2021}, author = {Rocco, A and Sgamato, C and Compare, D and Coccoli, P and Nardone, OM and Nardone, G}, title = {Gut Microbes and Hepatic Encephalopathy: From the Old Concepts to New Perspectives.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {748253}, doi = {10.3389/fcell.2021.748253}, pmid = {34900994}, issn = {2296-634X}, abstract = {Hepatic encephalopathy (HE) is a severe complication of advanced liver disease and acute liver failure. The clinical spectrum ranges from minor cognitive dysfunctions to lethargy, depressed consciousness, and coma and significantly impact the quality of life, morbidity, and mortality of the patients. It is commonly accepted that the gut milieu is essential for the development of HE; however, despite intensive research efforts, the pathogenesis of HE is still not fully elucidated. As our knowledge of gut microbiota moves from the pioneering era of culture-dependent studies, the connection between microbes, inflammation, and metabolic pathways in the pathogenesis of HE is becoming increasingly clear, providing exciting therapeutic perspectives. This review will critically examine the latest research findings on the role of gut microbes in the pathophysiological pathways underlying HE. Moreover, currently available therapeutic options and novel treatment strategies are discussed.}, }
@article {pmid34900069, year = {2021}, author = {Shi, CY and Yu, CH and Yu, WY and Ying, HZ}, title = {Gut-Lung Microbiota in Chronic Pulmonary Diseases: Evolution, Pathogenesis, and Therapeutics.}, journal = {The Canadian journal of infectious diseases &amp; medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale}, volume = {2021}, number = {}, pages = {9278441}, doi = {10.1155/2021/9278441}, pmid = {34900069}, issn = {1712-9532}, abstract = {The microbiota colonized in the human body has a symbiotic relationship with human body and forms a different microecosystem, which affects human immunity, metabolism, endocrine, and other physiological processes. The imbalance of microbiota is usually linked to the aberrant immune responses and inflammation, which eventually promotes the occurrence and development of respiratory diseases. Patients with chronic respiratory diseases, including asthma, COPD, bronchiectasis, and idiopathic pulmonary fibrosis, often have alteration of the composition and function of intestinal and lung microbiota. Gut microbiota affects respiratory immunity and barrier function through the lung-gut microbiota, resulting in altered prognosis of chronic respiratory diseases. In turn, lung dysbiosis promotes aggravation of lung diseases and causes intestinal dysfunction through persistent activation of lymphoid cells in the body. Recent advances in next-generation sequencing technology have disclosed the pivotal roles of lung-gut microbiota in the pathogenesis of chronic respiratory diseases. This review focuses on the association between the gut-lung dysbiosis and respiratory diseases pathogenesis. In addition, potential therapeutic modalities, such as probiotics and fecal microbiota transplantation, are also evaluated for the prevention of chronic respiratory diseases.}, }
@article {pmid34896553, year = {2021}, author = {Gotoh, K and Sakaguchi, Y and Kato, H and Osaki, H and Jodai, Y and Wakuda, M and Také, A and Hayashi, S and Morita, E and Sugie, T and Ito, Y and Ohmiya, N}, title = {Fecal microbiota transplantation as therapy for recurrent Clostridioides difficile infection is associated with amelioration of delirium and accompanied by changes in fecal microbiota and the metabolome.}, journal = {Anaerobe}, volume = {}, number = {}, pages = {102502}, doi = {10.1016/j.anaerobe.2021.102502}, pmid = {34896553}, issn = {1095-8274}, abstract = {Recurrent Clostridioides difficile infection (rCDI) is a frustrating condition that may affect a person's quality of life for months. Microbiome-based therapy such as fecal microbiota transplantation (FMT) has been effective for the treatment of rCDI by correcting the imbalance of the gut microbiota. Appropriate antibiotic treatment is recommended for at least two recurrences before offering FMT. Here, we report the case of a 92-year-old woman who experienced five recurrences of Clostridioides difficile infection (CDI) (six episodes in total) complicated by dementia and delirium, both of which were dramatically improved by FMT, which was associated with alterations in fecal microbiota and the metabolome. Analyses of whole microbial communities and metabolomic analyses were performed on stool specimens collected from the patient on the first episode, the third episode, the day of FMT (before FMT), and 2, 8, and 23 weeks after the FMT and from the donor. The patient had various fecal dysbioses on the first and third episodes and on the day of FMT. Two weeks after FMT, diversity of the gut bacteriome as well as the virome increased dramatically and was reflected in a positive clinical outcome for this patient. Metabolomic analysis revealed that short-chain fatty acids, which have been reported to be associated with improved memory function, were increased after FMT.}, }
@article {pmid34893247, year = {2022}, author = {Wu, W and Zhou, J and Xuan, R and Chen, J and Han, H and Liu, J and Niu, T and Chen, H and Wang, F}, title = {Dietary κ-carrageenan facilitates gut microbiota-mediated intestinal inflammation.}, journal = {Carbohydrate polymers}, volume = {277}, number = {}, pages = {118830}, doi = {10.1016/j.carbpol.2021.118830}, pmid = {34893247}, issn = {1879-1344}, abstract = {The inflammatory effects of carrageenan (CGN), a ubiquitous food additive, remains controversial. Gut microbiota and intestinal homeostasis may be a breakthrough in resolving this controversy. Here we show that, κ-CGN did not cause significant inflammatory symptoms, but it did cause reduced bacteria-derived short-chain fatty acids (SCFAs) and decreased thickness of the mucus layer by altering microbiota composition. Administration of the pathogenic bacterium Citrobacter rodentium, further aggravated the inflammation and mucosal damage in the presence of κ-CGN. Mucus layer degradation and altered SCFA levels could be reproduced by fecal transplantation from κ-CGN-fed mice, but not from germ-free κ-CGN-fed mice. These symptoms could be partially repaired by administering probiotics. Our results suggest that κ-CGN may not be directly inflammatory, but it creates an environment that favors inflammation by perturbation of gut microbiota composition and then facilitates expansion of pathogens, and this effect may be partially reversed by the introduction of probiotics.}, }
@article {pmid34889135, year = {2021}, author = {Parnell, JM and Nicholson, MR and Kellermayer, R and Kahn, SA}, title = {Pediatric Fecal Microbiota Transplantation in Recurrent Clostridioides Difficile.}, journal = {Pediatric annals}, volume = {50}, number = {12}, pages = {e515-e521}, doi = {10.3928/19382359-20211111-01}, pmid = {34889135}, issn = {1938-2359}, abstract = {With the rising rates of Clostridioides (Clostridium) difficile infection (CDI) in children, recognizing the limitations of CDI-directed antibiotic therapy, especially in recurrent CDI (rCDI), is important. Fecal microbiota transplantation (FMT), which directly targets the underlying gut dysbiosis present in rCDI, is an important treatment option to consider in rCDI. This article will summarize indications, procedures, effectiveness, and the safety of FMT for rCDI in pediatric patients. [Pediatr Ann. 2021;50(12):e515-e521.].}, }
@article {pmid34888262, year = {2021}, author = {Li, N and Chen, H and Cheng, Y and Xu, F and Ruan, G and Ying, S and Tang, W and Chen, L and Chen, M and Lv, L and Ping, Y and Chen, D and Wei, Y}, title = {Corrigendum: Fecal Microbiota Transplantation Relieves Gastrointestinal and Autism Symptoms by Improving the Gut Microbiota in an Open-Label Study.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {801376}, doi = {10.3389/fcimb.2021.801376}, pmid = {34888262}, issn = {2235-2988}, abstract = {[This corrects the article DOI: 10.3389/fcimb.2021.759435.].}, }
@article {pmid34887627, year = {2021}, author = {Barone, M and D'Amico, F and Fabbrini, M and Rampelli, S and Brigidi, P and Turroni, S}, title = {Over-feeding the gut microbiome: A scoping review on health implications and therapeutic perspectives.}, journal = {World journal of gastroenterology}, volume = {27}, number = {41}, pages = {7041-7064}, pmid = {34887627}, issn = {2219-2840}, abstract = {The human gut microbiome has gained increasing attention over the past two decades. Several findings have shown that this complex and dynamic microbial ecosystem can contribute to the maintenance of host health or, when subject to imbalances, to the pathogenesis of various enteric and non-enteric diseases. This scoping review summarizes the current knowledge on how the gut microbiota and microbially-derived compounds affect host metabolism, especially in the context of obesity and related disorders. Examples of microbiome-based targeted intervention strategies that aim to restore and maintain an eubiotic layout are then discussed. Adjuvant therapeutic interventions to alleviate obesity and associated comorbidities are traditionally based on diet modulation and the supplementation of prebiotics, probiotics and synbiotics. However, these approaches have shown only moderate ability to induce sustained changes in the gut microbial ecosystem, making the development of innovative and tailored microbiome-based intervention strategies of utmost importance in clinical practice. In this regard, the administration of next-generation probiotics and engineered microbiomes has shown promising results, together with more radical intervention strategies based on the replacement of the dysbiotic ecosystem by means of fecal microbiota transplantation from healthy donors or with the introduction of synthetic communities specifically designed to achieve the desired therapeutic outcome. Finally, we provide a perspective for future translational investigations through the implementation of bioinformatics approaches, including machine and deep learning, to predict health risks and therapeutic outcomes.}, }
@article {pmid34884466, year = {2021}, author = {Yu, D and Meng, X and de Vos, WM and Wu, H and Fang, X and Maiti, AK}, title = {Implications of Gut Microbiota in Complex Human Diseases.}, journal = {International journal of molecular sciences}, volume = {22}, number = {23}, pages = {}, doi = {10.3390/ijms222312661}, pmid = {34884466}, issn = {1422-0067}, support = {YDZJ202101ZYTS080//Jilin Province Science and Technology Department/ ; }, abstract = {Humans, throughout the life cycle, from birth to death, are accompanied by the presence of gut microbes. Environmental factors, lifestyle, age and other factors can affect the balance of intestinal microbiota and their impact on human health. A large amount of data show that dietary, prebiotics, antibiotics can regulate various diseases through gut microbes. In this review, we focus on the role of gut microbes in the development of metabolic, gastrointestinal, neurological, immune diseases and, cancer. We also discuss the interaction between gut microbes and the host with respect to their beneficial and harmful effects, including their metabolites, microbial enzymes, small molecules and inflammatory molecules. More specifically, we evaluate the potential ability of gut microbes to cure diseases through Fecal Microbial Transplantation (FMT), which is expected to become a new type of clinical strategy for the treatment of various diseases.}, }
@article {pmid34881818, year = {2021}, author = {Jian, YP and Yang, G and Zhang, LH and Liang, JY and Zhou, HL and Wang, YS and Xu, ZX}, title = {Lactobacillus plantarum alleviates irradiation-induced intestinal injury by activation of FXR-FGF15 signaling in intestinal epithelia.}, journal = {Journal of cellular physiology}, volume = {}, number = {}, pages = {}, doi = {10.1002/jcp.30651}, pmid = {34881818}, issn = {1097-4652}, support = {81573087//National Natural Science Foundation of China/ ; 81772924//National Natural Science Foundation of China/ ; 82020108024//National Natural Science Foundation of China/ ; 20190701006GH//International Cooperation Foundation Grant of Jilin Province/ ; }, abstract = {Abdominal irradiation (IR) may destroy the intestinal mucosal barrier, leading to severe intestinal infection and multiple organ dysfunction syndromes. The role of intestinal microbiota in the development of IR-induced intestinal injury remains largely unknown. Herein, we reported that abdominal IR altered the composition of the microbiota and reduced the abundance and diversity of the gut microbiome. Alterations of bacteria, in particular reduction of Lactobacillus, played a critical role in IR-induced intestinal injury. Fecal microbiota transplant (FMT) from normal mice or administration of Lactobacillus plantarum to intestinal microbiota-eliminated mice substantially reduced IR-induced intestinal damage and prevented mice from IR-induced death. We further characterized that L. plantarum activated the farnesoid X receptor (FXR) - fibroblast growth factor 15 (FGF15) signaling in intestinal epithelial cells and hence promoted DNA-damage repair. Application of GW4064, an activator of FXR, to microbiota eliminated mice markedly mitigated IR-induced intestinal damage, reduced intestinal epithelial cell death and promoted the survival of IR mice. In contrast, suppression of FXR with Gly-β-MCA, a bile acid and an intestine-selective and high-affinity FXR inhibitor, abrogated L. Plantarum-mediated protection on the ileum of IR mice. Taken together, our findings not only provide new insights into the role of intestinal flora in radiation-induced intestinal injury but also shed new light on the application of probiotics for the protection of radiation-damaged individuals.}, }
@article {pmid34881280, year = {2021}, author = {Sun, C and Chen, L and Yang, H and Sun, H and Xie, Z and Zhao, B and Jiang, X and Qin, B and Shen, Z}, title = {Involvement of Gut Microbiota in the Development of Psoriasis Vulgaris.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {761978}, pmid = {34881280}, issn = {2296-861X}, abstract = {Objectives: Psoriasis is a common chronic recurrent dermatitis. Accumulating observations show gut microbiota dysbiosis in psoriasis. We intend to further investigate the relationship between intestinal microbiota and psoriasis development. Design: We first performed an epidemiological investigation on differences of gastrointestinal discomfort symptoms between patients with psoriasis and general population. Then variation of gut microbiota in patients with psoriasis (un)treated with acitretin plus narrow-band ultraviolet B (NB-UVB) was analyzed by 16S rRNA sequencing. We last compared recovery status and vital cytokines (lesion and intestine) of mouse psoriasiform models, which were transplanted with fecal microbiota from patients with psoriasis or healthy controls. Results: (1) About 85.5% of patients with psoriasis vs. 58.1% of healthy controls presented with at least one gastrointestinal symptom. The prevalence of investigated symptoms (e.g., abdominal distension and constipation) were significantly higher in patients, compared with controls (p < 0.05). Passing flatus and constipation were significantly correlated with psoriasis (p < 0.05 in both cases). (2) The abundance of Ruminococcaceae family, Coprococcus_1 genus, and Blautia genus were decreased with psoriasis improvement (p < 0.05, respectively), which had been demonstrated significantly increased in psoriasis. (3) Mice receiving psoriatic microbes transplantation showed delayed recovery of psoriasiform dermatitis and less reduction of interleukin (IL)-17A than those receiving healthy microbiota or blank control (p < 0.05 and p < 0.01, respectively). Conclusion: Multiple evidence we provided here preliminarily demonstrates the involvement of gut microbiota in the different degree of psoriasis activity. The strategy based on overall microbial communities is expected to be a promising supplementary for long-term management of psoriasis.}, }
@article {pmid34880502, year = {2021}, author = {Fluhr, L and Mor, U and Kolodziejczyk, AA and Dori-Bachash, M and Leshem, A and Itav, S and Cohen, Y and Suez, J and Zmora, N and Moresi, C and Molina, S and Ayalon, N and Valdés-Mas, R and Hornstein, S and Karbi, H and Kviatcovsky, D and Livne, A and Bukimer, A and Eliyahu-Miller, S and Metz, A and Brandis, A and Mehlman, T and Kuperman, Y and Tsoory, M and Stettner, N and Harmelin, A and Shapiro, H and Elinav, E}, title = {Gut microbiota modulates weight gain in mice after discontinued smoke exposure.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {34880502}, issn = {1476-4687}, abstract = {Cigarette smoking constitutes a leading global cause of morbidity and preventable death1, and most active smokers report a desire or recent attempt to quit2. Smoking-cessation-induced weight gain (SCWG; 4.5 kg reported to be gained on average per 6-12 months, >10 kg year-1 in 13% of those who stopped smoking3) constitutes a major obstacle to smoking abstinence4, even under stable5,6 or restricted7 caloric intake. Here we use a mouse model to demonstrate that smoking and cessation induce a dysbiotic state that is driven by an intestinal influx of cigarette-smoke-related metabolites. Microbiome depletion induced by treatment with antibiotics prevents SCWG. Conversely, fecal microbiome transplantation from mice previously exposed to cigarette smoke into germ-free mice naive to smoke exposure induces excessive weight gain across diets and mouse strains. Metabolically, microbiome-induced SCWG involves a concerted host and microbiome shunting of dietary choline to dimethylglycine driving increased gut energy harvest, coupled with the depletion of a cross-regulated weight-lowering metabolite, N-acetylglycine, and possibly by the effects of other differentially abundant cigarette-smoke-related metabolites. Dimethylglycine and N-acetylglycine may also modulate weight and associated adipose-tissue immunity under non-smoking conditions. Preliminary observations in a small cross-sectional human cohort support these findings, which calls for larger human trials to establish the relevance of this mechanism in active smokers. Collectively, we uncover a microbiome-dependent orchestration of SCWG that may be exploitable to improve smoking-cessation success and to correct metabolic perturbations even in non-smoking settings.}, }
@article {pmid34877470, year = {2021}, author = {Chauhan, U and Popov, J and Farbod, Y and Kalantar, M and Wolfe, M and Moayyedi, P and Marshall, JK and Halder, S and Kaasalainen, S}, title = {Fecal Microbiota Transplantation for the Treatment of Ulcerative Colitis: A Qualitative Assessment of Patient Perceptions and Experiences.}, journal = {Journal of the Canadian Association of Gastroenterology}, volume = {4}, number = {6}, pages = {e120-e129}, pmid = {34877470}, issn = {2515-2092}, abstract = {Background: Fecal microbiota transplantation (FMT) is a promising experimental therapy for ulcerative colitis (UC), yet patient acceptance remains poorly understood.<br><br>Aims: The aim of this study was to explore perceptions and experiences of adult patients who received FMT for UC.<br><br>Methods: This study used a qualitative descriptive design with thematic content analysis. Patients who were approached for enrollment in a clinical trial (NCT02606032) were invited to participate in face-to-face semistructured interviews. Two groups were interviewed: those who chose to pursue FMT and those who declined FMT. Non-FMT patients were interviewed once; FMT patients were interviewed twice at pre- and post-treatment.<br><br>Results: Nine FMT patients (78% female, average age 46.7 years old) and eight non-FMT patients (50% female, average age 39.5 years old) were enrolled. Pretreatment themes included FMT as a natural therapy, external barriers to pursuing FMT, concerns with FMT and factors influencing the decision to pursue FMT. While both groups generally perceived FMT as a natural therapy, pre-FMT patients showed greater acceptance of alternative medicine. Both groups demonstrated poor understanding and similar initial concerns with product cleanliness. Pre-FMT patients were motivated to pursue FMT by feelings of last resort. Post-FMT themes included therapeutic impact of FMT and psychosocial impact of FMT. Post-FMT patients reported overall satisfaction and a unanimous preference for FMT over conventional medications.<br><br>Conclusion: This is the first study to assess adult patient perceptions and real-life experiences with FMT for the treatment of UC. By improving patient education, we may achieve greater acceptance of FMT.}, }
@article {pmid34876784, year = {2021}, author = {Phanchana, M and Harnvoravongchai, P and Wongkuna, S and Phetruen, T and Phothichaisri, W and Panturat, S and Pipatthana, M and Charoensutthivarakul, S and Chankhamhaengdecha, S and Janvilisri, T}, title = {Frontiers in antibiotic alternatives for Clostridioides difficile infection.}, journal = {World journal of gastroenterology}, volume = {27}, number = {42}, pages = {7210-7232}, pmid = {34876784}, issn = {2219-2840}, abstract = {Clostridioides difficile (C. difficile) is a gram-positive, anaerobic spore-forming bacterium and a major cause of antibiotic-associated diarrhea. Humans are naturally resistant to C. difficile infection (CDI) owing to the protection provided by healthy gut microbiota. When the gut microbiota is disturbed, C. difficile can colonize, produce toxins, and manifest clinical symptoms, ranging from asymptomatic diarrhea and colitis to death. Despite the steady-if not rising-prevalence of CDI, it will certainly become more problematic in a world of antibiotic overuse and the post-antibiotic era. C. difficile is naturally resistant to most of the currently used antibiotics as it uses multiple resistance mechanisms. Therefore, current CDI treatment regimens are extremely limited to only a few antibiotics, which include vancomycin, fidaxomicin, and metronidazole. Therefore, one of the main challenges experienced by the scientific community is the development of alternative approaches to control and treat CDI. In this Frontier article, we collectively summarize recent advances in alternative treatment approaches for CDI. Over the past few years, several studies have reported on natural product-derived compounds, drug repurposing, high-throughput library screening, phage therapy, and fecal microbiota transplantation. We also include an update on vaccine development, pre- and pro-biotics for CDI, and toxin antidote approaches. These measures tackle CDI at every stage of disease pathology via multiple mechanisms. We also discuss the gaps and concerns in these developments. The next epidemic of CDI is not a matter of if but a matter of when. Therefore, being well-equipped with a collection of alternative therapeutics is necessary and should be prioritized.}, }
@article {pmid34872097, year = {2021}, author = {Xie, WR and Yang, XY and Deng, ZH and Zheng, YM and Zhang, R and Wu, LH and Cai, JY and Kong, LP and Xia, HH and He, XX}, title = {Effects of washed microbiota transplantation on serum uric acid levels, symptoms and intestinal barrier function in patients with acute and recurrent gout: a pilot study.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {}, number = {}, pages = {}, doi = {10.1159/000521273}, pmid = {34872097}, issn = {1421-9875}, abstract = {INTRODUCTION: Gut dysbiosis has been reported to be closely associated with gout. Washed microbiota transplantation (WMT) is considered as an effective way to restore a healthy gut microbiota with less adverse events than the conventional fecal microbiota transplantation. In this study, we aimed to evaluate the effects of WMT on serum uric acid levels, symptoms and the intestinal barrier function in patients with acute and recurrent gout.<br><br>METHODS: We performed a pilot study of WMT for acute and recurrent gout. The primary outcome was the changes in serum uric acid level and gout symptoms. The secondary outcomes included the changes in levels of diamine oxidase (DAO), D-lactic acid and endotoxin.<br><br>RESULTS: Eleven patients received WMT treatment. The averaged serum uric acid levels in patients with gout reduced after WMT (P = 0.031), accompanied with a decrease in the frequency and duration time of acute gout flares (P < 0.01). The levels of DAO, D-lactic acid and endotoxin were higher in patients than in healthy donors (P < 0.05). After WMT treatment, the levels of DAO and endotoxin decreased (P < 0.05).<br><br>CONCLUSIONS: WMT is effective for reducing serum uric acid levels and improving gout symptoms in patients with gout, and contributes to improve their impaired intestinal barrier function.}, }
@article {pmid34870313, year = {2021}, author = {Huang, HC and Tsai, MH and Chang, CC and Pun, CK and Huang, YH and Hou, MC and Lee, FY and Hsu, SJ}, title = {Microbiota transplants from feces or gut content attenuated portal hypertension and portosystemic collaterals in cirrhotic rats.}, journal = {Clinical science (London, England : 1979)}, volume = {}, number = {}, pages = {}, doi = {10.1042/CS20210602}, pmid = {34870313}, issn = {1470-8736}, abstract = {Liver cirrhosis and portal hypertension is the end of chronic liver injury with hepatic, splanchnic and portosystemic collateral systems dysregulation. Liver injury is accompanied by gut dysbiosis whereas dysbiosis induces liver fibrosis, splanchnic angiogenesis and dysregulated vascular tones vice versa, making portal hypertension aggravated. It has been proved that intestinal microbiota transplantation alleviates dysbiosis. Nevertheless, the influences of microbiota transplantation on cirrhosis related portal hypertension are not so clear. Liver cirrhosis with portal hypertension was induced by bile duct ligation in rats. Sham rats were surgical controls. Rats randomly received vehicle, fecal or gut (terminal ileum) material transplantation. The results showed that microbiota transplantation from feces or gut material significantly reduced portal pressure in cirrhotic rats (P = .010, .044). Hepatic resistance, vascular contractility, fibrosis and relevant protein expressions were not significantly different among cirrhotic rats. However, microbiota transplantation ameliorated splanchnic hyperdynamic flow and vasodilatation. Mesenteric angiogenesis, defined by whole mesenteric window vascular density, decreased in both transplantation groups and phosphorylated eNOS was downregulated. Portosystemic shunts determined by splenorenal shunt flow decreased in both transplantation groups (P = .037, .032). Shunting severity assessed by microsphere distribution method showed consistent results. Compared to sham rats, cirrhotic rats lacked Lachnospiraceae. Both microbiota transplants increased Bifidobacterium. In conclusion, microbiota transplantation in cirrhotic rats reduced portal pressure, alleviated splanchnic hyperdynamic circulation and portosystemic shunts. The main beneficial effects may be focused on portosystemic collaterals-related events, such as hepatic encephalopathy and gastroesophageal variceal hemorrhage. Further clinical investigations are mandatory.}, }
@article {pmid34867873, year = {2021}, author = {Lin, H and Guo, Q and Ran, Y and Lin, L and Chen, P and He, J and Chen, Y and Wen, J}, title = {Multiomics Study Reveals Enterococcus and Subdoligranulum Are Beneficial to Necrotizing Enterocolitis.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {752102}, pmid = {34867873}, issn = {1664-302X}, abstract = {Necrotizing enterocolitis (NEC) is a life-threatening disease for premature infants with low body weight. Due to its fragile gut microbiome and successful treatment of fecal microbiota transplantation (FMT) for intestinal disease, we aimed to reveal the multiple-omics changes after FMT and/or sulperazone treatment. In this study, 2-week-old newborn rabbits were used to simulate the NEC model and grouped into healthy control, NEC, sulperazone treatment, FTM treatment, and FMT and sulperazone combination treatment. We evaluated the intestinal pathology and survival to define the benefit from each treatment and performed microbiome and transcriptome analysis to reveal the changes in microcosmic level, which could be helpful to understand the pathogenesis of NEC and develop new strategy. We found NEC rabbits benefit more from the combination of FMT and sulperazone treatment. Combination treatment reverses a lot of microorganisms dysregulated by NEC and showed the most similar transcript profiler with healthy control. Moreover, a combination of FMT and sulperazone significantly prolonged the survival of NEC rabbits. Function enrichment showed that metabolism and viral life cycle are the most significant changes in NEC. FMT is a common therapy method for NEC. Meanwhile, in the severe situation of NEC with intestinal infection, the first therapy strategy is preferred the third-generation cephalosporin, among which sulperazone is used widely and the effect is remarkable. So, we used sulperazone to treat the rabbits with the NEC. In this research, we aim to explore the different effects on NEC between FMT and sulperazone as well as the combination. Considering the microbiome and transcriptome result, we make a conclusion that the Enterococcus and Subdoligranulum benefits NEC by influencing the bacterial phages and butyrate production, respectively.}, }
@article {pmid34867859, year = {2021}, author = {Ren, R and Gao, X and Shi, Y and Li, J and Peng, L and Sun, G and Wang, Z and Yan, B and Zhi, J and Yang, Y}, title = {Long-Term Efficacy of Low-Intensity Single Donor Fecal Microbiota Transplantation in Ulcerative Colitis and Outcome-Specific Gut Bacteria.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {742255}, pmid = {34867859}, issn = {1664-302X}, abstract = {Aims: To assess the long-term efficacy and safety of single-donor, low-intensity fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), and to identify the outcome-specific gut bacteria. Design: Thirty-one patients with active UC (Mayo scores ≥ 3) were recruited, and all received FMT twice, at the start of the study and 2∼3 months later, respectively, with a single donor and a long-term follow-up. The fecal microbiome profile was accessed via 16S rRNA sequencing before and after FMT. Results: After the first FMT, 22.58% (7/31) of patients achieved clinical remission and endoscopy remission, with the clinical response rate of 67.74% (21/31), which increased to 55% (11/20) and 80% (16/20), respectively, after the second FMT. No serious adverse events occurred in all patients. During 4 years of follow-up, the mean remission period of patients was 26.5 ± 19.98 m; the relapse rate in the 12 remission patients was 33.33% within 1 year, and 58.3% within 4 years. At baseline, UC patients showed an enrichment in some proinflammatory microorganisms compared to the donor, such as Bacteroides fragilis, Clostridium difficile, and Ruminococcus gnavus, and showed reduced amounts of short-chain fatty acid (SCFA) producing bacteria especially Faecalibacterium prausnitzii. FMT induced taxonomic compositional changes in the recipient gut microbiota, resulting in a donor-like state. Given this specific donor, UC recipients with different outcomes showed distinct gut microbial features before and after FMT. In prior to FMT, relapse was characterized by higher abundances of Bacteroides fragilis and Lachnospiraceae incertae sedis, together with lower abundances of Bacteroides massiliensis, Roseburia, and Ruminococcus; Prevotella copri was more abundant in the non-responders (NR); and the patients with sustained remission (SR) had a higher abundance of Bifidobacterium breve. After FMT, the NR patients had a lower level of Bifidobacterium compared to those with relapse (Rel) and SR, while a higher level of Bacteroides spp. was observed in the Rel group. Conclusion: Low-intensity single donor FMT could induce long remission in active UC. The gut microbiota composition in UC patients at baseline may be predictive of therapeutic response to FMT.}, }
@article {pmid34867850, year = {2021}, author = {Nothaft, H and Perez-Muñoz, ME and Yang, T and Murugan, AVM and Miller, M and Kolarich, D and Plastow, GS and Walter, J and Szymanski, CM}, title = {Improving Chicken Responses to Glycoconjugate Vaccination Against Campylobacter jejuni.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {734526}, pmid = {34867850}, issn = {1664-302X}, abstract = {Campylobacter jejuni is a common cause of diarrheal disease worldwide. Human infection typically occurs through the ingestion of contaminated poultry products. We previously demonstrated that an attenuated Escherichia coli live vaccine strain expressing the C. jejuni N-glycan on its surface reduced the Campylobacter load in more than 50% of vaccinated leghorn and broiler birds to undetectable levels (responder birds), whereas the remainder of the animals was still colonized (non-responders). To understand the underlying mechanism, we conducted three vaccination and challenge studies using 135 broiler birds and found a similar responder/non-responder effect. Subsequent genome-wide association studies (GWAS), analyses of bird sex and levels of vaccine-induced IgY responses did not correlate with the responder versus non-responder phenotype. In contrast, antibodies isolated from responder birds displayed a higher Campylobacter-opsonophagocytic activity when compared to antisera from non-responder birds. No differences in the N-glycome of the sera could be detected, although minor changes in IgY glycosylation warrant further investigation. As reported before, the composition of the microbiota, particularly levels of OTU classified as Clostridium spp., Ruminococcaceae and Lachnospiraceae are associated with the response. Transplantation of the cecal microbiota of responder birds into new birds in combination with vaccination resulted in further increases in vaccine-induced antigen-specific IgY responses when compared to birds that did not receive microbiota transplants. Our work suggests that the IgY effector function and microbiota contribute to the efficacy of the E. coli live vaccine, information that could form the basis for the development of improved vaccines targeted at the elimination of C. jejuni from poultry.}, }
@article {pmid34866923, year = {2021}, author = {Chang, TT and Chen, JW}, title = {Direct CCL4 Inhibition Modulates Gut Microbiota, Reduces Circulating Trimethylamine N-Oxide, and Improves Glucose and Lipid Metabolism in High-Fat-Diet-Induced Diabetes Mellitus.}, journal = {Journal of inflammation research}, volume = {14}, number = {}, pages = {6237-6250}, pmid = {34866923}, issn = {1178-7031}, abstract = {Purpose: Modulation of the gut microbiota may lead to changes in pathological conditions. C-C chemokine motif ligand (CCL) 4 was upregulated in diabetes mellitus (DM) and was shown to play a significant role in pancreatic inflammation and glucose metabolism. The detailed in vivo mechanisms have not been well explored. This study aimed to investigate the hypothesis that direct CCL4 inhibition could modify gut microbiota and systemic metabolism in diet-induced DM mice.<br><br>Methods: C57BL/6 mice fed a high-fat diet (HFD) were used as a diet-induced DM model. CCL4 inhibition was conducted by anti-CCL4 neutralizing monoclonal antibodies. The gut microbiota was analyzed by high-throughput sequencing of the 16S rRNA. Fecal microbiota transplantation (FMT) was used to verify the effect of CCL4 deficiency on gut microbiota and the linkage between CCL4-modulated gut microbiota and HFD-induced DM.<br><br>Results: CCL4 inhibition stabilized glucose homeostasis, modulated lipid parameter, and decreased inflammatory markers in HFD-induced DM mice. Moreover, CCL4 inhibition reversed HFD-induced gut dysbiosis, evidenced by the decreased abundance of family Muribaculaceae and increased abundance of family Atopobiaceae when CCL4 antibodies were administrated. CCL4 inhibition led to a decrease in circulating trimethylamine N-oxide levels, a proinflammatory metabolite from gut microbiota. Taken together, CCL4 inhibition could modify gut microbiota profiles, suppress proinflammatory metabolites, reduce systemic inflammation, improve insulin resistance, and retard the progression of hyperglycemia in HFD-induced DM. Furthermore, FMT from CCL4 knockout mice rescued the glucose homeostasis in HFD-induced DM mice.<br><br>Conclusion: Our findings may not only provide a novel rationale to in vivo CCL4-based therapeutic approach in diet-induced DM but also indicate the significance of gut microbiota profile including the family Muribaculaceae and the family Atopobiaceae as a potential modifiable target for systemic metabolism.}, }
@article {pmid34864789, year = {2021}, author = {Tariq, R and Syed, T and Yadav, D and Prokop, LJ and Singh, S and Loftus, EV and Pardi, DS and Khanna, S}, title = {Outcomes of Fecal Microbiota Transplantation for C. difficile Infection in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000001633}, pmid = {34864789}, issn = {1539-2031}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a safe and effective therapy for recurrent Clostridioides difficile infection (CDI). Data on FMT for CDI in patients with underlying inflammatory bowel disease (IBD) are emerging but conflicting. We performed a systematic review and meta-analysis to describe the efficacy and safety of FMT for CDI in IBD and its impact on IBD outcomes.<br><br>METHODS: A systematic search of multiple databases including Embase, Scopus, and Web of Science was performed. Our primary analysis focused on pooled rate of CDI resolution after single and multiple FMTs in IBD patients. Additional analyses included rates of IBD-associated outcomes (flare, surgery, symptom improvement) after FMT. The random-effects model was used to calculate pooled rates.<br><br>RESULTS: Among 457 adult patients, 363 had CDI resolution after first FMT with a pooled cure rate of 78% [95% confidence interval (CI): 73%-83%; I2=39%]. Overall pooled rate cure rate with single and multiple FMTs was 88% (95% CI: 81%-94%; I2=73%). The pooled rate of an IBD flare after FMT was 26.8% (95% CI: 22.5%-31.6%; I2=9%) and of colectomy was 7.3% (95% CI: 4.7%-10.5%; I2=56%). Among 141 pediatric patients, 106 had CDI resolution after first FMT with pooled cure rate of 78% (95% CI: 58%-93%; I2=59%). Overall pooled cure rate with single and multiple FMTs was 77% (95% CI: 50%-96%; I2=63%). The pooled rate of an IBD flare after FMT was 10.8% (95% CI: 5.7%-18.5% I2=43%), and of colectomy was 10.3% (95% CI: 2.1%-30.2% I2=23%).<br><br>CONCLUSIONS: FMT appears to be a highly effective therapy for preventing recurrent CDI in patients with IBD. Patients who fail a single FMT may benefit from multiple FMTs.}, }
@article {pmid34864312, year = {2021}, author = {Hang, Z and Lei, T and Zeng, Z and Cai, S and Bi, W and Du, H}, title = {Composition of intestinal flora affects the risk relationship between Alzheimer's disease/Parkinson's disease and cancer.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {145}, number = {}, pages = {112343}, doi = {10.1016/j.biopha.2021.112343}, pmid = {34864312}, issn = {1950-6007}, abstract = {An increasing number of epidemiological studies have shown that there is a significant inverse relationship between the onset of Alzheimer's disease/Parkinson's disease (AD/PD) and cancer, but the mechanism is still unclear. Considering that intestinal flora can connect them, we tried to explain this phenomenon from the intestinal flora. This review briefly introduced the relationship among AD/PD, cancer, and intestinal flora, studied metabolites or components of the intestinal flora and the role of intestinal barriers and intestinal hormones in AD/PD and cancer. After screening, a part of the flora capable of participating in the occurrence processes of the three diseases at the same time was obtained, the abundance changes of the special flora in AD/PD and various types of cancers were summarized, and they were classified according to the flora function and abundance, which in turn innovatively and reasonably explained the fact that AD/PD and cancer showed certain antagonism in epidemiological statistics from the perspective of intestinal flora. This review also proposed that viewing the risk relationship between diseases from the perspective of intestinal flora may provide new research ideas for the treatment of fecal microbiota transplantation (FMT) and related diseases.}, }
@article {pmid34864150, year = {2021}, author = {Trinei, M and Carpi, A and Menabo, R and Storto, M and Fornari, M and Marinelli, A and Minardi, S and Riboni, M and Casciaro, F and DiLisa, F and Petroni, K and Tonelli, C and Giorgio, M}, title = {Dietary intake of cyanidin-3-glucoside induces a long-lasting cardioprotection from ischemia/reperfusion injury by altering the microbiota.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {108921}, doi = {10.1016/j.jnutbio.2021.108921}, pmid = {34864150}, issn = {1873-4847}, abstract = {BACKGROUND: The anthocyanin class of flavonoids, including cyanidin-3-glucoside (C3G) present in berries, blood oranges and pigmented cereal crops, are food bioactives with antioxidant and anti-inflammatory action, capable to reduce myocardial ischemia/reperfusion (I/R) injury by unclear mechanism.<br><br>OBJECTIVE: Assessing the value of sporadic beneficial diet is critical for practical application. We aimed to determine whether and how the cardioptotective effect of dietary intake of anthocyanins persists.<br><br>METHODS: Gene expression, histology and resistance to I/R were investigated ex vivo in hearts from mice after a month beyond the cease of the C3G-enriched diet.<br><br>RESULTS: Cardiac injury, oxidative stress and mitochondrial damage following I/R was effectively reduced in mice fed C3G-enriched diet, even after a month of wash out with standard diet. Cardioprotection was observed also in immune-deficient mice lacking mature B and T cells indicating the anti-inflammatory activity of C3G was not involved. Moreover, the transcription reprogramming induced by the C3G-enriched diets was rescued by the wash out treatment. Instead, we found C3G-enriched diet changed the microbiome and the transplantation of the fecal microbiota transferred the cardioprotection from mice fed C3G-enriched diet to mice fed standard diet.<br><br>CONCLUSIONS: These findings established the effect of C3G dietary intake on gut microbiota determines long lasting cardioprotection.}, }
@article {pmid34863789, year = {2021}, author = {Nooij, S and Terveer, EM and , }, title = {Rational donor selection for fecal microbiota transplantation.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2021.11.036}, pmid = {34863789}, issn = {1528-0012}, }
@article {pmid34862475, year = {2021}, author = {Luo, H and Wu, H and Wang, L and Xiao, S and Lu, Y and Liu, C and Yu, X and Zhang, X and Wang, Z and Tang, L}, title = {Hepatoprotective effects of Cassiae Semen on mice with non-alcoholic fatty liver disease based on gut microbiota.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {1357}, pmid = {34862475}, issn = {2399-3642}, abstract = {Cassiae Semen (CS), the seeds of Cassia obtusifolia L. and C. tora L, have a long medicinal history in China, with suggestions for it to relieve constipation and exert hepatoprotective effects. However, the underlying mechanisms are still unclear. In this study, mice with high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) were used to study the hepatoprotective effects of CS. The relationship between gut microbiota and hepatoprotective effect mechanisms mediated by CS extracts, the total aglycone extracts of CS, rubrofusarin-6-β-gentiobioside, and aurantio-obtusin were examined. Our data indicate that CS extracts and components confer a protective effect by ameliorating lipid accumulation, intestinal barrier damage, liver damage, and inflammation on HFD-induced liver injury. Meanwhile, fecal microbe transplantation exerted the pharmacological effect of CS on HFD-fed mice; however, the efficacy of CS was inhibited or eliminated by antibiotic-induced dysbiosis. In conclusion, the therapeutic effects of CS on NAFLD were closely related to the gut microbiota, suggesting a role for TCM in treating disease.}, }
@article {pmid34855639, year = {2021}, author = {Gao, ZY and Cui, Z and Yan, YQ and Ning, LJ and Wang, ZH and Hong, J}, title = {Microbe-based management for colorectal cancer.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, doi = {10.1097/CM9.0000000000001887}, pmid = {34855639}, issn = {2542-5641}, abstract = {ABSTRACT: Colorectal cancer (CRC) is one of the most prevalent, most lethal cancers in the world. Increasing evidence suggests that the intestinal microbiota is closely related to the pathogenesis and prognosis of CRC. The normal microbiota plays an essential role in maintaining gut barrier function and the immune microenvironment. Recent studies have identified carcinogenic bacteria such as enterotoxigenic Bacteroides fragilis (ETBF) and Streptococcus gallolyticus (S. gallolyticus), as well as protective bacterial such as Akkermansia muciniphila (A. muciniphila), as potential targets of CRC treatment. Gut microbiota modulation aims to restore gut dysbiosis, regulate the intestinal immune system and prevent from pathogen invasion, all of which are beneficial for CRC prevention and prognosis. The utility of probiotics, prebiotics, postbiotics, fecal microbiota transplantation and dietary inventions to treat CRC makes them novel microbe-based management tools. In this review, we describe the mechanisms involved in bacteria-derived colorectal carcinogenesis and summarized novel bacteria-related therapies for CRC. In summary, we hope to facilitate clinical applications of intestinal bacteria for preventing and treating CRC.}, }
@article {pmid34854953, year = {2021}, author = {Secombe, KR and Crame, EE and Tam, JSY and Wardill, HR and Gibson, RJ and Coller, JK and Bowen, JM}, title = {Intestinal toll-like receptor 4 knockout alters the functional capacity of the gut microbiome following irinotecan treatment.}, journal = {Cancer chemotherapy and pharmacology}, volume = {}, number = {}, pages = {}, pmid = {34854953}, issn = {1432-0843}, abstract = {PURPOSE: Irinotecan can cause high levels of diarrhea caused by toxic injury to the gastrointestinal microenvironment. Toll-like receptor 4 (TLR4) and the gut microbiome have previously been implicated in gastrointestinal toxicity and diarrhea; however, the link between these two factors has not been definitively determined. We used a tumor-bearing, intestinal epithelial cell (IEC) TLR4 knockout model (Tlr4ΔIEC) to assess microbiome changes following irinotecan treatment. We then determined if a fecal microbiota transplant (FMT) between Tlr4ΔIEC and wild-type (WT) mice altered irinotecan-induced gastrointestinal toxicity.<br><br>METHODS: MC-38 colorectal cancer cells were injected into WT and Tlr4ΔIEC mice. Fecal samples were collected prior to tumor inoculation, prior to irinotecan treatment and at cull. 16S rRNA gene sequencing was used to assess changes in the microbiome. Next, FMT was used to transfer the microbiome phenotype between Tlr4ΔIEC and WT mice prior to irinotecan treatment. Gastrointestinal toxicity symptoms were assessed.<br><br>RESULTS: In study 1, there were no compositional differences in the microbiome between Tlr4ΔIEC and WT mice at baseline. However, predicted functional capacity of the microbiome was different between WT and Tlr4ΔIEC at baseline and post-irinotecan. In study 2, Tlr4ΔIEC mice were protected from grade 3 diarrhea. Additionally, WT mice who did not receive FMT had more colonic damage in the colon compared to controls (P = 0.013). This was not seen in Tlr4ΔIEC mice or WT mice who received FMT (P > 0.05).<br><br>CONCLUSION: Tlr4ΔIEC and WT had no baseline compositional microbiome differences, but functional differences at baseline and following irinotecan. FMT altered some aspects of irinotecan-induced gastrointestinal toxicity.}, }
@article {pmid34854884, year = {2022}, author = {Dodiya, HB and Lutz, HL and Weigle, IQ and Patel, P and Michalkiewicz, J and Roman-Santiago, CJ and Zhang, CM and Liang, Y and Srinath, A and Zhang, X and Xia, J and Olszewski, M and Zhang, X and Schipma, MJ and Chang, EB and Tanzi, RE and Gilbert, JA and Sisodia, SS}, title = {Gut microbiota-driven brain Aβ amyloidosis in mice requires microglia.}, journal = {The Journal of experimental medicine}, volume = {219}, number = {1}, pages = {}, pmid = {34854884}, issn = {1540-9538}, support = {//Cure Alzheimer's Fund/ ; //Open Philanthropy Project/ ; //Good Ventures Foundation/ ; A2019032F//Bright Focus Foundation/ ; /ALZ/Alzheimer's Association/United States ; //Luminescence Foundation/ ; }, abstract = {We previously demonstrated that lifelong antibiotic (ABX) perturbations of the gut microbiome in male APPPS1-21 mice lead to reductions in amyloid β (Aβ) plaque pathology and altered phenotypes of plaque-associated microglia. Here, we show that a short, 7-d treatment of preweaned male mice with high-dose ABX is associated with reductions of Aβ amyloidosis, plaque-localized microglia morphologies, and Aβ-associated degenerative changes at 9 wk of age in male mice only. More importantly, fecal microbiota transplantation (FMT) from transgenic (Tg) or WT male donors into ABX-treated male mice completely restored Aβ amyloidosis, plaque-localized microglia morphologies, and Aβ-associated degenerative changes. Transcriptomic studies revealed significant differences between vehicle versus ABX-treated male mice and FMT from Tg mice into ABX-treated mice largely restored the transcriptome profiles to that of the Tg donor animals. Finally, colony-stimulating factor 1 receptor (CSF1R) inhibitor-mediated depletion of microglia in ABX-treated male mice failed to reduce cerebral Aβ amyloidosis. Thus, microglia play a critical role in driving gut microbiome-mediated alterations of cerebral Aβ deposition.}, }
@article {pmid34853754, year = {2021}, author = {Jena, R and Jain, R and Muralidharan, S and Yanamala, VL and Zubair, Z and Kantamaneni, K and Jalla, K and Renzu, M and Alfonso, M}, title = {Role of Gastrointestinal Dysbiosis and Fecal Transplantation in Parkinson's Disease.}, journal = {Cureus}, volume = {13}, number = {10}, pages = {e19035}, pmid = {34853754}, issn = {2168-8184}, abstract = {Parkinson's disease (PD) is one of the most common neurodegenerative diseases with a high rate of morbidity. It is associated with dopaminergic neuron loss and is fairly common in the elderly population. Recently, there has been a growing interest in the role of the gut microbiome in the pathogenesis of PD and thus studies addressing the methods to modulate the microbiota are becoming increasingly popular. Fecal microbiota transplant (FMT) is one of these methods and is effective in certain intestinal and extraintestinal conditions. This review aims to talk about gastrointestinal dysbiosis and how the reconstruction of this microbiome via FMT could potentially be used as a treatment modality in the future. We went through various studies and collected data relevant to our topic from the previous five years. The studies selected include reviews, observational studies, animal studies, case reports, and some grey literature. We concluded that although it has great potential as a therapeutic modality in the future, it is limited by several factors such as variability among the results of most clinical studies and the lack of large sample sizes. Therefore, there is a need for high-quality clinical trials with larger sample sizes to gather enough clinical evidence so that FMT can qualify as a widely recommended therapeutic measure.}, }
@article {pmid34853526, year = {2021}, author = {Chen, HL and Zeng, YB and Zhang, ZY and Kong, CY and Zhang, SL and Li, ZM and Huang, JT and Xu, YY and Mao, YQ and Cai, PR and Han, B and Wang, WQ and Wang, LS}, title = {Gut and Cutaneous Microbiome Featuring Abundance of Lactobacillus reuteri Protected Against Psoriasis-Like Inflammation in Mice.}, journal = {Journal of inflammation research}, volume = {14}, number = {}, pages = {6175-6190}, pmid = {34853526}, issn = {1178-7031}, abstract = {Background: Psoriasis is a chronic autoinflammatory skin disease, and its aetiology remains incompletely understood. Recently, gut microbial dysbiosis is found to be tightly associated with psoriasis.<br><br>Objective: We sought to reveal the causal role of gut microbiota dysbiosis in psoriasis pathogenesis and investigate the protective effect of healthy commensal bacteria against imiquimod -induced psoriasis-like skin response.<br><br>Methods: By using fecal microbial transplantation (FMT), 16S rRNA gene-based taxonomic profiling and Lactobacillus supplement, we have assessed the effect of FMT from healthy individuals on psoriasis-like skin inflammation and associated immune disorders in imiquimod-induced psoriasis mice.<br><br>Results: Here, by using psoriasis mice humanized with the stools from healthy donors and psoriasis patients, the imiquimod-induced psoriasis in mice with psoriasis patient stool was found to be significantly aggravated as compared to the mice with healthy donor stools. Further analysis showed fecal microbiota of healthy individuals protected against Treg/Th17 imbalance in psoriasis. Moreover, we found the gut and skin microbiome in mice receipted with gut microbiota of healthy individuals (HD) differed from those of mice receipted with gut microbiota of psoriasis patients (PSD). 16S rRNA sequencing revealed that Lactobacillus reuteri was greatly enriched in fecal and cutaneous microbiome of HD mice as compared to PSD mice. Intriguingly, supplement with Lactobacillus reuteri was sufficient to increase the expression of anti-inflammatory gene IL-10, reduce Th17 cells counts and confer resistance to imiquimod-induced inflammation on the mice with gut microbiota dysbiosis.<br><br>Conclusion: Our results suggested that the gut microbiota dysbiosis is the potential causal factor for psoriasis and the gut microbiota may serve as promising therapy target for psoriasis patients.}, }
@article {pmid34852831, year = {2021}, author = {Xie, L and Xu, C and Fan, Y and Li, Y and Wang, Y and Zhang, X and Yu, S and Wang, J and Chai, R and Zhao, Z and Jin, Y and Xu, Z and Zhao, S and Bian, Y}, title = {Effect of fecal microbiota transplantation in patients with slow transit constipation and the relative mechanisms based on the protein digestion and absorption pathway.}, journal = {Journal of translational medicine}, volume = {19}, number = {1}, pages = {490}, pmid = {34852831}, issn = {1479-5876}, support = {ZC20097//Tianjin Municipal Health Bureau/ ; 2020YJ017//tianjin union medical center/ ; 2017YJZD005//tianjin union dedical center/ ; 81873100//National Natural Science Foundation of China/ ; No.82174374//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is considered an effective treatment for slow transit constipation (STC); nevertheless, the mechanism remains unclear.<br><br>METHODS: In this study, eight patients with STC were selected according to the inclusion and exclusion criteria; they then received three treatments of FMT. The feces and serum of STC patients were collected after each treatment and analyzed by integrating 16 s rRNA microbiome and metabolomic analyses.<br><br>RESULTS: The results showed that the percentage of clinical improvement reached 62.5% and the rates of patients' clinical remission achieved 75% after the third treatment. At the same time, FMT improved the Wexner constipation scale (WCS), the Gastrointestinal Quality-of-Life Index (GIQLI) and Hamilton Depression Scale (HAMD). Fecal microbiome alpha diversity and beta diversity altered significantly after FMT. Analysis of the 16 s rRNA microbiome showed that the numbers of Bacteroidetes (Prevotell/Bacteroides) and Firmicute (Roseburia/Blautia) decreased, whereas Actinobacteria (Bifidobacterium), Proteobacteria (Escherichia), and Firmicute (Lactobacillus) increased after FMT. The metabolomics analyses showed that the stool of FMT-treated patients were characterized by relatively high levels of N-Acetyl-L-glutamate, gamma-L-glutamyl-L-glutamic acid, Glycerophosphocholine, et al., after FMT. Compared with baseline, the serum of treated patients was characterized by relatively high levels of L-Arginine, L-Threonine, Ser-Arg, Indoleacrylic acid, Phe-Tyr, 5-L-Glutamyl-L-alanine, and lower levels of Erucamide after the treatment. The correlation analysis between the metabolites and gut microbiota showed a significant correlation. For example, L-Arginine was positively correlated with lactobacillus, et al. L-Threonine was positively correlated with Anaerovibrio, Sediminibacterium but negatively correlated with Phascolarctobacterium. Erucamide had significant negative correlations with Sediminibacterium and Sharpea, while being positively correlated with Phascolarctobacterium. Enriched KEGG pathways analysis demonstrated that the protein digestion and absorption pathways gradually upregulated with the increase of FMT frequency. The L-Arginine and L-Threonine were also involved in the pathway. A large amount of Na + was absorbed in the pathway, so that it might increase mucus secretion and electrical excitability of GI smooth muscle.<br><br>CONCLUSIONS: Therefore, we speculated that FMT changed the patients' gut microbiota and metabolites involved in the protein digestion and absorption pathways, thereby improving the symptoms of STC. Study on the effectiveness and safety of FMT in the treatment of STC. The study was reviewed and approved by Ethics Committee of Tianjin People's Hospital (ChiCTR2000033227) in 2020.}, }
@article {pmid34841787, year = {2021}, author = {Wei, K and Chen, T}, title = {[Vaginal microbiota transplantation for treatment of bacterial vaginosis: a review].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {37}, number = {11}, pages = {3820-3827}, doi = {10.13345/j.cjb.210163}, pmid = {34841787}, issn = {1872-2075}, mesh = {Dysbiosis/therapy ; Female ; Humans ; *Microbiota ; Vagina ; *Vaginosis, Bacterial/therapy ; }, abstract = {Bacterial vaginosis (BV) is a disease caused by vaginal microbiota dysbiosis. The conventional antibiotic treatment can aggravate microbial dysbiosis, alter the acid environment of the vagina and lead to drug resistance, thus shows low cure rate and high recurrence rate. This poses significant physiological and psychological burden to the BV patients. Vaginal microbiota transplantation (VMT) is a novel live biotherapeutic approach. It directly engrafts the whole vaginal microbiota from healthy women to the vaginal tract of patients to rapidly reconstruct the vaginal microbiota environment and restore the vaginal health. This article summarizes the development, present challenges, and future directions of using VMT, with the aim to explore new strategies for treatment of BV and promote the clinical use of VMT.}, }
@article {pmid34841786, year = {2021}, author = {Zhang, M and Wang, H and Xue, L and Yang, X}, title = {[Advances in fecal microbiota transplantation for treatment of Parkinson's disease].}, journal = {Sheng wu gong cheng xue bao = Chinese journal of biotechnology}, volume = {37}, number = {11}, pages = {3812-3819}, doi = {10.13345/j.cjb.200770}, pmid = {34841786}, issn = {1872-2075}, mesh = {Aged ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Middle Aged ; *Neurodegenerative Diseases ; *Parkinson Disease/therapy ; }, abstract = {Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. Patients with PD often suffer from gastrointestinal symptoms in the early stage of the disease. Several studies have confirmed that gut microbiota is involved in the progress of PD. As one of the most effective ways to reconstruct the gut microbiota, fecal microbiota transplantation (FMT) has shown potential therapeutic effects on PD. This review summarizes the basic and clinical studies of FMT in the treatment of PD.}, }
@article {pmid34841294, year = {2021}, author = {Hiltunen, H and Hanani, H and Luoto, R and Turjeman, S and Ziv, O and Isolauri, E and Salminen, S and Koren, O and Rautava, S}, title = {Preterm infant meconium microbiota transplant induces growth failure, inflammatory activation, and metabolic disturbances in germ-free mice.}, journal = {Cell reports. Medicine}, volume = {2}, number = {11}, pages = {100447}, pmid = {34841294}, issn = {2666-3791}, abstract = {Preterm birth may result in adverse health outcomes. Very preterm infants typically exhibit postnatal growth restriction, metabolic disturbances, and exaggerated inflammatory responses. We investigated the differences in the meconium microbiota composition between very preterm (<32 weeks), moderately preterm (32-37 weeks), and term (>37 weeks) human neonates by 16S rRNA gene sequencing. Human meconium microbiota transplants to germ-free mice were conducted to investigate whether the meconium microbiota is causally related to the preterm infant phenotype in an experimental model. Our results indicate that very preterm birth is associated with a distinct meconium microbiota composition. Fecal microbiota transplant of very preterm infant meconium results in impaired growth, altered intestinal immune function, and metabolic parameters as compared to term infant meconium transplants in germ-free mice. This finding suggests that measures aiming to minimize the long-term adverse consequences of very preterm birth should be commenced during pregnancy or directly after birth.}, }
@article {pmid34840686, year = {2021}, author = {Gunardi, TH and Susantono, DP and Victor, AA and Sitompul, R}, title = {Atopobiosis and Dysbiosis in Ocular Diseases: Is Fecal Microbiota Transplant and Probiotics a Promising Solution?.}, journal = {Journal of ophthalmic &amp; vision research}, volume = {16}, number = {4}, pages = {631-643}, pmid = {34840686}, issn = {2008-2010}, abstract = {Purpose: To highlight the role of atopobiosis and dysbiosis in the pathomechanism of autoimmune uveitis, therefore supporting fecal microbiota transplant (FMT) and probiotics as potential targeted-treatment for uveitis.<br><br>Methods: This review synthesized literatures upon the relation between gut microbiota, autoimmune uveitis, FMT, and probiotics, published from January 2001 to March 2021 and indexed in PubMed, Google Scholar, CrossRef.<br><br>Results: The basis of the gut-eye axis revolves around occurrences of molecular mimicry, increase in pro-inflammatory cytokines, gut epithelial barrier disruption, and translocation of microbes to distant sites. In patients with autoimmune uveitis, an increase of gut Fusobacterium and Enterobacterium were found. With current knowledge of aforementioned mechanisms, studies modifying the gut microbiome and restoring the physiologic gut barrier has been the main focus for pathomechanism-based therapy. In mice models, FMT and probiotics targeting repopulation of gut microbiota has shown significant improvement in clinical manifestations of uveitis. Consequently, a better understanding in the homeostasis of gut microbiome along with their role in the gut-eye axis is needed to develop practical targeted treatment.<br><br>Conclusion: Current preliminary studies are promising in establishing a causative gut-eye axis relationship and the possibility of conducting FMT and probiotics as targeted treatment to mitigate autoimmune uveitis, to shorten disease duration, and to prevent further complications.}, }
@article {pmid34836663, year = {2021}, author = {Lee, PC and Chang, TE and Wang, YP and Lee, KC and Lin, YT and Chiou, JJ and Huang, CW and Yang, UC and Li, FY and Huang, HC and Wu, CY and Huang, YH and Hou, MC}, title = {Alteration of gut microbial composition associated with the therapeutic efficacy of fecal microbiota transplantation in Clostridium difficile infection.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jfma.2021.11.001}, pmid = {34836663}, issn = {0929-6646}, abstract = {BACKGROUND/PURPOSE: Clostridium difficile infection (CDI) leads to a significant cause of hospital-acquired morbidity and mortality. Fecal microbiota transplantation (FMT) is effective to treat recurrent or refractory CDI (rCDI). However, the change of microbial composition contributed by FMT and its association with treatment outcomes is not well determined in Taiwan. We aimed to investigate the efficacy of FMT and the association with microbial alteration endemically.<br><br>METHODS: Twelve patients who received FMT for rCDI in Taipei Veterans General Hospital were prospectively enrolled from April 2019 to July 2020. The clinical assessments and fecal microbial analyses in comparison with fecal materials of unrelated donors were conducted before and after FMT.<br><br>RESULTS: The overall success rate of FMT for rCDI was 91.7%. A prominence of Proteobacteria, Gammaproteobacteria and Enterobacteriales were observed in the feces of patients with rCDI. Increased fecal phylogenetic diversities and a significant microbial dissimilarity were provided by successful FMT compared to patients before treatment. However, the distinctness was not obvious between patients' feces at baseline and after unsuccessful FMT. Moreover, dynamic change of fecal microbial composition after FMT was observed during follow-up but did not interrupt the treatment effects of FMT.<br><br>CONCLUSION: Gut dysbiosis commonly co-exists in patients with rCDI. Restoration of gut microbial communities by FMT provides a promising strategy to treat antibiotic-failed CDI, and the extent of microbial change would be related to the treatment outcomes of FMT. Besides, the effectiveness of FMT for CDI could be maintained even the gut microbiota has diverged over time.}, }
@article {pmid34835981, year = {2021}, author = {Houron, C and Ciocan, D and Trainel, N and Mercier-Nomé, F and Hugot, C and Spatz, M and Perlemuter, G and Cassard, AM}, title = {Gut Microbiota Reshaped by Pectin Treatment Improves Liver Steatosis in Obese Mice.}, journal = {Nutrients}, volume = {13}, number = {11}, pages = {}, pmid = {34835981}, issn = {2072-6643}, support = {CT0069291-01//Servier (France)/ ; DEQ-20170336743//Fondation pour la Recherche Médicale/ ; }, abstract = {Pectin, a soluble fiber, improves non-alcoholic fatty-liver disease (NAFLD), but its mechanisms are unclear. We aimed to investigate the role of pectin-induced changes in intestinal microbiota (IM) in NAFLD. We recovered the IM from mice fed a high-fat diet, treated or not with pectin, to perform a fecal microbiota transfer (FMT). Mice fed a high-fat diet, which induces NAFLD, were treated with pectin or received a fecal microbiota transfer (FMT) from mice treated with pectin before (preventive FMT) or after (curative FMT) being fed a high-fat diet. Pectin prevented the development of NAFLD, induced browning of adipose tissue, and modified the IM without increasing the abundance of proteobacteria. Preventive FMT also induced browning of white adipose tissue but did not improve liver steatosis, in contrast to curative FMT, which induced an improvement in steatosis. This was associated with an increase in the concentration of short-chain fatty acids (SCFAs), in contrast to preventive FMT, which induced an increase in the concentration of branched SCFAs. Overall, we show that the effect of pectin may be partially mediated by gut bacteria.}, }
@article {pmid34835406, year = {2021}, author = {Sun, P and Su, L and Zhu, H and Li, X and Guo, Y and Du, X and Zhang, L and Qin, C}, title = {Gut Microbiota Regulation and Their Implication in the Development of Neurodegenerative Disease.}, journal = {Microorganisms}, volume = {9}, number = {11}, pages = {}, pmid = {34835406}, issn = {2076-2607}, abstract = {In recent years, human gut microbiota have become one of the most promising areas of microorganism research; meanwhile, the inter-relation between the gut microbiota and various human diseases is a primary focus. As is demonstrated by the accumulating evidence, the gastrointestinal tract and central nervous system interact through the gut-brain axis, which includes neuronal, immune-mediated and metabolite-mediated pathways. Additionally, recent progress from both preclinical and clinical studies indicated that gut microbiota play a pivotal role in gut-brain interactions, whereas the imbalance of the gut microbiota composition may be associated with the pathogenesis of neurological diseases (particularly neurodegenerative diseases), the underlying mechanism of which is insufficiently studied. This review aims to highlight the relationship between gut microbiota and neurodegenerative diseases, and to contribute to our understanding of the function of gut microbiota in neurodegeneration, as well as their relevant mechanisms. Furthermore, we also discuss the current application and future prospects of microbiota-associated therapy, including probiotics and fecal microbiota transplantation (FMT), potentially shedding new light on the research of neurodegeneration.}, }
@article {pmid34831456, year = {2021}, author = {Monaghan, TM and Duggal, NA and Rosati, E and Griffin, R and Hughes, J and Roach, B and Yang, DY and Wang, C and Wong, K and Saxinger, L and Pučić-Baković, M and Vučković, F and Klicek, F and Lauc, G and Tighe, P and Mullish, BH and Blanco, JM and McDonald, JAK and Marchesi, JR and Xue, N and Dottorini, T and Acharjee, A and Franke, A and Li, Y and Wong, GK and Polytarchou, C and Yau, TO and Christodoulou, N and Hatziapostolou, M and Wang, M and Russell, LA and Kao, DH}, title = {A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection.}, journal = {Cells}, volume = {10}, number = {11}, pages = {}, pmid = {34831456}, issn = {2073-4409}, support = {ZI418//University of Alberta Hospital Foundation/ ; MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Fecal microbiota transplantation (FMT) is highly effective in recurrent Clostridioides difficile infection (CDI); increasing evidence supports FMT in severe or fulminant Clostridioides difficile infection (SFCDI). However, the multifactorial mechanisms that underpin the efficacy of FMT are not fully understood. Systems biology approaches using high-throughput technologies may help with mechanistic dissection of host-microbial interactions. Here, we have undertaken a deep phenomics study on four adults receiving sequential FMT for SFCDI, in which we performed a longitudinal, integrative analysis of multiple host factors and intestinal microbiome changes. Stool samples were profiled for changes in gut microbiota and metabolites and blood samples for alterations in targeted epigenomic, metabonomic, glycomic, immune proteomic, immunophenotyping, immune functional assays, and T-cell receptor (TCR) repertoires, respectively. We characterised temporal trajectories in gut microbial and host immunometabolic data sets in three responders and one non-responder to sequential FMT. A total of 562 features were used for analysis, of which 78 features were identified, which differed between the responders and the non-responder. The observed dynamic phenotypic changes may potentially suggest immunosenescent signals in the non-responder and may help to underpin the mechanisms accompanying successful FMT, although our study is limited by a small sample size and significant heterogeneity in patient baseline characteristics. Our multi-omics integrative longitudinal analytical approach extends the knowledge regarding mechanisms of efficacy of FMT and highlights preliminary novel signatures, which should be validated in larger studies.}, }
@article {pmid34830388, year = {2021}, author = {Eindor-Abarbanel, A and Healey, GR and Jacobson, K}, title = {Therapeutic Advances in Gut Microbiome Modulation in Patients with Inflammatory Bowel Disease from Pediatrics to Adulthood.}, journal = {International journal of molecular sciences}, volume = {22}, number = {22}, pages = {}, pmid = {34830388}, issn = {1422-0067}, abstract = {There is mounting evidence that the gut microbiota plays an important role in the pathogenesis of inflammatory bowel disease (IBD). For the past decade, high throughput sequencing-based gut microbiome research has identified characteristic shifts in the composition of the intestinal microbiota in patients with IBD, suggesting that IBD results from alterations in the interactions between intestinal microbes and the host's mucosal immune system. These studies have been the impetus for the development of new therapeutic approaches targeting the gut microbiome, such as nutritional therapies, probiotics, fecal microbiota transplant and beneficial metabolic derivatives. Innovative technologies can further our understanding of the role the microbiome plays as well as help to evaluate how the different approaches in microbiome modulation impact clinical responses in adult and pediatric patients. In this review, we highlight important microbiome studies in patients with IBD and their response to different microbiome modulation therapies, and describe the differences in therapeutic response between pediatric and adult patient cohorts.}, }
@article {pmid34818535, year = {2021}, author = {Chang, CS and Liao, YC and Huang, CT and Lin, CM and Cheung, CHY and Ruan, JW and Yu, WH and Tsai, YT and Lin, IJ and Huang, CH and Liou, JS and Chou, YH and Chien, HJ and Chuang, HL and Juan, HF and Huang, HC and Chan, HL and Liao, YC and Tang, SC and Su, YW and Tan, TH and Bäumler, AJ and Kao, CY}, title = {Identification of a gut microbiota member that ameliorates DSS-induced colitis in intestinal barrier enhanced Dusp6-deficient mice.}, journal = {Cell reports}, volume = {37}, number = {8}, pages = {110016}, doi = {10.1016/j.celrep.2021.110016}, pmid = {34818535}, issn = {2211-1247}, abstract = {Strengthening the gut epithelial barrier is a potential strategy for management of gut microbiota-associated illnesses. Here, we demonstrate that dual-specificity phosphatase 6 (Dusp6) knockout enhances baseline colon barrier integrity and ameliorates dextran sulfate sodium (DSS)-induced colonic injury. DUSP6 mutation in Caco-2 cells enhances the epithelial feature and increases mitochondrial oxygen consumption, accompanied by altered glucose metabolism and decreased glycolysis. We find that Dusp6-knockout mice are more resistant to DSS-induced dysbiosis, and the cohousing and fecal microbiota transplantation experiments show that the gut/fecal microbiota derived from Dusp6-knockout mice also confers protection against colitis. Further culturomics and mono-colonialization experiments show that one gut microbiota member in the genus Duncaniella confers host protection from DSS-induced injury. We identify Dusp6 deficiency as beneficial for shaping the gut microbiota eubiosis necessary to protect against gut barrier-related diseases.}, }
@article {pmid34815646, year = {2021}, author = {Michailidis, L and Currier, AC and Le, M and Flomenhoft, DR}, title = {Adverse events of fecal microbiota transplantation: a meta-analysis of high-quality studies.}, journal = {Annals of gastroenterology}, volume = {34}, number = {6}, pages = {802-814}, pmid = {34815646}, issn = {1108-7471}, abstract = {Background: Fecal microbiota transplantation (FMT) has shown excellent efficacy in treating Clostridioides difficile infection, as well as promise in several other diseases. The heightened interest is accompanied by concerns over adverse events (AE) and safety. To further understand that in FMT, we performed a systematic review of the literature and a meta-analysis of high-quality, prospective randomized controlled trials FMT.<br><br>Methods: Studies were selected based on predefined exclusion criteria and were assessed for quality. Only prospective, randomized, controlled studies of high quality were included in the final analysis. Data were extracted on demographics, AE, indication, delivery method and follow-up duration.<br><br>Results: Out of 334 articles reviewed, 9 high quality studies with 756 FMTs were selected for final analysis. The pooled rate of AE was 39.3% (95% confidence interval [CI] 0.19-0.642) as they were reported by 112 patients who received FMT. The SAE rate was 5.3% (95%CI 3.1-8.8%). The most common AE reported was abdominal pain, followed by diarrhea. The most common SAE was Clostridium difficile infection. Upper gastrointestinal tract delivery was associated with a higher rate of total AE, but not SAE.<br><br>Conclusions: Based on the selected studies, the AE rate of FMT is 39.3%, with most AE being mild and self-limiting. SAE were uncommon at 5.3%, and many were only possibly related to the FMT. Adherence to standardized reporting of AE as well as longitudinal studies and registries will help further clarify the safety of FMT in the future.}, }
@article {pmid34813937, year = {2021}, author = {Ma, Y and Guo, R and Sun, Y and Li, X and He, L and Li, Z and Silverman, GJ and Chen, G and Gao, F and Yuan, J and Wei, Q and Li, M and Lu, L and Niu, H}, title = {Lupus gut microbiota transplants cause autoimmunity and inflammation.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {233}, number = {}, pages = {108892}, doi = {10.1016/j.clim.2021.108892}, pmid = {34813937}, issn = {1521-7035}, abstract = {BACKGROUND: The etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16 s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free (GF) mice.<br><br>RESULTS: Compared to the healthy controls, we found no significant different microbial diversity but some significantly different species in SLE patients including Turicibacter genus and other 5 species. Fecal transfer from SLE patients to GF mice caused GF mice to develop a series of lupus-like phenotypic features, including increased serum autoimmune antibodies, imbalanced cytokines, altered distribution of immune cells in mucosal and peripheral immune response, and upregulated expression of genes related to SLE in recipient mice that received SLE fecal microbiota transplantation (FMT). Moreover, the metabolism of histidine was significantly altered in GF mice treated with SLE patient feces, as compared to those which received healthy fecal transplants.<br><br>CONCLUSIONS: Overall, our results describe a causal role of aberrant gut microbiota in contributing to the pathogenesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms intertwined with autoimmune activation in SLE.}, }
@article {pmid34812117, year = {2021}, author = {Zhilu, X and Xiangqian, D and Keli, Y and Caroline, C and Jingwan, Z and Yu, L and Tao, Z and Cheung, CL and Yang, S and Fengrui, Z and Kl, CF and Jy, SJ and Jun, Y and Anthony, B and Nicolas, B and Jean-Frédéric, C and Sunny Hei, W and Yinglei, M and Siew C, N}, title = {Association of Adherent-invasive Escherichia coli with severe Gut Mucosal dysbiosis in Hong Kong Chinese population with Crohn's disease.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1994833}, pmid = {34812117}, issn = {1949-0984}, abstract = {Adherent invasive Escherichia Coli (AIEC) has been implicated in the pathogenesis of Crohn's disease (CD) in Western populations. Whether the presence of AIEC is also seen in CD populations of different genetic susceptibility and has negative impact on host microbiota ecology and therapeutics are unclear. AIEC presence was assessed in ileal tissues of 60 Hong Kong Chinese patients with CD and 56 healthy subjects. Mucosa microbiota was analyzed by 16s rRNA sequencing. Impact of AIEC on the gut microbiota was determined in a mouse model. AIEC was significantly more prevalent in ileal tissues of patients with CD than controls (30% vs 7.1%). Presence of AIEC in ileal tissues was associated with more severe mucosa microbiota dysbiosis in CD with decreased diversity and lower abundance of Firmicutes including butyrate producing Roseburia and probiotic Bacillus. A random forest model predicted the presence of AIEC with area under the curve of 0.89. AIEC exacerbated dysbiosis in dextran sodium sulfate (DSS)-induced colitis mice and led to resistance to restoration of normal gut microbiota by fecal microbiota transplantation (FMT). Proportion of donor-derived bacteria in AIEC-colonized mice was significantly lower than that in uninfected mice. AIEC was prevalent and associated with severe mucosa microbiota dysbiosis in CD in Hong Kong Chinese population. The presence of AIEC impeded restoration of normal gut microbiota. AIEC may serve as a keystone bacterium in CD and impact the efficacy of FMT.}, }
@article {pmid34807442, year = {2022}, author = {Mu, C and Pi, Y and Zhang, C and Zhu, W}, title = {Microbiomes in the Intestine of Developing Pigs: Implications for Nutrition and Health.}, journal = {Advances in experimental medicine and biology}, volume = {1354}, number = {}, pages = {161-176}, pmid = {34807442}, issn = {0065-2598}, mesh = {Animals ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Intestines ; *Microbiota ; Swine ; }, abstract = {The past decade has seen an expansion of studies on the role of gut microbiome in piglet nutrition and health. With the help of culture-independent sequencing techniques, the colonization of gut microbiota and their implication in physiology are being investigated in depth. Immediately after birth, the microbes begin to colonize following an age-dependent trajectory, which can be modified by maternal environment, diet, antibiotics, and fecal microbiota transplantation. The early-life gut microbiome is relatively simple but enriched with huge metabolic potential to utilize milk oligosaccharides and affect the epithelial function. After weaning, the gut microbiome develops towards a gradual adaptation to the introduction of solid food, with an enhanced ability to metabolize amino acids, fibers, and bile acids. Here we summarize the compositional and functional difference of the gut microbiome in the keystone developing phases, with a specific focus on the use of different nutritional approaches based on the phase-specific gut microbiome.}, }
@article {pmid34805249, year = {2021}, author = {Yang, J and Xiong, P and Bai, L and Zhang, Z and Zhou, Y and Chen, C and Xie, Z and Xu, Y and Chen, M and Wang, H and Zhu, M and Yu, J and Wang, K}, title = {The Association of Altered Gut Microbiota and Intestinal Mucosal Barrier Integrity in Mice With Heroin Dependence.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {765414}, pmid = {34805249}, issn = {2296-861X}, abstract = {The gut microbiota is believed to play a significant role in psychological and gastrointestinal symptoms in heroin addicts. However, the underlying mechanism remains largely unknown. We show here that heroin addicts had a decrease in body mass index (BMI) and abnormal serum D-lactic acid (DLA), endotoxin (ET) and diamine oxidase (DAO) levels during their withdrawal stage, suggesting a potential intestinal injury. The gut microbial profiles in the mouse model with heroin dependence showed slightly decreased alpha diversity, as well as higher levels of Bifidobacterium and Sutterella and a decrease in Akkermansia at genus level compared to the control group. Fecal microbiota transplantation (FMT) further confirmed that the microbiota altered by heroin dependence was sufficient to impair body weight and intestinal mucosal barrier integrity in recipient mice. Moreover, short-chain fatty acids (SCFAs) profiling revealed that microbiota-derived propionic acid significantly decreased in heroin dependent mice compared to controls. Overall, our study shows that heroin dependence significantly altered gut microbiota and impaired intestinal mucosal barrier integrity in mice, highlighting the role of the gut microbiota in substance use disorders and the pathophysiology of withdrawal symptoms.}, }
@article {pmid34804275, year = {2021}, author = {Hazan, S and Dave, S and Papoutsis, AJ and Barrows, BD and Borody, TJ}, title = {Successful Bacterial Engraftment Identified by Next-Generation Sequencing Predicts Success of Fecal Microbiota Transplant for Clostridioides difficile.}, journal = {Gastroenterology research}, volume = {14}, number = {5}, pages = {304-309}, pmid = {34804275}, issn = {1918-2805}, abstract = {Background: The effectiveness of fecal microbiota transplantation (FMT), a treatment for Clostridioides difficile infection (CDI), is dependent on successful engraftment (incorporation) of donor stool. We present a method for evaluating engraftment success based on next-generation sequencing (NGS)-based profiling of bacterial strains present in donor and recipient stool, and we suggest its potential to guide treatment decisions.<br><br>Methods: Bacterial strains in stool samples from three patients from the clinic and one donor were analyzed via NGS and metagenomic sequencing, before and 1 month after FMT for CDI. The similarity of strains present was assessed via relative abundance, principal component analysis, Shannon and Simpson diversity indexes, and Bray-Curtis dissimilarity matrix. A positive outcome was successful engraftment, where the post-FMT sample closely resembled that of the donor and CDI was cured.<br><br>Results: Patients (Pts.) 1 and 2, but not Pt. 3's stool samples closely resembled the donor specimen post-FMT. Noteworthy, Pt. 3 pre-FMT sample was less similar to the donor than that of Pts. 1 and 2. All methods of assessing similarity and dissimilarity used yielded virtually identical conclusions. Pts. 1 and 2 which closely resembled donor specimen, eradicated CDI giving a surrogate objective measure of engraftment.<br><br>Conclusions: Success of engraftment in FMT can be assessed using NGS and metagenomic analysis and parallels success in curing CDI of the microbiome. The statistical methods we present here are reliable and consistent for such purposes. The dissimilarity of Pt. 3 to the donor combined with the failure of engraftment and failure to cure CDI in Pt. 3 suggests that FMT success may be predictable by comparing pre-FMT samples to donor. There is no clinical trial registry listing this study.}, }
@article {pmid34804005, year = {2021}, author = {Sun, Y and Xie, R and Li, L and Jin, G and Zhou, B and Huang, H and Li, M and Yang, Y and Liu, X and Cao, X and Wang, B and Liu, W and Jiang, K and Cao, H}, title = {Prenatal Maternal Stress Exacerbates Experimental Colitis of Offspring in Adulthood.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {700995}, pmid = {34804005}, issn = {1664-3224}, abstract = {The prevalence of inflammatory bowel disease (IBD) is increasing worldwide and correlates with dysregulated immune response because of gut microbiota dysbiosis. Some adverse early life events influence the establishment of the gut microbiota and act as risk factors for IBD. Prenatal maternal stress (PNMS) induces gut dysbiosis and perturbs the neuroimmune network of offspring. In this study, we aimed to investigate whether PNMS increases the susceptibility of offspring to colitis in adulthood. The related index was assessed during the weaning period and adulthood. We found that PNMS impaired the intestinal epithelial cell proliferation, goblet cell and Paneth cell differentiation, and mucosal barrier function in 3-week-old offspring. PNMS induced low-grade intestinal inflammation, but no signs of microscopic inflammatory changes were observed. Although there was no pronounced difference between the PNMS and control offspring in terms of their overall measures of alpha diversity for the gut microbiota, distinct microbial community changes characterized by increases in Desulfovibrio, Streptococcus, and Enterococcus and decreases in Bifidobacterium and Blautia were induced in the 3-week-old PNMS offspring. Notably, the overgrowth of Desulfovibrio persisted from the weaning period to adulthood, consistent with the results observed using fluorescence in situ hybridization in the colon mucosa. Mechanistically, the fecal microbiota transplantation experiment showed that the gut microbiota from the PNMS group impaired the intestinal barrier function and induced low-grade inflammation. The fecal bacterial solution from the PNMS group was more potent than that from the control group in inducing inflammation and gut barrier disruption in CaCo-2 cells. After treatment with a TNF-α inhibitor (adalimumab), no statistical difference in the indicators of inflammation and intestinal barrier function was observed between the two groups. Finally, exposure to PNMS remarkably increased the values of the histopathological parameters and the inflammatory cytokine production in a mouse model of experimental colitis in adulthood. These findings suggest that PNMS can inhibit intestinal development, impair the barrier function, and cause gut dysbiosis characterized by the persistent overgrowth of Desulfovibrio in the offspring, resulting in exacerbated experimental colitis in adulthood.}, }
@article {pmid34803700, year = {2021}, author = {Wang, Y and Zhang, J and Xu, L and Ma, J and Lu, M and Ma, J and Liu, Z and Wang, F and Tang, X}, title = {Modified Gegen Qinlian Decoction Regulates Treg/Th17 Balance to Ameliorate DSS-Induced Acute Experimental Colitis in Mice by Altering the Gut Microbiota.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {756978}, pmid = {34803700}, issn = {1663-9812}, abstract = {Inflammatory bowel disease (IBD) is characterized by chronic pathology associated with extensive intestinal microbial dysregulation and intestinal inflammation. Thus, efforts are underway to manipulate the gut microbiome to improve inflammatory pathology. Gegen Qinlian decoction (GQD), a traditional Chinese medicine prescription, has been widely utilized for treating diarrhea and ulcerative colitis (UC) for thousands of years. However, the underlying mechanism of its efficacy and whether its protective effect against colitis is mediated by the gut microbiota are poorly understood. In the present study, our data demonstrated that modified GQD (MGQD) administration significantly improved the pathological phenotypes and colonic inflammation challenged by DSS in mice, which were specifically manifested as reduced loss of body weight, shortening of colon length, DAI score, histological score and suppressed inflammatory response. 16S rRNA sequencing and targeted metabonomics analysis showed that MQGD altered the diversity and community landscape of the intestinal microbiota and the metabolic profiles. In particular, MQGD significantly boosted the abundance of the intestinal microbiota producing short-chain fatty acids (SCFAs), which are causally associated with promoting the development of Treg cells and suppressing the differentiation of pro-inflammatory Th17 cells. More importantly, transferring fecal microbiota from MGQD-treated or healthy controls exhibited equivalent alleviative effects on colitis mice. However, this protective effect could not be replicated in experiments of mice with depleted intestinal microbes through broad-spectrum antibiotic cocktails (ABX), further supporting the importance of SCFA-producing gut microbiota in the beneficial role of MGQD. In general, MGQD therapy has the potential to remodel the intestinal microbiome and reestablish immune homeostasis to ameliorate DSS-induced colitis.}, }
@article {pmid34803517, year = {2021}, author = {Amedei, A and Capasso, C and Nannini, G and Supuran, CT}, title = {Microbiota, Bacterial Carbonic Anhydrases, and Modulators of Their Activity: Links to Human Diseases?.}, journal = {Mediators of inflammation}, volume = {2021}, number = {}, pages = {6926082}, pmid = {34803517}, issn = {1466-1861}, abstract = {The involvement of the human microbiome is crucial for different host functions such as protection, metabolism, reproduction, and especially immunity. However, both endogenous and exogenous factors can affect the balance of the microbiota, creating a state of dysbiosis, which can start various gastrointestinal or systemic diseases. The challenge of future medicine is to remodel the intestinal microbiota to bring it back to healthy equilibrium (eubiosis) and, thus, counteract its negative role in the diseases' onset. The shaping of the microbiota is currently practiced in different ways ranging from diet (or use of prebiotics, probiotics, and synbiotics) to phage therapy and antibiotics, including microbiota fecal transplantation. Furthermore, because microbiota modulation is a capillary process, and because many microbiota bacteria (both beneficial and pathogenic) have carbonic anhydrases (specifically the four classes α, β, γ, and ι), we believe that the use of CA inhibitors and activators can open up new therapeutic strategies for many diseases associated with microbial dysbiosis, such as the various gastrointestinal disorders and the same colorectal cancer.}, }
@article {pmid34801432, year = {2021}, author = {Ciftciler, R and Ciftciler, AE}, title = {The importance of microbiota in hematology.}, journal = {Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis}, volume = {}, number = {}, pages = {103320}, doi = {10.1016/j.transci.2021.103320}, pmid = {34801432}, issn = {1473-0502}, abstract = {Whilst particular infectious bacteria are well-established to be associated with hematological diseases, more recent interest has focused on the entire microbial community of mucosal surfaces. In particular, the link between hematology and the microbiota (defined as the total assemblage of microorganisms in a mucosal environment)/ microbiome (i.e. the entire ecological habitat, including organisms, their genomes and environmental conditions) is becoming more well-known. Dysbiosis, or a change in the microbiome, has been linked to the development of neoplasms, infections, inflammatory illnesses, and immune-mediated disorders, according to growing data. Microbiota may influence distant tumor microenvironment through a variety of methods, including cytokine release control, dendritic cell activation, and T-cell lymphocyte stimulation. There are numerous major implications to study the microbiome in patients with benign and malignant hematologic disorders. In this review, we investigated the structure and function of the microbiome in patients with benign and malignant hematological diseases. Chemotherapy and immunosuppressive agents used in treatment of these benign and malignant hematological diseases may cause or exacerbate dysbiosis and infectious problems. After understanding the importance of microbiota in hematological diseases, we think that use of probiotics and dietary prebiotic substances targeting microbiota modification aiming to improve hematological disease outcomes should be investigated in future studies.}, }
@article {pmid34795654, year = {2021}, author = {Han, T and Hu, X and Li, K and Zhang, D and Zhang, Y and Li, J}, title = {Bifidobacterium infantis Maintains Genome Stability in Ulcerative Colitis via Regulating Anaphase-Promoting Complex Subunit 7.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {761113}, pmid = {34795654}, issn = {1664-302X}, abstract = {Probiotics represents a promising intestinal microbiota-targeted therapeutic method for the treatment of ulcerative colitis (UC). Several lines of evidence implicate that Bifidobacterium infantis serves as a probiotic strain with proven efficacy in maintaining the remission of UC. However, the exact mechanisms underlying the beneficial effects of B. infantis on UC progression have yet to be elucidated. Herein, we provide evidence that B. infantis acts as a key predisposing factor for the maintenance of host genome stability. First, we showed that the fecal microbiota transplantation (FMT) of UC-derived feces contributes to more severely DNA damage in dextran sodium sulfate (DSS)-induced mice likely due to mucosa-associated microbiota alterations, as reflected by the rapid appearance of DNA double strand breaks (DSBs), a typical marker of genome instability. Genomic DNA damage analysis of colon tissues derived from healthy controls, patients with UC or dysplasia, and colitis associated cancer (CAC) patients, revealed an enhanced level of DSBs with aggravation in the degree of the intestinal mucosal lesions. To evaluate whether B. infantis modulates the host genome stability, we employed the DSS-induced colitis model and a TNFα-induced intestinal epithelial cell model. Following the administration of C57BL/6 mice with B. infantis via oral gavage, we found that the development of DSS-induced colitis in mice was significantly alleviated, in contrast to the colitis model group. Notably, B. infantis administration decreased DSB levels in both DSS-induced colitis and TNF-treated colonial cell model. Accordingly, our bioinformatic and functional studies demonstrated that B. infantis altered signal pathways involved in ubiquitin-mediated proteolysis, transcriptional misregulation in cancer, and the bacterial invasion of epithelial cells. Mechanistically, B. infantis upregulated anaphase-promoting complex subunit 7 (APC7), which was significantly suppressed in colitis condition, to activate the DNA repair pathway and alter the genome stability, while downregulation of APC7 abolished the efficiency of B. infantis treatment to induce a decrease in the level of DSBs in TNFα-induced colonial cells. Collectively, our results support that B. infantis orchestrates a molecular network involving in APC7 and genome stability, to control UC development at the clinical, biological, and mechanistic levels. Supplying B. infantis and targeting its associated pathway will yield valuable insight into the clinical management of UC patients.}, }
@article {pmid34795283, year = {2021}, author = {Vandeputte, D and De Commer, L and Tito, RY and Kathagen, G and Sabino, J and Vermeire, S and Faust, K and Raes, J}, title = {Temporal variability in quantitative human gut microbiome profiles and implications for clinical research.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {6740}, pmid = {34795283}, issn = {2041-1723}, support = {SYSCID (grant number 733100)//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Euratom (H2020 Euratom Research and Training Programme 2014-2018)/ ; G0G4118N//KU Leuven (Katholieke Universiteit Leuven)/ ; }, abstract = {While clinical gut microbiota research is ever-expanding, extending reference knowledge of healthy between- and within-subject gut microbiota variation and its drivers remains essential; in particular, temporal variability is under-explored, and a comparison with cross-sectional variation is missing. Here, we perform daily quantitative microbiome profiling on 713 fecal samples from 20 Belgian women over six weeks, combined with extensive anthropometric measurements, blood panels, dietary data, and stool characteristics. We show substantial temporal variation for most major gut genera; we find that for 78% of microbial genera, day-to-day absolute abundance variation is substantially larger within than between individuals, with up to 100-fold shifts over the study period. Diversity, and especially evenness indicators also fluctuate substantially. Relative abundance profiles show similar but less pronounced temporal variation. Stool moisture, and to a lesser extent diet, are the only significant host covariates of temporal microbiota variation, while menstrual cycle parameters did not show significant effects. We find that the dysbiotic Bact2 enterotype shows increased between- and within-subject compositional variability. Our results suggest that to increase diagnostic as well as target discovery power, studies could adopt a repeated measurement design and/or focus analysis on community-wide microbiome descriptors and indices.}, }
@article {pmid34791396, year = {2021}, author = {Bernard, R and Hourigan, SK and Nicholson, MR}, title = {Fecal Microbiota Transplantation and Microbial Therapeutics for the Treatment of Clostridioides difficile Infection in Pediatric Patients.}, journal = {Journal of the Pediatric Infectious Diseases Society}, volume = {10}, number = {Supplement_3}, pages = {S58-S63}, pmid = {34791396}, issn = {2048-7207}, support = {1K23AI156132-01//National Institute of Allergy and Infectious Diseases/ ; K23HD099240//National Institute of Child Health and Human Development Award/ ; }, mesh = {Adult ; Child ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridioides difficile infection (CDI) is the most common cause of antibiotic-associated diarrhea and has high rates of recurrent disease. As a disease associated with intestinal dysbiosis, gastrointestinal microbiome manipulation and fecal microbiota transplantation (FMT) have evolved as effective, although relatively unregulated therapeutics and not without safety concerns. FMT for the treatment of CDI has been well studied in adults with increasing data reported in children. In this review, we discuss the current body of literature on the use of FMT in children including effectiveness, safety, risk factors for a failed FMT, and the role of FMT in children with comorbidities. We also review emerging microbial therapeutics for the treatment of rCDI.}, }
@article {pmid34788420, year = {2021}, author = {Nicholson, MR and Alexander, E and Ballal, S and Davidovics, Z and Docktor, M and Dole, M and Gisser, JM and Goyal, A and Hourigan, SK and Jensen, MK and Kaplan, JL and Kellermayer, R and Kelsen, JR and Kennedy, MA and Khanna, S and Knackstedt, ED and Lentine, J and Lewis, JD and Michail, S and Mitchell, PD and Oliva-Hemker, M and Patton, T and Queliza, K and Sidhu, S and Solomon, AB and Suskind, DL and Weatherly, M and Werlin, S and de Zoeten, EF and Kahn, SA and , }, title = {Efficacy and Outcomes of Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection in Children with Inflammatory Bowel Disease.}, journal = {Journal of Crohn's &amp; colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjab202}, pmid = {34788420}, issn = {1876-4479}, abstract = {BACKGROUND: Children with inflammatory bowel disease (IBD) are disproportionally affected by recurrent Clostridioides difficile infection (rCDI). Although fecal microbiota transplantation (FMT) has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in pediatric IBD.<br><br>METHODS: We performed a retrospective review of FMT at 20 pediatric centers in the United States (US) from March 2012-March 2020. Children with and without IBD were compared to determine differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared to determine predictors of success. Safety data and IBD-specific outcomes were obtained.<br><br>RESULTS: A total of 396 pediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort (76% vs 81%, P=0.17). Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool (P=0.03), were without diarrhea prior to FMT (P=0.03), or had a shorter time from rCDI diagnosis until FMT (P=0.04). Children with a failed FMT were more likely to have clinically active IBD post-FMT (P=0.002) and 19 (13%) patients had an IBD-related hospitalization in the 3 month follow-up.<br><br>CONCLUSIONS: Based on the findings from this large US multi-center cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD.}, }
@article {pmid34784980, year = {2021}, author = {Zhao, Z and Ning, J and Bao, XQ and Shang, M and Ma, J and Li, G and Zhang, D}, title = {Fecal microbiota transplantation protects rotenone-induced Parkinson's disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {226}, pmid = {34784980}, issn = {2049-2618}, support = {81773718//National Sciences Foundation of China/ ; 81630097//National Sciences Foundation of China/ ; 81773589//National Sciences Foundation of China/ ; SQ2018YFA090025-04//The National Key Research and Development Program of China/ ; 2016-I2M-3-011//CAMS Innovation Fund for Medical Sciences/ ; 2018ZX09711001-003-020//The Drug Innovation Major Project/ ; 2018ZX09711001-003-005//The Drug Innovation Major Project/ ; 2018ZX09711001-008-005//The Drug Innovation Major Project/ ; 2018RC350002//CAMS The Fundamental Research Funds for the Central Universities/ ; 2019-1007-23//CAMS &amp; PUMC Innovation Fund for Graduate/ ; }, abstract = {BACKGROUND: Parkinson's disease (PD) is a prevalent neurodegenerative disorder, displaying not only well-known motor deficits but also gastrointestinal dysfunctions. Consistently, it has been increasingly evident that gut microbiota affects the communication between the gut and the brain in PD pathogenesis, known as the microbiota-gut-brain axis. As an approach to re-establishing a normal microbiota community, fecal microbiota transplantation (FMT) has exerted beneficial effects on PD in recent studies. Here, in this study, we established a chronic rotenone-induced PD mouse model to evaluate the protective effects of FMT treatment on PD and to explore the underlying mechanisms, which also proves the involvement of gut microbiota dysbiosis in PD pathogenesis via the microbiota-gut-brain axis.<br><br>RESULTS: We demonstrated that gut microbiota dysbiosis induced by rotenone administration caused gastrointestinal function impairment and poor behavioral performances in the PD mice. Moreover, 16S RNA sequencing identified the increase of bacterial genera Akkermansia and Desulfovibrio in fecal samples of rotenone-induced mice. By contrast, FMT treatment remarkably restored the gut microbial community, thus ameliorating the gastrointestinal dysfunctions and the motor deficits of the PD mice. Further experiments revealed that FMT administration alleviated intestinal inflammation and barrier destruction, thus reducing the levels of systemic inflammation. Subsequently, FMT treatment attenuated blood-brain barrier (BBB) impairment and suppressed neuroinflammation in the substantia nigra (SN), which further decreased the damage of dopaminergic neurons. Additional mechanistic investigation discovered that FMT treatment reduced lipopolysaccharide (LPS) levels in the colon, the serum, and the SN, thereafter suppressing the TLR4/MyD88/NF-κB signaling pathway and its downstream pro-inflammatory products both in the SN and the colon.<br><br>CONCLUSIONS: Our current study demonstrates that FMT treatment can correct the gut microbiota dysbiosis and ameliorate the rotenone-induced PD mouse model, in which suppression of the inflammation mediated by the LPS-TLR4 signaling pathway both in the gut and the brain possibly plays a significant role. Further, we prove that rotenone-induced microbiota dysbiosis is involved in the genesis of PD via the microbiota-gut-brain axis. Video abstract.}, }
@article {pmid34784410, year = {2021}, author = {Wu, J and Qiu, M and Zhang, C and Zhang, C and Wang, N and Zhao, F and Lv, L and Li, J and Lyu-Bu, AGA and Wang, T and Zhao, B and You, S and Wu, Y and Wang, X}, title = {Type 3 resistant starch from Canna edulis modulates obesity and obesity-related low-grade systemic inflammation in mice by regulating gut microbiota composition and metabolism.}, journal = {Food &amp; function}, volume = {12}, number = {23}, pages = {12098-12114}, doi = {10.1039/d1fo02208c}, pmid = {34784410}, issn = {2042-650X}, abstract = {Obesity is a most prevalent human health problem. Several studies showed that appropriate modulation of gut microbiota could help reshape the metabolic profile of obese individuals, thereby altering the development of obesity. A nutritional strategy for treating obesity includes prebiotics. Type 3 Resistant Starch from Canna edulis (Ce-RS3) is a dietary fiber that exerts potential effects on the intestinal microbial community; however, the metabolic landscape and anti-obesity mechanism remain unclear. In the present study, obese mice were treated with Ce-RS3, and 16S rRNA gene sequencing and metabolomics were used to measure changes in gut microbiota and fecal metabolic profiles, respectively. At the end of the treatment (13 weeks), we observed slow weight gain in the mice, and pathological damage and inflammation were substantially reduced. Ce-RS3 constructs a healthy gut microbiota structure and can enhance intestinal immunity and reduce metabolic inflammation. Ce-RS3 increased the diversity of gut microbiota with enrichment of Bifidobacterium and Roseburia. Ce-RS3 regulated the systemic metabolic dysbiosis in obese mice and adjusted 26 abnormal metabolites in amino acids and lipids metabolism, many of which are related to the microbiome. More importantly, we found that the anti-obesity effect of Ce-RS3 can be transferred by fecal transplantation. The beneficial effects of Ce-RS3 might derive from gut microbiota changes, which might improve obesity and metabolic inflammation by altering host-microbiota interactions with impacts on the metabolome. In conclusion, Ce-RS3 can be used as a prebiotic with potential value for the treatment of obesity.}, }
@article {pmid34781411, year = {2021}, author = {Sivaraj, S and Copeland, JK and Malik, A and Pasini, E and Angeli, M and Azhie, A and Husain, S and Kumar, D and Allard, J and Guttman, DS and Humar, A and Bhat, M}, title = {Characterization and predictive functional profiles on metagenomic 16S rRNA data of liver transplant recipients: A longitudinal study.}, journal = {Clinical transplantation}, volume = {}, number = {}, pages = {e14534}, doi = {10.1111/ctr.14534}, pmid = {34781411}, issn = {1399-0012}, support = {//Canadian Donation and Transplant Research Program/ ; //Astellas program grant-Multi Organ Transplant, University Health Network/ ; }, abstract = {Long-term survival after Liver Transplantation (LT) is often compromised by infectious and metabolic complications. We aimed to delineate alterations in intestinal microbiome (IM) over time that could contribute to medical complications compromising long-term survival following LT. Fecal samples from LT recipients were collected at 3 months (3 M) and 6 months (6 M) post-LT. The bacterial DNA was extracted using E.Z.N.A. Stool DNA Kit and 16S rRNA gene sequencing at V4 hypervariable region was performed. DADA2 and Phyloseq was implemented to analyze the taxonomic composition. Differentially abundant taxa were identified by metagenomeSeq and LEfSe. Piphillin, an Inferred functional metagenomic analysis tool was used to study the bacterial functional content. For comparison, healthy samples were extracted from NCBI and analyzed similarly. The taxonomic &amp; functional profiles of LT recipients were validated with metagenomic sequencing data from animals exposed to immunosuppressants using Venny. Our findings provide a new perspective on longitudinal increase in specific IM communities post-LT along with an increase in bacterial genes associated with metabolic and infectious disease.}, }
@article {pmid34781002, year = {2021}, author = {Chen, CC and Chiu, CH}, title = {Current and future applications of fecal microbiota transplantation for children.}, journal = {Biomedical journal}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bj.2021.11.004}, pmid = {34781002}, issn = {2320-2890}, abstract = {Fecal microbiota transplantation (FMT) is a new and adequate route to modify the microbial ecosystem in gastrointestinal tract of the hosts. Intestinal microbiota is highly associated with human health and disease. According to the reports of human clinical trials or case series, the application of FMT ranged from Clostridiodes difficile infection (CDI), inflammatory bowel disease (IBD), irritable bowel syndrome, refractory diarrhea, diabetes mellitus, metabolic syndrome, and even neurologic diseases, including Parkinson disease, and neuropsychiatric disorder (autism spectrum disorder, ASD). Although the current allowed indication of FMT is CDI in Taiwan, more application and development are expectable in the future. There is a relative rare data available for children in application of fecal microbiota transplantation. Thus, we review previous published research inspecting FMT in children, and address particular considerations when conducting FMT in pediatric patients.}, }
@article {pmid34773257, year = {2021}, author = {Kim, ER and Park, JS and Kim, JH and Oh, JY and Oh, IJ and Choi, DH and Lee, YS and Park, IS and Kim, S and Lee, DH and Cheon, JH and Bae, JW and Lee, M and Cho, JW and An, IB and Nam, EJ and Yang, SI and Lee, MS and Bae, SH and Lee, YH}, title = {A GLP-1/GLP-2 receptor dual agonist to treat non-alcoholic steatohepatitis: targeting the gut-liver axis and microbiome.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/hep.32235}, pmid = {34773257}, issn = {1527-3350}, abstract = {Currently there is no FDA-approved drug to treat nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), rates of which are increasing worldwide. Although NAFLD/NASH are highly complex and heterogeneous conditions, most pharmacotherapy pipelines focus on a single mechanistic target. Considering the importance of the gut-liver axis in their pathogenesis, we investigated the therapeutic effect of a long-acting dual agonist of glucagon-like peptide (GLP)-1 and GLP-2 receptors in mice with NAFLD/NASH. C57BL/6J mice were fed a choline-deficient high fat diet/high fructose and sucrose solution. After 16 weeks, mice were randomly allocated to receive vehicle, GLP1-Fc, GLP2-Fc, or GLP1/2-Fc subcutaneously every two days for four weeks. Body weight was monitored, insulin/glucose tolerance tests were performed, feces were collected, and microbiome profiles were analyzed. Immobilized cell systems were utilized to evaluate direct peptide effect. Immunohistochemistry, qPCR, immunoblot analysis, tunnel assay, and biochemical assays were performed to assess drug effects on inflammation, hepatic fibrosis, cell death, and intestinal structures. The mice had well-developed NASH phenotypes. GLP1/2-Fc reduced body weight, glucose levels, hepatic triglyceride levels, and cellular apoptosis. It improved liver fibrosis, insulin sensitivity, and intestinal tight junctions, and increased microvillus height, crypt depth, goblet cells of intestine compared to a vehicle group. Similar effects of GLP1/2-Fc were found in in vitro cell systems. GLP1/2-Fc also changed microbiome profiles. We applied fecal microbiota transplantation (FMT) in order to gain further insight into the mechanism of GLP1/2-Fc-mediated protection. We confirmed that FMT exerted an additive effect on GLP1-Fc group, including the body weight change, liver weight, hepatic fat accumulation, inflammation and hepatic fibrosis. CONCLUSION: A long-acting dual agonist of GLP-1 and GLP-2 receptors is a promising therapeutic strategy to treat NAFLD/NASH.}, }
@article {pmid34769321, year = {2021}, author = {Gao, T and Wang, Z and Dong, Y and Cao, J and Chen, Y}, title = {Melatonin-Mediated Colonic Microbiota Metabolite Butyrate Prevents Acute Sleep Deprivation-Induced Colitis in Mice.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34769321}, issn = {1422-0067}, abstract = {Radical cure colitis is a severe public health threat worldwide. Our previous studies have confirmed that melatonin can effectively improve gut microbiota disorder and mucosal injury caused by sleep deprivation (SD). The present study further explored the mechanism whereby exogenous melatonin prevented SD-induced colitis. 16S rRNA high-throughput sequencing and metabolomics analysis were used to explore the correlation between SD-induced colitis and intestinal microbiota and metabolite composition in mice. Fecal microbiota transplantation (FMT) and melatonin or butyrate supplementation tests verified the core role of gut microbiota in melatonin-alleviating SD-induced colitis. Further, in vitro tests studied the modulatory mechanism of metabolite butyrate. The results demonstrated that SD leads to reductions in plasma melatonin levels and colonic Card9 expression and consequent occurrence of colitis and gut microbiota disorder, especially the downregulation of Faecalibacterium and butyrate levels. The FMT from SD-mice to normal mice could restore SD-like colitis, while butyrate supplementation to SD-mice inhibited the occurrence of colitis, but with no change in the plasma melatonin level in both treatments. However, melatonin supplementation reversed all inductions in SD-mice. In intestinal epithelial cells, the inflammatory ameliorative effect of butyrate was blocked with pretreatments of HDAC3 agonist and HIF-1α antagonist but was mimicked by GSK-3β and p-P65 antagonists. Therefore, the administration of MLT may be a better therapy for SD-induced colitis relative to butyrate. A feasible mechanism would involve that melatonin up-regulated the Faecalibacterium population and production of its metabolite butyrate and MCT1 expression and inhibited HDAC3 in the colon, which would allow p-GSK-3β/β-catenin/HIF-1α activation and NF-κB/NLRP3 suppression to up-regulate Card9 expression and suppress inflammation response.}, }
@article {pmid34768867, year = {2021}, author = {Chen, Z and Wang, B and Dong, J and Li, Y and Zhang, S and Zeng, X and Xiao, H and Fan, S and Cui, M}, title = {Gut Microbiota-Derived l-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34768867}, issn = {1422-0067}, support = {81872555, 81803062, 82003399 and 81730086//National Natural Science Foundation of China/ ; 20JCJQJC00100//Science Foundation for Distinguished Young Scholars of Tianjin/ ; }, abstract = {Radiation-induced cardiopulmonary injuries are the most common and intractable side effects that are entwined with radiotherapy for thorax cancers. However, the therapeutic options for such complications have yielded disappointing results in clinical applications. Here, we reported that gut microbiota-derived l-Histidine and its secondary metabolite imidazole propionate (ImP) fought against radiation-induced cardiopulmonary injury in an entiric flora-dependent manner in mouse models. Local chest irradiation decreased the level of l-Histidine in fecal pellets, which was increased following fecal microbiota transplantation. l-Histidine replenishment via an oral route retarded the pathological process of lung and heart tissues and improved lung respiratory and heart systolic function following radiation exposure. l-Histidine preserved the gut bacterial taxonomic proportions shifted by total chest irradiation but failed to perform radioprotection in gut microbiota-deleted mice. ImP, the downstream metabolite of l-Histidine, accumulated in peripheral blood and lung tissues following l-Histidine replenishment and protected against radiation-induced lung and heart toxicity. Orally gavaged ImP could not enter into the circulatory system in mice through an antibiotic cocktail treatment. Importantly, ImP inhibited pyroptosis to nudge lung cell proliferation after radiation challenge. Together, our findings pave a novel method of protection against cardiopulmonary complications intertwined with radiotherapy in pre-clinical settings and underpin the idea that gut microbiota-produced l-Histidine and ImP are promising radioprotective agents.}, }
@article {pmid34768795, year = {2021}, author = {Popov, J and Caputi, V and Nandeesha, N and Rodriguez, DA and Pai, N}, title = {Microbiota-Immune Interactions in Ulcerative Colitis and Colitis Associated Cancer and Emerging Microbiota-Based Therapies.}, journal = {International journal of molecular sciences}, volume = {22}, number = {21}, pages = {}, pmid = {34768795}, issn = {1422-0067}, abstract = {Ulcerative colitis (UC) is a chronic autoimmune disorder affecting the colonic mucosa. UC is a subtype of inflammatory bowel disease along with Crohn's disease and presents with varying extraintestinal manifestations. No single etiology for UC has been found, but a combination of genetic and environmental factors is suspected. Research has focused on the role of intestinal dysbiosis in the pathogenesis of UC, including the effects of dysbiosis on the integrity of the colonic mucosal barrier, priming and regulation of the host immune system, chronic inflammation, and progression to tumorigenesis. Characterization of key microbial taxa and their implications in the pathogenesis of UC and colitis-associated cancer (CAC) may present opportunities for modulating intestinal inflammation through microbial-targeted therapies. In this review, we discuss the microbiota-immune crosstalk in UC and CAC, as well as the evolution of microbiota-based therapies.}, }
@article {pmid34764691, year = {2021}, author = {Zhou, H and Yuan, Y and Wang, H and Xiang, W and Li, S and Zheng, H and Wen, Y and Ming, Y and Chen, L and Zhou, J}, title = {Gut Microbiota: A Potential Target for Cancer Interventions.}, journal = {Cancer management and research}, volume = {13}, number = {}, pages = {8281-8296}, pmid = {34764691}, issn = {1179-1322}, abstract = {The gut microbiota plays a crucial role in many physiological processes in the human body. Dysbiosis can disrupt the intestinal barrier and alter metabolism and immune responses, leading to the development of diseases. Over the past few decades, evidence has accumulated linking changes in the composition of the gut microbiota to dozens of seemingly unrelated conditions, including cancer. Overall, the gut microbiota mainly affects the occurrence and development of cancer by damaging host DNA, forming and maintaining a pro-inflammatory environment, and affecting host immune responses. In addition, the gut microbiota can also affect the efficacy and toxicity of chemotherapy, radiotherapy, and immunotherapy. Scientists attempt to improve the efficacy and decrease the toxicity of these treatment modalities by fine-tuning the gut microbiota. The aim of this review is to assist researchers and clinicians in developing new strategies for the detection and treatment of tumors by providing the latest information on the intestinal microbiome and cancer, as well as exploring potential application prospects and mechanisms of action.}, }
@article {pmid34761734, year = {2021}, author = {Hou, K and Zhang, S and Wu, Z and Zhu, D and Chen, F and Lei, ZN and Liu, W and Xiao, C and Chen, ZS}, title = {Reconstruction of intestinal microecology of Type 2 diabetes by fecal microbiota transplantation: Why and how.}, journal = {Bosnian journal of basic medical sciences}, volume = {}, number = {}, pages = {}, doi = {10.17305/bjbms.2021.6323}, pmid = {34761734}, issn = {1840-4812}, abstract = {Type 2 diabetes (T2D) is a chronic metabolic disease characterized by hyperglycemia due to insulin resistance. Mounting evidence has correlated T2D to alterations in the composition of gut microbiota. Accordingly, targeting the gut microbiota has become an emerging strategy for T2D management. The aim of this article is to get a better insight into the rationale for targeting gut microbiota in T2D treatment. Thus, we herein reviewed the change of gut microbiota composition in T2D, factors shaping gut microbiota, and potential mechanisms behind the contribution of gut microbiota to T2D pathogenesis. At present, it has become possible to use intestinal microorganism capsules, bacteria liquid, and other preparations to carry out fecal microbiota transplantation for the treatment and intervention of T2D with insulin resistance and immune-mediated Type 1 diabetes (T1D).}, }
@article {pmid34759928, year = {2021}, author = {Pan, P and Atkinson, SN and Taylor, B and Zhu, H and Zhou, D and Flejsierowicz, P and Wang, LS and Morse, M and Liu, C and Gunsolus, IL and Chen, X}, title = {Retinoic Acid Signaling Modulates Recipient Gut Barrier Integrity and Microbiota After Allogeneic Hematopoietic Stem Cell Transplantation in Mice.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {749002}, pmid = {34759928}, issn = {1664-3224}, abstract = {Graft-versus-host disease (GVHD) remains a major complication after allogeneic hematopoietic stem cell transplantation (HSCT). An impaired intestinal epithelial barrier is an important component of GVHD pathogenesis. However, contributing host factors that modulate mucosal barrier integrity during GVHD are poorly defined. We hypothesized that vitamin A and retinoic acid (RA) exert positive impacts on maintaining intestinal barrier function after HSCT, thus preventing or dampening GVHD severity. Unexpectedly, we found that exogenous RA increased intestinal permeability of recipient mice after allogeneic HSCT. Serum bacterial endotoxin levels were significantly higher in GVHD mice fed a vitamin A-high (VAH) diet compared to those fed a vitamin A-normal (VAN) diet, indicating a more compromised intestinal barrier function. Furthermore, VAH mice showed more severe lung GVHD with increased donor T cell infiltration in this tissue and died significantly faster than VAN recipients. 16S rRNA sequencing of fecal samples revealed significant differences in the diversity and composition of gut microbiota between VAN and VAH transplant recipients. Collectively, we show that retinoic acid signaling may negatively impact intestinal barrier function during GVHD. Mild vitamin A supplementation is associated with increased lung GVHD and more profound gut dysbiosis. Micronutrients such as vitamin A could modulate complications of allogeneic HSCT, which may be mediated by shaping gut microbiota.}, }
@article {pmid34754163, year = {2021}, author = {Baldi, S and Mundula, T and Nannini, G and Amedei, A}, title = {Microbiota shaping - the effects of probiotics, prebiotics, and fecal microbiota transplant on cognitive functions: A systematic review.}, journal = {World journal of gastroenterology}, volume = {27}, number = {39}, pages = {6715-6732}, pmid = {34754163}, issn = {2219-2840}, mesh = {Cognition ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics/therapeutic use ; *Synbiotics ; }, abstract = {BACKGROUND: Dementia is a chronic progressive neurological disease affecting millions of people worldwide, and represents a relevant economic burden for healthcare systems. Although its pathogenesis is still unknown, recent findings have reported that a dysregulated gut-brain axis communication, a fundamental relationship mediated by several host and microbial molecules, is associated with cognitive disorders. In addition, gut microbiota manipulation reduces neuroinflammation, improving cognitive function by restoring the functional gut-brain axis.<br><br>AIM: To better define the effects of probiotics, prebiotics, synbiotics, and fecal microbiota transplant (FMT) on cognitive function.<br><br>METHODS: We performed a literature search of human randomized clinical trials to examine the effects of the administration of probiotics, prebiotics, synbiotics, or FMT on cognition outcomes in healthy or sick people of every age, sex, and nationality. We systematically searched Embase, Medline/PubMed, Cochrane Library, central and clinicaltrials.gov databases with a combination of comprehensive terms related to cognition and gut microbiota manipulation. Then we carefully reviewed and synthesized the data by type of study design and setting, characteristics of the studied population, kind of intervention (strain type or mixture type, dosage, and frequency of administration), control treatment, inclusion and exclusion criteria, follow-up duration, and cognitive or memory outcomes.<br><br>RESULTS: After examining the titles and abstracts, the initial literature screening identified 995 articles, but we added 23 papers in our systematic review. The analyses of these selected studies highlighted that both probiotic supplementation and FMT improved cognitive function regardless of the type and posology of administration and the adopted cognitive tests and questionnaires. We found that most of the studies conducted in healthy people showed a significant positive effect of the intervention on at least one of the performed cognitive tests. Regarding unhealthy subjects, while FMT and especially probiotic administration had multiple beneficial effects on different cognitive functions, supplementation with prebiotics did not provide any cognitive improvement.<br><br>CONCLUSION: Probiotic supplementation and FMT may represent a promising strategy to restore gut eubiosis and enhance the cognitive functions of healthy people and patients with neurological disorders.}, }
@article {pmid34752816, year = {2021}, author = {Zhang, S and Chen, Q and Kelly, CR and Kassam, Z and Qin, H and Li, N and , }, title = {Donor screening for fecal microbiota transplantation in China: Evaluation of 8,483 candidates.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2021.11.004}, pmid = {34752816}, issn = {1528-0012}, }
@article {pmid34752587, year = {2021}, author = {Urbonas, T and Ianiro, G and Gedgaudas, R and Sabanas, P and Urba, M and Kiudelis, V and Kiudelis, G and Petkevicius, V and Vitkauskiene, A and Cammarota, G and Gasbarrini, A and Kupcinskas, J}, title = {Fecal Microbiome Transplantation for Recurrent Clostridioides difficile Infection: Treatment Efficacy, Short and Long-term Follow-up Results from Consecutive Case Series.}, journal = {Journal of gastrointestinal and liver diseases : JGLD}, volume = {}, number = {}, pages = {}, doi = {10.15403/jgld-3800}, pmid = {34752587}, issn = {1842-1121}, abstract = {BACKGROUND AND AIMS: Many studies have shown a high effectiveness of fecal microbiota transplantation (FMT) in treatment of recurrent or refractory Clostridioides difficile infection (CDI). Nevertheless, data on long term outcomes and complications after FMT are still lacking. We aimed to evaluate the efficacy, the peri- procedural safety profile and the long-term efficacy and safety of FMT for recurrent CDI during a median follow up period of 24 months.<br><br>METHODS: Our study included 60 consecutive patients that were treated from 2015 to 2019 for recurrent CDI. In all patients FMT was performed through the nasoenteric tube placed during gastroscopy. Fresh donor feces were used for FMT from unrelated donors. Pre-FMT preparation included CDI treatment with oral vancomycin 500 mg q.i.d. for at least five days and proton pump inhibitor (PPI) administration before FMT. Follow up data included information about recurrent CDI episodes, early and late complications, health status at 3, 12 and 24 months after FMT.<br><br>RESULTS: FMT was performed for 60 patients (median age 72.5 years) with recurrent CDI. Clinical improvement after the first FMT procedure was observed in 48 patients (80%). Ten of 12 initially non-responding patients had a clinical resolution after a second FMT leading to an increased overall cure rate of 96.7 %. The remaining two patients needed a third FMT with a final overall cure rate of 100%. Nine of 60 patients were under immunosuppressive therapy. Six immunosuppressed patients were in the group of initial responders and the remaining three in the initially non-responder group. We observed a very low rate of adverse events in the short and long-term after FMT. During the first eight weeks after the FMT procedure, the death of three patients occurred, but they were not related to the FMT procedure. Patients were followed up for a median of 20 months, with the range from 12 to 55 months. During the follow-up period no long-term serious adverse events (SAE) were documented.<br><br>CONCLUSIONS: Our study confirms excellent efficacy rates of FMT in the treatment of recurrent CDI. In addition, this study shows that it is possible to avoid short term SAE when FMT is administered via a nasoenteric tube by following a very stringent peri-procedural patient follow-up protocol. Our study also demonstrates good safety with a low rate of long-term adverse events after FMT.}, }
@article {pmid34752089, year = {2021}, author = {Zhou, F and Li, YL and Zhang, X and Wang, KB and Huang, JA and Liu, ZH and Zhu, MZ}, title = {Polyphenols from Fu Brick Tea Reduce Obesity via Modulation of Gut Microbiota and Gut Microbiota-Related Intestinal Oxidative Stress and Barrier Function.}, journal = {Journal of agricultural and food chemistry}, volume = {69}, number = {48}, pages = {14530-14543}, doi = {10.1021/acs.jafc.1c04553}, pmid = {34752089}, issn = {1520-5118}, abstract = {Fu brick tea (FBT) is a microbial-fermented tea, which is produced by the solid-state fermentation of tea leaves. Previous studies have proved that FBT aqueous extracts could attenuate obesity and gut microbiota dysbiosis. However, the bioactive components in FBT that contribute to these activities remain unclear. In this study, we aimed to investigate the effects of FBT polyphenols (FBTPs) on obesity, gut microbiota, and gut microbiota-related intestinal oxidative stress and barrier function and to further investigate whether the antiobesity effect of FBTPs was dependent on the alteration of gut microbiota. The results showed that FBTP supplementation effectively attenuated obesity in high-fat diet (HFD)-fed rats. FBTP supplementation improved the intestinal oxidative stress and intestinal barrier function, including intestinal inflammation and the integrity of the intestinal barrier. Furthermore, FBTP intervention significantly attenuated HFD-induced gut microbiota dysbiosis, characterized by increased phylogenetic diversity and decreased Firmicutes/Bacteroidetes ratio. Certain core microbes, including Akkermansia muciniphila, Alloprevotella, Bacteroides, and Faecalibaculum, were also found to be improved by FBTPs. Moreover, the antiobesity effect of FBTPs was gut microbiota-dependent, as demonstrated by a fecal microbiota transplantation experiment. Collectively, we concluded that FBTPs reduced obesity by modulating the gut microbiota and gut microbiota-related intestinal oxidative stress and barrier function. Therefore, FBTPs may be used as prebiotic agents to treat obesity and gut microbiota dysbiosis in obese individuals.}, }
@article {pmid34751747, year = {2021}, author = {Dai, C and Liu, WX}, title = {Refractory Immune Checkpoint Inhibitor-induced Colitis Improved by Fecal Microbiota Transplantation: A Case Report.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izab265}, pmid = {34751747}, issn = {1536-4844}, }
@article {pmid34750307, year = {2022}, author = {Berding, K and Cryan, JF}, title = {Microbiota-targeted interventions for mental health.}, journal = {Current opinion in psychiatry}, volume = {35}, number = {1}, pages = {3-9}, doi = {10.1097/YCO.0000000000000758}, pmid = {34750307}, issn = {1473-6578}, abstract = {PURPOSE OF REVIEW: The gut microbiota has emerged as a key conduit in mental health and is a promising target for interventions. This review provides an update on recent advances in using microbiota-targeted approaches for the management of mental health.<br><br>RECENT FINDINGS: Approaches that have emerged as microbiota-targeted interventions in the management of mental health include probiotics, prebiotics, synbiotics, fecal microbiota transplant as well as diet. Among these approaches, probiotic supplementation has been investigated most prominently, providing promising evidence for its use in improving mood and anxiety. There is also growing interest in the use of multistrain probiotics, whole dietary interventions or combined approaches, with encouraging results emerging from recent studies.<br><br>SUMMARY: Although the current literature preliminarily supports targeting the microbiota to manage mental health and use as adjuvant therapies for certain brain disorders, large gaps remain and especially data including clinical cohorts remains scarce. Research studies including larger cohorts, well-characterized clinical populations and defined duration and dosage of the intervention are required to develop evidence-based guidelines for microbiota-targeted strategies.}, }
@article {pmid34747338, year = {2021}, author = {van der Vossen, EWJ and Bastos, D and Stols-Gonçalves, D and de Goffau, MC and Davids, M and Pereira, JPB and Li Yim, AYF and Henneman, P and Netea, MG and de Vos, WM and de Jonge, W and Groen, AK and Nieuwdorp, M and Levin, E}, title = {Effects of fecal microbiota transplant on DNA methylation in subjects with metabolic syndrome.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1993513}, pmid = {34747338}, issn = {1949-0984}, abstract = {Accumulating evidence shows that microbes with their theater of activity residing within the human intestinal tract (i.e., the gut microbiome) influence host metabolism. Some of the strongest results come from recent fecal microbial transplant (FMT) studies that relate changes in intestinal microbiota to various markers of metabolism as well as the pathophysiology of insulin resistance. Despite these developments, there is still a limited understanding of the multitude of effects associated with FMT on the general physiology of the host, beyond changes in gut microbiome composition. We examined the effect of either allogenic (lean donor) or autologous FMTs on the gut microbiome, plasma metabolome, and epigenomic (DNA methylation) reprogramming in peripheral blood mononuclear cells in individuals with metabolic syndrome measured at baseline (pre-FMT) and after 6 weeks (post-FMT). Insulin sensitivity was determined with a stable isotope-based 2 step hyperinsulinemic clamp and multivariate machine learning methodology was used to uncover discriminative microbes, metabolites, and DNA methylation loci. A larger gut microbiota shift was associated with an allogenic than with autologous FMT. Furthemore, the data results of the the allogenic FMT group data indicates that the introduction of new species can potentially modulate the plasma metabolome and (as a result) the epigenome. Most notably, the introduction of Prevotella ASVs directly correlated with methylation of AFAP1, a gene involved in mitochondrial function, insulin sensitivity, and peripheral insulin resistance (Rd, rate of glucose disappearance). FMT was found to have notable effects on the gut microbiome but also on the host plasma metabolome and the epigenome of immune cells providing new avenues of inquiry in the context of metabolic syndrome treatment for the manipulation of host physiology to achieve improved insulin sensitivity.}, }
@article {pmid34746183, year = {2021}, author = {Yang, B and Tian, H and Ye, C and Lin, Z and Zhao, D and Ma, C and Zhao, J and Wu, S and Jiang, R and Li, N and Qin, H and Chen, Q}, title = {The Efficacy and Safety of Fecal Microbiota Transplantation Combined With Biofeedback for Mixed Constipation: A Retrospective Cohort Study.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {746990}, pmid = {34746183}, issn = {2296-858X}, abstract = {This study aims to assess the effectiveness and safety of fecal microbiota transplantation (FMT) combined with biofeedback for patients with mixed constipation. Patients who received biofeedback (biofeedback group, n = 40) and those who received FMT combined with biofeedback (FMT combination group, n = 45) were enrolled. Spontaneous bowel movements (SBMs) frequency, Bristol Stool Form Scale (BSFS), and Patient Assessment of Constipation Symptoms (PAC-SYM) score were analyzed to evaluate the effect of treatment. Gastrointestinal Quality of Life Index (GIQLI) scores of patients were used to assess the quality of life, and the safety of FMT combination therapy was evaluated by the presence of adverse events. The 16S rRNA gene sequencing was performed on the fecal samples of 12 donors, feces of 31 patients before and after receiving FMT combination treatment. Comparing the biofeedback group and the FMT combination group 1 month after the treatment, significant differences were observed in the mean value of SBM frequency, BSFS, and PAC-SYM scores, which were 2.15 ± 1.05 vs. 3.61 ± 0.89 (p = 0.0031), 2.1 ± 0.9 vs. 2.5 ± 1.2 (p = 0.008), and 2.4 ± 0.5 vs. 2.2 ± 0.6 (p = 0.0021), respectively. Meanwhile, FMT combination therapy had long-term beneficial effects according to the data collected at six months and 12 months after the treatment. With respect to the quality of life, GIQLI scores were higher in the FMT combination group (103.6 ± 15.1) compared with that in the biofeedback group (88.7 ± 10.1) one month after administration (p = 0.0042). In addition, there were no significant differences between the two groups in adverse events, including abdominal pain, diarrhea, dizziness, nausea, vomiting, and other side effects. Results of 16S rRNA gene sequencing showing some well-known probiotics had significantly increased after FMT combination treatment compared with pre-FMT samples, such as Prevotella and Bifidobacterium. Findings of this study suggested that FMT combined with biofeedback could be effective and safe for patients with mixed constipation.}, }
@article {pmid34746161, year = {2021}, author = {Xiang, L and Yu, Y and Ding, X and Zhang, H and Wen, Q and Cui, B and Zhang, F}, title = {Exclusive Enteral Nutrition Plus Immediate vs. Delayed Washed Microbiota Transplantation in Crohn's Disease With Malnutrition: A Randomized Pilot Study.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {666062}, pmid = {34746161}, issn = {2296-858X}, abstract = {Background: The potential of washed microbiota transplantation (WMT) in Crohn's disease (CD) has been reported. This study aimed to explore the suitable timing of WMT in patients with CD complicated with malnutrition. Methods: This is a randomized, open-label study. Patients with active CD complicated with malnutrition were included and 1:1 randomized to undergo WMT at day 1 (group WMT-DAY1) or day 8 (group WMT-DAY8). The observation duration was 15 days. Exclusive enteral nutrition (EEN) was administered in both groups. The primary outcome was the improvement in nutritional parameters at day 8 and day 15 in two groups. The secondary outcome was the rate of clinical remission at day 15 in two groups. Results: Totally 19 patients completed the trial. At day 8, the lymphocyte count, albumin and prealbumin increased significantly compared to those at day 1 in group WMT-DAY1 (p = 0.018, p = 0.028, p = 0.028, respectively), while no significant increase in any nutritional parameter was shown in group WMT-DAY8. At day 15, albumin increased significantly compared to that at day 1 in both groups (p < 0.05), while significant increase in prealbumin was only shown in group WMT-DAY1 (p = 0.004) compared to that at day 1. The rate of clinical remission at day 15 in group WMT-DAY1 and group WMT-DAY8 was 87.5% (7/8) and 72.7% (8/11), respectively (p = 0.603). Conclusion: EEN combined with immediate WMT intervention could rapidly improve the nutritional status and induce clinical remission in malnourished patients with CD. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02897661.}, }
@article {pmid34746023, year = {2021}, author = {Liu, J and Gu, L and Zhang, M and Zhang, S and Wang, M and Long, Y and Zhang, X}, title = {The Fecal Microbiota Transplantation: A Remarkable Clinical Therapy for Slow Transit Constipation in Future.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {732474}, pmid = {34746023}, issn = {2235-2988}, mesh = {Bacteria ; *Constipation/therapy ; *Fecal Microbiota Transplantation ; Humans ; }, abstract = {Slow transit constipation is a common condition that would be difficult to treat in clinical practice with a widespread incidence in the population. Pharmacotherapy and surgery are common treatment modalities. However, the clinical effect is limited, and patients still suffer from it. As the researchers strived in this field for decades, the profound relationship between slow transit constipation and fecal microbiota transplantation has comprehensively been sustained. It is very pivotal to maintain intestinal homeostasis, the structure function and metabolic function of symbiotic bacteria, which can inhibit the engraftment of intestinal pathogens. This mini review explains the treatment effects and possible mechanisms of the fecal microbiota transplantation in treating slow transit constipation. Simultaneously, it is found that there is significant improvement in the disease by adjusting the intestinal microbes like fecal microbiota transplantation. Fecal microbiota transplantation has efficient therapeutic effects in slow transit constipation compared with traditional therapies.}, }
@article {pmid34745944, year = {2021}, author = {Alexander, T and Snowden, JA and Burman, J and Chang, HD and Del Papa, N and Farge, D and Lindsay, JO and Malard, F and Muraro, PA and Nitti, R and Salas, A and Sharrack, B and Mohty, M and Greco, R}, title = {Intestinal Microbiome in Hematopoietic Stem Cell Transplantation For Autoimmune Diseases: Considerations and Perspectives on Behalf of Autoimmune Diseases Working Party (ADWP) of the EBMT.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {722436}, pmid = {34745944}, issn = {2234-943X}, abstract = {Over the past decades, hematopoietic stem cell transplantation (HSCT) has been evolving as specific treatment for patients with severe and refractory autoimmune diseases (ADs), where mechanistic studies have provided evidence for a profound immune renewal facilitating the observed beneficial responses. The intestinal microbiome plays an important role in host physiology including shaping the immune repertoire. The relationships between intestinal microbiota composition and outcomes after HSCT for hematologic diseases have been identified, particularly for predicting the mortality from infectious and non-infectious causes. Furthermore, therapeutic manipulations of the gut microbiota, such as fecal microbiota transplant (FMT), have emerged as promising therapeutic approaches for restoring the functional and anatomical integrity of the intestinal microbiota post-transplantation. Although changes in the intestinal microbiome have been linked to various ADs, studies investigating the effect of intestinal dysbiosis on HSCT outcomes for ADs are scarce and require further attention. Herein, we describe some of the landmark microbiome studies in HSCT recipients and patients with chronic ADs, and discuss the challenges and opportunities of microbiome research for diagnostic and therapeutic purposes in the context of HSCT for ADs.}, }
@article {pmid34744165, year = {2021}, author = {Liu, Y and Wang, H and Gui, S and Zeng, B and Pu, J and Zheng, P and Zeng, L and Luo, Y and Wu, Y and Zhou, C and Song, J and Ji, P and Wei, H and Xie, P}, title = {Proteomics analysis of the gut-brain axis in a gut microbiota-dysbiosis model of depression.}, journal = {Translational psychiatry}, volume = {11}, number = {1}, pages = {568}, pmid = {34744165}, issn = {2158-3188}, abstract = {Major depressive disorder (MDD) is a serious mental illness. Increasing evidence from both animal and human studies suggested that the gut microbiota might be involved in the onset of depression via the gut-brain axis. However, the mechanism in depression remains unclear. To explore the protein changes of the gut-brain axis modulated by gut microbiota, germ-free mice were transplanted with gut microbiota from MDD patients to induce depression-like behaviors. Behavioral tests were performed following fecal microbiota transplantation. A quantitative proteomics approach was used to examine changes in protein expression in the prefrontal cortex (PFC), liver, cecum, and serum. Then differential protein analysis and weighted gene coexpression network analysis were used to identify microbiota-related protein modules. Our results suggested that gut microbiota induced the alteration of protein expression levels in multiple tissues of the gut-brain axis in mice with depression-like phenotype, and these changes of the PFC and liver were model specific compared to chronic stress models. Gene ontology enrichment analysis revealed that the protein changes of the gut-brain axis were involved in a variety of biological functions, including metabolic process and inflammatory response, in which energy metabolism is the core change of the protein network. Our data provide clues for future studies in the gut-brain axis on protein level and deepen the understanding of how gut microbiota cause depression-like behaviors.}, }
@article {pmid34743650, year = {2021}, author = {Bajaj, JS and Shamsaddini, A and Acharya, C and Fagan, A and Sikaroodi, M and Gavis, E and McGeorge, S and Khoruts, A and Fuchs, M and Sterling, RK and Lee, H and Gillevet, PM}, title = {Multiple bacterial virulence factors focused on adherence and biofilm formation associate with outcomes in cirrhosis.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1993584}, pmid = {34743650}, issn = {1949-0984}, support = {I01 CX001076/CX/CSRD VA/United States ; R01 HS025412/HS/AHRQ HHS/United States ; R21 TR003095/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND &amp; AIMS: Altered gut microbiota is associated with poor outcomes in cirrhosis, including infections and hepatic encephalopathy (HE). However, the role of bacterial virulence factors (VFs) is unclear. Aim: Define association of VFs with cirrhosis severity and infections, their linkage with outcomes, and impact of fecal microbiota transplant (FMT).<br><br>METHODS: VF abundances were determined using metagenomic analysis in stools from controls and cirrhosis patients (compensated, HE-only, ascites-only, both and infected). Patients were followed for 90-day hospitalizations and 1-year death. Stool samples collected before/after a placebo-controlled FMT trial were also analyzed. Bacterial species and VFs for all species and selected pathogens (Escherichia, Klebsiella, Pseudomonas, Staphylococcus, Streptococcus, and Enterococcus spp) were compared between groups. Multi-variable analyses were performed for clinical biomarkers and VFs for outcome prediction. Changes in VFs pre/post-FMT and post-FMT/placebo were analyzed. Results: We included 233 subjects (40 controls, 43 compensated, 30 HE-only, 20 ascites-only, 70 both, and 30 infected). Decompensated patients, especially those with infections, had higher VFs coding for siderophores, biofilms, and adhesion factors versus the rest. Biofilm and adhesion VFs from Enterobacteriaceae and Enterococcus spp associated with death and hospitalizations independent of clinical factors regardless of when all VFs or selected pathogens were analyzed. FMT was associated with reduced VF post-FMT versus pre-FMT and post-placebo groups.<br><br>CONCLUSIONS: Virulence factors from multiple species focused on adhesion and biofilms increased with decompensation and infections, associated with death and hospitalizations independent of clinical factors, and were attenuated with FMT. Strategies focused on targeting multiple virulence factors could potentially impact outcomes in cirrhosis.<br><br>PRESENTATIONS: Portions of this manuscript were an oral presentation in the virtual International Liver Congress 2021.<br><br>ABBREVIATIONS: VF: virulence factors, HE: hepatic encephalopathy, FMT: Fecal microbiota transplant, PPI: proton pump inhibitors, LPS: lipopolysaccharides, VFDB: Virulence factor database, OTU: operational taxonomic units, SBP: spontaneous bacterial peritonitis, UTI: urinary tract infections, MRSA: methicillin resistant Staphylococcus aureus, VRE: vancomycin-resistant Enterococcus, MAAsLin2: Microbiome Multivariable Associations with Linear Models, LPS: lipopolysaccharides, AKI: acute kidney injury.}, }
@article {pmid34737978, year = {2021}, author = {Li, N and Chen, H and Cheng, Y and Xu, F and Ruan, G and Ying, S and Tang, W and Chen, L and Chen, M and Lv, L and Ping, Y and Chen, D and Wei, Y}, title = {Fecal Microbiota Transplantation Relieves Gastrointestinal and Autism Symptoms by Improving the Gut Microbiota in an Open-Label Study.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {759435}, pmid = {34737978}, issn = {2235-2988}, mesh = {*Autism Spectrum Disorder/therapy ; *Autistic Disorder ; Child ; Eubacterium ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Autism spectrum disorder (ASD) is a severe brain development disorder that is characterized by deficits in social communication and restricted, repetitive and stereotyped behaviors. Accumulating evidence has suggested that gut microbiota disorders play important roles in gastrointestinal symptoms and neurodevelopmental dysfunction in ASD patients. Manipulation of the gut microbiota by fecal microbiota transplantation (FMT) was recently shown to be a promising therapy for the treatment of various diseases. Here, we performed a clinical trial to evaluate the effect of FMT on gastrointestinal (GI) and ASD symptoms and gut microbiota alterations in children with ASD. We found that there was a large difference in baseline characteristics of behavior, GI symptoms, and gut microbiota between children with ASD and typically developing (TD) control children. FMT could improve GI symptoms and ASD symptoms without inducing any severe complications. Similarly, FMT significantly changed the serum levels of neurotransmitters. We further observed that FMT could promote the colonization of donor microbes and shift the bacterial community of children with ASD toward that of TD controls. The abundance of Eubacterium coprostanoligenes pre-FMT was positively correlated with high GSRS scores, whereas a decrease in Eubacterium coprostanoligenes abundance induced by FMT was associated with the FMT response. Our data suggest that FMT might be a promising therapeutic strategy to improve the GI and behavioral symptoms of patients with ASD, possibly due to its ability to alter gut microbiota and highlight a specific microbiota intervention that targets Eubacterium coprostanoligenes that can enhance the FMT response. This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) (trial registration number ChiCTR1800014745).}, }
@article {pmid34737977, year = {2021}, author = {Genton, L and Lazarevic, V and Stojanovic, O and Spiljar, M and Djaafar, S and Koessler, T and Dutoit, V and Gaïa, N and Mareschal, J and Macpherson, AJ and Herrmann, F and Trajkovski, M and Schrenzel, J}, title = {Metataxonomic and Metabolic Impact of Fecal Microbiota Transplantation From Patients With Pancreatic Cancer Into Germ-Free Mice: A Pilot Study.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {752889}, pmid = {34737977}, issn = {2235-2988}, mesh = {Animals ; Bacteroidetes ; Clostridiales ; *Fecal Microbiota Transplantation ; Humans ; Mice ; *Pancreatic Neoplasms ; Pilot Projects ; RNA, Ribosomal, 16S/genetics ; Veillonellaceae ; }, abstract = {Background: Body weight (BW) loss is prevalent in patients with pancreatic cancer (PC). Gut microbiota affects BW and is known to directly shape the host immune responses and antitumor immunity. This pilot study evaluated the link between gut microbiota, metabolic parameters and inflammatory/immune parameters, through the fecal material transplantation (FMT) of PC patients and healthy volunteers into germ-free (GF) mice.<br><br>Methods: We transplanted the feces from five PC patients and five age- and gender-matched healthy volunteers into two GF mice each. Mouse BW and energy intake were measured every 1-5 days, oral glucose on day 21, insulin tolerance on day 26, fecal bacterial taxonomic profile by 16S rRNA gene sequencing on day 5, 10, 15 and 30, and gut-associated lymphoid tissue T cells, plasma cytokines and weights of fat and muscle mass at sacrifice (day 34). Results are presented as mean ± SD. The continuous parameters of mice groups were compared by linear univariate regressions, and their bacterial communities by Principal Coordinates Analysis (PCoA), Bray-Curtis similarity and ANCOM test.<br><br>Results: Recipients of feces from PC patients and healthy volunteers had similar BW gain and food intake. Visceral fat was lower in recipients of feces from PC patients than from healthy individuals (0.72 ± 0.17 vs. 0.92 ± 0.14 g; coeff -0.19, 95% CI -0.38, -0.02, p=0.035). The other non-metataxonomic parameters did not differ between groups. In PCoA, microbiota from PC patients clustered apart from those of healthy volunteers and the same pattern was observed in transplanted mice. The proportions of Clostridium bolteae, Clostridium scindens, Clostridium_g24_unclassified and Phascolarctobacterium faecium were higher, while those of Alistipes obesi, Lachnospiraceae PAC000196_s and Coriobacteriaceae_unclassified species were lower in PC patients and in mice transplanted with the feces from these patients.<br><br>Conclusion: In this pilot study, FMT from PC patients was associated with a decrease in visceral fat as compared to FMT from healthy individuals. Some of the differences in fecal microbiota between PC and control samples are common to humans and mice. Further research is required to confirm that feces contain elements involved in metabolic and immune alterations.}, }
@article {pmid34737725, year = {2021}, author = {Arora, T and Tremaroli, V}, title = {Therapeutic Potential of Butyrate for Treatment of Type 2 Diabetes.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {761834}, pmid = {34737725}, issn = {1664-2392}, abstract = {Metagenomics studies have shown that type 2 diabetes (T2D) is associated with an altered gut microbiota. Whereas different microbiota patterns have been observed in independent human cohorts, reduction of butyrate-producing bacteria has consistently been found in individuals with T2D, as well as in those with prediabetes. Butyrate is produced in the large intestine by microbial fermentations, particularly of dietary fiber, and serves as primary fuel for colonocytes. It also acts as histone deacetylase inhibitor and ligand to G-protein coupled receptors, affecting cellular signaling in target cells, such as enteroendocrine cells. Therefore, butyrate has become an attractive drug target for T2D, and treatment strategies have been devised to increase its intestinal levels, for example by supplementation of butyrate-producing bacteria and dietary fiber, or through fecal microbiota transplant (FMT). In this review, we provide an overview of current literature indicating that these strategies have yielded encouraging results and short-term benefits in humans, but long-term improvements of glycemic control have not been reported so far. Further studies are required to find effective approaches to restore butyrate-producing bacteria and butyrate levels in the human gut, and to investigate their impact on glucose regulation in T2D.}, }
@article {pmid34735024, year = {2021}, author = {Waller, KMJ and Leong, RW and Paramsothy, S}, title = {An update on fecal microbiota transplantation for the treatment of gastrointestinal diseases.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.15731}, pmid = {34735024}, issn = {1440-1746}, abstract = {Our understanding of the microbiome and its implications for human health and disease continues to develop. Fecal microbiota transplantation (FMT) is now an established treatment for recurrent Clostridioides difficile infection. There is also increasing evidence for the efficacy of FMT in inducing remission for mild-moderate ulcerative colitis. However, for other indications, data for FMT are limited, with randomized controlled trials rare, typically small and often conflicting. Studies are continuing to explore the role of FMT for many other conditions, including Crohn's disease, functional gut disorders, metabolic syndrome, modulating responses to chemotherapy, eradication of multidrug resistant organisms, and the gut-brain axis. In light of safety, logistical, and regulatory challenges, there is a move to standardized products including narrow spectrum consortia. However, the mechanisms underpinning FMT remain incompletely understood, including the role of non-bacterial components, which may limit success of novel microbial approaches.}, }
@article {pmid34734433, year = {2021}, author = {Suk, KT and Koh, H}, title = {A New Perspective on Fecal Microbiota Transplantation in Liver Diseases.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.15729}, pmid = {34734433}, issn = {1440-1746}, abstract = {Chronic liver disease including non-alcoholic fatty liver disease and alcohol-related liver disease is one of the most common diseases worldwide. The gut-liver axis plays an important role in the pathogenesis of liver disease. Small intestinal bacterial overgrowth, dysbiosis, leaky bowel, bacterial translocation, and imbalanced metabolites are related to the progression of chronic liver disease. Recently, novel therapeutic approaches for microbiota-modulation such as personalized diet, probiotics, prebiotics, antibiotics, engineered microbiotas, phage therapy, stomach operation and fecal microbial transplantation (FMT) have been proposed with numerous promising results in the effectiveness and clinical application. Although the evidence is still lacking, FMT, a type of fecal bacteriotherapy, has been known as a candidate for the treatment of liver disease. This review article focuses on the most recent advances in our understanding of FMT in chronic liver disease such as non-alcoholic and alcohol-related liver disease.}, }
@article {pmid34734369, year = {2021}, author = {An, L and Wirth, U and Koch, D and Schirren, M and Drefs, M and Koliogiannis, D and Nieß, H and Andrassy, J and Guba, M and Bazhin, AV and Werner, J and Kühn, F}, title = {The Role of Gut-Derived Lipopolysaccharides and the Intestinal Barrier in Fatty Liver Diseases.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {}, number = {}, pages = {}, pmid = {34734369}, issn = {1873-4626}, abstract = {BACKGROUND: Hepatosteatosis is the earliest stage in the pathogenesis of nonalcoholic fatty (NAFLD) and alcoholic liver disease (ALD). As NAFLD is affecting 10-24% of the general population and approximately 70% of obese patients, it carries a large economic burden and is becoming a major reason for liver transplantation worldwide. ALD is a major cause of morbidity and mortality causing 50% of liver cirrhosis and 10% of liver cancer related death. Increasing evidence has accumulated that gut-derived factors play a crucial role in the development and progression of chronic liver diseases.<br><br>METHODS: A selective literature search was conducted in Medline and PubMed, using the terms "nonalcoholic fatty liver disease," "alcoholic liver disease," "lipopolysaccharide," "gut barrier," and "microbiome."<br><br>RESULTS: Gut dysbiosis and gut barrier dysfunction both contribute to chronic liver disease by abnormal regulation of the gut-liver axis. Thereby, gut-derived lipopolysaccharides (LPS) are a key factor in inducing the inflammatory response of liver tissue. The review further underlines that endotoxemia is observed in both NAFLD and ALD patients. LPS plays an important role in conducting liver damage through the LPS-TLR4 signaling pathway. Treatments targeting the gut microbiome and the gut barrier such as fecal microbiota transplantation (FMT), probiotics, prebiotics, synbiotics, and intestinal alkaline phosphatase (IAP) represent potential treatment modalities for NAFLD and ALD.<br><br>CONCLUSIONS: The gut-liver axis plays an important role in the development of liver disease. Treatments targeting the gut microbiome and the gut barrier have shown beneficial effects in attenuating liver inflammation and need to be further investigated.}, }
@article {pmid34733783, year = {2021}, author = {Zhang, W and An, Y and Qin, X and Wu, X and Wang, X and Hou, H and Song, X and Liu, T and Wang, B and Huang, X and Cao, H}, title = {Gut Microbiota-Derived Metabolites in Colorectal Cancer: The Bad and the Challenges.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {739648}, pmid = {34733783}, issn = {2234-943X}, abstract = {Accumulating evidence from studies in humans and animal models has elucidated that gut microbiota, acting as a complex ecosystem, contributes critically to colorectal cancer (CRC). The potential mechanisms often reported emphasize the vital role of carcinogenic activities of specific pathogens, but in fact, a series of metabolites produced from exogenous dietary substrates or endogenous host compounds occupy a decisive position similarly. Detrimental gut microbiota-derived metabolites such as trimethylamine-N-oxide, secondary bile acids, hydrogen sulfide and N-nitroso compounds could reconstruct the ecological composition and metabolic activity of intestinal microorganisms and formulate a microenvironment that opens susceptibility to carcinogenic stimuli. They are implicated in the occurrence, progression and metastasis of CRC through different mechanisms, including inducing inflammation and DNA damage, activating tumorigenic signaling pathways and regulating tumor immunity. In this review, we mainly summarized the intimate relationship between detrimental gut microbiota-derived metabolites and CRC, and updated the current knowledge about detrimental metabolites in CRC pathogenesis. Then, multiple interventions targeting these metabolites for CRC management were critically reviewed, including diet modulation, probiotics/prebiotics, fecal microbiota transplantation, as well as more precise measures such as engineered bacteria, phage therapy and chemopreventive drugs. A better understanding of the interplay between detrimental microbial metabolites and CRC would hold great promise against CRC.}, }
@article {pmid34733507, year = {2021}, author = {Sahitya, DSK and Jandiyal, A and Jain, A and Senapati, J and Nanda, S and Aggarwal, M and Kumar, P and Mohapatra, S and Ray, P and Malhotra, P and Mahapatra, M and Dhawan, R}, title = {Prevention and management of carbapenem-resistant Enterobacteriaceae in haematopoietic cell transplantation.}, journal = {Therapeutic advances in infectious disease}, volume = {8}, number = {}, pages = {20499361211053480}, pmid = {34733507}, issn = {2049-9361}, abstract = {Carbapenem-resistant Enterobacteriaceae (CRE) infections are associated with high morbidity and mortality rates in haematopoietic cell transplantation (HCT) recipients. Factors like mucositis, neutropenia, prolonged hospital stay, and frequent use of prophylactic antimicrobials make HCT recipients especially susceptible to CRE infections. Low culture positivity rates, delay in microbiological diagnosis, and resistance to empirical antimicrobial therapy for febrile neutropenia are responsible for high mortality rates in HCT recipients infected with CRE. In this review we discuss the epidemiology, diagnosis, and management of CRE infections with particular emphasis on patients undergoing HCT. We emphasise the need for preventive strategies like multidisciplinary antimicrobial stewardship, and pre-emptive screening for CRE colonisation in prospective HCT patients as measures to mitigate the adverse impact of CRE on HCT outcomes. Newer diagnostic tests like polymerase chain reaction and matrix-assisted laser desorption ionisation-time of flight (MALDI-TOF) assay that enable earlier and better identification of CRE isolates are discussed. Antimicrobial agents available against CRE, including newer agents like ceftazidime-avibactam and meropenem-vaborbactam, have been reviewed. We also discuss the data on promising experimental treatments against CRE: phage therapy and healthy donor faecal microbiota transplant. Finally, this review puts forth recommendations as per existing literature on diagnosis and management of CRE infections in blood and marrow transplant (BMT) unit.}, }
@article {pmid34731398, year = {2021}, author = {Davrandi, M and Harris, S and Smith, PJ and Murray, CD and Lowe, DM}, title = {The Relationship Between Mucosal Microbiota, Colitis, and Systemic Inflammation in Chronic Granulomatous Disorder.}, journal = {Journal of clinical immunology}, volume = {}, number = {}, pages = {}, pmid = {34731398}, issn = {1573-2592}, support = {Grants 1915//BC Children's Hospital Foundation/ ; 1920//BC Children's Hospital Foundation/ ; BRC299/III/DL/101350//UCLH Biomedical Research Centre/ ; }, abstract = {PURPOSE: Chronic granulomatous disorder (CGD) is a primary immunodeficiency which is frequently complicated by inflammatory colitis and is associated with systemic inflammation. Herein, we aimed to investigate the role of the microbiome in the pathogenesis of colitis and systemic inflammation.<br><br>METHODS: We performed 16S rDNA sequencing on mucosal biopsy samples from each segment of 10 CGD patients' colons and conducted compositional and functional pathway prediction analyses.<br><br>RESULTS: The microbiota in samples from colitis patients demonstrated reduced taxonomic alpha-diversity compared to unaffected patients, even in apparently normal bowel segments. Functional pathway richness was similar between the colitic and non-colitic mucosa, although metabolic pathways involved in butyrate biosynthesis or utilization were enriched in patients with colitis and correlated positively with fecal calprotectin levels. One patient with very severe colitis was dominated by Enterococcus spp., while among other patients Bacteroides spp. abundance correlated with colitis severity measured by fecal calprotectin and an endoscopic severity score. In contrast, Blautia abundance is associated with low severity scores and mucosal health. Several taxa and functional pathways correlated with concentrations of inflammatory cytokines in blood but not with colitis severity. Notably, dividing patients into "high" and "low" systemic inflammation groups demonstrated clearer separation than on the basis of colitis status in beta-diversity analyses.<br><br>CONCLUSION: The microbiome is abnormal in CGD-associated colitis and altered functional characteristics probably contribute to pathogenesis. Furthermore, the relationship between the mucosal microbiome and systemic inflammation, independent of colitis status, implies that the microbiome in CGD can influence the inflammatory phenotype of the condition.}, }
@article {pmid34724447, year = {2021}, author = {Kellermayer, R and Wu, Q and Nagy-Szakal, D and Queliza, K and Ihekweazu, FD and Bocchini, CE and Magee, AR and Oezguen, N and Spinler, JK and Hollister, EB and Shulman, RJ and Versalovic, J and Luna, RA and Savidge, TC}, title = {Fecal Microbiota Transplantation Commonly Failed in Children with Co-Morbidities.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1097/MPG.0000000000003336}, pmid = {34724447}, issn = {1536-4801}, support = {K24 AI121296/AI/NIAID NIH HHS/United States ; P01 AI152999/AI/NIAID NIH HHS/United States ; U01 AI124290/AI/NIAID NIH HHS/United States ; }, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) is arguably the most effective treatment for recurrent Clostridioides difficile infection (rCDI). Clinical reports on pediatric FMT have not systematically evaluated microbiome restoration in patients with co-morbidities. Here we determined whether FMT recipient age and underlying co-morbidity influenced clinical outcomes and microbiome restoration when treated from shared fecal donor sources.<br><br>METHODS: Eighteen rCDI patients participating in a single-center, open-label prospective cohort study received fecal preparation from a self-designated (single case) or two universal donors. Twelve age-matched healthy children and 4 pediatric ulcerative colitis (UC) cases from an independent serial FMT trial, but with a shared fecal donor were examined as controls for microbiome restoration using 16S rRNA gene sequencing of longitudinal fecal specimens.<br><br>RESULTS: FMT was significantly more effective in rCDI recipients without underlying chronic co-morbidities where fecal microbiome composition in post-transplant responders was restored to levels of healthy children. Microbiome reconstitution was not associated with symptomatic resolution in some rCDI patients who had co-morbidities. Significant elevation in Bacteroidaceae, Bifidobacteriaceae, Lachnospiraceae, Ruminococcaceae and Erysipelotrichaceae was consistently observed in pediatric rCDI responders, while Enterobacteriaceae decreased, correlating with augmented complex carbohydrate degradation capacity.<br><br>CONCLUSION: Recipient background disease was a significant risk factor influencing FMT outcomes. Special attention should be taken when considering FMT for pediatric rCDI patients with underlying co-morbidities.}, }
@article {pmid34722332, year = {2021}, author = {Chen, T and Wang, R and Duan, Z and Yuan, X and Ding, Y and Feng, Z and Bu, F and Liu, L and Wang, Q and Zhou, J and Zhu, L and Ni, Q and Shi, G and Chen, Y}, title = {Akkermansia muciniphila Protects Against Psychological Disorder-Induced Gut Microbiota-Mediated Colonic Mucosal Barrier Damage and Aggravation of Colitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {723856}, pmid = {34722332}, issn = {2235-2988}, mesh = {Akkermansia ; Animals ; *Colitis ; *Gastrointestinal Microbiome ; Humans ; Mice ; Verrucomicrobia ; }, abstract = {Psychological disorders are associated with increased risk of severe inflammatory bowel disease (IBD) by causing gut microbiota dysbiosis and colonic mucosal barrier damage. However, the interaction between chronic restraint stress (CRS), gut microbiota composition, and colonic mucus remains unclear. We demonstrated that mice under CRS conditions exhibited alterations in microbiota composition, disruption of colonic mucus, and aggravation of colitis. In addition, the abundance of Akkermansia muciniphila was significantly decreased in mice under CRS and UC patients with depression, and positively associated with the expression of MUC2. After antibiotic treatment, the recipient mice colonized with CRS microbiota showed barrier defects and severe colitis. Administration of Akkermansia muciniphila was found to restore colonic mucus and modify the gut microbiota. We confirm that CRS-mediated gut microbiota dysbiosis results in colonic mucosal barrier damage and aggravation of colitis. Our results suggest that A. muciniphila is expected to be a potential probiotic to protect and treat colonic mucus that is involved in IBD with psychological disorders.}, }
@article {pmid34721980, year = {2021}, author = {Ma, S and Wang, N and Zhang, P and Wu, W and Fu, L}, title = {Fecal microbiota transplantation mitigates bone loss by improving gut microbiome composition and gut barrier function in aged rats.}, journal = {PeerJ}, volume = {9}, number = {}, pages = {e12293}, pmid = {34721980}, issn = {2167-8359}, abstract = {Background: Gut microbiota (GM) dysbiosis is closely related to bone loss and the occurrence of osteoporosis in animals and human. However, little is known about the effect and the mechanisms of fecal microbiota transplantation (FMT) on bone in the treatment of senile osteoporosis.<br><br>Methods: Aged female rats were randomly divided into the FMT group and the control group. 3-month-old female rats were used as fecal donors. The rats were sacrificed at 12 and 24 weeks following transplantation and the serum, intestine, bone, and feces were collected for subsequent analyses.<br><br>Results: The bone turnover markers of osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), and carboxy-terminal peptide (CTX) decreased significantly at 12 and 24 weeks following FMT (P < 0.05). At 12 weeks following transplantation, histomorphometric parameters including the bone volume (BV), trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) of the FMT group were comparable to the control group. However, at 24 weeks following transplantation, these parameters of the FMT group were significantly higher than those of the control group (P < 0.05). Besides, the GM aggregated at 12 and 24 weeks following FMT, and the ecological distance was close between the rats in the FMT group and the donor rats. Alpha diversity, shown by the Shannon index and Simpson index, and the Firmicutes/Bacteroidetes ratio decreased significantly after FMT at 24 weeks. Furthermore, FMT restored the GM composition in aged rats at the phylum and family level, and the intestinal microbiota of the aged rats was similar to that of the donor rats. Correlation network analysis indirectly suggested the causality of FMT on alleviating osteoporosis. FMT improved the intestinal structure and up-regulated the expression of tight junction proteins of occludin, claudin, and ZO-1, which might be associated with the protective effects of FMT on bone.<br><br>Conclusions: GM transplanted from young rats alleviated bone loss in aged rats with senile osteoporosis by improving gut microbiome composition and intestinal barrier function. These data might provide a scientific basis for future clinical treatment of osteoporosis through FMT.}, }
@article {pmid34721757, year = {2021}, author = {Hong, MK and Liu, HH and Chen, GH and Zhu, JQ and Zheng, SY and Zhao, D and Diao, J and Jia, H and Zhang, DD and Chen, SX and Gao, L and Li, J}, title = {Oridonin Alters Hepatic Urea Cycle via Gut Microbiota and Protects against Acetaminophen-Induced Liver Injury.}, journal = {Oxidative medicine and cellular longevity}, volume = {2021}, number = {}, pages = {3259238}, pmid = {34721757}, issn = {1942-0994}, abstract = {Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the western world. Oridonin (OD), which is the major active ingredient of the traditional Chinese medicine Rabdosia rubescens, reportedly exerts anti-inflammatory and antioxidative effects. Here, we first find that OD protects against APAP-induced hepatotoxicity. The results of hepatic tissue-associated RNA-seq and metabolomics showed that the protective effects of OD were dependent upon urea cycle regulation. And such regulation of OD is gut microbiota partly dependent, as demonstrated by fecal microbiota transplantation (FMT). Furthermore, using 16S rRNA sequencing, we determined that OD significantly enriched intestinal Bacteroides vulgatus, which activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to regulate redox homeostasis against APAP by urea cycle. In conclusion, our study suggests that the Bacteroides vulgatus-urea cycle-Nrf2 axis may be a potential target for reducing APAP-induced liver injury, which is altered by OD.}, }
@article {pmid34721365, year = {2021}, author = {Zhong, Y and Cao, J and Deng, Z and Ma, Y and Liu, J and Wang, H}, title = {Effect of Fiber and Fecal Microbiota Transplantation Donor on Recipient Mice Gut Microbiota.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {757372}, pmid = {34721365}, issn = {1664-302X}, abstract = {Both fecal microbiota transplantation (FMT) and dietary fiber intervention were verified as effective ways to manipulate the gut microbiota, whereas little is known about the influence of the combined methods on gut microbiota. Here, we constructed "non-industrialized" and "industrialized" gut microbiota models to investigate the donor effect of FMT and diet effect in shaping the gut microbiota. Mice were transplanted fecal microbiota from domestic pig and received a diet with low-fiber (D) or high-fiber (DF), whereas the other two groups were transplanted fecal microbiota from wild pig and then received a diet with low-fiber (W) or high-fiber (WF), respectively. Gut microbiota of WF mice showed a lower Shannon and Simpson index (P < 0.05), whereas gut microbiota of W mice showed no significant difference than that of D and DF mice. Random forest models revealed the major differential bacteria genera between four groups, including Anaeroplasma or unclassified_o_Desulfovibrionales, which were influenced by FMT or diet intervention, respectively. Besides, we found a lower out-of-bag rate in the random forest model constructed for dietary fiber (0.086) than that for FMT (0.114). Linear discriminant analysis effective size demonstrated that FMT combined with dietary fiber altered specific gut microbiota, including Alistipes, Clostridium XIVa, Clostridium XI, and Akkermansia, in D, DF, W, and WF mice, respectively. Our results revealed that FMT from different donors coupled with dietary fiber intervention could lead to different patterns of gut microbiota composition, and dietary fiber might play a more critical role in shaping gut microbiota than FMT donor. Strategies based on dietary fiber can influence the effectiveness of FMT in the recipient.}, }
@article {pmid34712743, year = {2021}, author = {Niu, M and Chen, P}, title = {Crosstalk between gut microbiota and sepsis.}, journal = {Burns &amp; trauma}, volume = {9}, number = {}, pages = {tkab036}, pmid = {34712743}, issn = {2321-3868}, abstract = {Sepsis is an overwhelming inflammatory response to microbial infection. Sepsis management remains a clinical challenge. The role of the gut microbiome in sepsis has gained some attention. Recent evidence has demonstrated that gut microbiota regulate host physiological homeostasis mediators, including the immune system, gut barrier function and disease susceptibility pathways. Therefore, maintenance or restoration of microbiota and metabolite composition might be a therapeutic or prophylactic target against critical illness. Fecal microbiota transplantation and supplementation of probiotics are microbiota-based treatment methods that are somewhat limited in terms of evidence-based efficacy. This review focuses on the importance of the crosstalk between the gastrointestinal ecosystem and sepsis to highlight novel microbiota-targeted therapies to improve the outcomes of sepsis treatment.}, }
@article {pmid34712655, year = {2021}, author = {Zhou, J and Hou, C and Chen, H and Qin, Z and Miao, Z and Zhao, J and Wang, Q and Cui, M and Xie, C and Wang, R and Li, Q and Zuo, G and Miao, D and Jin, J}, title = {P16 I NK 4a Deletion Ameliorates Damage of Intestinal Epithelial Barrier and Microbial Dysbiosis in a Stress-Induced Premature Senescence Model of Bmi-1 Deficiency.}, journal = {Frontiers in cell and developmental biology}, volume = {9}, number = {}, pages = {671564}, pmid = {34712655}, issn = {2296-634X}, abstract = {This study aimed to determine whether Bmi-1 deficiency leads to intestinal epithelial barrier destruction and microbiota dysfunction, which members of the microbial community alter barrier function with age, and whether p16 INK4a deletion could reverse the damage of intestinal epithelial barrier and microbial dysbiosis. Intestines from Bmi-1-deficient (Bmi-1-/-), Bmi-1 and p16 INK4a double-knockout (Bmi-1-/-p16 INK4a-/-), and wild-type mice were observed for aging and inflammation. Duolink Proximity Ligation Assay, immunoprecipitation, and construction of p16 INK4a overexpressed adenovirus and the overexpressed plasmids of full-length, mutant, or truncated fragments for occludin were used for analyzing the interaction between p16 INK4a and occludin. High-throughput sequencing of V4 region amplicon of 16S ribosomal RNA was conducted using intestinal microbiota. We found Bmi-1 deficiency destructed barrier structure, barrier function, and tight junction (TJ) in intestinal epithelium; decreased the TJ proteins; increased tumor necrosis factor α (TNF-α)-dependent barrier permeability; and up-regulated proinflammatory level of macrophages induced by intestinal microbial dysbiosis. The transplantation of fecal microbiota from wild-type mice ameliorated TJ in intestinal epithelium of Bmi-1-/- and Bmi-1-/-p16 INK4a-/- mice. Harmful bacteria including Desulfovibrio, Helicobacter, and Oscillibacter were at a higher level in Bmi-1-/- mice. More harmful bacteria Desulfovibrio entered the epithelium and promoted macrophages-secreted TNF-α and caused TNF-α-dependent barrier permeability and aging. Accumulated p16 INK4a combined with occludin at the 1st-160th residue in cytoplasm of intestinal epithelium cells from Bmi-1-/- mice, which blocked formation of TJ and the repair of intestinal epithelium barrier. P16 INK4a deletion could maintain barrier function and microbiota balance in Bmi-1-/- mice through strengthening formation of TJ and decreasing macrophages-secreted TNF-α induced by Desulfovibrio entering the intestinal epithelium. Thus, Bmi-1 maintained intestinal TJ, epithelial barrier function, and microbiota balance through preventing senescence characterized by p16 INK4a accumulation. The clearance of p16 INK4a -positive cells in aging intestinal epithelium would be a new method for maintaining barrier function and microbiota balance. The residues 1-160 of occludin could be a novel therapeutic target for identifying small molecular antagonistic peptides to prevent the combination of p16 INK4a with occludin for protecting TJ.}, }
@article {pmid34712223, year = {2021}, author = {Lauriero, G and Abbad, L and Vacca, M and Celano, G and Chemouny, JM and Calasso, M and Berthelot, L and Gesualdo, L and De Angelis, M and Monteiro, RC}, title = {Fecal Microbiota Transplantation Modulates Renal Phenotype in the Humanized Mouse Model of IgA Nephropathy.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {694787}, pmid = {34712223}, issn = {1664-3224}, abstract = {Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis. Several observations suggest that gut microbiota could be implicated in IgAN pathophysiology. Aiming at exploring whether microbiota modulation is able to influence disease outcome, we performed fecal microbiota transplantation (FMT) from healthy controls (HC-sbjs), non-progressor (NP-pts) and progressor (P-pts) IgAN patients to antibiotic-treated humanized IgAN mice (α1KI-CD89Tg), by oral gavage. FMT was able to modulate renal phenotype and inflammation. On one hand, the microbiota from P-pts was able to induce an increase of serum BAFF and galactose deficient-IgA1 levels and a decrease of CD89 cell surface expression on blood CD11b+ cells which was associated with soluble CD89 and IgA1 mesangial deposits. On the other hand, the microbiota from HC-sbjs was able to induce a reduction of albuminuria immediately after gavage, an increased cell surface expression of CD89 on blood CD11b+ cells and a decreased expression of KC chemokine in kidney. Higher serum BAFF levels were found in mice subjected to FMT from IgAN patients. The main bacterial phyla composition and volatile organic compounds profile significantly differed in mouse gut microbiota. Microbiota modulation by FMT influences IgAN phenotype opening new avenues for therapeutic approaches in IgAN.}, }
@article {pmid34711461, year = {2021}, author = {Lythgoe, MP and Ghani, R and Mullish, BH and Marchesi, JR and Krell, J}, title = {The potential of fecal microbiota transplantation in oncology.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2021.10.003}, pmid = {34711461}, issn = {1878-4380}, abstract = {Immune checkpoint inhibitors (ICPIs) are efficacious treatments for several cancers. However, most patients fail to demonstrate durable complete responses. The gut microbiome composition influences the ICPI response. Two recent proof-of-concept studies have demonstrated the utility of fecal microbiota transplantation to transform ICPI responsiveness in refractory patients, providing intriguing evidence for the future of microbiota modulation within oncology.}, }
@article {pmid34709989, year = {2021}, author = {Ianiro, G and Bibbò, S and Porcari, S and Settanni, CR and Giambò, F and Curta, AR and Quaranta, G and Scaldaferri, F and Masucci, L and Sanguinetti, M and Gasbarrini, A and Cammarota, G}, title = {Fecal microbiota transplantation for recurrent C. difficile infection in patients with inflammatory bowel disease: experience of a large-volume European FMT center.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1994834}, pmid = {34709989}, issn = {1949-0984}, abstract = {Inflammatory bowel disease (IBD) is a risk factor for C. difficile infection (CDI), which, in turn, complicates the clinical course of IBD. Fecal microbiota transplantation (FMT) is safe and effective in patients with IBD and recurrent CDI (rCDI). In our study, patients with IBD and rCDI received FMT by colonoscopy and were followed-up for 8 weeks. The primary outcome was negative C. difficile toxin 8 weeks after FMT. Eighteen patients with IBD were enrolled. Eight patients received sequential FMT either for pseudomembranous colitis or failure of single fecal infusion. At 8-week follow-up the C. difficile toxin was negative in 17 patients, and most (83%) experienced also improvement of IBD disease activity. Overall, we did not observe any serious adverse event.FMT appears to be highly effective and safe in patients with IBD and rCDI and is likely not only to eradicate CDI but also to improve disease activity of IBD.}, }
@article {pmid34708542, year = {2021}, author = {Xie, J and Li, LF and Dai, TY and Qi, X and Wang, Y and Zheng, TZ and Gao, XY and Zhang, YJ and Ai, Y and Ma, L and Chang, SL and Luo, FX and Tian, Y and Sheng, J}, title = {Short-Chain Fatty Acids Produced by Ruminococcaceae Mediate α-Linolenic Acid Promote Intestinal Stem Cells Proliferation.}, journal = {Molecular nutrition &amp; food research}, volume = {}, number = {}, pages = {e2100408}, doi = {10.1002/mnfr.202100408}, pmid = {34708542}, issn = {1613-4133}, abstract = {SCOPE: The proliferation and differentiation of intestinal stem cells (ISCs) are the basis of intestinal renewal and regeneration, and gut microbiota plays an important role in it. Dietary nutrition has the effect of regulating the activity of ISCs; however, the regulation effect of α-linolenic acid (ALA) has seldom been reported.<br><br>METHODS AND RESULTS: After intervening mice with different doses of ALA for 30 days, it is found that ALA (0.5 g kg-1) promotes small intestinal and villus growth by activating the Wnt/β-catenin signaling pathway to stimulate the proliferation of ISCs. Furthermore, ALA administration increases the abundance of the Ruminococcaceae and Prevotellaceae, and promotes the production of short-chain fatty acids (SCFAs). Subsequent fecal transplantation and antibiotic experiments demonstrate that ALA on the proliferation of ISCs are gut microbiota dependent, among them, the functional microorganism may be derived from Ruminococcaceae. Administration of isobutyrate shows a similar effect to ALA in terms of promoting ISCs proliferation. Furthermore, ALA mitigates 5-fluorouracil-induced intestinal mucosal damage by promoting ISCs proliferation.<br><br>CONCLUSION: These results indicate that SCFAs produced by Ruminococcaceae mediate ALA promote ISCs proliferation by activating the Wnt/β-catenin signaling pathway, and suggest the possibility of ALA as a prebiotic agent for the prevention and treatment of intestinal mucositis.}, }
@article {pmid34706782, year = {2021}, author = {Lin, D and Hu, B and Li, P and Zhao, Y and Xu, Y and Wu, D}, title = {Roles of the intestinal microbiota and microbial metabolites in acute GVHD.}, journal = {Experimental hematology &amp; oncology}, volume = {10}, number = {1}, pages = {49}, pmid = {34706782}, issn = {2162-3619}, support = {BE2019655//social development project of jiangsu province/ ; BE2019798//jiangsu province key r&amp;d program/ ; 2019YFC0840604//national key research and development program/ ; 82020108003//national natural science foundation of china/ ; 82070187//national natural science foundation of china/ ; }, abstract = {Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most curative strategies for the treatment of many hematologic malignancies and diseases. However, acute graft-versus-host disease (GVHD) limits the success of allo-HSCT. The prevention and treatment of acute GVHD is the key issue for improving the efficacy of allo-HSCT and has become a research hotspot. The intestine is the primary organ targeted by acute GVHD, and the intestinal microbiota is critical for maintaining the homeostasis of the intestinal microenvironment and the immune response. Many studies have demonstrated the close association between the intestinal microbiota and the pathogenesis of acute GVHD. Furthermore, dysbiosis of the microbiota, which manifests as alterations in the diversity and composition of the intestinal microbiota, and alterations of microbial metabolites are pronounced in acute GVHD and associated with poor patient prognosis. The microbiota interacts with the host directly via microbial surface antigens or microbiota-derived metabolites to regulate intestinal homeostasis and the immune response. Therefore, intervention strategies targeting the intestinal microbiota, including antibiotics, prebiotics, probiotics, postbiotics and fecal microbiota transplantation (FMT), are potential new treatment options for acute GVHD. In this review, we discuss the alterations and roles of the intestinal microbiota and its metabolites in acute GVHD, as well as interventions targeting microbiota for the prevention and treatment of acute GVHD.}, }
@article {pmid34704776, year = {2021}, author = {Jan, N and Hays, RA and Oakland, DN and Kumar, P and Ramakrishnan, G and Behm, BW and Petri, WA and Marie, C}, title = {Fecal Microbiota Transplantation Increases Colonic IL-25 and Dampens Tissue Inflammation in Patients with Recurrent Clostridioides difficile.}, journal = {mSphere}, volume = {6}, number = {5}, pages = {e0066921}, pmid = {34704776}, issn = {2379-5042}, support = {R01 AI124214/AI/NIAID NIH HHS/United States ; R01 AI148518/AI/NIAID NIH HHS/United States ; R01 AI152477/AI/NIAID NIH HHS/United States ; }, abstract = {Clostridioides difficile infection (CDI) is the most common hospital-acquired infection in the United States. Antibiotic-induced dysbiosis is the primary cause of susceptibility, and fecal microbiota transplantation (FMT) has emerged as an effective therapy for recurrence. We previously demonstrated in the mouse model of CDI that antibiotic-induced dysbiosis reduced colonic expression of interleukin 25 (IL-25) and that FMT protected in part by restoring IL-25 signaling. Here, we conducted a prospective study in humans to test if FMT induced IL-25 expression in the colons of patients with recurrent CDI (rCDI). Colonic biopsy specimens and blood were collected at the time of FMT and 60 days later. Colon biopsy specimens were analyzed for IL-25 protein levels, total tissue transcriptome, and epithelium-associated microbiota before and after FMT, and peripheral immune cells were immunophenotyped. FMT increased alpha diversity of the colonic microbiota and levels of IL-25 in colonic tissue. In addition, FMT increased expression of homeostatic genes and repressed inflammatory genes. Finally, circulating Th17 cells were decreased post-FMT. The increase in levels of the cytokine IL-25 accompanied by decreased inflammation is consistent with FMT acting in part to protect from recurrent CDI via restoration of commensal activation of type 2 immunity. IMPORTANCE Fecal microbiota transplantation (FMT) is an effective treatment for C. difficile infection for most patients; however, introducing a complex mixture of microbes also has had unintended consequences for some patients. Attempts to create a standardized probiotic therapeutic that recapitulates the efficacy of FMT have been unsuccessful to date. We sought to understand what immune markers are changed in patients undergoing FMT to treat recurrent C. difficile infection and identified an immune signaling molecule, IL-25, that was restored by FMT. This finding indicates that adjunctive therapy with IL-25 could be useful in treating C. difficile infection.}, }
@article {pmid34699042, year = {2021}, author = {Mehmood, K and Moin, A and Hussain, T and Rizvi, SMD and Gowda, DV and Shakil, S and Kamal, MA}, title = {Can manipulation of gut microbiota really be transformed into an intervention strategy for cardiovascular disease management?.}, journal = {Folia microbiologica}, volume = {66}, number = {6}, pages = {897-916}, pmid = {34699042}, issn = {1874-9356}, mesh = {*Cardiovascular Diseases/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics ; *Synbiotics ; }, abstract = {Recent advancement in manipulation techniques of gut microbiota either ex vivo or in situ has broadened its plausible applicability for treating various diseases including cardiovascular disease. Several reports suggested that altering gut microbiota composition is an effective way to deal with issues associated with managing cardiovascular diseases. However, actual translation of gut microbiota manipulation-based techniques into cardiovascular-therapeutic approach is still questionable. This review summarized the evidence on challenges, opportunities, recent development, and future prospects of gut microbiota manipulation for targeting cardiovascular diseases. Initially, issues associated with current cardiovascular diseases treatment strategy, association of gut microbiota with cardiovascular disease, and its influence on cardiovascular drugs were discussed, followed by applicability of gut microbiota manipulation as a cardiovascular disease intervention strategy along with its challenges and future prospects. Despite the fact that the gut microbiota is rugged, interventions like probiotics, prebiotics, synbiotics, fecal microbiota transplantation, fecal virome transplantation, antibiotics, diet changes, and exercises could manipulate it. Advanced techniques like administration of engineered bacteriophages and bacteria could also be employed. Intensive exploration revealed that if sufficiently controlled approach and proper monitoring were applied, gut microbiota could provide a compelling answer for cardiovascular therapy.}, }
@article {pmid34696775, year = {2021}, author = {Li, N and Dai, Z and Wang, Z and Deng, Z and Zhang, J and Pu, J and Cao, W and Pan, T and Zhou, Y and Yang, Z and Li, J and Li, B and Ran, P}, title = {Gut microbiota dysbiosis contributes to the development of chronic obstructive pulmonary disease.}, journal = {Respiratory research}, volume = {22}, number = {1}, pages = {274}, pmid = {34696775}, issn = {1465-993X}, abstract = {BACKGROUND: Dysbiosis of the gut microbiome is involved in the pathogenesis of various diseases, but the contribution of gut microbes to the progression of chronic obstructive pulmonary disease (COPD) is still poorly understood.<br><br>METHODS: We carried out 16S rRNA gene sequencing and short-chain fatty acid analyses in stool samples from a cohort of 73 healthy controls, 67 patients with COPD of GOLD stages I and II severity, and 32 patients with COPD of GOLD stages III and IV severity. Fecal microbiota from the three groups were then inoculated into recipient mice for a total of 14 times in 28 days to induce pulmonary changes. Furthermore, fecal microbiota from the three groups were inoculated into mice exposed to smoke from biomass fuel to induce COPD-like changes.<br><br>RESULTS: We observed that the gut microbiome of COPD patients varied from that of healthy controls and was characterized by a distinct overall microbial diversity and composition, a Prevotella-dominated gut enterotype and lower levels of short-chain fatty acids. After 28 days of fecal transplantation from COPD patients, recipient mice exhibited elevated lung inflammation. Moreover, when mice were under both fecal transplantation and biomass fuel smoke exposure for a total of 20 weeks, accelerated declines in lung function, severe emphysematous changes, airway remodeling and mucus hypersecretion were observed.<br><br>CONCLUSION: These data demonstrate that altered gut microbiota in COPD patients is associated with disease progression in mice model.}, }
@article {pmid34691318, year = {2021}, author = {Alagiakrishnan, K and Halverson, T}, title = {Microbial Therapeutics in Neurocognitive and Psychiatric Disorders.}, journal = {Journal of clinical medicine research}, volume = {13}, number = {9}, pages = {439-459}, pmid = {34691318}, issn = {1918-3003}, abstract = {Microbial therapeutics, which include gut biotics and fecal transplantation, are interventions designed to improve the gut microbiome. Gut biotics can be considered as the administration of direct microbial populations. The delivery of this can be done through live microbial flora, certain food like fiber, microbial products (metabolites and elements) obtained through the fermentation of food products, or as genetically engineered substances, that may have therapeutic benefit on different health disorders. Dietary intervention and pharmacological supplements with gut biotics aim at correcting disruption of the gut microbiota by repopulating with beneficial microorganism leading to decrease in gut permeability, inflammation, and alteration in metabolic activities, through a variety of mechanisms of action. Our understanding of the pharmacokinetics of microbial therapeutics has improved with in vitro models, sampling techniques in the gut, and tools for the reliable identification of gut biotics. Evidence from human studies points out that prebiotics, probiotics and synbiotics have the potential for treating and preventing mental health disorders, whereas with paraprobiotics, proteobiotics and postbiotics, the research is limited at this point. Some animal studies point out that gut biotics can be used with conventional treatments for a synergistic effect on mental health disorders. If future research shows that there is a possibility of synergistic effect of psychotropic medications with gut biotics, then a gut biotic or nutritional prescription can be given along with psychotropics. Even though the overall safety of gut biotics seems to be good, caution is needed to watch for any known and unknown side effects as well as the need for risk benefit analysis with certain vulnerable populations. Future research is needed before wide spread use of natural and genetically engineered gut biotics. Regulatory framework for gut biotics needs to be optimized. Holistic understanding of gut dysbiosis, along with life style factors, by health care providers is necessary for the better management of these conditions. In conclusion, microbial therapeutics are a new psychotherapeutic approach which offer some hope in certain conditions like dementia and depression. Future of microbial therapeutics will be driven by well-done randomized controlled trials and longitudinal research, as well as by replication studies in human subjects.}, }
@article {pmid34690981, year = {2021}, author = {Fu, X and Chen, T and Cai, J and Liu, B and Zeng, Y and Zhang, X}, title = {The Microbiome-Gut-Brain Axis, a Potential Therapeutic Target for Substance-Related Disorders.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {738401}, pmid = {34690981}, issn = {1664-302X}, abstract = {Substance addiction is a complex worldwide public health problem. It endangers both personal life and social stability, causing great loss on economy. Substance-related disorder is considered to be a complicated chronic brain disorder. It resulted from interactions among pharmacological properties of addictive substances, individual susceptibility, and social-environmental factors. Unfortunately, there is still no ideal treatment for this disorder. Recent lines of evidence suggest that gut microbiome may play an important role in the pathogenesis of neuropsychiatric disorders, including substance-related disorders. This review summarizes the research on the relationship between gut microbiome and substance-related disorders, including different types of substance, different individual susceptibility, and the occurrence and development of substance-induced mental disorders. We also discuss the potentiation of gut microbiome in the treatment of substance-related disorders, especially in the treatment of substance-induced mental disorders and manipulation on individuals' responsiveness to addictive substances.}, }
@article {pmid34690948, year = {2021}, author = {Zhang, X and Li, N and Chen, Q and Qin, H}, title = {Fecal Microbiota Transplantation Modulates the Gut Flora Favoring Patients With Functional Constipation.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {700718}, pmid = {34690948}, issn = {1664-302X}, abstract = {Intestinal dysmotility is common in many diseases and is correlated with gut microbiota dysbiosis and systemic inflammation. Functional constipation (FC) is the most typical manifestation of intestinal hypomotility and reduces patients' quality of life. Some studies have reported that fecal micriobiota transplantation (FMT) may be an effective and safe therapy for FC as it corrects intestinal dysbiosis. This study was conducted to evaluate how FMT remodels the gut microbiome and to determine a possible correlation between certain microbes and clinical symptoms in constipated individuals. Data were retrospectively collected on 18 patients who underwent FMT between January 1, 2019 and June 30, 2020. The fecal bacterial genome was detected by sequencing the V3-V4 hypervariable regions of the 16S rDNA gene. Fecal short chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry, and serum inflammatory factor concentrations were detected via enzyme-linked immunosorbent assay. Comparing the changes in fecal microbiome compositions before and after FMT revealed a significant augmentation in the alpha diversity and increased abundances of some flora such as Clostridiales, Fusicatenibacter, and Paraprevotella. This was consistent with the patients experiencing relief from their clinical symptoms. Abundances of other flora, including Lachnoanaerobaculum, were decreased, which might correlate with the severity of patients' constipation. Although no differences were found in SCFA production, the butyric acid concentration was correlated with both bacterial alterations and clinical symptoms. Serum IL-8 levels were significantly lower after FMT than at baseline, but IL-4, IL-6, IL-10, and IL-12p70 levels were not noticeably changed. This study showed how FMT regulates the intestinal microenvironment and affects systemic inflammation in constipated patients, providing direction for further research on the mechanisms of FMT. It also revealed potential microbial targets for precise intervention, which may bring new breakthroughs in treating constipation.}, }
@article {pmid34684330, year = {2021}, author = {Tanaka, Y and Shimizu, S and Shirotani, M and Yorozu, K and Kitamura, K and Oehorumu, M and Kawai, Y and Fukuzawa, Y}, title = {Nutrition and Cancer Risk from the Viewpoint of the Intestinal Microbiome.}, journal = {Nutrients}, volume = {13}, number = {10}, pages = {}, pmid = {34684330}, issn = {2072-6643}, mesh = {Dysbiosis/microbiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Neoplasms/*epidemiology/*microbiology ; *Nutritional Status ; Risk Factors ; }, abstract = {There are various important factors in reducing the risk of cancer development and progression; these factors may correct an unbalanced intake of nutrients to maintain the living body's homeostasis, detoxify toxic materials, acting as an external factor, and maintain and strengthen the body's immune function. In a normal cell environment, nutrients, such as carbohydrates, lipids, proteins, vitamins, and minerals, are properly digested and absorbed into the body, and, as a result, an environment in which cancer can develop and progress is prevented. It is necessary to prevent toxic materials from entering the body and to detoxify poisons in the body. If these processes occur correctly, cells work normally, and genes cannot be damaged. The most important factor in the fight against cancer and prevention of the development and progression of cancer is the immune system. This requires a nutritional state in which the immune system works well, allowing the intestinal microbiome to carry out all of its roles. In order to grow intestinal microbiota, the consumption of prebiotics, such as organic vegetables, fruits, and dietary fiber, and probiotics of effective intestinal microbiota, such as fermented foods and supplements, is required. Symbiosis, in which these organisms work together, is an effective means of reducing the risk of cancer. In addition, fecal microbiota transplantation (FMT) using ultrafine bubble water, produced specially by the Association for Clinical Research of Fecal Microbiota Transplantation Japan, is also useful for improving the nutritional condition and reducing the risk of cancer.}, }
@article {pmid34680092, year = {2021}, author = {Cibulková, I and Řehořová, V and Hajer, J and Duška, F}, title = {Fecal Microbial Transplantation in Critically Ill Patients-Structured Review and Perspectives.}, journal = {Biomolecules}, volume = {11}, number = {10}, pages = {}, pmid = {34680092}, issn = {2218-273X}, abstract = {The human gut microbiota consists of bacteria, archaea, fungi, and viruses. It is a dynamic ecosystem shaped by several factors that play an essential role in both healthy and diseased states of humans. A disturbance of the gut microbiota, also termed "dysbiosis", is associated with increased host susceptibility to a range of diseases. Because of splanchnic ischemia, exposure to antibiotics, and/or the underlying disease, critically ill patients loose 90% of the commensal organisms in their gut within hours after the insult. This is followed by a rapid overgrowth of potentially pathogenic and pro-inflammatory bacteria that alter metabolic, immune, and even neurocognitive functions and that turn the gut into the driver of systemic inflammation and multiorgan failure. Indeed, restoring healthy microbiota by means of fecal microbiota transplantation (FMT) in the critically ill is an attractive and plausible concept in intensive care. Nonetheless, available data from controlled studies are limited to probiotics and FMT for severe C. difficile infection or severe inflammatory bowel disease. Case series and observational trials have generated hypotheses that FMT might be feasible and safe in immunocompromised patients, refractory sepsis, or severe antibiotic-associated diarrhea in ICU. There is a burning need to test these hypotheses in randomized controlled trials powered for the determination of patient-centered outcomes.}, }
@article {pmid34678515, year = {2021}, author = {van Prehn, J and Reigadas, E and Vogelzang, EH and Bouza, E and Hristea, A and Guery, B and Krutova, M and Norén, T and Allerberger, F and Coia, J and Goorhuis, A and van Rossen, TM and Ooijevaar, RE and Burns, K and Scharvik Olesen, BR and Tschudin-Sutter, S and Wilcox, MH and Vehreschild, M and Fitzpatrick, F and Kuijper, EJ and , }, title = {European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2021.09.038}, pmid = {34678515}, issn = {1469-0691}, abstract = {SCOPE: In 2009, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first treatment guidance document for Clostridioides difficile infection (CDI). This document was updated in 2014. The growing literature on CDI antimicrobial treatment and novel treatment approaches, such as fecal microbiota transplantation (FMT) and toxin-binding monoclonal antibodies, prompted the ESCMID study group on C. difficile (ESGCD) to update the 2014 treatment guidance document for CDI in adults.<br><br>METHODS AND QUESTIONS: Key questions on CDI treatment were formulated by the guideline committee and included: what is the best treatment for initial, severe, severe-complicated, refractory, recurrent and multiple recurrent CDI; what is the best treatment when no oral therapy is possible; can prognostic factors identify patients at risk for severe and recurrent CDI; and is there a place for CDI prophylaxis? Outcome measures for treatment strategy were: clinical cure, recurrence, and sustained cure. For studies on surgical interventions and severe-complicated CDI the outcome was mortality. Appraisal of available literature and drafting of recommendations was performed by the guideline drafting group. The total body of evidence for the recommendations on CDI treatment consists of the literature described in the previous guidelines, supplemented with a systematic literature search on randomized clinical trials and observational studies from 2012 and onwards. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The guideline committee was invited to comment on the recommendations. The guideline draft was sent to external experts and a patients' representative for review. Full ESCMID endorsement was obtained after a public consultation procedure.<br><br>RECOMMENDATIONS: Important changes compared with previous guideline include but are not limited to: (1) metronidazole is no longer recommended for treatment of CDI when fidaxomicin or vancomycin are available, (2) fidaxomicin is the preferred agent for treatment of initial CDI and the first recurrence of CDI when available and feasible, (3) FMT or bezlotoxumab in addition to Standard of Care antibiotics (SoC) are preferred for treatment of a second or further recurrence of CDI, (4) bezlotoxumab in addition to SoC is recommended for the first recurrence of CDI when fidaxomicin was used to manage the initial CDI episode, and (5) bezlotoxumab is considered as an ancillary treatment to vancomycin for a CDI episode with high risk of recurrence when fidaxomicin is not available. Contrary to the previous guideline, in the current guideline emphasis is placed on risk for recurrence as a factor that determines treatment strategy for the individual patient, rather than the disease severity.}, }
@article {pmid34675599, year = {2021}, author = {Zheng, Y and Ding, Y and Xu, M and Chen, H and Zhang, H and Liu, Y and Shen, W and Li, J}, title = {Gut Microbiota Contributes to Host Defense Against Klebsiella pneumoniae-Induced Liver Abscess.}, journal = {Journal of inflammation research}, volume = {14}, number = {}, pages = {5215-5225}, pmid = {34675599}, issn = {1178-7031}, abstract = {Purpose: Klebsiella pneumoniae-induced liver abscess (KLA) is a type of pyogenic liver abscess (PLA), which is a distinct invasive syndrome that has been increasingly reported worldwide over the past two decades. The intestinal microbiota is increasingly recognized as an important modulator that can promote and maintain host immune homeostasis. However, its precise role in liver abscess is unknown. We aimed to investigate the function of the gut microbiota in the host defense against K. pneumoniae infection.<br><br>Methods: We constructed C57BL/6J mice with KLA and analyzed the diversity and richness of the intestinal microflora by 16S rRNA sequencing. Next, to create a microbiota-depleted (MD) mouse model, we administered multiple broad-spectrum antibiotics and validated the model using 16S rRNA sequencing. At 48 h after K. pneumoniae infection, we assessed the general health condition, liver injury, bacterial loads, and inflammatory factor levels in MD+KLA mice. Additionally, fecal microbiota transplantation (FMT) was conducted in another group of MD+KLA mice prior to K. pneumoniae infection, and we assessed whether the transplantation changed the outcomes.<br><br>Results: The diversity of the intestinal flora was significantly changed in KLA mice compared to control mice, with a decrease in beneficial bacteria and an increase in harmful bacteria. The MD+KLA mice exhibited impaired antimicrobial capacity, reduced survival, increased inflammation and liver damage at 48 h after K. pneumoniae infection compared to the KLA mice. However, FMT normalized the inflammatory cytokine levels, reduced liver damage, and increased survival.<br><br>Conclusion: This study identified the gut microbiota as a protective factor against K. pneumoniae infection. The role of FMT in KLA should be investigated in future clinical studies.}, }
@article {pmid34670821, year = {2021}, author = {Zheng, Z and Aweya, JJ and Bao, S and Yao, D and Li, S and Tran, NT and Ma, H and Zhang, Y}, title = {The Microbial Composition of Penaeid Shrimps' Hepatopancreas Is Modulated by Hemocyanin.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {207}, number = {11}, pages = {2733-2743}, doi = {10.4049/jimmunol.2100746}, pmid = {34670821}, issn = {1550-6606}, mesh = {Animals ; Energy Metabolism ; Hemocyanins/immunology/*metabolism ; Hepatopancreas/immunology/*metabolism ; Penaeidae/immunology/metabolism/*microbiology ; }, abstract = {Aquatic organisms have to produce proteins or factors that help maintain a stable relationship with microbiota and prevent colonization by pathogenic microorganisms. In crustaceans and other aquatic invertebrates, relatively few of these host factors have been characterized. In this study, we show that the respiratory glycoprotein hemocyanin is a crucial host factor that modulates microbial composition and diversity in the hepatopancreas of penaeid shrimp. Diseased penaeid shrimp (Penaeus vannamei), had an empty gastrointestinal tract with atrophied hepatopancreas, expressed low hemocyanin, and high total bacterial abundance, with Vibrio as the dominant bacteria. Similarly, shrimp depleted of hemocyanin had mitochondrial depolarization, increased reactive oxygen species (ROS) levels, and dysregulation of several energy metabolism-related genes. Hemocyanin silencing together with ROS scavenger (N-acetylcysteine) treatment improved microbial diversity and decreased Vibrio dominance in the hepatopancreas. However, fecal microbiota transplantation after hemocyanin knockdown could not restore the microbial composition in the hepatopancreas. Collectively, our data provide, to our knowledge, new insight into the pivotal role of hemocyanin in modulating microbial composition in penaeid shrimp hepatopancreas via its effect on mitochondrial integrity, energy metabolism, and ROS production.}, }
@article {pmid34668228, year = {2021}, author = {Sung, JJY and Wong, SH}, title = {What is unknown in using microbiota as a therapeutic?.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.15716}, pmid = {34668228}, issn = {1440-1746}, abstract = {Fecal microbiota transplantation (FMT) has been used extensively in the treatment of various gastrointestinal and extraintestinal conditions, despite that there are still a lot of missing gaps in our knowledge in the gut microbiota and its behavior. This article describes the unknowns in microbiota biology (undetected microbes, uncertain colonization, unclear mechanisms of action, uncertain indications, unsure long-term efficacy, or side effects). We discuss how these unknowns may affect the therapeutic uses of FMT, and the potentials and caveats of other related microbiota-based therapies. When used as an experimental therapy or last resort in difficult conditions, caution should be taken against inadvertent complications. Clear documentations of post-treatment events should be made mandatory, classified, and graded as in clinical trials. Further robust scientific experiments and properly designed clinical studies are needed.}, }
@article {pmid34666171, year = {2021}, author = {Wu, W and Zhou, D and Xuan, R and Zhou, J and Liu, J and Chen, J and Han, H and Niu, T and Li, X and Chen, H and Wang, F}, title = {λ-carrageenan exacerbates Citrobacter rodentium-induced infectious colitis in mice by targeting gut microbiota and intestinal barrier integrity.}, journal = {Pharmacological research}, volume = {174}, number = {}, pages = {105940}, doi = {10.1016/j.phrs.2021.105940}, pmid = {34666171}, issn = {1096-1186}, abstract = {For nearly half a century, the scientific community has been unable to agree upon the safety profile of carrageenan (CGN), a ubiquitous food additive. Little is known about the mechanisms by which consumption of CGN aggravates the etiopathogenesis of murine colitis. However, analyses of gut microbiota and intestinal barrier integrity have provided a breakthrough in explaining the synergistic effect of CGN upon colitis. In Citrobacter rodentium-induced infectious murine colitis, inflammation and the clinical severity of gut tissue were aggravated in the presence of λ-CGN. Using fecal transplantation and germ-free mice experiments, we evaluated the role of intestinal microbiota on the pro-inflammatory effect of λ-CGN. Mice with high dietary λ-CGN consumption showed altered colonic microbiota composition that resulted in degradation of the colonic mucus layer, a raised fecal LPS level, and a decrease in the presence of bacterially derived short-chain fatty acids (SCFAs). Mucus layer defects and altered fecal LPS and SCFA levels could be reproduced in germ-free mice by fecal transplantation from CGN-H-fed mice, but not from germ-free CGN-H-fed mice. Our results confirm that λ-CGN may create an environment that favors inflammation by altering gut microbiota composition and gut bacterial metabolism. The present study provides evidence that the "gut microbiota-barrier axis" could be an alternative target for ameliorating the colitis promoting effect of λ-CGN.}, }
@article {pmid34664371, year = {2021}, author = {Fehily, SR and Basnayake, C and Wright, EK and Kamm, MA}, title = {The gut microbiota and gut disease.}, journal = {Internal medicine journal}, volume = {51}, number = {10}, pages = {1594-1604}, doi = {10.1111/imj.15520}, pmid = {34664371}, issn = {1445-5994}, support = {//Leona M. and Harry B. Helmsley Charitable Trust/ ; //National Health and Medical Research Council; Clinical investigator grant; Postgraduate scholarship/ ; }, mesh = {*Clostridioides difficile ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/therapy ; *Microbiota ; *Probiotics/therapeutic use ; }, abstract = {The gut microbiota has a key role in the maintenance of good health, and in the pathogenesis of gastrointestinal diseases. These conditions include the inflammatory bowel diseases, colorectal cancer, coeliac disease and metabolic liver disease. Although the nature of the microbial disturbance in these conditions has not been fully characterised, this has not prevented the development of microbially based therapies. Microbial-changing therapies may address newly recognised pathophysiological contributors of disease and have the potential to replace or supplement standard therapies. Antibiotics play a role in initial Clostridiodes difficile disease and some specific inflammatory disorders. Probiotics have a more limited proven role. Faecal microbiota transplantation is of proven therapeutic benefit in recurrent C. difficile disease and ulcerative colitis. We review the current literature for microbiota-targeted therapies in gut disorders.}, }
@article {pmid34660756, year = {2021}, author = {Yan, C and Xiao, J and Li, Z and Liu, H and Zhao, X and Liu, J and Chen, S and Zhao, X}, title = {Exogenous Fecal Microbial Transplantation Alters Fearfulness, Intestinal Morphology, and Gut Microbiota in Broilers.}, journal = {Frontiers in veterinary science}, volume = {8}, number = {}, pages = {706987}, pmid = {34660756}, issn = {2297-1769}, abstract = {Fecal microbiota transplantation (FMT) documented transplanting a donor fecal sample to a receipt individual for a desired physiologic effect. However, whether the gut microbiota construction, intestinal maturation, and behavioral plasticity are modulated by FMT during the early life of broilers is waiting for verification. To evaluate the role of transfer of fecal microbiota from aged broilers donor (BD) to another individual, 96 birds were equally divided into a check (CK, control) group and a broiler recipient (BR) group. FMT was conducted daily from 5 to 12 days of age to determine the future impact on body weight, behavior, intestinal development, and gut microbiota. Results indicated that fearfulness in the CK group was higher than the BR group in both the behavioral tests (p < 0.05). The muscularis mucosa, thickness of muscle layer, and thickness of serous membrane layer in the BR group were higher compared with those of the CK group in the jejunum (p < 0.05). In the gut microbiota, Shannon diversity showed no difference, while beta diversity presented a difference in principal coordination analysis (PCoA) between the CK and BR groups. At the phylum level, the relative abundance of Lentisphaerae in the CK group was lower than the BR (p = 0.052) and BD (p = 0.054) groups. The relative abundance of Tenericutes in the BD group was higher than that in the CK and BR groups (p < 0.05). At the genus level, Megamonas in the CK group was higher than the BR (p = 0.06) and BD (p < 0.05) groups. In the BR group, the functional capabilities of microbial communities analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were increased in the glutamatergic synapse and N-glycan biosynthesis pathways in comparison with the CK and BD groups (p < 0.05). Some characteristics of gut microbiota in the donor chickens could be transferred to recipient chickens by FMT. In conclusion, exogenous FMT as a probiotic-like administration might be an efficient way to improve the physiology and behavior of chickens. Notably, the role of microbiota for various individuals and periods remains undefined, and the mechanism of microbiota on behaviors still needs further investigation.}, }
@article {pmid34659541, year = {2021}, author = {Ali, H and Khurana, S and Ma, W and Peng, Y and Jiang, ZD and DuPont, H and Zhang, HC and Thomas, AS and Okhuysen, P and Wang, Y}, title = {Safety and efficacy of fecal microbiota transplantation to treat and prevent recurrent Clostridioides difficile in cancer patients.}, journal = {Journal of Cancer}, volume = {12}, number = {21}, pages = {6498-6506}, pmid = {34659541}, issn = {1837-9664}, abstract = {Background: Cancer patients are at increased risk of recurrent Clostridioides difficile infection (rCDI) due to malignancy itself, cancer therapy, and frequent antibiotic use and have a lower response rate to standard oral antibiotics. There are limited data on the safety and efficacy of fecal microbiota transplantation (FMT) for treating rCDI in cancer patients. We aim to describe our experience of using FMT to treat rCDI at a tertiary cancer center. Methods: We conducted a retrospective study of cancer patients who underwent FMT for rCDI at The University of Texas MD Anderson Cancer Center from June 2017 through January 2020. Baseline clinical data and risk factors related to rCDI and FMT were evaluated and compared between cancer types and between cases with remission and recurrence. Results: A total of 19 patients were studied: 12 with solid malignancies and 7 with hematologic malignancies. Most patients had stage IV cancer, and 21% of patients were in cancer remission. On average, patients had 2 episodes of CDI and received 3 courses of antibiotics within 1 year before FMT. 84% of patients with rCDI responded to FMT. Compared with patients who had CDI remission following FMT, non-remission cases were more likely to have received antibiotics following FMT. There were no serious adverse events or mortality within 30 days associated with FMT. Conclusions: FMT is safe, well-tolerated, and efficacious in treating rCDI in selected cancer patients. However, additional antibiotic use for complications from chemotherapy or immunosuppression negatively affected the efficacy of FMT in this population with advanced cancer.}, }
@article {pmid34652093, year = {2021}, author = {Durovic, A and Tschudin-Sutter, S}, title = {Cutting edges in Clostridioides difficile infections.}, journal = {Swiss medical weekly}, volume = {151}, number = {}, pages = {w30033}, doi = {10.4414/smw.2021.w30033}, pmid = {34652093}, issn = {1424-3997}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Child ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/drug therapy/epidemiology ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {Clostridioides difficile is the most common cause of hospital-acquired diarrhoea and one of the most important causes of hospital-acquired infections. It results in significant morbidity, mortality and economic burden - especially in the context of recurrent infections. After initial antibiotic therapy of a C. difficile infection, recurrence occurs in about 20% of all patients, which increases the risk of further recurrence to about 45%. Traditional therapeutic options for treatment of C. difficile infection include metronidazole or vancomycin. Newer therapy options such as fidaxomicin, the administration of monoclonal antibodies or faecal microbiota transplantation demonstrate significant advantages over traditional therapies, particularly regarding the reduction of the recurrence rate. This article highlights the main differences between the recommendations of the Swiss Society for Infectious Diseases on the management of "Clostridioides difficile infection" and the IDSA/SHEA reference guideline "Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)" and discusses some important challenges in -treatment of C. difficile.}, }
@article {pmid34650107, year = {2021}, author = {Jang, HM and Kim, JK and Joo, MK and Shin, YJ and Lee, CK and Kim, HJ and Kim, DH}, title = {Transplantation of fecal microbiota from patients with inflammatory bowel disease and depression alters immune response and behavior in recipient mice.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {20406}, pmid = {34650107}, issn = {2045-2322}, support = {2017R1A5A2014768//National Research Foundation of Korea/ ; }, abstract = {Gut dysbiosis is closely associated with the occurrence of inflammatory bowel disease (IBD) and psychiatric disorder. Here, to understand the difference of gut microbiota composition and physiological effect between IBD patients with (IBD/D+) or without depression (IBD/D-), we analyzed the fecal microbiota composition of patients with IBD with (/D+) or without depression (/D-) and healthy volunteers (HVs) and examined the effects of these fecal microbiota transplantations (FMTs) on the occurrence of systemic inflammation and anxiety/depression in mice. FMTs from patients with IBD/D+ or IBD/D- caused IBD-like colitis in the transplanted mice: they increased the myeloperoxidase activity, IL-1β and IL-6 expression, and NF-κB+/CD11c+ cell population in the colon. Transplantation of the IBD/D+ patient feces (IBD/D+-F) caused IBD-like colitis more strongly than that of IBD/D--F. FMTs from patients with IBD/D+ also caused anxiety-/depression-like behaviors, increased the NF-κB+/Iba1+ and lipopolysaccharide (LPS)+/Iba1+ cell populations, and decreased the BDNF+/NeuN+ cell population in the hippocampus. They increased LPS levels in the blood. FMTs from patients with IBD/D- caused anxiety-like, but not depression-like, behaviors. α-/β-diversities and composition of gut microbiota in IBD-F were different from those of HV feces (HV-F). The Enterobacteriaceae and Enterococcaceae populations and LPS levels were higher in the IBD-F than in the HV-F. The Enterococcaceae population was higher in IBD/D+-F vs. IBD/D--F. However, the transplantation of HV-F into mice previously transplanted with IBD/D+-F significantly reduced depression-like behaviors, NF-κB+/Iba1+ and LPS+/Iba1+ cell populations in the hippocampus, LPS levels in the feces and blood, and IL-1β expression in the colon. These findings suggest that the outbreak of depression/anxiety may be dependent on the systemic inflammation with a leaky gut through the gut dysbiosis-attributable overproduction of bacterial LPS and suppression of tight junction protein expression in patients with IBD.}, }
@article {pmid34647152, year = {2021}, author = {Nie, D and Fang, Q and Cheng, J and Li, B and Li, M and Wang, H and Li, C and Gui, S and Zhang, Y and Zhao, P}, title = {The intestinal flora of patients with GHPA affects the growth and the expression of PD-L1 of tumor.}, journal = {Cancer immunology, immunotherapy : CII}, volume = {}, number = {}, pages = {}, pmid = {34647152}, issn = {1432-0851}, abstract = {CONTEXT: Pituitary adenoma (PA) is a common intracranial tumor. The evidence indicates that the tumor immune microenvironment (TIME) is associated with PA and that the intestinal flora influences other tumors' growth through interacting with the TIME. However, how the intestinal microbial flora contributes to the development of PA through the immune response is unknown.<br><br>OBJECTIVE AND METHODS: Here we used high-throughput Illumina MiSeq sequencing targeting the V3-V4 region of the 16S ribosomal RNA gene to investigate the intestinal flora of patients with growth hormone-secreting pituitary adenoma (GHPA), nonfunctional pituitary adenoma (NFPA), and healthy controls. We determined their effects on tumor growth and the TIME. Fecal microbiota transplantation (FMT) was performed after adoptive transfer via peripheral blood mononuclear cells to tumor-bearing nude mice, which allowed the study of the immune response.<br><br>RESULT: We discovered differences in the structures and quantities of intestinal flora between patients with GHPA, patients with NFPA, and healthy controls. After FMT, the intestinal flora of GHPA patients promoted the growth of tumors in mouse models. The number of programmed cell death ligand 1 (PD-L1)-positive cells increased in tumor tissues as well as the extent of infiltration of CD8+ cells. Increased numbers of CD3+CD8+ cells and increased levels of sPD-L1 were detected in peripheral blood.<br><br>CONCLUSION: These findings indicated that the intestinal flora of patients with GHPA promoted tumor growth and that the immune system may mediate this change.}, }
@article {pmid34644375, year = {2021}, author = {Eshel, A and Sharon, I and Nagler, A and Bomze, D and Danylesko, I and Fein, JA and Geva, M and Henig, I and Shimoni, A and Zuckerman, T and Youngster, I and Koren, O and Shouval, R}, title = {Bloodstream infections' origins following fecal microbiota transplantation: a strain-level analysis.}, journal = {Blood advances}, volume = {}, number = {}, pages = {}, doi = {10.1182/bloodadvances.2021005110}, pmid = {34644375}, issn = {2473-9537}, abstract = {We observed high rates of bloodstream infections (BSIs) following fecal microbiota transplantation (FMT) for graft-versus-host-disease (33 events in 22 patients). To trace the BSIs' origin, we applied a metagenomic bioinformatic pipeline screening donor and recipient stool samples for bacteremia-causing strains in 13 cases. Offending strains were not detected in FMT donations. Enterococcus faecium, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii could be detected in stool samples before emerging in the blood. In this largest report of BSIs post-FMT, we present an approach that may be applicable for evaluating BSI origin following microbiota-based interventions. Our findings support FMT safety in immunocompromised patients but do not rule out FMT as an inducer of bacterial translocation.}, }
@article {pmid34638430, year = {2021}, author = {Oldenburg, M and Rüchel, N and Janssen, S and Borkhardt, A and Gössling, KL}, title = {The Microbiome in Childhood Acute Lymphoblastic Leukemia.}, journal = {Cancers}, volume = {13}, number = {19}, pages = {}, pmid = {34638430}, issn = {2072-6694}, support = {428917761//Deutsche Forschungsgemeinschaft/ ; 2020-24//Research Committee of the Heinrich Heine University Duesseldorf/ ; }, abstract = {For almost 30 years, the term "holobiont" has referred to an ecological unit where a host (e.g., human) and all species living in or around it are considered together. The concept highlights the complex interactions between the host and the other species, which, if disturbed may lead to disease and premature aging. Specifically, the impact of microbiome alterations on the etiology of acute lymphoblastic leukemia (ALL) in children is not fully understood, but has been the focus of much research in recent years. In ALL patients, significant reductions in microbiome diversity are already observable at disease onset. It remains unclear whether such alterations at diagnosis are etiologically linked with leukemogenesis or simply due to immunological alteration preceding ALL onset. Regardless, all chemotherapeutic treatment regimens severely affect the microbiome, accompanied by severe side effects, including mucositis, systemic inflammation, and infection. In particular, dominance of Enterococcaceae is predictive of infections during chemotherapy. Long-term dysbiosis, like depletion of Faecalibacterium, has been observed in ALL survivors. Modulation of the microbiome (e.g., by fecal microbiota transplant, probiotics, or prebiotics) is currently being researched for potential protective effects. Herein, we review the latest microbiome studies in pediatric ALL patients.}, }
@article {pmid34638308, year = {2021}, author = {Oh, B and Boyle, F and Pavlakis, N and Clarke, S and Eade, T and Hruby, G and Lamoury, G and Carroll, S and Morgia, M and Kneebone, A and Stevens, M and Liu, W and Corless, B and Molloy, M and Kong, B and Libermann, T and Rosenthal, D and Back, M}, title = {The Gut Microbiome and Cancer Immunotherapy: Can We Use the Gut Microbiome as a Predictive Biomarker for Clinical Response in Cancer Immunotherapy?.}, journal = {Cancers}, volume = {13}, number = {19}, pages = {}, pmid = {34638308}, issn = {2072-6694}, abstract = {Background: Emerging evidence suggests that gut microbiota influences the clinical response to immunotherapy. This review of clinical studies examines the relationship between gut microbiota and immunotherapy outcomes. Method: A literature search was conducted in electronic databases Medline, PubMed and ScienceDirect, with searches for "cancer" and "immunotherapy/immune checkpoint inhibitor" and "microbiome/microbiota" and/or "fecal microbiome transplant FMT". The relevant literature was selected for this article. Results: Ten studies examined patients diagnosed with advanced metastatic melanoma (n = 6), hepatocellular carcinoma (HCC) (n = 2), non-small cell lung carcinoma (NSCLC) (n = 1) and one study examined combination both NSCLC and renal cell carcinoma (RCC) (n = 1). These studies consistently reported that the gut microbiome profile prior to administering immune checkpoint inhibitors (ICIs) was related to clinical response as measured by progression-free survival (PFS) and overall survival (OS). Two studies reported that a low abundance of Bacteroidetes was associated with colitis. Two studies showed that patients with anti-PD-1 refractory metastatic melanoma experienced improved response rates and no added toxicity when receiving fecal microbiota transplant (FMT) from patients with anti-PD-1 responsive disease. Conclusions: Overall, significant differences in the diversity and composition of the gut microbiome were identified in ICIs responders and non-responders. Our findings provide new insights into the value of assessing the gut microbiome in immunotherapy. Further robust randomized controlled trials (RCTs) examining the modulatory effects of the gut microbiome and FMT on ICIs in patients not responding to immunotherapy are warranted.}, }
@article {pmid34634946, year = {2021}, author = {Mo, Q and Liu, T and Fu, A and Ruan, S and Zhong, H and Tang, J and Zhao, M and Li, Y and Zhu, S and Cai, H and Feng, F}, title = {Novel Gut Microbiota Patterns Involved in the Attenuation of Dextran Sodium Sulfate-Induced Mouse Colitis Mediated by Glycerol Monolaurate via Inducing Anti-inflammatory Responses.}, journal = {mBio}, volume = {12}, number = {5}, pages = {e0214821}, doi = {10.1128/mBio.02148-21}, pmid = {34634946}, issn = {2150-7511}, support = {LD19C200001//Key Project of Natural Science Foundation of Zhejiang Province/ ; 32072224//National Natural Science Foundation of China (NSFC)/ ; 31972079//National Natural Science Foundation of China (NSFC)/ ; 2017ZDNT006//Zhejiang University New Rural Development Research Institute Agricultural Thchnology Promotion Fund/ ; 20161631E01//Achievement transformation Project of Hangzhou, China/ ; }, abstract = {Inflammatory bowel disease (IBD) is a type of immune-mediated chronic and relapsing inflammatory gastrointestinal symptoms. IBD cannot be completely cured because of the complex pathogenesis. Glycerol monolaurate (GML), naturally found in breast milk and coconut oil, has excellent antimicrobial, anti-inflammatory, and immunoregulatory functions. Here, the protective effect of GML on dextran sodium sulfate (DSS)-induced mouse colitis and the underlying gut microbiota-dependent mechanism were assessed in C57BL/6 mice pretreated or cotreated with GML and in antibiotic-treated mice transplanted with GML-modulated microbiota. Results showed that GML pretreatment has an advantage over GML cotreatment in alleviating weight loss and reducing disease activity index (DAI), colonic histological scores, and proinflammatory responses. Moreover, the amounts of Lactobacillus and Bifidobacterium and fecal propionic acid and butyric acid were elevated only in mice pretreated with GML upon DSS induction. Of note, fecal microbiota transplantation (FMT) from GML-pretreated mice achieved faster and more significant remission of DSS-induced colitis, manifested as reduced DAI, longer colon, decreased histological scores, and enhanced colonic Foxp3+ regulatory T cells (Tregs) and ratio of serum anti-inflammatory/proinflammatory cytokines, as well as the reconstruction of microbial communities, including elevated Helicobacter ganmani and decreased pathogenic microbes. In conclusion, GML-mediated enhancement of Bifidobacterium and fecal short-chain fatty acids (SCFAs) could be responsible for the anticolitis effect. FMT assay confirmed that gut microbiota modulated by GML was more resistant to DSS-induced colitis via elevating beneficial H. ganmani and establishing Treg tolerant phenotype. Importantly, colitis remission induced by GML is associated with novel gut microbiota patterns, even though different microbial contexts were involved. IMPORTANCE The gut microbiota, which can be highly and dynamically affected by dietary components, is closely related to IBD pathogenesis. Here, we demonstrated that food-grade glycerol monolaurate (GML)-mediated enhancement of Bifidobacterium and fecal SCFAs could be responsible for the anticolitis effect. FMT assay confirmed that gut microbiota modulated by GML was more resistant to DSS-induced colitis via elevating beneficial H. ganmani and establishing Treg tolerant phenotype. Collectively, colitis remission induced by GML is associated with novel gut microbiota patterns, even though different microbial contexts were involved, which further provided a perspective to identify specific microbial members and those responsible for the anticolitis effect, such as Bifidobacterium and Helicobacter.}, }
@article {pmid34631604, year = {2021}, author = {Gai, X and Wang, H and Li, Y and Zhao, H and He, C and Wang, Z and Zhao, H}, title = {Fecal Microbiota Transplantation Protects the Intestinal Mucosal Barrier by Reconstructing the Gut Microbiota in a Murine Model of Sepsis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {736204}, pmid = {34631604}, issn = {2235-2988}, mesh = {Animals ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa ; Mice ; *Sepsis/therapy ; }, abstract = {The gastrointestinal (GI) tract has long been hypothesized to play an integral role in the pathophysiology of sepsis, and gut microbiota (GM) dysbiosis may be the key factor. Previous studies have shown that the gut flora was significantly altered in critically ill patients. This study aimed to observe what kind of GM dysbiosis is in the early stage of sepsis and whether the application of fecal microbiota transplantation (FMT) can reconstruct the GM of septic mice and restore its protective function on the intestinal mucosal barrier. The study investigated the effect of FMT on gut microbiota, mucosal barrier function, inflammatory response, and survival in a murine model of sepsis established by cecal ligation and puncture (CLP). It is found that FMT can not only reduce morbidity and mortality and restore the abundance and diversity of the gut flora in septic mice, but can also improve the intestinal barrier function by reducing epithelial cell apoptosis, improving the composition of the mucus layer, upregulating the expression of tight junction proteins, and reducing intestinal permeability and the inflammatory response. After FMT, Lachnospiraceae contributed the most to intestinal protection through enhancement of the L-lysine fermentation pathway. FMT offers a microbe-mediated survival advantage in a murine model of sepsis. Therefore, an improved understanding of the connection between microbiota, and systemic illness may yield new therapeutic strategies for patients with sepsis.}, }
@article {pmid34627951, year = {2021}, author = {Shao, X and Sun, S and Zhou, Y and Wang, H and Yu, Y and Hu, T and Yao, Y and Zhou, C}, title = {Bacteroides fragilis restricts colitis-associated cancer via negative regulation of the NLRP3 axis.}, journal = {Cancer letters}, volume = {523}, number = {}, pages = {170-181}, doi = {10.1016/j.canlet.2021.10.002}, pmid = {34627951}, issn = {1872-7980}, abstract = {Patients with persistent ulcerative colitis (UC) are at a higher risk of developing colitis-associated cancer (CAC). Previous studies have reported that intestinal microbiota disturbance plays an important role in the process of CAC development in patients with UC, indicating that targeted intervention of intestinal microbiota and its metabolites may be a potential therapeutic strategy. Gut microbiota in the process of colorectal cancer development in UC patients was analyzed using the gutMEGA database and verified in fecal samples. The abundance of Bacteroides fragilis reduced significantly in the process of colitis associated cancer development. Broad-spectrum antibiotics (BSAB) intervene with the intestinal microbiota of mice and accelerate the process of colon cancer development. However, gavage transplantation with B. fragilis can effectively reverse the effects of BSAB. In the intestinal tract, B. fragilis promotes the secretion of short-chain fatty acids (SCFAs). Subsequently, SCFAs, especially butyrate, negatively regulate the inflammatory signaling pathway mediated by NLRP3 to inhibit the activation of macrophages and the secretion of proinflammatory mediators such as IL-18 and IL-1β, reducing the level of intestinal inflammation and restricting CAC development. In conclusion, colonization with B. fragilis has been shown to be effective in ameliorating intestinal epithelial damage caused by chronic inflammation and preventing the development of colonic tumors. Thus, it can be a therapeutic intervention strategy with good clinical application prospects.}, }
@article {pmid34627858, year = {2021}, author = {Brusilovsky, M and Bao, R and Rochman, M and Kemter, AM and Nagler, CR and Rothenberg, ME}, title = {Host-Microbiota Interactions in the Esophagus During Homeostasis and Allergic Inflammation.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2021.10.002}, pmid = {34627858}, issn = {1528-0012}, abstract = {BACKGROUND &amp; AIMS: Microbiota composition and mechanisms of host-microbiota interactions in the esophagus are unclear. We aimed to uncover fundamental information about the esophageal microbiome and its potential significance to eosinophilic esophagitis (EoE).<br><br>METHODS: Microbiota composition, transplantation potential, and antibiotic responsiveness in the esophagus were established via 16S ribosomal RNA sequencing. Functional outcomes of microbiota colonization were assessed by RNA sequencing analysis of mouse esophageal epithelium and compared with the human EoE transcriptome. The impact of dysbiosis was assessed using a preclinical model of EoE.<br><br>RESULTS: We found that the murine esophagus is colonized with diverse microbial communities within the first month of life. The esophageal microbiota is distinct, dominated by Lactobacillales, and demonstrates spatial heterogeneity as the proximal and distal esophagus are enriched in Bifidobacteriales and Lactobacillales, respectively. Fecal matter transplantation restores the esophageal microbiota, demonstrating that the local environment drives diversity. Microbiota colonization modifies esophageal tissue morphology and gene expression that is enriched in pathways associated with epithelial barrier function and overlapping with genes involved in EoE, including POSTN, KLK5, and HIF1A. Finally, neonatal antibiotic treatment reduces the abundance of Lactobacillales and exaggerates type 2 inflammation in the esophagus. Clinical data substantiated loss of esophageal Lactobacillales in EoE compared with controls.<br><br>CONCLUSIONS: The esophagus has a unique microbiome with notable differences between its proximal and distal regions. Fecal matter transplantation restores the esophageal microbiome. Antibiotic-induced dysbiosis exacerbates disease in a murine model of EoE. Collectively, these data establish the composition, transplantation potential, antibiotic responsiveness, and host-microbiota interaction in the esophagus and have implications for gastrointestinal health and disease.}, }
@article {pmid34627158, year = {2021}, author = {Shimizu, H and Arai, K and Asahara, T and Takahashi, T and Tsuji, H and Matsumoto, S and Takeuchi, I and Kyodo, R and Yamashiro, Y}, title = {Stool preparation under anaerobic conditions contributes to retention of obligate anaerobes: potential improvement for fecal microbiota transplantation.}, journal = {BMC microbiology}, volume = {21}, number = {1}, pages = {275}, pmid = {34627158}, issn = {1471-2180}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) in patients with ulcerative colitis has shown variable efficacy depending on the protocol used. A previous randomized controlled trial reported that anaerobic preparation of donor stool contributes to improved efficacy. Despite the suggestion that viable obligate anaerobes would be decreased through aerobic handling, there have been only a limited number of reports on how these aerobic or anaerobic procedures affect the composition of viable microbiota in the fecal slurries used for FMT.<br><br>METHODS: We adopted 16S and 23S rRNA-targeted reverse transcription-quantitative polymerase chain reaction to quantify viable bacteria in fecal slurries. This study utilized specific primers designed to detect obligate anaerobes (including Clostridium coccoides group, C. leptum subgroup, Bacteroides fragilis group, Bifidobacterium, Atopobium cluster, and Prevotella) and facultative anaerobes (including total lactobacilli, Enterobacteriaceae, Enterococcus, Streptococcus, and Staphylococcus). We then calculated the ratio change (RC) between before and after mixing, and compared the resulting values between anaerobic-prep and aerobic-prep in samples fixed immediately after blending (RCAn0 vs. RCAe0) and in samples maintained (under anaerobic or aerobic conditions) for 1 h after blending (RCAn1 vs. RCAe1).<br><br>RESULTS: For most obligate anaerobes, the median RC tended to be less than 1, indicating that the number of obligate anaerobes was decreased by the blending procedure. However, in samples maintained for 1 h after blending, anaerobic-prep counteracted the decrease otherwise seen for the C. coccoides group and B. fragilis groups (P < 0.01 for both). The C. leptum subgroup also tended to show higher RC by anaerobic-prep than by aerobic-prep, although this effect was not statistically significant. Among facultative anaerobes, Enterobacteriaceae, Enterococcus, and Staphylococcus showed median RC values of more than 1, indicating that these organisms survived and even grew after mixing. Moreover, oxygen exposure had no significant influence on the survival of the facultative anaerobes.<br><br>CONCLUSIONS: The conditions under which the blending procedure was performed affected the proportion of live anaerobes in fecal slurries. The obligate anaerobes tended to be decreased by blending processes, but anaerobic-prep significantly mitigated this effect. Anaerobic-prep may improve the efficacy of FMT by permitting the efficient transfer of obligate anaerobes to patients with ulcerative colitis.}, }
@article {pmid34624222, year = {2021}, author = {Lam, KC and Araya, RE and Huang, A and Chen, Q and Di Modica, M and Rodrigues, RR and Lopès, A and Johnson, SB and Schwarz, B and Bohrnsen, E and Cogdill, AP and Bosio, CM and Wargo, JA and Lee, MP and Goldszmid, RS}, title = {Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment.}, journal = {Cell}, volume = {184}, number = {21}, pages = {5338-5356.e21}, pmid = {34624222}, issn = {1097-4172}, support = {R01 CA219896/CA/NCI NIH HHS/United States ; ZIA BC011670/ImNIH/Intramural NIH HHS/United States ; }, abstract = {The tumor microenvironment (TME) influences cancer progression and therapy response. Therefore, understanding what regulates the TME immune compartment is vital. Here we show that microbiota signals program mononuclear phagocytes in the TME toward immunostimulatory monocytes and dendritic cells (DCs). Single-cell RNA sequencing revealed that absence of microbiota skews the TME toward pro-tumorigenic macrophages. Mechanistically, we show that microbiota-derived stimulator of interferon genes (STING) agonists induce type I interferon (IFN-I) production by intratumoral monocytes to regulate macrophage polarization and natural killer (NK) cell-DC crosstalk. Microbiota modulation with a high-fiber diet triggered the intratumoral IFN-I-NK cell-DC axis and improved the efficacy of immune checkpoint blockade (ICB). We validated our findings in individuals with melanoma treated with ICB and showed that the predicted intratumoral IFN-I and immune compositional differences between responder and non-responder individuals can be transferred by fecal microbiota transplantation. Our study uncovers a mechanistic link between the microbiota and the innate TME that can be harnessed to improve cancer therapies.}, }
@article {pmid34623758, year = {2021}, author = {Yau, YK and Mak, WYJ and Lui, NSR and Ng, WYR and Cheung, CYK and Li, YLA and Ching, YLJ and Chin, ML and Lau, HSL and Chan, KLF and Chan, KSP and Ng, SC}, title = {High prevalence of extended-spectrum beta-lactamase organisms and the COVID-19 pandemic impact on donor recruitment for fecal microbiota transplantation in Hong Kong.}, journal = {United European gastroenterology journal}, volume = {9}, number = {9}, pages = {1027-1038}, pmid = {34623758}, issn = {2050-6414}, mesh = {Adolescent ; Adult ; COVID-19 ; *Donor Selection ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Hong Kong ; Humans ; Male ; Middle Aged ; Pandemics ; Prevalence ; Young Adult ; beta-Lactamases ; }, abstract = {BACKGROUND: With increasing number of clinical trials relating to fecal microbiota transplantation (FMT), it is crucial to identify and recruit long-term, healthy, and regular fecal donors.<br><br>OBJECTIVE: We aimed to report the outcomes of screening and recruitment of fecal donors for FMT.<br><br>METHODS: Potential donors were recruited via advertisement through internal mass emails at a university. They were required to undergo a pre-screening telephone interview, a detailed questionnaire, followed by blood and stool investigations.<br><br>RESULTS: From January 2017 to December 2020, 119 potential donors were assessed with 75 failed pre-screening. Reasons for failure included: inability to come back for regular and long-term donation (n = 19), high body mass index (n = 17), underlying chronic illness or on long-term medications (n = 11), being healthcare professionals (n = 10), use of antibiotics within 3 months (n = 5) and others (n = 13). Forty-four donors completed questionnaires and 11 did not fulfill the clinical criteria. Of the remaining 33 potential donors who had stool and blood tests, 21 failed stool investigations (19 extended-spectrum beta-lactamase [ESBL] organisms, one Clostridioides difficile, one C. difficile plus Methicillin Resistant Staphylococcus aureus), one failed blood tests (high serum alkaline phosphatase level), one required long-term medication and nine withdrew consent and/or lost to follow-up. In total, only one out of 119 (0.8%) potential donors was successfully recruited as a regular donor.<br><br>CONCLUSION: There was a high failure rate in donor screening for FMT. Main reasons for screening failure included high prevalence of positive ESBL organisms in stool and failed commitment to regular stool donation.}, }
@article {pmid34622239, year = {2021}, author = {Hanssen, NMJ and Nieuwdorp, M}, title = {Fecal microbiota transplantation and fiber supplementation, better together?.}, journal = {Cell reports. Medicine}, volume = {2}, number = {9}, pages = {100403}, pmid = {34622239}, issn = {2666-3791}, abstract = {Fecal microbiota transplantation (FMT) is emerging as a tool to study the microbiome and as a potential treatment for several non-infectious diseases. Recently, Mocanu et al. showed that supplementing low fermentable fiber after FMT may improve insulin sensitivity in severely obese individuals.1.}, }
@article {pmid34622234, year = {2021}, author = {Ahmed, BA and Ong, FJ and Barra, NG and Blondin, DP and Gunn, E and Oreskovich, SM and Szamosi, JC and Syed, SA and Hutchings, EK and Konyer, NB and Singh, NP and Yabut, JM and Desjardins, EM and Anhê, FF and Foley, KP and Holloway, AC and Noseworthy, MD and Haman, F and Carpentier, AC and Surette, MG and Schertzer, JD and Punthakee, Z and Steinberg, GR and Morrison, KM}, title = {Lower brown adipose tissue activity is associated with non-alcoholic fatty liver disease but not changes in the gut microbiota.}, journal = {Cell reports. Medicine}, volume = {2}, number = {9}, pages = {100397}, pmid = {34622234}, issn = {2666-3791}, abstract = {In rodents, lower brown adipose tissue (BAT) activity is associated with greater liver steatosis and changes in the gut microbiome. However, little is known about these relationships in humans. In adults (n = 60), we assessed hepatic fat and cold-stimulated BAT activity using magnetic resonance imaging and the gut microbiota with 16S sequencing. We transplanted gnotobiotic mice with feces from humans to assess the transferability of BAT activity through the microbiota. Individuals with NAFLD (n = 29) have lower BAT activity than those without, and BAT activity is inversely related to hepatic fat content. BAT activity is not related to the characteristics of the fecal microbiota and is not transmissible through fecal transplantation to mice. Thus, low BAT activity is associated with higher hepatic fat accumulation in human adults, but this does not appear to have been mediated through the gut microbiota.}, }
@article {pmid34621688, year = {2021}, author = {Bokoliya, SC and Dorsett, Y and Panier, H and Zhou, Y}, title = {Procedures for Fecal Microbiota Transplantation in Murine Microbiome Studies.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {711055}, pmid = {34621688}, issn = {2235-2988}, support = {R01 NS102633/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Mice ; *Microbiota ; }, abstract = {Fecal microbiota transplantation (FMT) has been widely recognized as an approach to determine the microbiome's causal role in gut dysbiosis-related disease models and as a novel disease-modifying therapy. Despite potential beneficial FMT results in various disease models, there is a variation and complexity in procedural agreement among research groups for performing FMT. The viability of the microbiome in feces and its successful transfer depends on various aspects of donors, recipients, and lab settings. This review focuses on the technical practices of FMT in animal studies. We first document crucial factors required for collecting, handling, and processing donor fecal microbiota for FMT. Then, we detail the description of gut microbiota depletion methods, FMT dosages, and routes of FMT administrations in recipients. In the end, we describe assessments of success rates of FMT with sustainability. It is critical to work under the anaerobic condition to preserve as much of the viability of bacteria. Utilization of germ- free mice or depletion of recipient gut microbiota by antibiotics or polyethylene glycol are two common recipient preparation approaches to achieve better engraftment. Oral-gastric gavage preferred by most researchers for fast and effective administration of FMT in mice. Overall, this review highlights various methods that may lead to developing the standard and reproducible protocol for FMT.}, }
@article {pmid34618582, year = {2021}, author = {Pernigoni, N and Zagato, E and Calcinotto, A and Troiani, M and Mestre, RP and Calì, B and Attanasio, G and Troisi, J and Minini, M and Mosole, S and Revandkar, A and Pasquini, E and Elia, AR and Bossi, D and Rinaldi, A and Rescigno, P and Flohr, P and Hunt, J and Neeb, A and Buroni, L and Guo, C and Welti, J and Ferrari, M and Grioni, M and Gauthier, J and Gharaibeh, RZ and Palmisano, A and Lucchini, GM and D'Antonio, E and Merler, S and Bolis, M and Grassi, F and Esposito, A and Bellone, M and Briganti, A and Rescigno, M and Theurillat, JP and Jobin, C and Gillessen, S and de Bono, J and Alimonti, A}, title = {Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis.}, journal = {Science (New York, N.Y.)}, volume = {374}, number = {6564}, pages = {216-224}, doi = {10.1126/science.abf8403}, pmid = {34618582}, issn = {1095-9203}, mesh = {Aged ; Aged, 80 and over ; Androgen Antagonists/therapeutic use ; Androgens/*biosynthesis ; Animals ; Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects/genetics/*metabolism ; Cell Line, Tumor ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/genetics/*physiology ; *Host Microbial Interactions ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; Neoplasms, Experimental ; Prevotella/metabolism ; Prostatic Neoplasms, Castration-Resistant/drug therapy/*metabolism/*microbiology ; Symbiosis ; Xenograft Model Antitumor Assays ; }, abstract = {[Figure: see text].}, }
@article {pmid34617582, year = {2021}, author = {Real-López, M and Peraire, M and Ramos-Vidal, C and Nath, D and Hervás, A and Cortés, X}, title = {[Involvement of intestinal dysbiosis in the etiopathogenesis and treatment of autism spectrum disorder: a bibliographic review].}, journal = {Revista de neurologia}, volume = {73}, number = {8}, pages = {282-295}, doi = {10.33588/rn.7308.2021189}, pmid = {34617582}, issn = {1576-6578}, abstract = {INTRODUCTION: Autism spectrum disorder is a neurodevelopmental disorder with phenotypic heterogeneity and variable symptomatic course of partly unknown etiology. The prevalence of gastrointestinal disorders in autism leads to investigate the role that intestinal microbiota may have as a causal factor and to propose specific therapeutic interventions. The role of microbiota in brain development and function, demonstrated in animal models, justifies its investigation in this neuropsychiatric disorder.<br><br>OBJECTIVE: The aim was to investigate the relationship between altered microbiota composition and autism spectrum disorder, and to assess the therapeutic role of prebiotics, probiotics and fecal transplantation in this neurodevelopmental disorder.<br><br>DEVELOPMENT: A literature review was conducted in PubMed, Cochrane Library and Google Scholar to select relevant articles related to the topic that were published between January 2012 and April 2020. Thirty-five relevant articles were selected. In 23 of them, significant differences were found in the composition and diversity of the microbiota in children with ASD, as well as in the biomolecules involved in certain metabolic pathways. The other 12 investigations reported gastrointestinal and behavioral improvements after therapeutic intervention.<br><br>CONCLUSIONS: It is reasonable to state that there is enough evidence to support the existence of a relationship between intestinal microbiota and autism spectrum disorders. This fact should be explored in depth to assess the etiopathogenic burden of dysbiosis and the possible therapeutic tools.}, }
@article {pmid34616650, year = {2021}, author = {Zhu, LB and Zhang, YC and Huang, HH and Lin, J}, title = {Prospects for clinical applications of butyrate-producing bacteria.}, journal = {World journal of clinical pediatrics}, volume = {10}, number = {5}, pages = {84-92}, pmid = {34616650}, issn = {2219-2808}, abstract = {As the major source of energy for colonic mucosal cells and as an important regulator of gene expression, inflammation, differentiation, and apoptosis in host cells, microbiota-derived butyrate can enhance the intestinal mucosal immune barrier, modulate systemic immune response, and prevent infections. Maintaining a certain level of butyrate production in the gut can help balance intestinal microbiota, regulate host immune response, and promote the development and maintenance of the intestinal mucosal barrier. Butyrate-producing bacteria act as probiotics and play important roles in a variety of normal biological functions. Bacteriotherapeutic supplementation by using fecal microbiota transplantation to restore butyrate-producing commensal bacteria in the gut has been very successful in the treatment of recurrent and refractory Clostridium difficile (C. difficile) infection or C. difficile-negative nosocomial diarrhea. Administration of probiotics that include butyrate-producing bacteria may have a role in the treatment of inflammatory bowel diseases and in the prevention of necrotizing enterocolitis and late-onset sepsis in premature infants. Furthermore, modulating gut microbiota with dietary approaches may improve intestinal dysbiosis commonly seen in patients with obesity-associated metabolic disorders. Supplementation with a butyrate-producing bacterial stain might be used to increase energy expenditure, improve insulin sensitivity, and to help control obesity and metabolic syndrome.}, }
@article {pmid34612696, year = {2021}, author = {Wang, H and Song, W and Wu, Q and Gao, X and Li, J and Tan, C and Zhou, H and Zhu, J and He, Y and Yin, J}, title = {Fecal Transplantation from db/db Mice Treated with Sodium Butyrate Attenuates Ischemic Stroke Injury.}, journal = {Microbiology spectrum}, volume = {9}, number = {2}, pages = {e0004221}, pmid = {34612696}, issn = {2165-0497}, support = {NSFC81870936//National Natural Science Foundation of China (NSFC)/ ; LC2016PY025//Department of Education of Guangdong Province (DEGP)/ ; 2018CR024//Nanfang Hospital/ ; }, abstract = {The complication of type 2 diabetes (T2D) exacerbates brain infarction in acute ischemic stroke (AIS). Because butyrate-producing bacteria are decreased in T2D and butyrate has been reported to be associated with attenuated brain injury in AIS, we hypothesize that administering butyrate could ameliorate T2D-associated exacerbation of brain infarction in AIS. Therefore, we first validated that Chinese AIS patients with T2D comorbidity have significantly lower levels of fecal butyrate-producing bacteria and butyrate than AIS patients without T2D. Then, we performed a 4-week intervention in T2D mice receiving either sodium butyrate (SB) or sodium chloride (NaCl) and found that SB improved the diabetic phenotype, altered the gut microbiota, and ameliorated brain injury after stroke. Fecal samples were collected from T2D mice after SB or NaCl treatment and were transplanted into antibiotic-treated C57BL/6 mice. After 2 weeks of transplantation, the gut microbiota profile and butyrate level of recipient mice were tested, and then the recipient mice were subjected to ischemic stroke. Stroke mice that received gut microbiota from SB-treated mice had a smaller cerebral infarct volume than mice that received gut microbiota from NaCl-treated mice. This protection was also associated with improvements in gut barrier function, reduced serum levels of lipopolysaccharide (LPS), LPS binding protein (LBP), and proinflammatory cytokines, and improvements in the blood-brain barrier. IMPORTANCE Ischemic stroke is a major global health burden, and T2D is a well-known comorbidity that aggravates brain injury after ischemic stroke. However, the underlying mechanism by which T2D exacerbates stroke injury has not been completely elucidated. A large amount of evidence suggests that the gut microbiota composition affects stroke outcomes. Our results showed that the gut microbiota of T2D aggravated brain injury after ischemic stroke and could be modified by SB to afford neuroprotection against stroke injury. These findings suggest that supplementation with SB is a potential therapeutic strategy for T2D patients with ischemic stroke.}, }
@article {pmid34611194, year = {2021}, author = {Karlsen, TR and Kong, XY and Holm, S and Quiles-Jiménez, A and Dahl, TB and Yang, K and Sagen, EL and Skarpengland, T and S Øgaard, JD and Holm, K and Vestad, B and Olsen, MB and Aukrust, P and Bjørås, M and Hov, JR and Halvorsen, B and Gregersen, I}, title = {NEIL3-deficiency increases gut permeability and contributes to a pro-atherogenic metabolic phenotype.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {19749}, pmid = {34611194}, issn = {2045-2322}, abstract = {Atherosclerosis and its consequences cause considerable morbidity and mortality world-wide. We have previously shown that expression of the DNA glycosylase NEIL3 is regulated in human atherosclerotic plaques, and that NEIL3-deficiency enhances atherogenesis in Apoe-/- mice. Herein, we identified a time point prior to quantifiable differences in atherosclerosis between Apoe-/-Neil3-/- mice and Apoe-/- mice. Mice at this age were selected to explore the metabolic and pathophysiological processes preceding extensive atherogenesis in NEIL3-deficient mice. Untargeted metabolomic analysis of young Apoe-/-Neil3-/- mice revealed significant metabolic disturbances as compared to mice expressing NEIL3, particularly in metabolites dependent on the gut microbiota. 16S rRNA gene sequencing of fecal bacterial DNA indeed confirmed that the NEIL3-deficient mice had altered gut microbiota, as well as increased circulating levels of the bacterially derived molecule LPS. The mice were challenged with a FITC-conjugated dextran to explore gut permeability, which was significantly increased in the NEIL3-deficient mice. Further, immunohistochemistry showed increased levels of the proliferation marker Ki67 in the colonic epithelium of NEIL3-deficient mice, suggesting increased proliferation of intestinal cells and gut leakage. We suggest that these metabolic alterations serve as drivers of atherosclerosis in NEIL3-deficient mice.}, }
@article {pmid34608030, year = {2021}, author = {Jeney, SES and Avelar-Barragan, J and Whiteson, K and Chang, J and Dutta, S and Lane, F}, title = {Fecal Putative Uropathogen Abundance and Antibiotic Resistance Gene Carriage in Women With Refractory Recurrent Urinary Tract Infection Treated With Fecal Microbiota Transplantation.}, journal = {Female pelvic medicine &amp; reconstructive surgery}, volume = {}, number = {}, pages = {}, doi = {10.1097/SPV.0000000000001090}, pmid = {34608030}, issn = {2154-4212}, abstract = {OBJECTIVE: The aims of this study were to describe the fecal relative abundance of potentially uropathogenic bacteria and to analyze antibiotic resistance genes before and after fecal microbiota transplantation in women with recurrent urinary tract infection (UTI).<br><br>METHODS: Shotgun sequencing was performed on fecal samples from 3 donors and 4 women with recurrent UTI who underwent transplantation. Recipient samples were sequenced at baseline and at 4 time points through 6 months postintervention. Relative fecal uropathogen abundance was analyzed by species and participant using descriptive statistics. Antibiotic resistance gene abundance was assigned, normalized, and compared between donors and recipients at baseline and postintervention using an abundance bar plot, nonmetric multidimensional scaling, and pairwise permutational multivariate analysis of variance.<br><br>RESULTS: The median (range) relative abundance of Escherichia coli in all fecal samples from women with recurrent UTI was 0% (0%-5.10%); Enterococcus faecalis, 0% (0%-0.20%); Enterococcus faecium, 0% (0%-1.90%); Klebsiella pneumoniae, 0% (0%-0.10%); and Pseudomonas aeruginosa, 0% (0%-0.10%). Gut microbes carried genes conferring resistance to antibiotics used for UTI. No significant difference was seen in antibiotic resistance gene carriage after transplantation compared with baseline (P=0.22, R2=0.08 at 3 months). Antibiotic gene composition and abundance were significantly associated with the individual from whom the sample came (P=0.004, R2=0.78 at 3 months).<br><br>CONCLUSIONS: Exploratory analysis of gut microbiomes in women with recurrent UTI identifies no or low relative putative uropathogen abundance for all species examined. Antibiotic resistance gene carriage persisted after fecal microbiota transplantation, although conclusions are limited by small sample size.}, }
@article {pmid34606847, year = {2021}, author = {Lima, S and Gogokhia, L and Viladomiu, M and Chou, L and Putzel, G and Jin, W and Pires, S and Guo, CJ and Gerardin, Y and Crawford, CV and Jacob, V and Scherl, E and Brown, SE and Hambor, J and Longman, R}, title = {Transferable Immunoglobulin A-Coated Odoribacter splanchnicus in Responders to Fecal Microbiota Transplantation for Ulcerative Colitis Limits Colonic Inflammation.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2021.09.061}, pmid = {34606847}, issn = {1528-0012}, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) is an emerging treatment modality for ulcerative colitis (UC). Several randomized controlled trials have shown efficacy for FMT in the treatment of UC, but a better understanding of the transferable microbiota and their immune impact is needed to develop more efficient microbiome-based therapies for UC.<br><br>METHODS: Metagenomic analysis and strain tracking was performed on 60 donor and recipient samples receiving FMT for active UC. Sorting and sequencing of immunoglobulin (Ig) A-coated microbiota (called IgA-seq) was used to define immune-reactive microbiota. Colonization of germ-free or genetically engineered mice with patient-derived strains was performed to determine the mechanism of microbial impact on intestinal immunity.<br><br>RESULTS: Metagenomic analysis defined a core set of donor-derived transferable bacterial strains in UC subjects achieving clinical response, which predicted response in an independent trial of FMT for UC. IgA-seq of FMT recipient samples and gnotobiotic mice colonized with donor microbiota identified Odoribacter splanchnicus as a transferable strain shaping mucosal immunity, which correlated with clinical response and the induction of mucosal regulatory T cells. Colonization of mice with O splanchnicus led to an increase in Foxp3+/RORγt+ regulatory T cells, induction of interleukin10, and production of short chain fatty acids, all of which were required for O splanchnicus to limit colitis in mouse models.<br><br>CONCLUSIONS: This work provides the first evidence of transferable, donor-derived strains that correlate with clinical response to FMT in UC and reveals O splanchnicus as a key component promoting both metabolic and immune cell protection from colitis. These mechanistic features will help enable strategies to enhance the therapeutic efficacy of microbial therapy for UC. Clinicaltrials.gov ID NCT02516384.}, }
@article {pmid34604008, year = {2021}, author = {Al-Ali, D and Ahmed, A and Shafiq, A and McVeigh, C and Chaari, A and Zakaria, D and Bendriss, G}, title = {Fecal microbiota transplants: A review of emerging clinical data on applications, efficacy, and risks (2015-2020).}, journal = {Qatar medical journal}, volume = {2021}, number = {1}, pages = {5}, pmid = {34604008}, issn = {0253-8253}, abstract = {As the importance of the gut microbiota in health and disease is a subject of growing interest, fecal microbiota transplantation (FMT) was suggested as an attractive therapeutic strategy to restore homeostasis of the gut microbiota, thereby treating diseases that were associated with alteration of the gut microbiota. FMT involves the administration of fresh, frozen, or dried fecal microorganisms from the gut of a healthy donor into the intestinal tract of a patient. This rediscovery of the potential benefits of an ancient practice was accompanied by a rapid progression of our understanding of the roles and mechanisms of gut microbes in the pathogenesis of disease. With a growing number of diseases being associated with dysbiosis or the alteration of gut microbiota, FMT was suggested as an attractive therapeutic strategy to "reset the gut" and initiate clinical resolutions or remissions. The number of FMT clinical trials is increasing worldwide, but no trials are registered in the Gulf region; this suggested the need for raising awareness of the latest studies on FMT. This review presented the emergent preclinical and clinical data to give an overview of the potential clinical applications, the benefits, and inconveniences that were worth considering for eventual future testing of fecal transplants in Qatar and the Middle East. This study highlighted the diversity of methods tested and commented on the variables that can affect the assessment of the effectiveness of FMT in specific diseases. The risks associated with FMT and the threat of antimicrobial resistance for this therapeutic approach were reviewed. From gastrointestinal diseases to neurodevelopmental disorders, understanding the roles of the gut microbiota in health and disease should be at the heart of developing novel, standardized, yet personalized, methods for this ancient therapeutic approach.}, }
@article {pmid34603515, year = {2021}, author = {Baruch, EN and Gaglani, T and Wargo, JA}, title = {Fecal microbiota transplantation as a mean of overcoming immunotherapy-resistant cancers - hype or hope?.}, journal = {Therapeutic advances in medical oncology}, volume = {13}, number = {}, pages = {17588359211045853}, pmid = {34603515}, issn = {1758-8340}, }
@article {pmid34602643, year = {2021}, author = {Costa, M and Di Pietro, R and Bessegatto, JA and Pereira, PFV and Stievani, FC and Gomes, RG and Lisbôa, JAN and Weese, JS}, title = {Evaluation of changes in microbiota after fecal microbiota transplantation in 6 diarrheic horses.}, journal = {The Canadian veterinary journal = La revue veterinaire canadienne}, volume = {62}, number = {10}, pages = {1123-1130}, pmid = {34602643}, issn = {0008-5286}, mesh = {Animals ; Bacteria ; Diarrhea/therapy/veterinary ; *Fecal Microbiota Transplantation/veterinary ; Feces ; Horses ; *Microbiota ; Treatment Outcome ; }, abstract = {The purpose of this study was to characterize the fecal microbiota of horses with acute and chronic diarrhea before and after fecal microbiota transplantation (FMT). Six client-owned horses with acute and chronic diarrhea received FMT from 2 healthy donor horses. Microbiota analysis using next-generation sequencing was performed on fecal samples collected before and 2 and 7 d after FMT. Signs of diarrhea improved in 4 horses, whereas the remaining 2 horses did not survive. There was a significant difference in the number of bacterial species between donors and recipients (P < 0.05). The Order Lactobacillales and the genera Lactobacillus, Intestinimonas, and Streptococcus were increased in the microbiota of diarrheic horses, and Saccharofermentans genus increased in healthy donors. The results suggest that FMT from the healthy donors was not effective over a 7-day period as it did not change the fecal microbiota of the diarrheic horses. Further research to improve the efficacy of FMT in horses is needed.}, }
@article {pmid34598315, year = {2021}, author = {Czarnecka, K and Czarnecka, P and Tronina, O and Bączkowska, T and Durlik, M}, title = {Multidirectional facets of obesity management in the metabolic syndrome population after liver transplantation.}, journal = {Immunity, inflammation and disease}, volume = {}, number = {}, pages = {}, doi = {10.1002/iid3.538}, pmid = {34598315}, issn = {2050-4527}, abstract = {The obesity pandemic has resulted in an increasing demand for liver transplantation and has significantly altered the profile of liver transplant candidates in addition to affecting posttransplantation outcomes. In this review, we discuss a broad range of clinical approaches that warrant attention to provide comprehensive and patient-centred medical care to liver transplant recipients, and to be prepared to confront the rapidly changing clinical challenges and ensuing dilemmas. Adipose tissue is a complex and metabolically active organ. Visceral fat deposition is a key predictor of overall obesity-related morbidity and mortality. Limited pharmacological options are available for the treatment of obesity in the liver transplant population. Bariatric surgery may be an alternative in eligible patients. The rapidly increasing prevalence of nonalcoholic fatty liver disease (NAFLD) is a global concern; NAFLD affects both pre- and posttransplantation outcomes. Numerous studies have investigated pharmacological and nonpharmacological management of NAFLD and some of these have shown promising results. Liver transplant recipients are constantly exposed to numerous factors that result in intestinal microbiota alterations, which were linked to the development of obesity, diabetes type 2, metabolic syndrome (MS), NAFLD, and hepatocellular cancer. Microbiota modifications with probiotics and prebiotics bring gratifying results in the management of metabolic complications. Fecal microbiota transplantation (FMT) is successfully performed in many medical indications. However, the safety and efficacy profiles of FMT in immunocompromised patients remain unclear. Obesity together with immunosuppressive treatment, may affect the pharmacokinetic and/or pharmacodynamic properties of coadministered medications. Individualized immunosuppressive regimens are recommended following liver transplantation to address possible metabolic concerns. Effective and comprehensive management of metabolic complications is shown to yield multiple beneficial results in the liver transplant population and may bring gratifying results in improving long-term survival rates.}, }
@article {pmid34596608, year = {2021}, author = {Nicholson, MR and Kahn, SA}, title = {Fecal Microbiota Transplantation for Ulcerative Colitis: Dispelling the "Yuck Factor".}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {73}, number = {6}, pages = {663-664}, doi = {10.1097/MPG.0000000000003315}, pmid = {34596608}, issn = {1536-4801}, }
@article {pmid34589510, year = {2021}, author = {Rong, Z and Huang, Y and Cai, H and Chen, M and Wang, H and Liu, G and Zhang, Z and Wu, J}, title = {Gut Microbiota Disorders Promote Inflammation and Aggravate Spinal Cord Injury Through the TLR4/MyD88 Signaling Pathway.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {702659}, pmid = {34589510}, issn = {2296-861X}, abstract = {Background: In spinal cord injury (SCI), systemic inflammation and the death of nerve cells in the spinal cord are life threatening. The connection between gut microbiota and signaling pathways has been a hot research topic in recent years. The Toll-like receptor 4/Myeloid differentiation factor 88 (TLR4/MyD88) signaling pathway is closely related to the inflammatory response. This study explored whether the gut microbiota imbalance could affect the TLR4/MyD88 signaling pathway to regulate SCI to provide a new basis for SCI research and treatment. Methods: An SCI model was constructed to study the influence on the injury of gut microbiota. 16S amplicon sequencing was used to identify the diversity and abundance of gut microbes. Fecal microbiota transplantation was performed in mice with SCI. ELISA was used to detect the serum levels of pro-inflammatory and anti-inflammatory factors in mice. Hematoxylin and eosin staining was used to observe SCI in mice. Immunofluorescence was used to detect the rates of loss glial fibrillary acidic protein (GFAP), neuronal nuclear protein (NeuN), and ionized calcium-binding adapter molecule 1 (IBA1) in the spinal cord as indicators of apoptosis. The expression of the TLR4/MyD88 signaling pathway was detected by qRT-PCR and western blotting. Results: Significant differences were observed in the gut microbiota of SCI mice and normal mice. The gut microbiota of SCI mice was imbalanced. The levels of pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in SCI mice were increased, as was the level of the toxic induced nitric oxide synthase. The levels of anti-inflammatory factors IL-4, transforming growth factor-β, and IL-10 were decreased, as was the level of arginase-1. The apoptosis rates of GFAP, NeuN, and IBA1 were increased. The TLR4/MyD88 signaling pathway was activated. In the SCI group, inflammation increased after fecal transplantation, apoptosis of GFAP, NeuN, and IBA1 increased, and SCI was more serious. Conclusion: The TLR4/MyD88 signaling pathway promotes the death of nerve cells by inducing inflammation. Gut microbiota dysregulation can lead to aggravated SCI by activating the TLR4/MyD88 signaling pathway.}, }
@article {pmid34589427, year = {2021}, author = {Li, B and Gong, T and Hao, Y and Zhou, X and Cheng, L}, title = {Mining the Gut Microbiota for Microbial-Based Therapeutic Strategies in Cancer Immunotherapy.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {721249}, pmid = {34589427}, issn = {2234-943X}, abstract = {The past two decades witnessed a revolution in our understanding of host-microbiota interactions that led to the concept of the super-organism consisting of a eukaryotic part and a prokaryotic part. Owing to the critical role of gut microbiota in modulating the host immune system, it is not beyond all expectations that more and more evidence indicated that the shift of gut microbiota influenced responses to numerous forms of cancer immunotherapy. Therapy targeting gut microbiota is becoming a promising strategy to improve cancer immunotherapy. In this review, we discuss the role of the gut microbiota in response to cancer immunotherapy, the mechanisms that the gut microbiota influences cancer immunotherapy, and therapeutic strategies targeting gut microbiota to improve cancer immunotherapy.}, }
@article {pmid34588747, year = {2021}, author = {Milosevic, I and Russo, E and Vujovic, A and Barac, A and Stevanovic, O and Gitto, S and Amedei, A}, title = {Microbiota and viral hepatitis: State of the art of a complex matter.}, journal = {World journal of gastroenterology}, volume = {27}, number = {33}, pages = {5488-5501}, pmid = {34588747}, issn = {2219-2840}, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Hepatitis, Viral, Human ; Humans ; *Microbiota ; }, abstract = {Changes in gut microbiota influence both the gut and liver, which are strictly connected by the so-called "gut-liver axis". The gut microbiota acts as a major determinant of this relationship in the onset and clinical course of liver diseases. According to the results of several studies, gut dysbiosis is linked to viral hepatitis, mainly hepatitis C virus and hepatitis B virus infection. Gut bacteria-derived metabolites and cellular components are key molecules that affect liver function and modulate the pathology of viral hepatitis. Recent studies showed that the gut microbiota produces various molecules, such as peptidoglycans, lipopolysaccharides, DNA, lipoteichoic acid, indole-derivatives, bile acids, and trimethylamine, which are translocated to the liver and interact with liver immune cells causing pathological effects. Therefore, the existence of crosstalk between the gut microbiota and the liver and its implications on host health and pathologic status are essential factors impacting the etiology and therapeutic approach. Concrete mechanisms behind the pathogenic role of gut-derived components on the pathogenesis of viral hepatitis remain unclear and not understood. In this review, we discuss the current findings of research on the bidirectional relationship of the components of gut microbiota and the progression of liver diseases and viral hepatitis and vice versa. Moreover, this paper highlights the current therapeutic and preventive strategies, such as fecal transplantation, used to restore the gut microbiota composition and so improve host health.}, }
@article {pmid34588617, year = {2021}, author = {Xie, X and Liu, J and Chen, X and Zhang, S and Tang, R and Wu, X and Zhang, W and Cao, Y}, title = {Gut microbiota involved in leptospiral infections.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, pmid = {34588617}, issn = {1751-7370}, support = {32172872//National Natural Science Foundation of China (National Science Foundation of China)/ ; 31572582//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Leptospirosis is a re-emerging zoonotic disease worldwide. Intestinal bleeding is a common but neglected symptom in severe leptospirosis. The regulatory mechanism of the gut microbiota on leptospirosis is still unclear. In this study, we found that Leptospira interrogans infection changed the composition of the gut microbiota in mice. Weight loss and an increased leptospiral load in organs were observed in the gut microbiota-depleted mice compared with those in the control mice. Moreover, fecal microbiota transplantation (FMT) to the microbiota-depleted mice reversed these effects. The phagocytosis response and inflammatory response in bone marrow-derived macrophages and thioglycolate-induced peritoneal macrophages were diminished in the microbiota-depleted mice after infection. However, the phagocytosis response and inflammatory response in resident peritoneal macrophage were not affected in the microbiota-depleted mice after infection. The diminished macrophage disappearance reaction (bacterial entry into the peritoneum acutely induced macrophage adherence to form local clots and out of the fluid phase) led to an increased leptospiral load in the peritoneal cavity in the microbiota-depleted mice. In addition, the impaired capacity of macrophages to clear leptospires increased leptospiral dissemination in Leptospira-infected microbiota-depleted mice. Our study identified the microbiota as an endogenous defense against L. interrogans infection. Modulating the structure and function of the gut microbiota may provide new individualized preventative strategies for the control of leptospirosis and related spirochetal infections.}, }
@article {pmid34587331, year = {2021}, author = {Biliński, J and Jasiński, M and Tomaszewska, A and Lis, K and Kacprzyk, P and Chmielewska, L and Karakulska-Prystupiuk, E and Mullish, BH and Basak, GW}, title = {Fecal microbiota transplantation with ruxolitinib as a treatment modality for steroid-refractory/dependent acute, gastrointestinal graft-versus-host disease: A case series.}, journal = {American journal of hematology}, volume = {96}, number = {12}, pages = {E461-E463}, doi = {10.1002/ajh.26365}, pmid = {34587331}, issn = {1096-8652}, support = {//Imperial College London/ ; //NIHR Imperial Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust/ ; CL-2019-21-002//NIHR Academic Clinical Lectureship/ ; }, }
@article {pmid34586012, year = {2021}, author = {Pothuraju, R and Chaudhary, S and Rachagani, S and Kaur, S and Roy, HK and Bouvet, M and Batra, SK}, title = {Mucins, gut microbiota, and postbiotics role in colorectal cancer.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1974795}, pmid = {34586012}, issn = {1949-0984}, support = {R01 CA247471/CA/NCI NIH HHS/United States ; R01 CA254036/CA/NCI NIH HHS/United States ; I01 BX004494/BX/BLRD VA/United States ; R43 CA235984/CA/NCI NIH HHS/United States ; P01 CA217798/CA/NCI NIH HHS/United States ; }, abstract = {An imbalance in the crosstalk between the host and gut microbiota affects the intestinal barrier function, which results in inflammatory diseases and colorectal cancer. The colon epithelium protects itself from a harsh environment and various pathogenic organisms by forming a double mucus layer, primarily comprising mucins. Recent studies are focusing on how dietary patterns alter the gut microbiota composition, which in turn regulates mucin expression and maintains the intestinal layers. In addition, modulation of gut microbiota by microbiotic therapy (involving fecal microbiota transplantation) has emerged as a significant factor in the pathologies associated with dysbiosis. Therefore, proper communication between host and gut microbiota via different dietary patterns (prebiotics and probiotics) is needed to maintain mucus composition, mucin synthesis, and regulation. Here, we review how the interactions between diet and gut microbiota and bacterial metabolites (postbiotics) regulate mucus layer functionalities and mucin expression in human health and disease.}, }
@article {pmid34586011, year = {2021}, author = {Secombe, KR and Al-Qadami, GH and Subramaniam, CB and Bowen, JM and Scott, J and Van Sebille, YZA and Snelson, M and Cowan, C and Clarke, G and Gheorghe, CE and Cryan, JF and Wardill, HR}, title = {Guidelines for reporting on animal fecal transplantation (GRAFT) studies: recommendations from a systematic review of murine transplantation protocols.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1979878}, pmid = {34586011}, issn = {1949-0984}, abstract = {Fecal microbiota transplant (FMT) is a powerful tool used to connect changes in gut microbial composition with a variety of disease states and pathologies. While FMT enables potential causal relationships to be identified, the experimental details reported in preclinical FMT protocols are highly inconsistent and/or incomplete. This limitation reflects a current lack of authoritative guidance on reporting standards that would facilitate replication efforts and ultimately reproducible science. We therefore systematically reviewed all FMT protocols used in mouse models with the goal of formulating recommendations on the reporting of preclinical FMT protocols. Search strategies were applied across three databases (PubMed, EMBASE, and Ovid Medline) until June 30, 2020. Data related to donor attributes, stool collection, processing/storage, recipient preparation, administration, and quality control were extracted. A total of 1753 papers were identified, with 241 identified for data extraction and analysis. Of the papers included, 92.5% reported a positive outcome with FMT intervention. However, the vast majority of studies failed to address core methodological aspects including the use of anaerobic conditions (91.7% of papers lacked information), storage (49.4%), homogenization (33.6%), concentration (31.5%), volume (19.9%) and administration route (5.3%). To address these reporting limitations, we developed theGuidelines for Reporting Animal Fecal Transplant (GRAFT) that guide reporting standards for preclinical FMT. The GRAFT recommendations will enable robust reporting of preclinical FMT design, and facilitate high-quality peer review, improving the rigor and translation of knowledge gained through preclinical FMT studies.}, }
@article {pmid34585961, year = {2021}, author = {Zhang, Z and Xu, D and Fang, J and Wang, D and Zeng, J and Liu, X and Hong, S and Xue, Y and Zhang, X and Zhao, X}, title = {In Situ Live Imaging of Gut Microbiota.}, journal = {mSphere}, volume = {6}, number = {5}, pages = {e0054521}, pmid = {34585961}, issn = {2379-5042}, support = {SKLVD2018KF005//Open Research of the State Key Laboratory of Molecular Vaccinology and Molecular Diagnosis/ ; 31741006//National Natural Science Foundation of China (NSFC)/ ; }, abstract = {Most studies of gut microbiota have focused on relationships between a specific disease and the presence/abundance of one or a few bacterial species/genera. Whether the spatial and temporal distribution of gut microbiota, as a whole, affects or correlates with health is unknown, largely due to the absence of tools for dynamically monitoring the overall gut microbiota landscape inside living subjects. Here, we describe a novel, noninvasive, live imaging method for gut microbiota using 2-deoxy-2-[18F]fluoro-d-sorbitol (18F-FDS), a compound that specifically labeled gut bacteria in mice and hamsters following oral administration. Positron emission tomography-computed tomography (PET-CT) scanning showed that the radiolabel signal was concentrated in the gut (especially the large intestine), was absent when mice gut microbiota was depleted by antibiotic treatment, and was restored after transplanting antibiotic-treated mice with a fecal or probiotic bacterial mixture. Thus, 18F-FDS images microbiota, not gut tissue. The tissue distribution of 18F-FDS was the highest in the gut (∼3-fold higher than average), in contrast to 2-deoxy-2-[18F]fluoro-d-glucose, which concentrated in brain and many other organs. 2-[18F]fluoro-aminobenzoic acid, another bacterium-specific radioactive tracer, was unsuited for gut microbiota imaging due to unexpected stomach retention following oral administration. When similar gut microbiota imaging was done with hamsters, the spatial resolution increased significantly over that with mice, suggesting that even higher spatial resolution can be achieved with humans or large animals. Thus, our work establishes a new tool for noninvasive, live imaging of gut microbiota; the new tool may enable exploration of relationships between gut microbiota landscape and diseases in clinical settings. IMPORTANCE Gut microbiota dysbiosis correlates with many diseases, but such correlations derive mostly from relationships between one or a few bacteria and a particular disease. Since microbiota resemble complex forest ecosystems more closely than individual patches of trees, the overall landscape (spatial and temporal distribution) of gut bacteria may also affect/reflect disease development. Such a possibility has not been explored due to a lack of tools for directly visualizing natural landscape patterns of gut microbiota. The present work identified 2-deoxy-2-[18F]fluoro-d-sorbitol as a gut microbiota-specific radioactive tracer and developed a novel PET-CT scan-based imaging method that enables noninvasive, real-time imaging of the overall gut bacterial landscape. The method showed increased spatial resolution when hamsters replaced mice, suggesting that even higher spatial resolution could be achieved with larger animals such as humans. This novel technology establishes the feasibility of investigating spatial-temporal distribution dynamics of gut microbiota with many human diseases.}, }
@article {pmid34584982, year = {2021}, author = {Bryant, RV and Day, AS and McGrath, KC and Telfer, K and Yao, CK and Costello, SP}, title = {Fecal microbiota transplantation augmented by a sulfide-reducing diet for refractory ulcerative colitis: A case report with functional metagenomic analysis.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {5}, number = {9}, pages = {1099-1102}, pmid = {34584982}, issn = {2397-9070}, abstract = {Fecal microbiota transplantation (FMT) is effective for induction of remission in ulcerative colitis (UC). Diet has potential to augment the efficacy and durability of FMT by encouraging engraftment of transplanted microorganisms. A trial of FMT combined with a defined diet was undertaken as salvage therapy for a 71-year-old woman with active steroid-refractory extensive UC. A multidimensional sulfide-reducing diet (4-SURE diet) was commenced followed by single-donor FMT administered by colonoscopy and then enemas over 7 days. Dietary adherence, clinical evaluation, and stool samples for metagenomic profiling were undertaken at weeks 0, 4, 8, and 24. Colonoscopy was performed 8 weeks post-FMT. Shotgun metagenomic profiling of the donor fecal suspension was also performed. A rapid clinical response to FMT and 4-SURE diet was observed with normalization of stool frequency (≤2 motions/day) and resolution of rectal bleeding within 2 weeks. Dietary adherence was excellent. Colonoscopy at week 8 revealed no evidence of active colitis (Mayo endoscopic sub-score 0) with histology showing no evidence of acute or chronic lamina propria inflammatory cell infiltrate. Sustained clinical and endoscopic remission out to 24 weeks was observed. Metagenomic sequencing confirmed sustained engraftment of beneficial donor microbiota with increased alpha-diversity and capacity for short-chain fatty acid production, including Faecalibacterium prauznitzii and Eubacterium hallii. This case report supports the rationale of prescribed diet therapy to support engraftment of donor microbiota following FMT for UC. Further large trials with a diet-arm control group are needed to evaluate FMT augmented by a defined diet in UC.}, }
@article {pmid34584964, year = {2021}, author = {Wei, L and Singh, R and Ro, S and Ghoshal, UC}, title = {Gut microbiota dysbiosis in functional gastrointestinal disorders: Underpinning the symptoms and pathophysiology.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {5}, number = {9}, pages = {976-987}, pmid = {34584964}, issn = {2397-9070}, abstract = {Functional gastrointestinal disorders (FGIDs), currently known as disorders of gut-brain interaction, are emerging microbiota-gut-brain abnormalities that are prevalent worldwide. The pathogenesis of FGIDs is heterogeneous and is intertwined with gut microbiota and its derived molecule-modulated mechanisms, including gut dysmotility, visceral hypersensitivity, gut immune abnormalities, abnormal secretion, and impaired barrier function. There has been phenomenal progress in understanding the role of gut microbiota in FGIDs by underpinning the species alternations between healthy and pathological conditions such as FGIDs. However, the precise gut microbiota-directed cellular and molecular pathogeneses of FGIDs are yet enigmatic. Determining the mechanistic link between the gut microbiota and gastrointestinal (GI) diseases has been difficult due to (i) the lack of robust animal models imitating the various aspects of human FGID pathophysiology; (ii) the absence of longitudinal human and/or animal studies to unveil the interaction of the gut microbiota with FGID-relevant pathogenesis; (iii) uncertainty about connections between human and animal studies; and (iv) insufficient data supporting a holistic view of disease-specific pathophysiological changes in FGID patients. These unidentified gaps open possibilities to explore pathological mechanisms directed through gut microbiota dysbiosis in FGIDs. The current treatment options for dysbiotic gut microbiota are limited; dietary interventions, antibiotics, probiotics, and fecal microbiota transplantation are the front-line clinical options. Here, we review the contribution of gut microbiota and its derived molecules in gut homeostasis and explore the possible pathophysiological mechanisms involved in FGIDs leading to potential therapeutics options.}, }
@article {pmid34580907, year = {2021}, author = {Huang, HL and Xu, HM and Liu, YD and Shou, DW and Nie, YQ and Chen, HT and Zhou, YJ}, title = {Fecal microbiota transplantation as a novel approach for the treatment of atopic dermatitis.}, journal = {The Journal of dermatology}, volume = {48}, number = {12}, pages = {e574-e576}, doi = {10.1111/1346-8138.16169}, pmid = {34580907}, issn = {1346-8138}, }
@article {pmid34580445, year = {2021}, author = {Aggarwala, V and Mogno, I and Li, Z and Yang, C and Britton, GJ and Chen-Liaw, A and Mitcham, J and Bongers, G and Gevers, D and Clemente, JC and Colombel, JF and Grinspan, A and Faith, J}, title = {Precise quantification of bacterial strains after fecal microbiota transplantation delineates long-term engraftment and explains outcomes.}, journal = {Nature microbiology}, volume = {6}, number = {10}, pages = {1309-1318}, pmid = {34580445}, issn = {2058-5276}, support = {R01 DK123749/DK/NIDDK NIH HHS/United States ; U01 DK124165/DK/NIDDK NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 DK124133/DK/NIDDK NIH HHS/United States ; }, mesh = {Algorithms ; Bacteria/classification/genetics/*isolation &amp; purification ; Benchmarking ; Clostridioides difficile/physiology ; Clostridium Infections/microbiology/therapy ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Longitudinal Studies ; Metagenome/genetics ; Recurrence ; Tissue Donors ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) has been successfully applied to treat recurrent Clostridium difficile infection in humans, but a precise method to measure which bacterial strains stably engraft in recipients and evaluate their association with clinical outcomes is lacking. We assembled a collection of >1,000 different bacterial strains that were cultured from the fecal samples of 22 FMT donors and recipients. Using our strain collection combined with metagenomic sequencing data from the same samples, we developed a statistical approach named Strainer for the detection and tracking of bacterial strains from metagenomic sequencing data. We applied Strainer to evaluate a cohort of 13 FMT longitudinal clinical interventions and detected stable engraftment of 71% of donor microbiota strains in recipients up to 5 years post-FMT. We found that 80% of recipient gut bacterial strains pre-FMT were eliminated by FMT and that post-FMT the strains present persisted up to 5 years later, together with environmentally acquired strains. Quantification of donor bacterial strain engraftment in recipients independently explained (precision 100%, recall 95%) the clinical outcomes (relapse or success) after initial and repeat FMT. We report a compendium of bacterial species and strains that consistently engraft in recipients over time that could be used in defined live biotherapeutic products as an alternative to FMT. Our analytical framework and Strainer can be applied to systematically evaluate either FMT or defined live bacterial therapeutic studies by quantification of strain engraftment in recipients.}, }
@article {pmid34579027, year = {2021}, author = {Yang, M and Gu, Y and Li, L and Liu, T and Song, X and Sun, Y and Cao, X and Wang, B and Jiang, K and Cao, H}, title = {Bile Acid-Gut Microbiota Axis in Inflammatory Bowel Disease: From Bench to Bedside.}, journal = {Nutrients}, volume = {13}, number = {9}, pages = {}, pmid = {34579027}, issn = {2072-6643}, support = {82070545 and 81970477//National Natural Science Foundation of China/ ; 20YFZCSY00020//Key Project of Science and Technology Pillar Program of Tianjin/ ; }, mesh = {Animals ; Bile Acids and Salts/metabolism/*physiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammatory Bowel Diseases/*etiology ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, with increasing prevalence, and its pathogenesis remains unclear. Accumulating evidence suggested that gut microbiota and bile acids play pivotal roles in intestinal homeostasis and inflammation. Patients with IBD exhibit decreased microbial diversity and abnormal microbial composition marked by the depletion of phylum Firmicutes (including bacteria involved in bile acid metabolism) and the enrichment of phylum Proteobacteria. Dysbiosis leads to blocked bile acid transformation. Thus, the concentration of primary and conjugated bile acids is elevated at the expense of secondary bile acids in IBD. In turn, bile acids could modulate the microbial community. Gut dysbiosis and disturbed bile acids impair the gut barrier and immunity. Several therapies, such as diets, probiotics, prebiotics, engineered bacteria, fecal microbiota transplantation and ursodeoxycholic acid, may alleviate IBD by restoring gut microbiota and bile acids. Thus, the bile acid-gut microbiota axis is closely connected with IBD pathogenesis. Regulation of this axis may be a novel option for treating IBD.}, }
@article {pmid34578169, year = {2021}, author = {Goodman-Davis, R and Figurska, M and Cywinska, A}, title = {Gut Microbiota Manipulation in Foals-Naturopathic Diarrhea Management, or Unsubstantiated Folly?.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {9}, pages = {}, pmid = {34578169}, issn = {2076-0817}, abstract = {Diarrhea in foals is a problem of significant clinical and economic consequence, and there are good reasons to believe microbiota manipulation can play an important role in its management. However, given the dynamic development of the foal microbiota and its importance in health and disease, any prophylactic or therapeutic efforts to alter its composition should be evidence based. The few clinical trials of probiotic preparations conducted in foals to date show underwhelming evidence of efficacy and a demonstrated potential to aggravate rather than mitigate diarrhea. Furthermore, recent studies have affirmed that variable but universally inadequate quality control of probiotics enables inadvertent administration of toxin-producing or otherwise pathogenic bacterial strains, as well as strains bearing transferrable antimicrobial resistance genes. Consequently, it seems advisable to approach probiotic therapy in particular with caution for the time being. While prebiotics show initial promise, an even greater scarcity of clinical trials makes it impossible to weigh the pros and cons of their use. Advancing technology will surely continue to enable more detailed and accurate mapping of the equine adult and juvenile microbiota and potentially elucidate the complexities of causation in dysbiosis and disease. In the meantime, fecal microbiota transplantation may be an attractive therapeutic shortcut, allowing practitioners to reconstruct a healthy microbiota even without fully understanding its constitution.}, }
@article {pmid34576740, year = {2021}, author = {Kouidhi, S and Souai, N and Zidi, O and Mosbah, A and Lakhal, A and Ben Othmane, T and Belloumi, D and Ben Ayed, F and Asimakis, E and Stathopoulou, P and Cherif, A and Tsiamis, G}, title = {High Throughput Analysis Reveals Changes in Gut Microbiota and Specific Fecal Metabolomic Signature in Hematopoietic Stem Cell Transplant Patients.}, journal = {Microorganisms}, volume = {9}, number = {9}, pages = {}, pmid = {34576740}, issn = {2076-2607}, support = {KA107//Erasmus+/ ; LR11ES31//LBVBGR/ ; }, abstract = {There is mounting evidence for the emerging role of gut microbiota (GM) and its metabolites in profoundly impacting allogenic hematopoietic stem cell transplantation (allo-HSCT) and its subsequent complications, mainly infections and graft versus host-disease (GvHD). The present study was performed in order to investigate changes in GM composition and fecal metabolic signature between transplant patients (n = 15) and healthy controls (n = 18). The intestinal microbiota was characterized by NGS and gas chromatography-mass spectrometry was employed to perform untargeted analysis of fecal metabolites. We found lower relative abundances of Actinobacteria, Firmicutes, and Bacteroidetes and a higher abundance of Proteobacteria phylum after allo-HSCT. Particularly, the GvHD microbiota was characterized by a lower relative abundance of the short-chain fatty acid-producing bacteria, namely, the Feacalibacterium, Akkermansia, and Veillonella genera and the Lachnospiraceae family, and an enrichment in multidrug-resistant bacteria belonging to Escherichia, Shigella, and Bacteroides. Moreover, network analysis showed that GvHD was linked to a higher number of positive interactions of Blautia and a significant mutual-exclusion rate of Citrobacter. The fecal metabolome was dominated by lipids in the transplant group when compared with the healthy individuals (p < 0.05). Overall, 76 metabolites were significantly altered within transplant recipients, of which 24 were selected as potential biomarkers. Furthermore, the most notable altered metabolic pathways included the TCA cycle; butanoate, propanoate, and pyruvate metabolisms; steroid biosynthesis; and glycolysis/gluconeogenesis. Specific biomarkers and altered metabolic pathways were correlated to GvHD onset. Our results showed significant shifts in gut microbiota structure and fecal metabolites characterizing allo-HSCT.}, }
@article {pmid34575166, year = {2021}, author = {Stojek, M and Jabłońska, A and Adrych, K}, title = {The Role of Fecal Microbiota Transplantation in the Treatment of Inflammatory Bowel Disease.}, journal = {Journal of clinical medicine}, volume = {10}, number = {18}, pages = {}, pmid = {34575166}, issn = {2077-0383}, abstract = {The exact pathogenesis of inflammatory bowel disease (IBD) is still not completely understood. It is hypothesized that a genetic predisposition leads to an exaggerated immune response to an environmental trigger, leading to uncontrolled inflammation. As there is no known causative treatment, current management strategies for inflammatory bowel disease focus on correcting the excessive immune response to environmental (including microbial) triggers. In recent years, there has been growing interest in new avenues of treatment, including targeting the microbial environment itself. Fecal microbiota transplantation (FMT) is a novel treatment modality showing promising results in early studies. The article discusses the rationale for the use of FMT in inflammatory bowel disease and the yet-unresolved questions surrounding its optimal use in practice.}, }
@article {pmid34573670, year = {2021}, author = {Rosa, F and Michelotti, TC and St-Pierre, B and Trevisi, E and Osorio, JS}, title = {Early Life Fecal Microbiota Transplantation in Neonatal Dairy Calves Promotes Growth Performance and Alleviates Inflammation and Oxidative Stress during Weaning.}, journal = {Animals : an open access journal from MDPI}, volume = {11}, number = {9}, pages = {}, pmid = {34573670}, issn = {2076-2615}, support = {SD00H612-16//U.S. Department of Agriculture/ ; }, abstract = {This study aimed to evaluate the effects of early life fecal microbiota transplantation (FMT) on the health and performance of neonatal dairy calves. The donor was selected based on health and production records and fecal material testing negative for infectious pathogens. Sixteen healthy newborn Holstein calves were randomized to either a baseline nutritional program (CON) or 1×/d inoculations with 25 g of fecal donor material (FMT) mixed in the milk replacer (n = 8/TRT) from 8 to 12 days of age. Blood and fecal samples were collected weekly, and calves were weaned at 7 weeks of age. A TRT × Week interaction was observed in haptoglobin, which was reflected in a positive quadratic effect in FMT calves but not in CON. A trend for a TRT × Week interaction was observed in the liver function biomarker paraoxonase, which resulted in greater paraoxonase in FMT calves than CON at three weeks of age. Fecal microbial community analysis revealed a significant increase in the alpha-diversity between week 1 and week 5 for the FMT calves. These results suggest that early life FMT in neonatal calves has positive effects in mediating the inflammatory response and gut microbial maturation.}, }
@article {pmid34572894, year = {2021}, author = {Kaźmierczak-Siedlecka, K and Skonieczna-Żydecka, K and Biliński, J and Roviello, G and Iannone, LF and Atzeni, A and Sobocki, BK and Połom, K}, title = {Gut Microbiome Modulation and Faecal Microbiota Transplantation Following Allogenic Hematopoietic Stem Cell Transplantation.}, journal = {Cancers}, volume = {13}, number = {18}, pages = {}, pmid = {34572894}, issn = {2072-6694}, abstract = {Nowadays, allogenic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy that is mainly recommended for hematologic malignancies. However, complications (such as graft-versus-host disease, mucositis, disease relapse, and infections) associated with the HSCT procedure contribute to the development of gut microbiota imbalance, gut-barrier disruption, and increased intestinal permeability. In the present narrative review, the crosstalk between gut microbiota products and intestinal homeostasis is discussed. Notably, gut-microbiota-related aspects have an impact on patients' clinical outcomes and overall survival. In accordance with the most recent published data, gut microbiota is crucial for the treatment effectiveness of many diseases, not only gastrointestinal cancers but also hematologic malignancies. Therefore, it is necessary to indicate a therapeutic method allowing to modulate gut microbiota in HSCT recipients. Currently, fecal microbiota transplantation (FMT) is the most innovative method used to alter/restore gut microbiota composition, as well as modulate its activity. Despite the fact that some previous data have shown promising results, the knowledge regarding FMT in HSCT is still strongly limited, except for the treatment of Clostridium difficile infection. Additionally, administration of prebiotics, probiotics, synbiotics, and postbiotics can also modify gut microbiota; however, this strategy should be considered carefully due to the high risk of fungemia/septicemia (especially in case of fungal probiotics).}, }
@article {pmid34571151, year = {2021}, author = {Yu, DH and Ying, N and Lian, ZH and Fa, YQ}, title = {The Alteration human of gut microbiota and metabolites before and after renal transplantation.}, journal = {Microbial pathogenesis}, volume = {160}, number = {}, pages = {105191}, doi = {10.1016/j.micpath.2021.105191}, pmid = {34571151}, issn = {1096-1208}, mesh = {Feces ; *Gastrointestinal Microbiome ; Humans ; *Kidney Transplantation ; RNA, Ribosomal, 16S/genetics ; Transplant Recipients ; }, abstract = {BACKGROUND: Recent studies have revealed that gut microbiota play an important part in the regulation of the immune function. With the development of newer detection methods, our cognition of the human gut microbiota continues to evolve with startling speed, but our understanding of the changes in the structure and function of gut microbiota before and after renal transplantation and the practical applications of this knowledge are still in their infancy.<br><br>METHODS: We prospectively recruited 10 renal transplant recipients and collected serial fecal specimens (N = 30) before the operation, and on the 7th and 30th day after the operation, and characterized their gut microbiota structure through deep sequencing of the 16S rRNA V4-V5 variable region and analyzed the presence of metabolites using LC-MS methods.<br><br>RESULTS: A decrease in the relative abundance of overall gut microbiota was detected in post-transplantation samples compared to that in pre-transplantation samples. Principal coordinate analysis (PCoA) inhibited a obvious separation between the three groups, and the linear discriminant analysis effect size (LEfSe) method showed that Clostridiales, Clostridia, Ruminococcaceae, Faecalibacterium, and Veillonellaceae were all significantly more abundant in the fecal specimens from the pre-transplantation group while Bacilli, Enterococcaceae, and Enterococcus were significantly more abundant in the fecal specimens from the four weeks post-transplantation group. Anaerostipes and Clostridia-bacterium were detected in the fecal samples from the one week post-transplantation group. Analysis of community composition did not reveal any significant difference between the pre-transplantation group and the post-transplantation group. The metabolic profiling of the volunteers before renal transplantation were distinct from the post-transplantation profiling, which gather together in PCA (Fig. 4A). After renal transplantation, the metabolic profiling of post-transplantation specimens revealed marked diversity and complexity.<br><br>CONCLUSIONS: Our research indicated remarkable variations in the gut microbiota and metabolites following renal transplantation, and that the gut microbiota and metabolites of patients with uremia were relatively stable and showed reasonable concordance. Distinct microbial compositions and metabolites were observed in patients after transplantation.}, }
@article {pmid34560321, year = {2021}, author = {Zuo, T and Wu, X and Wen, W and Lan, P}, title = {Gut Microbiome Alterations in COVID-19.}, journal = {Genomics, proteomics &amp; bioinformatics}, volume = {}, number = {}, pages = {}, pmid = {34560321}, issn = {2210-3244}, abstract = {Since the outset of the coronavirus disease 2019 (COVID-19) pandemic, the gut microbiome in COVID-19 has garnered substantial interest, given its significant roles in human health and pathophysiology. Accumulating evidence is unveiling that the gut microbiome is broadly altered in COVID-19, including the bacterial microbiome, mycobiome, and virome. Overall, the gut microbial ecological network is significantly weakened and becomes sparse in patients with COVID-19, together with a decrease in gut microbiome diversity. Beyond the existence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the gut microbiome of patients with COVID-19 is also characterized by enrichment of opportunistic bacteria, fungi, and eukaryotic viruses, which are also associated with disease severity and presentation. Meanwhile, a multitude of symbiotic bacteria and bacteriophages are decreased in abundance in patients with COVID-19. Such gut microbiome features persist in a significant subset of patients with COVID-19 even after disease resolution, coinciding with 'long COVID' (also known as post-acute sequelae of COVID-19). The broadly-altered gut microbiome is largely a consequence of SARS-CoV-2 infection and its downstream detrimental effects on the systemic host immunity and the gut milieu. The impaired host immunity and distorted gut microbial ecology, particularly loss of low-abundance beneficial bacteria and blooms of opportunistic fungi including Candida, may hinder the re-assembly of the gut microbiome post COVID-19. Future investigation is necessary to fully understand the role of the gut microbiome in host immunity against SARS-CoV-2 infection, as well as the long-term effect of COVID-19 on the gut microbiome in relation to the host health after the pandemic.}, }
@article {pmid34557498, year = {2021}, author = {Liptak, R and Gromova, B and Gardlik, R}, title = {Fecal Microbiota Transplantation as a Tool for Therapeutic Modulation of Non-gastrointestinal Disorders.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {665520}, pmid = {34557498}, issn = {2296-858X}, abstract = {Fecal microbiota transplantation has been primarily investigated as a therapeutic tool for a number of gut disorders. Optimistic results from clinical studies on Clostridium difficile infection, inflammatory bowel disease and irritable bowel syndrome have stimulated the expansion of possible indications in which FMT might represent a game changing approach. Microbial dysbiosis was shown in a number of non-gastrointestinal disorders. Moreover, FMT was proven to be effective in therapy of numerous animal models of disease. However, only a proportion of these disorders have been addressed in clinical studies using FMT. These include obesity, non-alcoholic fatty liver disease, cardiovascular inflammation and neurological disorders such as autism, depression and Parkinson's disease. Results from preclinical and clinical studies also outlined possible molecular mechanisms that contribute to alleviation of the disease. These range from increasing the circulating levels of microbial metabolites (trimethylamine N-oxide, lipopolysaccharide, short chain fatty acids) to stimulation of the enteric nervous system. Several methodological shortcomings are still to be addressed; however, positive results of the clinical studies indicate that further investigation of FMT as a therapeutic tool for non-gastrointestinal disorders can be expected in upcoming years.}, }
@article {pmid34557102, year = {2021}, author = {Sun, Z and Li, J and Wang, W and Liu, Y and Liu, J and Jiang, H and Lu, Q and Ding, P and Shi, R and Zhao, X and Yuan, W and Tan, X and Shi, X and Xing, Y and Mao, T}, title = {Qingchang Wenzhong Decoction Accelerates Intestinal Mucosal Healing Through Modulation of Dysregulated Gut Microbiome, Intestinal Barrier and Immune Responses in Mice.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {738152}, pmid = {34557102}, issn = {1663-9812}, abstract = {Inflammatory bowel disease (IBD), a group of multifactorial and inflammatory infirmities, is closely associated with dysregulation of gut microbiota and host metabolome, but effective treatments are currently limited. Qingchang Wenzhong Decoction (QCWZD) is an effective and classical traditional herbal prescription for the treatment of IBD and has been proved to attenuate intestinal inflammation in a model of acute colitis. However, the role of QCWZD in recovery phase of colitis is unclear. Here, we demonstrated that mice treated with QCWZD showed a faster recovery from dextran sulfate sodium (DSS)-induced epithelial injury, accompanied by reduced mucosal inflammation and attenuated intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing compared to those receiving sterile water. The protective effects of QCWZD are gut microbiota dependent, as demonstrated by fecal microbiome transplantation and antibiotics treatment. Gut microbes transferred from QCWZD-treated mice displayed a similar role in mucosal protection and epithelial regeneration as QCWZD on colitis in mice, and depletion of the gut microbiota through antibiotics treatments diminished the beneficial effects of QCWZD on colitis mice. Moreover, metabolomic analysis revealed metabolic profiles alternations in response to the gut microbiota reprogrammed by QCWZD intervention, especially enhanced tryptophan metabolism, which may further accelerate intestinal stem cells-mediated epithelial regeneration to protect the integrity of intestinal mucosa through activation of Wnt/β-catenin signals. Collectively, our results suggested that orally administrated QCWZD accelerates intestinal mucosal healing through the modulation of dysregulated gut microbiota and metabolism, thus regulating intestinal stem cells-mediated epithelial proliferation, and hold promise for novel microbial-based therapies in the treatment of IBD.}, }
@article {pmid34554118, year = {2021}, author = {de Stefano, MC and Mazzanti, B and Vespasiano, F and Cammarota, G and Ianiro, G and Masucci, L and Sanguinetti, M and Gasbarrini, A and Lombardini, L and Cardillo, M}, title = {The Italian National Faecal Microbiota Transplantation Program: a coordinated effort against Clostridioides difficile infection.}, journal = {Annali dell'Istituto superiore di sanita}, volume = {57}, number = {3}, pages = {239-243}, doi = {10.4415/ANN_21_03_07}, pmid = {34554118}, issn = {2384-8553}, mesh = {Adult ; Aged ; Aged, 80 and over ; COVID-19 ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Italy ; Male ; Middle Aged ; Prospective Studies ; Young Adult ; }, abstract = {Clostridioides (previously Clostridium) difficile infection (CDI) is a common cause of antibiotic-associated diarrhea, whose symptoms range from mild diarrhea to life-threatening pseudomembranous colitis. CDI is characterized by significant recurrence rate following initial resolution and recurrent C. difficile infection (rCDI) represents an onerous burden for the healthcare systems. Conventional antibiotic-based approaches are generally used for the treatment of rCDI but the effective therapy remains elusive. Recently, the faecal microbiota transplantation (FMT) has emerged as an alternative therapeutic strategy against rCDI, with high treatment success rate. In 2018, the Italian National FMT Program was launched, with the aim to provide high quality standards in FMT application to adults with rCDI not responding to antibiotic therapy. Here, we sketch out the key characteristics and the progress of the Italian National FMT Program during the COVID-19 pandemic.}, }
@article {pmid34552222, year = {2021}, author = {Chaudhari, SN and McCurry, MD and Devlin, AS}, title = {Chains of evidence from correlations to causal molecules in microbiome-linked diseases.}, journal = {Nature chemical biology}, volume = {17}, number = {10}, pages = {1046-1056}, pmid = {34552222}, issn = {1552-4469}, support = {R01 DK126855/DK/NIDDK NIH HHS/United States ; R35 GM128618/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anti-Infective Agents/pharmacology ; Communicable Diseases/*microbiology ; Fecal Microbiota Transplantation ; Germ-Free Life ; Host Microbial Interactions/*physiology ; Humans ; Microbiota/*physiology ; }, abstract = {Human-associated microorganisms play a vital role in human health, and microbial imbalance has been linked to a wide range of disease states. In this Review, we explore recent efforts to progress from correlative studies that identify microorganisms associated with human disease to experiments that establish causal relationships between microbial products and host phenotypes. We propose that successful efforts to uncover phenotypes often follow a chain of evidence that proceeds from (1) association studies; to (2) observations in germ-free animals and antibiotic-treated animals and humans; to (3) fecal microbiota transplants (FMTs); to (4) identification of strains; and then (5) molecules that elicit a phenotype. Using this experimental 'funnel' as our guide, we explore how the microbiota contributes to metabolic disorders and hypertension, infections, and neurological conditions. We discuss the potential to use FMTs and microbiota-inspired therapies to treat human disease as well as the limitations of these approaches.}, }
@article {pmid34552194, year = {2021}, author = {Brunse, A and Deng, L and Pan, X and Hui, Y and Castro-Mejía, JL and Kot, W and Nguyen, DN and Secher, JB and Nielsen, DS and Thymann, T}, title = {Fecal filtrate transplantation protects against necrotizing enterocolitis.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, pmid = {34552194}, issn = {1751-7370}, support = {8022-00188B//Det Frie Forskningsråd (Danish Council for Independent Research)/ ; }, abstract = {Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disorder afflicting preterm infants, which is currently unpreventable. Fecal microbiota transplantation (FMT) is a promising preventive therapy, but the transfer of pathogenic microbes or toxic compounds raise concern. Removal of bacteria from donor feces by micropore filtering may reduce this risk of bacterial infection, while residual bacteriophages could maintain the NEC-preventive effects. We aimed to assess preclinical efficacy and safety of fecal filtrate transplantation (FFT). Using fecal material from healthy suckling piglets, we compared rectal FMT administration (FMT, n = 16) with cognate FFT by either rectal (FFTr, n = 14) or oro-gastric administration (FFTo, n = 13) and saline (CON, n = 16) in preterm, cesarean-delivered piglets as models for preterm infants. We assessed gut pathology and analyzed mucosal and luminal bacterial and viral composition using 16S rRNA gene amplicon and meta-virome sequencing. Finally, we used isolated ileal mucosa, coupled with RNA-Seq, to gauge the host response to the different treatments. Oro-gastric FFT completely prevented NEC, which was confirmed by microscopy, whereas FMT did not perform better than control. Oro-gastric FFT increased viral diversity and reduced Proteobacteria relative abundance in the ileal mucosa relative to control. An induction of mucosal immunity was observed in response to FMT but not FFT. As preterm infants are extremely vulnerable to infections, rational NEC-preventive strategies need incontestable safety profiles. We show in a clinically relevant animal model that FFT, as opposed to FMT, efficiently prevents NEC without any recognizable side effects.}, }
@article {pmid34550085, year = {2021}, author = {Chinna Meyyappan, A and Sgarbossa, C and Vazquez, G and Bond, DJ and Müller, DJ and Milev, R}, title = {The Safety and Efficacy of Microbial Ecosystem Therapeutic-2 in People With Major Depression: Protocol for a Phase 2, Double-Blind, Placebo-Controlled Study.}, journal = {JMIR research protocols}, volume = {10}, number = {9}, pages = {e31439}, pmid = {34550085}, issn = {1929-0748}, abstract = {BACKGROUND: The gut-brain axis is a bidirectional signaling pathway between the gastrointestinal tract and the brain; it is being studied because of its potential influence in mediating mood, anxiety, and other neuropsychiatric symptoms. Previous research examining the effects of gut microbiota on neuropsychiatric disorders suggests that gut repopulation treatments such as probiotics, microbe therapy, and fecal microbiota transplantation show promising results in treating symptoms of anxiety and depression. This study explores the use of an alternative gut repopulation treatment to fecal microbiota transplantation, known as Microbial Ecosystem Therapeutic (MET)-2, as an intervention against symptoms of depression. MET-2 is a daily, orally administered capsule containing 40 bacterial strains purified from a single healthy donor.<br><br>OBJECTIVE: The primary aim of this study is to assess changes in mood in people with major depression that occur pre-, post-, and during the administration of MET-2. The secondary aims are to assess changes in anxiety symptoms, blood biomarker concentrations, and the level of repopulation of healthy gut bacteria as a response to treatment.<br><br>METHODS: In this study, we will recruit 60 adults aged between 18 and 45 years old with major depression and randomly assign them to treatment or placebo groups. Patients in the treatment group will receive MET-2 once a day for 6 weeks, whereas patients in the placebo group will receive a matching placebo for 6 weeks. Participants will complete biweekly visits during the treatment period and a follow-up visit at 2 weeks post treatment. As a primary outcome measure, participants' mood will be assessed using the Montgomery-Asberg Depression Rating Scale. Secondary outcome measures include changes in mood, anxiety, early stress, gastrointestinal symptoms, and tolerability of MET-2 treatment using a series of clinical scales and changes in blood markers, particularly immunoglobulins (Igs; IgA, IgG, and IgM) and inflammatory markers (C-reactive protein, tumor necrosis factor-α, transforming growth factor-β, interleukin-6, and interleukin-10). Changes in the relative abundance, diversity, and level of engraftment in fecal samples will be assessed using 16S rRNA sequencing. All data will be integrated to identify biomarkers that could indicate disease state or predict improvement in depressive symptoms in response to MET-2 treatment.<br><br>RESULTS: Given the association between the gut microbiome and depression, we hypothesized that participants receiving MET-2 would experience greater improvement in depressive symptoms than those receiving placebo owing to the recolonization of the gut microbiome with healthy bacteria modulating the gut-brain axis connection.<br><br>CONCLUSIONS: This study is the first of its kind to evaluate the safety and efficacy of a microbial therapy such as MET-2 in comparison with placebo for major depressive disorder. We hope that this study will also reveal the potential capabilities of microbial therapies to treat other psychiatric illnesses and mood disorders.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT04602715; https://clinicaltrials.gov/ct2/show/NCT04602715.<br><br>DERR1-10.2196/31439.}, }
@article {pmid34549762, year = {2021}, author = {Yan, X and Wang, Y and Ren, XY and Liu, XY and Ma, JM and Song, RL and Wang, XH and Dong, Y and Yu, AX and Fan, QQ and Wei, J and She, GM}, title = {Gut dysbiosis correction contributes to the hepatoprotective effects of Thymus quinquecostatus Celak extract against alcohol through the gut-liver axis.}, journal = {Food &amp; function}, volume = {12}, number = {20}, pages = {10281-10290}, doi = {10.1039/d1fo01117k}, pmid = {34549762}, issn = {2042-650X}, abstract = {Alcoholic liver disease (ALD) is a major health issue globally due to the consumption of alcoholic beverages. Thymus quinquecostatus Celak is a food additive and an edible herb that is widely used in Asia and possesses hepatoprotective activity, but the underlying mechanisms behind this protective activity are not completely understood. The purpose of this study was to investigate the hepatoprotective effects of Thymus quinquecostatus Celak extract (TQE) against ALD as well as the underlying mechanism based on gut microbiota and the gut-liver axis. TQE supplementation markedly alleviated chronic alcohol-induced liver injury in C57 mice. TQE also ameliorated gut barrier dysfunction induced by alcohol. Consequently, the activation of the lipopolysaccharide (LPS) translocation-mediated TLR4 pathway and the subsequent inflammatory response and ROS overproduction in the liver were suppressed. Meanwhile, alcohol-induced gut microbiota dysbiosis was also corrected by TQE. To further investigate the contribution of gut dysbiosis correction to the beneficial effects of TQE on ALD, a fecal microbiota transplantation study was conducted. TQE-manipulated gut microbiota transplantation markedly counteracted the alcohol-induced gut dysbiosis in the recipient mice. In parallel with gut dysbiosis correction, liver damage was partly ameliorated in the recipient mice. Gut barrier dysfunction, endotoxemia, TLR4 pathway induction as well as downstream inflammatory response and ROS overproduction were also partly suppressed due to gut dysbiosis correction in alcohol-fed recipient mice. In summary, these results suggest that gut dysbiosis correction contributes to the hepatoprotective effects of TQE against alcohol through the gut-liver axis.}, }
@article {pmid34543718, year = {2021}, author = {Wah-Suárez, MI and Vázquez, MAM and Bosques-Padilla, FJ}, title = {Inflammatory bowel disease: The role of commensal microbiome in immune regulation.}, journal = {Gastroenterologia y hepatologia}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.gastrohep.2021.08.008}, pmid = {34543718}, issn = {0210-5705}, abstract = {The incidence of inflammatory bowel disease (IBD) is increasing. Microbiome is one of the most important factors in its development and affects the different clinical outcomes of IBD patients depending on its composition and different alterations. We conducted a systematic review to discuss the association between microbiome and IBD in terms of immune regulation, and therapies that can modify microbiota. A comprehensive systematic literature search was performed through April 2020 in PubMed, Web of Science, the Cochrane Library, and clinicaltrials.gov. Inclusion criteria required IBD immune regulation and alternate therapeutics for IBD. This analysis helps explain the multifactorial origin of microbiome diversity including normal immune regulation, immune pathophysiology of IBD, and shows the evidence of several therapeutic targets to change microbiome in patients with IBD, such as prebiotics, probiotics, antibiotics, fecal microbiota transplant, and others.}, }
@article {pmid34539138, year = {2021}, author = {Kang, YB and Cai, Y}, title = {Faecal microbiota transplantation enhances efficacy of immune checkpoint inhibitors therapy against cancer.}, journal = {World journal of gastroenterology}, volume = {27}, number = {32}, pages = {5362-5375}, pmid = {34539138}, issn = {2219-2840}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immune Checkpoint Inhibitors ; *Neoplasms/drug therapy ; Radioimmunotherapy ; }, abstract = {Even though immune checkpoint inhibitors (ICIs) are effective on multiple cancer types, there are still many non-responding patients. A possible factor put forward that may influence the efficacy of ICIs is the gut microbiota. Additionally, faecal microbiota transplantation may enhance efficacy of ICIs. Nevertheless, the data available in this field are insufficient, and relevant scientific work has just commenced. As a result, the current work reviewed the latest research on the association of gut microbiota with ICI treatments based on anti-programmed cell death protein 1 antibody and anti- cytotoxic T-lymphocyte-associated protein 4 antibody and explored the therapeutic potential of faecal microbiota transplantation in combination with ICI therapy in the future.}, }
@article {pmid34527093, year = {2021}, author = {Ashraf, MF and Tageldin, O and Nassar, Y and Batool, A}, title = {Fecal Microbiota Transplantation in Patients With Recurrent Clostridium difficile Infection: A Four-Year Single-Center Retrospective Review.}, journal = {Gastroenterology research}, volume = {14}, number = {4}, pages = {237-243}, pmid = {34527093}, issn = {1918-2805}, abstract = {Background: Clostridium difficile infection (CDI) is a common cause of hospital and community-acquired diarrhea with an annual incidence of 453,000 cases in the USA. The white race, female gender, and age over 65 years are known risk factors. Recurrence of CDI is a major problem in patients taking antibiotics for prolonged periods. These patients are observed to have reduced diversity of the intestinal microbiome. Fecal microbiota transplantation (FMT) can restore the healthy flora in the gut, thus breaking the cycle of recurrent infection. Our study aimed to analyze the efficacy of FMT and the recurrence of CDI after FMT. We also aimed to investigate the effects of comorbidities on the outcome of FMT.<br><br>Methods: After obtaining approval from the institutional review board, we included 64 patients who had received FMT at our institution from October 2015 to November 2019. All the patients over 16 years of age in both inpatient and outpatient settings were included. Patients under 16 years of age and patients treated without FMT were excluded. Frozen stool from a standardized stool bank (OpenBiome) was used. The thawed specimen was instilled into the terminal ileum or the cecum. Patients were followed up for the next 1 year for analysis of improvement in symptoms, recurrence, and repeat FMT.<br><br>Results: On the 2-months follow-up, 75% of patients reported symptomatic improvement, 15.6% reported no improvement while 9.4% did not follow up. Twenty-six (40.6%) patients had CDI recurrence in the following year; and 69.2% of patients with recurrence underwent a repeat FMT. There was no statistically significant correlation between CDI recurrence and the age (P value = 0.68), gender (P value = 0.61), previous use of proton pump inhibitors (PPIs, P value = 0.11) or antibiotics (P value = 0.45). There was a statistically significant correlation noted with the use of immunosuppressants and recurrence (P value = 0.04).<br><br>Conclusions: FMT is a successful treatment modality for refractory and recurrent CDI. Repeat treatments can be beneficial if there is a lack of initial response. Being immunosuppressed with medications is associated with the risk of recurrence.}, }
@article {pmid34525908, year = {2021}, author = {Zanza, C and Romenskaya, T and Thangathurai, D and Ojetti, V and Saviano, A and Abenavoli, L and Robba, C and Cammarota, G and Franceschi, F and Piccioni, A and Longhitano, Y}, title = {Microbiome in Critical illness: An Unconventional and Unknown Ally.}, journal = {Current medicinal chemistry}, volume = {}, number = {}, pages = {}, doi = {10.2174/0929867328666210915115056}, pmid = {34525908}, issn = {1875-533X}, abstract = {BACKGROUND: The digestive tract represents an interface between the external environment and the body where the interaction of a complex polymicrobial ecology has an important influence on health and disease. The physiological mechanisms that are altered during the hospitalization and in the intensive care unit (ICU) contribute to the pathobiota's growth. Intestinal dysbiosis occurs within hours of being admitted to ICU. This may be due to different factors, such as alterations of normal intestinal transit, administration of variuos medications or alterations in the intestinal wall which causes a cascade of events that will lead to the increase of nitrates and decrease of oxygen concentration, liberation of free radicals.<br><br>OBJECTIVE: This work aims to report the latest updates on the microbiota's contribution to developing sepsis in patients in the ICU department. In this short review were reviewed the latest scientific findings on the mechanisms of intestinal immune defenses performed both locally and systemically. In addition, we considered it necessary to review the literature to report the current best treatment strategies to prevent the infection spread which can bring systemic infections in patients admitted to ICU.<br><br>MATERIAL AND METHODS: This review has been written to answer at three main questions: what are the main intestinal flora's defense mechanisms that help us to prevent the risk of developing systemic diseases on a day-to-day basis? What are the main dysbiosis' systemic abnormalities? What are the modern strategies that are used in the ICU patients to prevent the infection spread? Using the combination of following keywords: microbiota and ICU, ICU and gut, microbiota and critical illness, microbiota and critical care, microbiota and sepsis, microbiota and infection, gastrointestinal immunity,in the Cochrane Controlled Trials Register, the Cochrane Library, medline and pubmed, google scholar, ovid/wiley. Finally, we reviewed and selected 72 articles. We also consulted the site ClinicalTrials.com to find out studies that are recently conducted or ongoing.<br><br>RESULTS: The critical illness can alter intestinal bacterial flora leading to homeostasis disequilibrium. Despite numerous mechanisms, such as epithelial cells with calciform cells that together build a mechanical barrier for pathogenic bacteria, the presence of mucous associated lymphoid tissue (MALT) which stimulates an immune response through the production of interferon-gamma (IFN-y) and THN-a or by stimulating lymphocytes T helper-2 produces anti-inflammatory cytokines. But these defenses can be altered following a hospitalization in ICU and lead to serious complications such as acute respiratory distress syndrome (ARDS), health care associated pneumonia (HAP) and ventilator associated pneumonia (VAP), Systemic infection and multiple organ failure (MOF), but also in the development of coronary artery disease (CAD). In addition, the microbiota has a significant impact on the development of intestinal complications and the severity of the SARS-COVID-19 patients.<br><br>CONCLUSION: The microbiota is recognized as one of the important factors that can worsen the clinical conditions of patients who are already very frailty in intensive care unit. At the same time, the microbiota also plays a crucial role in the prevention of ICU associated complications. By using the resources, we have available, such as probiotics, symbiotics or fecal microbiota transplantation (FMT), we can preserve the integrity of the microbiota and the GUT, which will later help maintain homeostasis in ICU patients.}, }
@article {pmid34521450, year = {2021}, author = {Wang, M and Zhu, Z and Lin, X and Li, H and Wen, C and Bao, J and He, Z}, title = {Gut microbiota mediated the therapeutic efficacies and the side effects of prednisone in the treatment of MRL/lpr mice.}, journal = {Arthritis research &amp; therapy}, volume = {23}, number = {1}, pages = {240}, pmid = {34521450}, issn = {1478-6362}, mesh = {Animals ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Glucocorticoids ; *Lupus Erythematosus, Systemic/drug therapy ; Mice ; Mice, Inbred MRL lpr ; Prednisone ; }, abstract = {BACKGROUND: Growing evidences indicate that the alterations in gut microbiota are associated with the efficacy of glucocorticoids (GCs) in the treatment of systemic lupus erythematosus (SLE). However, there is no evidence to prove whether gut microbiota directly mediates the effects of GCs.<br><br>METHODS: Using the MRL/lpr mice, this study firstly addressed the effects of three doses of prednisone on gut microbiota. Then, this study used fecal microbiota transplantation (FMT) to transfer the gut microbiota of prednisone-treated MRL/lpr mice into the blank MRL/lpr mice to reveal whether the gut microbiota regulated by prednisone had similar therapeutic efficiency and side effects as prednisone.<br><br>RESULTS: The effects of prednisone on gut microbiota were dose-dependent in the treatment of MRL/lpr mice. After transplantation into MRL/lpr mice, prednisone-regulated gut microbiota could alleviate lupus, which might be due to decreasing Ruminococcus and Alistipes and retaining the abundance of Lactobacillus. However, prednisone-regulated gut microbiota did not exhibit side effects as prednisone. The reason might be that the pathogens upregulated by prednisone could not survive in the MRL/lpr mice as exogenous microbiota, such as Parasutterella, Parabacteroides, and Escherichia-Shigella.<br><br>CONCLUSIONS: These data demonstrated that the transplantation of gut microbiota may be an effective method to obtain the therapeutic effects of GCs and avoid the side effects of GCs.}, }
@article {pmid34516460, year = {2021}, author = {Singh, T and Bedi, P and Bumrah, K and Gandhi, D and Arora, T and Verma, N and Schleicher, M and Rai, MP and Garg, R and Verma, B and Sanaka, MR}, title = {Fecal Microbiota Transplantation and Medical Therapy for Clostridium difficile Infection: Meta-analysis of Randomized Controlled Trials.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000001610}, pmid = {34516460}, issn = {1539-2031}, abstract = {GOALS: The aim was to assess the effectiveness of fecal microbiota transplantation (FMT) against medical therapy (MT).<br><br>BACKGROUND: FMT has shown good outcomes in the treatment of Clostridium difficile infection (CDI). We aimed to conduct a systematic review and meta-analysis to compare the effectiveness of FMT versus MT for CDI.<br><br>STUDY: We performed a comprehensive search to identify randomized controlled trials comparing FMT against MT in patients with CDI. Outcomes of interest were clinical cure as determined by the resolution of diarrhea and/or negative C. difficile testing. Primary CDI is defined as the first episode of CDI confirmed endoscopically or by laboratory analysis. Recurrent C. difficile infection (RCDI) is defined as laboratory or endoscopically confirmed episode of CDI after at least 1 course of approved antibiotic regimen.<br><br>RESULTS: A total of 7 studies with 238 patients were included in meta-analysis. Compared with MT, FMT did not have a statistically significant difference for clinical cure of combined primary and RCDI after first session [risk ratio (RR): 1.52, 95% confidence interval (CI): 0.90, 2.58; P=0.12; I2=77%] and multiple sessions of FMT (RR: 1.68; CI: 0.96, 2.94; P=0.07; I2=82%). On subgroup analysis, FMT has statistically higher rate of response than MT (RR: 2.41; CI: 1.20, 4.83; I2=78%) for RCDI. However, for primary CDI there is no statistically significant difference between FMT and MT (RR: 1.00; CI: 0.72, 1.39; I2=0%).<br><br>CONCLUSION: As per our analysis, FMT should not be utilized for every patient with CDI. It is more effective in RCDI, but the results were not significant in patients with primary CDI.}, }
@article {pmid34514619, year = {2021}, author = {Suchodolski, JS}, title = {Analysis of the gut microbiome in dogs and cats.}, journal = {Veterinary clinical pathology}, volume = {}, number = {}, pages = {}, doi = {10.1111/vcp.13031}, pmid = {34514619}, issn = {1939-165X}, abstract = {The gut microbiome is an important immune and metabolic organ. Intestinal bacteria produce various metabolites that influence the health of the intestine and other organ systems, including kidney, brain, and heart. Changes in the microbiome in diseased states are termed dysbiosis. The concept of dysbiosis is constantly evolving and includes changes in microbiome diversity and/or structure and functional changes (eg, altered production of bacterial metabolites). Molecular tools are now the standard for microbiome analysis. Sequencing of microbial genes provides information about the bacteria present and their functional potential but lacks standardization and analytical validation of methods and consistency in the reporting of results. This makes it difficult to compare results across studies or for individual clinical patients. The Dysbiosis Index (DI) is a validated quantitative PCR assay for canine fecal samples that measures the abundance of seven important bacterial taxa and summarizes the results as one single number. Reference intervals are established for dogs, and the DI can be used to assess the microbiome in clinical patients over time and in response to therapy (eg, fecal microbiota transplantation). In situ hybridization or immunohistochemistry allows the identification of mucosa-adherent and intracellular bacteria in animals with intestinal disease, especially granulomatous colitis. Future directions include the measurement of bacterial metabolites in feces or serum as markers for the appropriate function of the microbiome. This article summarizes different approaches to the analysis of gut microbiota and how they might be applicable to research studies and clinical practice in dogs and cats.}, }
@article {pmid34513724, year = {2021}, author = {Innes, AJ and Mullish, BH and Ghani, R and Szydlo, RM and Apperley, JF and Olavarria, E and Palanicawandar, R and Kanfer, EJ and Milojkovic, D and McDonald, JAK and Brannigan, ET and Thursz, MR and Williams, HRT and Davies, FJ and Marchesi, JR and Pavlů, J}, title = {Fecal Microbiota Transplant Mitigates Adverse Outcomes Seen in Patients Colonized With Multidrug-Resistant Organisms Undergoing Allogeneic Hematopoietic Cell Transplantation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {684659}, pmid = {34513724}, issn = {2235-2988}, support = {/DH_/Department of Health/United Kingdom ; MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; /WT_/Wellcome Trust/United Kingdom ; }, mesh = {Drug Resistance, Multiple, Bacterial ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation ; Humans ; Retrospective Studies ; }, abstract = {The gut microbiome can be adversely affected by chemotherapy and antibiotics prior to hematopoietic cell transplantation (HCT). This affects graft success and increases susceptibility to multidrug-resistant organism (MDRO) colonization and infection. We performed an initial retrospective analysis of our use of fecal microbiota transplantation (FMT) from healthy donors as therapy for MDRO-colonized patients with hematological malignancy. FMT was performed on eight MDRO-colonized patients pre-HCT (FMT-MDRO group), and outcomes compared with 11 MDRO colonized HCT patients from the same period. At 12 months, survival was significantly higher in the FMT-MDRO group (70% versus 36% p = 0.044). Post-HCT, fewer FMT-MDRO patients required intensive care (0% versus 46%, P = 0.045) or experienced fever (0.29 versus 0.11 days, P = 0.027). Intestinal MDRO decolonization occurred in 25% of FMT-MDRO patients versus 11% non-FMT MDRO patients. Despite the significant differences and statistically comparable patient/transplant characteristics, as the sample size was small, a matched-pair analysis between both groups to non-MDRO colonized control cohorts (2:1 matching) was performed. At 12 months, the MDRO group who did not have an FMT had significantly lower survival (36.4% versus 61.9% respectively, p=0.012), and higher non relapse mortality (NRM; 60.2% versus 16.7% respectively, p=0.009) than their paired non-MDRO-colonized cohort. Conversely, there was no difference in survival (70% versus 43.4%, p=0.14) or NRM (12.5% versus 31.2% respectively, p=0.24) between the FMT-MDRO group and their paired non-MDRO cohort. Collectively, these data suggest that negative clinical outcomes, including mortality associated with MDRO colonization, may be ameliorated by pre-HCT FMT, even in the absence of intestinal MDRO decolonization. Further work is needed to explore this observed benefit.}, }
@article {pmid34507723, year = {2021}, author = {Pang, B and Jin, H and Liao, N and Li, J and Jiang, C and Shi, J}, title = {Vitamin A supplementation ameliorates ulcerative colitis in gut microbiota-dependent manner.}, journal = {Food research international (Ottawa, Ont.)}, volume = {148}, number = {}, pages = {110568}, doi = {10.1016/j.foodres.2021.110568}, pmid = {34507723}, issn = {1873-7145}, mesh = {Animals ; *Colitis, Ulcerative/drug therapy ; Dextran Sulfate ; Dietary Supplements ; Gas Chromatography-Mass Spectrometry ; *Gastrointestinal Microbiome ; Mice ; RNA, Ribosomal, 16S/genetics ; Vitamin A ; }, abstract = {Ulcerative colitis (UC), is a chronic relapsing inflammatory condition of the gastrointestinal track. The purpose of this study is to explore whether Vitamin A (VA) can treat UC and its mechanisms. A mouse model of UC was established using 3.0% (w/v) dextran sodium sulfate (DSS). VA was used to treat UC by intragastric administration of 5000 international unit (IU) retinyl acetate. Fecal microbiota transplantation (FMT) was also used to treat the UC model mice to verify the effect of influenced gut microbiota. The content of short-chain fatty acids (SCFAs) in cecal contents was quantitatively detected by gas chromatography and mass spectrometry. VA supplementation significantly ameliorated UC. 16S rRNA sequencing indicated that VA-treated mice exhibited much more abundant gut microbial diversity and flora composition. Targeted metabolomics analysis manifested the increased production of SCFAs in VA-treated mice. Gut microbiota depletion and FMT results confirmed the gut microbiota-dependent mechanism as that VA relieved UC via regulating gut microbiota: increase in SCFA-producing genera and decrease in UC-related genera. The restore of intestinal barrier and the inhibition of inflammation were also found to contribute to the amelioration of UC by VA. It was concluded that a VA supplement was enough to cause a significant change in gut microbiota and amelioration of UC.}, }
@article {pmid34500036, year = {2021}, author = {Kim, N and Jeon, SH and Ju, IG and Gee, MS and Do, J and Oh, MS and Lee, JK}, title = {Transplantation of gut microbiota derived from Alzheimer's disease mouse model impairs memory function and neurogenesis in C57BL/6 mice.}, journal = {Brain, behavior, and immunity}, volume = {98}, number = {}, pages = {357-365}, doi = {10.1016/j.bbi.2021.09.002}, pmid = {34500036}, issn = {1090-2139}, abstract = {Alzheimer's disease (AD) is a neurodegenerative disease that causes memory and cognitive decline. Although many studies have attempted to clarify the causes of AD occurrence, it is not clearly understood. Recently, the emerging role of the gut microbiota in neurodegenerative diseases, including AD, has received much attention. The gut microbiota composition of AD patients and AD mouse models is different from that of healthy controls, and these changes may affect the brain environment. However, the specific mechanisms by which gut microbiota that influence memory decline are currently unclear. In this study, we performed fecal microbiota transplantation (FMT) to clarify the role of 5xFAD mouse-derived microbiota in memory decline. We observed that FMT from 5xFAD mice into normal C57BL/6 mice (5xFAD-FMT) decreased adult hippocampal neurogenesis and brain-derived neurotrophic factor expression and increased p21 expression, resulting in memory impairment. Microglia in the hippocampus of the 5xFAD-FMT mice were activated, which caused the elevation of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β). Moreover, we observed that pro-inflammatory cytokines increased in the colon and plasma of 5xFAD-FMT mice. The gut microbiota composition of the 5xFAD-FMT mice was different from that of the control mice or wild type-FMT mice. Collectively, 5xFAD mouse-derived microbiota decreased neurogenesis by increasing colonic inflammation, thereby contributing to memory loss. Our findings provide further evidence concerning the role of gut microbial dysbiosis in AD pathogenesis and suggest that targeting the gut microbiota may be a useful therapeutic strategy for the development of novel candidates for the treatment of AD.}, }
@article {pmid34495400, year = {2021}, author = {El Halabi, J and Palmer, N and Fox, K and Kohane, I and Farhat, MR}, title = {Fecal microbiota transplantation and Clostridioides difficile infection among privately insured patients in the United States.}, journal = {Journal of gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {34495400}, issn = {1435-5922}, support = {T15LM007092/NH/NIH HHS/United States ; K01 ES026835/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) may be rising in severity in the US over the past decade and its treatment landscape is changing given the recent adoption of fecal microbiota transplantation (FMT) METHODS: We built a retrospective observational cohort using a database of a national care-plan containing medical claims of over 50 million individuals between 2008 and 2019. We used International Classification of Disease (ICD) and prescription data to identify patients with CDI. We estimated trends in disease burden and FMT use, and evaluated complications post FMT using a phenome-wide association approach.<br><br>RESULTS: We identified 38,396 patients with CDI; the median age was 60 years (IQR 45-74) and 60% were female (n = 23,374). The rate of CDI increased from 33.4 to 69.46 cases per 100,000 person-years between 2008 and 2015, and stabilized from 2015 to 2019 (increase of 4.77 cases per 100,000 person-years per year, 95% CI 3.55-5.98 prior to 2015 vs. 2.01 95% CI - 10.16 to 14.18 after 2015). Of the 7715 patients with recurrent CDI, 407 patients (5%) underwent FMT. Gastrointestinal complications were increased within 1 month post FMT (OR 99.60, p < 0.001). Sepsis was identified in two individuals (0.49% 95% CI 0.05-1.7%) within the first month post FMT. The risk of CDI recurrence significantly decreased post FMT compared with anti-CDI antibiotics in the multivariable model (raw-recurrence rate 9.8% vs 36%, aOR = 0.21, 95% CI 0.12-0.53, p < 0.001).<br><br>CONCLUSION: We show that FMT is strongly associated with a decrease in CDI recurrence compared with the usual care with generally mild complications for up to 2 years.}, }
@article {pmid34494666, year = {2021}, author = {Mjaess, G and Karam, A and Aoun, F and Albisinni, S and Roumeguère, T}, title = {Fecal microbiota transplantation for immunotherapy-resistant urological tumors: Is it time? An update of the recent literature.}, journal = {Cancer}, volume = {}, number = {}, pages = {}, doi = {10.1002/cncr.33893}, pmid = {34494666}, issn = {1097-0142}, }
@article {pmid34493333, year = {2021}, author = {Wu, Z and Huang, S and Li, T and Li, N and Han, D and Zhang, B and Xu, ZZ and Zhang, S and Pang, J and Wang, S and Zhang, G and Zhao, J and Wang, J}, title = {Gut microbiota from green tea polyphenol-dosed mice improves intestinal epithelial homeostasis and ameliorates experimental colitis.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {184}, pmid = {34493333}, issn = {2049-2618}, mesh = {Animals ; *Colitis/chemically induced/drug therapy ; Dextran Sulfate ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Homeostasis ; Mice ; Mice, Inbred C57BL ; Polyphenols/pharmacology ; Tea ; }, abstract = {BACKGROUND: Alteration of the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Epigallocatechin-3-gallate (EGCG), a major bioactive constituent of green tea, is known to be beneficial in IBD alleviation. However, it is unclear whether the gut microbiota exerts an effect when EGCG attenuates IBD.<br><br>RESULTS: We first explored the effect of oral or rectal EGCG delivery on the DSS-induced murine colitis. Our results revealed that anti-inflammatory effect and colonic barrier integrity were enhanced by oral, but not rectal, EGCG. We observed a distinct EGCG-mediated alteration in the gut microbiome by increasing Akkermansia abundance and butyrate production. Next, we demonstrated that the EGCG pre-supplementation induced similar beneficial outcomes to oral EGCG administration. Prophylactic EGCG attenuated colitis and significantly enriched short-chain fatty acids (SCFAs)-producing bacteria such as Akkermansia and SCFAs production in DSS-induced mice. To validate these discoveries, we performed fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) to inoculate DSS-treated mice. Microbiota from EGCG-dosed mice alleviated the colitis over microbiota from control mice and SFF shown by superiorly anti-inflammatory effect and colonic barrier integrity, and also enriched bacteria such as Akkermansia and SCFAs. Collectively, the attenuation of colitis by oral EGCG suggests an intimate involvement of SCFAs-producing bacteria Akkermansia, and SCFAs, which was further demonstrated by prophylaxis and FMT.<br><br>CONCLUSIONS: This study provides the first data indicating that oral EGCG ameliorated the colonic inflammation in a gut microbiota-dependent manner. Our findings provide novel insights into EGCG-mediated remission of IBD and EGCG as a potential modulator for gut microbiota to prevent and treat IBD. Video Abstract.}, }
@article {pmid34490132, year = {2021}, author = {Jia, X and Xu, W and Zhang, L and Li, X and Wang, R and Wu, S}, title = {Impact of Gut Microbiota and Microbiota-Related Metabolites on Hyperlipidemia.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {634780}, pmid = {34490132}, issn = {2235-2988}, mesh = {Animals ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Hyperlipidemias ; *Metabolic Diseases ; Mice ; *Microbiota ; }, abstract = {Hyperlipidemia, defined as the presence of excess fat or lipids in the blood, has been considered as a high-risk factor and key indicator of many metabolic diseases. The gut microbiota has been reported playing a vital role in regulating host lipid metabolism. The pathogenic role of gut microbiota in the development of hyperlipidemia has been revealed through fecal microbiota transplantation experiment to germ-free mice. The effector mechanism of microbiota-related metabolites such as bile acids, lipopolysaccharide, and short-chain fatty acids in the regulation of hyperlipidemia has been partially unveiled. Moreover, studies on gut-microbiota-targeted hyperlipidemia interventions, including the use of prebiotics, probiotics, fecal microbiota transplantation, and natural herbal medicines, also have shown their efficacy in the treatment of hyperlipidemia. In this review, we summarize the relationship between gut microbiota and hyperlipidemia, the impact of gut microbiota and microbiota-related metabolites on the development and progression of hyperlipidemia, and the potential therapeutic management of hyperlipidemia targeted at gut microbiota.}, }
@article {pmid34490119, year = {2021}, author = {Liu, X and Cheng, Y and Zang, D and Zhang, M and Li, X and Liu, D and Gao, B and Zhou, H and Sun, J and Han, X and Lin, M and Chen, J}, title = {The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {720842}, pmid = {34490119}, issn = {2234-943X}, abstract = {The influence of microbiota on host health and disease has attracted adequate attention, and gut microbiota components and microbiota-derived metabolites affect host immune homeostasis locally and systematically. Some studies have found that gut dysbiosis, disturbance of the structure and function of the gut microbiome, disrupts pulmonary immune homeostasis, thus leading to increased disease susceptibility; the gut-lung axis is the primary cross-talk for this communication. Gut dysbiosis is involved in carcinogenesis and the progression of lung cancer through genotoxicity, systemic inflammation, and defective immunosurveillance. In addition, the gut microbiome harbors the potential to be a novel biomarker for predicting sensitivity and adverse reactions to immunotherapy in patients with lung cancer. Probiotics and fecal microbiota transplantation (FMT) can enhance the efficacy and depress the toxicity of immune checkpoint inhibitors by regulating the gut microbiota. Although current studies have found that gut microbiota closely participates in the development and immunotherapy of lung cancer, the mechanisms require further investigation. Therefore, this review aims to discuss the underlying mechanisms of gut microbiota influencing carcinogenesis and immunotherapy in lung cancer and to provide new strategies for governing gut microbiota to enhance the prevention and treatment of lung cancer.}, }
@article {pmid34489956, year = {2021}, author = {Roberto, M and Carconi, C and Cerreti, M and Schipilliti, FM and Botticelli, A and Mazzuca, F and Marchetti, P}, title = {The Challenge of ICIs Resistance in Solid Tumours: Could Microbiota and Its Diversity Be Our Secret Weapon?.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {704942}, pmid = {34489956}, issn = {1664-3224}, abstract = {The human microbiota and its functional interaction with the human body were recently returned to the spotlight of the scientific community. In light of the extensive implementation of newer and increasingly precise genome sequencing technologies, bioinformatics, and culturomic, we now have an extraordinary ability to study the microorganisms that live within the human body. Most of the recent studies only focused on the interaction between the intestinal microbiota and one other factor. Considering the complexity of gut microbiota and its role in the pathogenesis of numerous cancers, our aim was to investigate how microbiota is affected by intestinal microenvironment and how microenvironment alterations may influence the response to immune checkpoint inhibitors (ICIs). In this context, we show how diet is emerging as a fundamental determinant of microbiota's community structure and function. Particularly, we describe the role of certain dietary factors, as well as the use of probiotics, prebiotics, postbiotics, and antibiotics in modifying the human microbiota. The modulation of gut microbiota may be a secret weapon to potentiate the efficacy of immunotherapies. In addition, this review sheds new light on the possibility of administering fecal microbiota transplantation to modulate the gut microbiota in cancer treatment. These concepts and how these findings can be translated into the therapeutic response to cancer immunotherapies will be presented.}, }
@article {pmid34487914, year = {2021}, author = {Opoku-Acheampong, I and McLaud, T and Anderson, OS}, title = {Fecal Microbiota Transplantation to Prevent and Treat Chronic Disease: Implications for Dietetics Practice.}, journal = {Journal of the Academy of Nutrition and Dietetics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jand.2021.08.112}, pmid = {34487914}, issn = {2212-2672}, }
@article {pmid34486891, year = {2021}, author = {Sanlier, N and Kocabas, Ş}, title = {The effect of probiotic, prebiotic and gut microbiota on ASD: A review and future perspectives.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/10408398.2021.1973957}, pmid = {34486891}, issn = {1549-7852}, abstract = {Autism spectrum disorder is a serious neurodevelopmental disease that affects social communication and behavior, characterized by an increasingly common immune mechanism and various complications in the gastrointestinal system. Symptoms of autism can generally vary according to the genetic background of the individuals, the environment in which they live. The microbiota of individuals with autism is also different from healthy individuals. Recently, probiotics, prebiotic, fecal microbiota transplantation, diet therapy, etc. options have come to the fore. Cofactors are even more important at this stage. Since it is related to the gut microbiota, immune mechanism, gastrointestinal system, attention has been drawn to the relationship between dysbiosis, autism in the intestine. The component of the gut microbiota in individuals with autism has been linked with gastrointestinal symptoms that develop with autism severity. However, the role of the microbiota in diagnosis, follow-up, treatment is not clear yet, and its two-way relationship with the nervous system makes it difficult to establish a cause-effect relationship. Nutritional cofactors required in neurotransmitter synthesis and enzyme activation must be regularly and adequately taken to maximize brain functions in autistic individuals. Therefore, this study was conducted to investigate the cause-effect relationship of ASD with microbiota and brain-gut axis, probiotic-prebiotic use.}, }
@article {pmid34484158, year = {2021}, author = {Yang, Y and Li, X and Yang, Y and Shoaie, S and Zhang, C and Ji, B and Wei, Y}, title = {Advances in the Relationships Between Cow's Milk Protein Allergy and Gut Microbiota in Infants.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {716667}, pmid = {34484158}, issn = {1664-302X}, abstract = {Cow's milk protein allergy (CMPA) is an immune response to cow's milk proteins, which is one of the most common food allergies in infants and young children. It is estimated that 2-3% of infants and young children have CMPA. The diet, gut microbiota, and their interactions are believed to be involved in the alterations of mucosal immune tolerance, which might lead to the development of CMPA and other food allergies. In this review, the potential molecular mechanisms of CMPA, including omics technologies used for analyzing microbiota, impacts of early microbial exposures on CMPA development, and microbiota-host interactions, are summarized. The probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and other modulation strategies for gut microbiota and the potential application of microbiota-based design of diets for the CMPA treatment are also discussed. This review not only summarizes the current studies about the interactions of CMPA with gut microbiota but also gives insights into the possible CMPA treatment strategies by modulating gut microbiota, which might help in improving the life quality of CMPA patients in the future.}, }
@article {pmid34484126, year = {2021}, author = {Jo, S and Fang, S}, title = {Therapeutic Strategies for Diabetes: Immune Modulation in Pancreatic β Cells.}, journal = {Frontiers in endocrinology}, volume = {12}, number = {}, pages = {716692}, pmid = {34484126}, issn = {1664-2392}, abstract = {Increased incidence of type I and type II diabetes has been prevailed worldwide. Though the pathogenesis of molecular mechanisms remains still unclear, there are solid evidence that disturbed immune homeostasis leads to pancreatic β cell failure. Currently, autoimmunity and uncontrolled inflammatory signaling pathways have been considered the major factors in the pathogenesis of diabetes. Many components of immune system have been reported to implicate pancreatic β cell failure, including helper T cells, cytotoxic T cells, regulatory T cells and gut microbiota. Immune modulation of those components using small molecules and antibodies, and fecal microbiota transplantation are undergoing in many clinical trials for the treatment of type I and type II diabetes. In this review we will discuss the basis of molecular pathogenesis focusing on the disturbed immune homeostasis in type I and type II diabetes, leading to pancreatic β cell destruction. Finally, we will introduce current therapeutic strategies and clinical trials by modulation of immune system for the treatment of type I and type II diabetes patients.}, }
@article {pmid34480200, year = {2021}, author = {Wang, N and Ma, S and Fu, L}, title = {Gut Microbiota Dysbiosis as One Cause of Osteoporosis by Impairing Intestinal Barrier Function.}, journal = {Calcified tissue international}, volume = {}, number = {}, pages = {}, pmid = {34480200}, issn = {1432-0827}, support = {82172456//National Natural Science Foundation of China/ ; JYJC201809//the Cross-disciplinary Fund Projects of the Ninth People's Hospital/ ; 20210407//Seeds Fund of Engineering Research Center of Digital Medicine of the Ministry of Education/ ; 2017ZZ01023//Shanghai Clinical Medical Center/ ; }, abstract = {Gut microbiota (GM) dysbiosis is closely related to several metabolic diseases such as hypertension, obesity, and Alzheimer's disease. However, little is known about the causal relationship between GM dysbiosis and osteoporosis. In our work, 32 3-month-old female SD rats were randomly divided into two groups: the fecal microbiota transplantation (FMT) group and the control group. The supernatant of feces from senile osteoporotic rats was transplanted to the FMT group and the same amount of sterile saline was given to the control rats. After 12 and 24 weeks, all rats were sacrificed, and the serum, bone, fecal feces, and intestine tissue were collected for the subsequent analysis. The osteocalcin (OC), CTX, and P1NP of the FMT group increased significantly at 12 and 24 weeks compared with the control group (P < 0.05). Furthermore, the BV, BV/TV, Tb.N, and Tb.Th decreased significantly in the FMT group (P < 0.05). The alpha diversity (ACE, Chao) of the FMT group was higher than the control at 24 weeks (P < 0.05). The beta diversity was close between the FMT rats and the donor rats. In addition, GM from donor rats changed the GM composition and function of the FMT rats, which was similar to that of the donor rats at 24 weeks. The impaired intestinal structure and the decreased expression of occludin, claudin, and ZO-1 were found in FMT rats. In conclusion, GM dysbiosis by transferring the feces from senile osteoporotic rats to young rats could induce osteoporosis. The changed GM and the impaired intestinal barrier contributed to the pathogenesis of osteoporosis.}, }
@article {pmid34478286, year = {2021}, author = {Chen, S and Wu, X and Tang, S and Yin, J and Song, Z and He, X and Yin, Y}, title = {Eugenol Alleviates Dextran Sulfate Sodium-Induced Colitis Independent of Intestinal Microbiota in Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {69}, number = {36}, pages = {10506-10514}, doi = {10.1021/acs.jafc.1c00917}, pmid = {34478286}, issn = {1520-5118}, mesh = {Animals ; *Colitis/chemically induced/drug therapy/genetics ; Colon ; Cytokines/genetics ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Eugenol ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; }, abstract = {The present study investigated the effect of eugenol (EUG) on dextran sulfate sodium (DSS)-induced colitis and explored the underlying mechanisms. C57BL/6 mice were intragastrically administered normal saline or EUG (20 mg/kg body weight) for 17 days, and colitis was induced by using 3% DSS from day 7. The results showed that EUG increased the body weight and reduced the disease activity index score and colon pathological scores in DSS-treated mice (P < 0.05). Further, EUG preserved the proinflammatory cytokines (interleukin (IL)-6, -12, -21, and -23), lowered (P < 0.05) colonic malondialdehyde (MDA), uncoupling protein 2 (UCP2) expression and p65 phosphorylation, and activated (P < 0.05) colonic kelch-like ECH-associated protein 1 and nuclear factor (erythroid-derived 2)-like 2 expressions but did not affect the intestinal microbiota in DSS-treated mice. Furthermore, EUG ameliorated colitis in antibiotic-treated mice, while fecal microbiota transplantation from EUG preadministered mice failed to ameliorate colitis. In conclusion, EUG could alleviate colitis by attenuating colonic inflammation and oxidative stress independent of intestinal microbiota.}, }
@article {pmid34473644, year = {2021}, author = {Sui, G and Jia, L and Quan, D and Zhao, N and Yang, G}, title = {Activation of the gut microbiota-kynurenine-liver axis contributes to the development of nonalcoholic hepatic steatosis in nondiabetic adults.}, journal = {Aging}, volume = {13}, number = {17}, pages = {21309-21324}, pmid = {34473644}, issn = {1945-4589}, abstract = {The contribution of gut-liver signaling to the development of non-alcoholic hepatic steatosis (NHS) in non-diabetic adults remains unclear. We therefore performed comprehensive 16S ribosomal RNA sequencing and fecal metabolomics analyses in 32 controls and 59 non-diabetic adults with NHS and performed fecal microbiota transplantation into germ-free mice using controls and NHS patients as donors. Compared to controls, the abundance of the genera Collinsella and Acinetobacter were higher, while that of Lachnospira was lower, in NHS subjects. Fecal metabolomics analysis showed decreased L-tryptophan levels and increased abundance of the tryptophan metabolite kynurenine in individuals with NHS. Correlation analysis showed that kynurenine levels positively associated with the abundance of Collinsella and Acinetobacter. ROC analysis demonstrated that the combination of tryptophan and kynurenine could discriminate NHS patients from controls with good statistical power [P < 0.05; AUC = 0.833 (95% CI, 0.747 to 0.918)]. Supporting a key role of dysbiotic gut microbiota in NHS development, incipient hepatic steatosis and increased kynurenine levels were observed in GF mice colonized with samples from NHS patients. These results indicate that enhanced kynurenine production resulting from altered gut microbiota composition contributes to NHS in nondiabetic adults and suggest the relevance of tryptophan metabolites as diagnostic biomarkers.}, }
@article {pmid34473374, year = {2021}, author = {Liu, C and Wang, YL and Yang, YY and Zhang, NP and Niu, C and Shen, XZ and Wu, J}, title = {Novel approaches to intervene gut microbiota in the treatment of chronic liver diseases.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {35}, number = {10}, pages = {e21871}, doi = {10.1096/fj.202100939R}, pmid = {34473374}, issn = {1530-6860}, mesh = {Animals ; End Stage Liver Disease/*drug therapy/microbiology ; *Gastrointestinal Microbiome ; Humans ; Probiotics/*therapeutic use ; }, abstract = {Recent investigations of gut microbiota have contributed to understanding of the critical role of microbial community in pathophysiology. Dysbiosis not only causes disturbance directly to the gastrointestinal tract but also affects the liver through gut-liver axis. Various types of dysbiosis have been documented in alcoholic liver disease (ALD), nonalcoholic fatty liver disease, autoimmune hepatitis (AIH), primary sclerosing cholangitis, and may be crucial for the initiation, progression, or deterioration to end-stage liver disease. A few microbial species have been identified as the causal factors leading to these chronic illnesses that either do not have clear etiologies or lack effective treatment. Notably, cytolysin-producing Enterococcus faecalis, Klebsiella pneumoniae and Enterococcus gallinarum were defined for ALD, NASH, and AIH, respectively. These groundbreaking discoveries drive a rapid development in innovative therapeutics, such as fecal microbial transplantation and implementation of specific bacteriophages in addition to prebiotics, probiotics, or synbiotics for intervention of dysbiosis. Although most emerging interventions are in preclinical development or early clinical trials, a better delineation of specific dysbiosis in these disorders at metabolic, immunogenic, or molecular levels in establishing particular causal effects aids in modulating or correcting the microbial community which is the part of daily life for human being.}, }
@article {pmid34469716, year = {2021}, author = {Sun, WL and Li, XY and Dou, HY and Wang, XD and Li, JD and Shen, L and Ji, HF}, title = {Myricetin supplementation decreases hepatic lipid synthesis and inflammation by modulating gut microbiota.}, journal = {Cell reports}, volume = {36}, number = {9}, pages = {109641}, doi = {10.1016/j.celrep.2021.109641}, pmid = {34469716}, issn = {2211-1247}, abstract = {The relationship between poor in vivo bioavailability and effective pharmacological activity are not yet fully clarified for many flavonoids. The analysis of flavonoids-induced alterations in the gut microbiota represents a promising approach to provide useful clues to elucidate the mechanism of action. Here, we investigate the effect of myricetin supplementation on high-fat-diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) in rats and explore the associations with the gut microbiota through high-throughput analyses. The 12-week myricetin supplementation and fecal microbiota transplantation outcomes suggest that myricetin significantly slows the development of NAFLD. Meanwhile, the anti-NAFLD effects of myricetin are associated with the modulation of the gut microbiota composition. Myricetin reduces hepatic lipid synthesis and inflammation through modulations in fecal butyric-acid-related gut microbiota and protection of the gut barrier function. This study may facilitate the elucidation of the action mechanism of flavonoids with low bioavailability.}, }
@article {pmid34463082, year = {2021}, author = {Bonetto, S and Fagoonee, S and Battaglia, E and Grassini, M and Saracco, GM and Pellicano, R}, title = {Recent advances in the treatment of irritable bowel syndrome.}, journal = {Polish archives of internal medicine}, volume = {131}, number = {7-8}, pages = {709-715}, doi = {10.20452/pamw.16067}, pmid = {34463082}, issn = {1897-9483}, mesh = {Abdominal Pain ; Constipation ; Diarrhea ; Female ; Humans ; *Irritable Bowel Syndrome/therapy ; Male ; Quality of Life ; }, abstract = {Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder which presents with abdominal pain and altered bowel habits. It affects about 20% of the general population, mainly women, and has a considerable impact on the quality of life and health care costs. Four different entities of IBS have been identified: IBS with constipation (IBS‑ C), IBS with diarrhea (IBS D), IBS with a mixed pattern of constipation and diarrhea, and unclassified IBS. Although the precise pathogenesis of IBS remains unclear, its multifactorial nature is evident and includes environmental and host factors. Management of patients with this disease is challenging and a personalized approach is required. A strong, reassuring physician‑ patient relationship is crucial, followed by patient education, dietary advice, and stress reduction. For nonresponding patients, the therapeutic approach may include nonpharmacological therapies and / or pharmacotherapy. The choice of pharmacological treatment is based on the predominant symptom and a prespecified time point should be planned for effectiveness evaluation and dose adjustment. In patients with IBS‑ D, the therapeutic options include mainly antibiotics, such as rifaximin, peripheral opioid agonists, mixed opioid agonists / antagonists, bile acid sequestrants, and antagonists of serotonin 5‑ hydroxytryptamine type 3 receptors. Bulking agents and osmotic laxatives represent the first line therapy for IBS‑ C, while lubiprostone and linaclotide should be reserved for difficult to treat patients. The involvement of gastrointestinal microbiota constitutes a fascinating field of exploration as it offers the potential to be modulated by the use of probiotics, prebiotics, synbiotics as well as fecal microbiota transplantation. This review offers an updated overview on the recent advances in the treatment of IBS.}, }
@article {pmid34462225, year = {2021}, author = {Abu El Haija, M and Ye, Y and Chu, Y and Herz, H and Linden, B and Shahi, SK and Zarei, K and Mangalam, AK and Mcelroy, SJ and Mokadem, M}, title = {Toll-like receptor 4 and myeloid differentiation factor 88 are required for gastric bypass-induced metabolic effects.}, journal = {Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery}, volume = {17}, number = {12}, pages = {1996-2006}, doi = {10.1016/j.soard.2021.07.019}, pmid = {34462225}, issn = {1878-7533}, abstract = {BACKGROUND: Toll-like receptor 4 (TLR4) has been suggested as one of the forefront cross-communicators between the intestinal bacteria and the host to regulate inflammatory signals and energy homeostasis. High-fat diet-induced inflammation is mediated by changes in gut microbiota and requires a functional TLR-4, the deficiency of which renders mice resistant to diet-induced obesity and its associated metabolic dysfunction. Furthermore, gut microbiota was suggested to play a key role in the beneficial effects of Roux-en-Y gastric bypass (RYGB), a commonly performed bariatric procedure.<br><br>OBJECTIVES: To explore whether TLR4, myeloid differentiation factor 8 (MyD88; 1 of its key downstream signaling regulators) and gut microbiota play an integrative role in RYGB-induced metabolic outcomes.<br><br>SETTING: Animal- based study.<br><br>METHOD: We performed RYGB in TLR4 and MyD88 knock-out (KO) mice and used fecal microbiota transplant (FMT) from RYGB-operated animals to these genetic mouse models to address our questions.<br><br>RESULTS: We demonstrate that RYGB reduces TLR4 expression explicitly in the small and large intestine of C57Blc/6J mice. We also show that TLR4 KO mice have an attenuated glucoregulatory response to RYGB. In addition, we reveal that MyD88 KO mice fail to respond to all RYGB-induced metabolic effects. Finally, fecal microbiota transplant from RYGB-operated mice into TLR4 KO and MyD88 KO naïve recipients fails to induce a metabolic phenotype similar to that of the donors, as it does in wild-type recipients.<br><br>CONCLUSION: TLR4 and MyD88 are required for RYGB-induced metabolic response that is likely mediated by gut microbiome.}, }
@article {pmid34461052, year = {2021}, author = {Yang, J and Wei, H and Zhou, Y and Szeto, CH and Li, C and Lin, Y and Coker, OO and Lau, HCH and Chan, AWH and Sung, JJY and Yu, J}, title = {High-Fat Diet Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2021.08.041}, pmid = {34461052}, issn = {1528-0012}, abstract = {BACKGROUND AND AIMS: Dietary fat intake is associated with increased risk of colorectal cancer (CRC). We examined the role of high-fat diet (HFD) in driving CRC through modulating gut microbiota and metabolites.<br><br>METHODS: HFD or control diet was fed to mice littermates in CRC mouse models of an azoxymethane (AOM) model and Apcmin/+ model, with or without antibiotics cocktail treatment. Germ-free mice for fecal microbiota transplantation were used for validation. Gut microbiota and metabolites were detected using metagenomic sequencing and high-performance liquid chromatography-mass spectrometry, respectively. Gut barrier function was determined using lipopolysaccharides level and transmission electron microscopy.<br><br>RESULTS: HFD promoted colorectal tumorigenesis in both AOM-treated mice and Apcmin/+ mice compared with control diet-fed mice. Gut microbiota depletion using antibiotics attenuated colon tumor formation in HFD-fed mice. A significant shift of gut microbiota composition with increased pathogenic bacteria Alistipessp.Marseille-P5997 and Alistipessp.5CPEGH6, and depleted probiotic Parabacteroides distasonis, along with impaired gut barrier function was exhibited in HFD-fed mice. Moreover, HFD-modulated gut microbiota promotes colorectal tumorigenesis in AOM-treated germ-free mice, indicating gut microbiota was essential in HFD-associated colorectal tumorigenesis. Gut metabolites alteration, including elevated lysophosphatidic acid, which was confirmed to promote CRC cell proliferation and impair cell junction, was also observed in HFD-fed mice. Moreover, transfer of stools from HFD-fed mice to germ-free mice without interference increased colonic cell proliferation, impaired gut barrier function, and induced oncogenic genes expression.<br><br>CONCLUSIONS: HFD drives colorectal tumorigenesis through inducing gut microbial dysbiosis, metabolomic dysregulation with elevated lysophosphatidic acid, and gut barrier dysfunction in mice.}, }
@article {pmid34460287, year = {2021}, author = {Ancona, G and Alagna, L and Lombardi, A and Palomba, E and Castelli, V and Renisi, G and Dondossola, D and Iavarone, M and Muscatello, A and Gori, A and Bandera, A}, title = {The Interplay between Gut Microbiota and the Immune System in Liver Transplant Recipients and Its Role in Infections.}, journal = {Infection and immunity}, volume = {89}, number = {11}, pages = {e0037621}, pmid = {34460287}, issn = {1098-5522}, mesh = {Bacterial Infections/*etiology/immunology ; Drug Resistance, Multiple, Bacterial ; Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Host Microbial Interactions ; Humans ; Immune System/*physiology ; Liver Cirrhosis/complications/microbiology ; Liver Transplantation/*adverse effects ; Severity of Illness Index ; }, abstract = {Liver transplantation (LT) is a life-saving strategy for patients with end-stage liver disease, hepatocellular carcinoma, and acute liver failure. LT success can be hampered by several short-term and long-term complications. Among them, bacterial infections, especially those due to multidrug-resistant germs, are particularly frequent, with a prevalence between 19 and 33% in the first 100 days after transplantation. In the last decades, a number of studies have highlighted how the gut microbiota (GM) is involved in several essential functions to ensure intestinal homeostasis, becoming one of the most important virtual metabolic organs. The GM works through different axes with other organs, and the gut-liver axis is among the most relevant and investigated ones. Any alteration or disruption of the GM is defined as dysbiosis. Peculiar phenotypes of GM dysbiosis have been associated with several liver conditions and complications, such as chronic hepatitis, fatty liver disease, cirrhosis, and hepatocellular carcinoma. Moreover, there is growing evidence of the crucial role of the GM in shaping the immune response, both locally and systemically, against pathogens. This paves the way to the manipulation of the GM as a therapeutic instrument to modulate infectious risk and outcome. In this minireview, we provide an overview of the current understanding of the interplay between the gut microbiota and the immune system in liver transplant recipients and the role of the former in infections.}, }
@article {pmid34458158, year = {2021}, author = {Zhong, HJ and Zeng, HL and Cai, YL and Zhuang, YP and Liou, YL and Wu, Q and He, XX}, title = {Washed Microbiota Transplantation Lowers Blood Pressure in Patients With Hypertension.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {679624}, pmid = {34458158}, issn = {2235-2988}, mesh = {Animals ; Antihypertensive Agents/pharmacology/therapeutic use ; Blood Pressure ; Humans ; *Hypertension/therapy ; *Microbiota ; Retrospective Studies ; }, abstract = {Background: Although transplantation of the fecal microbiota from normotensive donors has been shown to have an antihypertensive effect in hypertensive animal models, its effect on blood pressure in patients with hypertension is unclear. This study aimed to assess the effect of washed microbiota transplantation (WMT) from normotensive donors on blood pressure regulation in hypertensive patients.<br><br>Methods: The clinical data of consecutive patients treated with washed microbiota transplantation (WMT) were collected retrospectively. The blood pressures of hypertensive patients before and after WMT were compared. The factors influencing the antihypertensive effect of WMT in hypertensive patients and fecal microbial composition of donors and hypertensive patients were also analyzed.<br><br>Results: WMT exhibited an antihypertensive effect on blood pressure: the blood pressure at hospital discharge was significantly lower than that at hospital admission (change in systolic blood pressure: -5.09 ± 15.51, P = 0.009; change in diastolic blood pressure: -7.74 ± 10.42, P < 0.001). Hypertensive patients who underwent WMT via the lower gastrointestinal tract (β = -8.308, standard error = 3.856, P = 0.036) and those not taking antihypertensive drugs (β = -8.969, standard error = 4.256, P = 0.040) had a greater decrease in systolic blood pressure, and hypertensive patients not taking antihypertensive drugs also had a greater decrease in diastolic blood pressure (β = -8.637, standard error = 2.861, P = 0.004). After WMT, the Shannon Diversity Index was higher in six of eight hypertensive patients and the microbial composition of post-WMT samples tended to be closer to that of donor samples.<br><br>Conclusion: WMT had a blood pressure-lowering effect in hypertensive patients, especially in those who underwent WMT via the lower gastrointestinal tract and in those not taking antihypertensive drugs. Therefore, modulation of the gut microbiota by WMT may offer a novel approach for hypertension treatment.}, }
@article {pmid34455517, year = {2021}, author = {Li, JJ and Zhu, M and Kashyap, PC and Chia, N and Tran, NH and McWilliams, RR and Bekaii-Saab, TS and Ma, WW}, title = {The role of microbiome in pancreatic cancer.}, journal = {Cancer metastasis reviews}, volume = {40}, number = {3}, pages = {777-789}, pmid = {34455517}, issn = {1573-7233}, abstract = {Recent studies of the human microbiome have offered new insights into how the microbiome can impact cancer development and treatment. Specifically, in pancreatic ductal adenocarcinoma (PDAC), the microbiota has been shown to modulate PDAC risk, contribute to tumorigenesis, impact the tumor microenvironment, and alter treatment response. These findings provide rationale for further investigations into leveraging the microbiome to develop new strategies to diagnose and treat PDAC patients. There is growing evidence that microbiome analyses have the potential to become easily performed, non-invasive diagnostic, prognostic, and predictive biomarkers in pancreatic cancer. More excitingly, there is now emerging interest in developing interventions based on the modulation of microbiota. Fecal microbiota transplantation, probiotics, dietary changes, and antibiotics are all potential strategies to augment the efficacy of current therapeutics and reduce toxicities. While there are still challenges to overcome, this is a rapidly growing field that holds promise for translation into clinical practice and provides a new approach to improving patient outcomes.}, }
@article {pmid34452466, year = {2021}, author = {Desselberger, U}, title = {Significance of the Gut Microbiome for Viral Diarrheal and Extra-Intestinal Diseases.}, journal = {Viruses}, volume = {13}, number = {8}, pages = {}, pmid = {34452466}, issn = {1999-4915}, abstract = {The composition of the mammalian gut microbiome is very important for the health and disease of the host. Significant correlations of particular gut microbiota with host immune responsiveness and various infectious and noninfectious host conditions, such as chronic enteric infections, type 2 diabetes, obesity, asthma, and neurological diseases, have been uncovered. Recently, research has moved on to exploring the causalities of such relationships. The metabolites of gut microbiota and those of the host are considered in a 'holobiontic' way. It turns out that the host's diet is a major determinant of the composition of the gut microbiome and its metabolites. Animal models of bacterial and viral intestinal infections have been developed to explore the interrelationships of diet, gut microbiome, and health/disease phenotypes of the host. Dietary fibers can act as prebiotics, and certain bacterial species support the host's wellbeing as probiotics. In cases of Clostridioides difficile-associated antibiotic-resistant chronic diarrhea, transplantation of fecal microbiomes has sometimes cured the disease. Future research will concentrate on the definition of microbial/host/diet interrelationships which will inform rationales for improving host conditions, in particular in relation to optimization of immune responses to childhood vaccines.}, }
@article {pmid34450312, year = {2021}, author = {Socała, K and Doboszewska, U and Szopa, A and Serefko, A and Włodarczyk, M and Zielińska, A and Poleszak, E and Fichna, J and Wlaź, P}, title = {The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders.}, journal = {Pharmacological research}, volume = {172}, number = {}, pages = {105840}, doi = {10.1016/j.phrs.2021.105840}, pmid = {34450312}, issn = {1096-1186}, abstract = {Emerging evidence indicates that the gut microbiota play a crucial role in the bidirectional communication between the gut and the brain suggesting that the gut microbes may shape neural development, modulate neurotransmission and affect behavior, and thereby contribute to the pathogenesis and/or progression of many neurodevelopmental, neuropsychiatric, and neurological conditions. This review summarizes recent data on the role of microbiota-gut-brain axis in the pathophysiology of neuropsychiatric and neurological disorders including depression, anxiety, schizophrenia, autism spectrum disorders, Parkinson's disease, migraine, and epilepsy. Also, the involvement of microbiota in gut disorders co-existing with neuropsychiatric conditions is highlighted. We discuss data from both in vivo preclinical experiments and clinical reports including: (1) studies in germ-free animals, (2) studies exploring the gut microbiota composition in animal models of diseases or in humans, (3) studies evaluating the effects of probiotic, prebiotic or antibiotic treatment as well as (4) the effects of fecal microbiota transplantation.}, }
@article {pmid34449321, year = {2021}, author = {Duan, L and An, X and Zhang, Y and Jin,  and Zhao, S and Zhou, R and Duan, Y and Zhang, Y and Liu, X and Lian, F}, title = {Gut microbiota as the critical correlation of polycystic ovary syndrome and type 2 diabetes mellitus.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {142}, number = {}, pages = {112094}, doi = {10.1016/j.biopha.2021.112094}, pmid = {34449321}, issn = {1950-6007}, abstract = {Gut microbiota forms a symbiotic relationship with the host and maintains the ecological balance of the internal and external environment of the human body. However, dysbiosis of the gut microbiota and immune deficiency, as well as environmental changes, can destroy the host-microbial balance, leading to the occurrence of a variety of diseases, such as polycystic ovary syndrome (PCOS), type 2 diabetes mellitus (T2DM), and obesity. Meanwhile, diseases can also affect gut microbiota, forming a vicious cycle. The role of the intestinal microbiota in different diseases have been proven by several studies; however, as a common target of PCOS and T2DM, there are few reports on the treatment of different diseases through the regulation of intestinal microbiota as the critical correlation. This review analyzed the common mechanisms of intestinal microbiota in PCOS and T2DM, including the dysbiosis of gut microbiota, endotoxemia, short-chain fatty acids, biotransformation of bile acids, and synthesis of amino acid in regulating insulin resistance, obesity, chronic inflammation, and mitochondrial dysfunction. The possible therapeutic effects of probiotics and/or prebiotics, fecal microbiota transplantation, bariatric surgery, dietary intervention, drug treatment, and other treatments targeted at regulating intestinal microbiota were also elucidated.}, }
@article {pmid34447287, year = {2021}, author = {Zhang, L and Chu, J and Hao, W and Zhang, J and Li, H and Yang, C and Yang, J and Chen, X and Wang, H}, title = {Gut Microbiota and Type 2 Diabetes Mellitus: Association, Mechanism, and Translational Applications.}, journal = {Mediators of inflammation}, volume = {2021}, number = {}, pages = {5110276}, pmid = {34447287}, issn = {1466-1861}, abstract = {Gut microbiota has attracted widespread attention due to its crucial role in disease pathophysiology, including type 2 diabetes mellitus (T2DM). Metabolites and bacterial components of gut microbiota affect the initiation and progression of T2DM by regulating inflammation, immunity, and metabolism. Short-chain fatty acids, secondary bile acid, imidazole propionate, branched-chain amino acids, and lipopolysaccharide are the main molecules related to T2DM. Many studies have investigated the role of gut microbiota in T2DM, particularly those butyrate-producing bacteria. Increasing evidence has demonstrated that fecal microbiota transplantation and probiotic capsules are useful strategies in preventing diabetes. In this review, we aim to elucidate the complex association between gut microbiota and T2DM inflammation, metabolism, and immune disorders, the underlying mechanisms, and translational applications of gut microbiota. This review will provide novel insight into developing individualized therapy for T2DM patients based on gut microbiota immunometabolism.}, }
@article {pmid34444932, year = {2021}, author = {Gibiino, G and Sartini, A and Gitto, S and Binda, C and Sbrancia, M and Coluccio, C and Sambri, V and Fabbri, C}, title = {The Other Side of Malnutrition in Inflammatory Bowel Disease (IBD): Non-Alcoholic Fatty Liver Disease.}, journal = {Nutrients}, volume = {13}, number = {8}, pages = {}, pmid = {34444932}, issn = {2072-6643}, mesh = {Colitis, Ulcerative/epidemiology ; Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*epidemiology ; Intestines/pathology ; Male ; Malnutrition/*epidemiology ; Metabolic Syndrome/epidemiology ; Non-alcoholic Fatty Liver Disease/*epidemiology/therapy ; Nutritional Status ; Obesity/epidemiology ; Prevalence ; Risk Factors ; }, abstract = {Steatohepatitis and hepatobiliary manifestations constitute some of the most common extra-intestinal manifestations of Inflammatory Bowel Disease (IBD). On the other hand, non-alcoholic fatty liver disease (NAFLD) affects around 25% of the world's population and is attracting ever more attention in liver transplant programs. To outline the specific pathways linking these two conditions is a pressing task for 21st-century researchers. We are accustomed to expecting the occurrence of fatty liver disease in obese people, but current evidence suggests that there are several different pathways also occurring in underweight patients. Genetic factors, inflammatory signals and microbiota are key players that could help in understanding the entire pathogenesis of NAFLD, with the aim of defining the multiple expressions of malnutrition. In the current review, we summarize the most recent literature regarding the epidemiology, pathogenesis and future directions for the management of NAFLD in patients affected by IBD.}, }
@article {pmid34439657, year = {2021}, author = {Abuaish, S and Al-Otaibi, NM and Abujamel, TS and Alzahrani, SA and Alotaibi, SM and AlShawakir, YA and Aabed, K and El-Ansary, A}, title = {Fecal Transplant and Bifidobacterium Treatments Modulate Gut Clostridium Bacteria and Rescue Social Impairment and Hippocampal BDNF Expression in a Rodent Model of Autism.}, journal = {Brain sciences}, volume = {11}, number = {8}, pages = {}, pmid = {34439657}, issn = {2076-3425}, support = {RGP-1441-0027//Deanship of Scientific Research, Princess Nourah bint Abdulrahman University, the Research Group Program/ ; }, abstract = {Autism is associated with gastrointestinal dysfunction and gut microbiota dysbiosis, including an overall increase in Clostridium. Modulation of the gut microbiota is suggested to improve autistic symptoms. In this study, we explored the implementation of two different interventions that target the microbiota in a rodent model of autism and their effects on social behavior: the levels of different fecal Clostridium spp., and hippocampal transcript levels. Autism was induced in young Sprague Dawley male rats using oral gavage of propionic acid (PPA) for three days, while controls received saline. PPA-treated animals were divided to receive either saline, fecal transplant from healthy donor rats, or Bifidobacterium for 22 days, while controls continued to receive saline. We found that PPA attenuated social interaction in animals, which was rescued by the two interventions. PPA-treated animals had a significantly increased abundance of fecal C. perfringens with a concomitant decrease in Clostridium cluster IV, and exhibited high hippocampal Bdnf expression compared to controls. Fecal microbiota transplantation or Bifidobacterium treatment restored the balance of fecal Clostridium spp. and normalized the level of Bdnf expression. These findings highlight the involvement of the gut-brain axis in the etiology of autism and propose possible interventions in a preclinical model of autism.}, }
@article {pmid34430117, year = {2021}, author = {Nandwana, V and Debbarma, S}, title = {Fecal Microbiota Transplantation: A Microbiome Modulation Technique for Alzheimer's Disease.}, journal = {Cureus}, volume = {13}, number = {7}, pages = {e16503}, pmid = {34430117}, issn = {2168-8184}, abstract = {Alzheimer's disease (AD) is the most common form of dementia and the fifth leading cause of death among the elderly. AD involves parts of the brain that can lead to progressive memory loss and impaired language skills and cognitive thinking, affecting one's ability to carry out daily activities. Aging, bad dietary habits, family history, as well as altered gut microbiota composition may play a role in the pathogenesis of AD. Although the association between the imbalance of gut microbiota and AD is still difficult to determine, it has been suggested that dysbiosis can lead to the increased secretion of lipopolysaccharides and amyloid, which may impair the permeability of the intestine and the blood-brain barrier. Moreover, it can progress the process of neuroinflammation, amyloid-beta formation, and ultimately neuronal death. Microbiota-targeted interventions such as personalized diet, probiotics, or fecal microbiota transplantation (FMT) might represent a potential therapeutic option for AD. This review article discusses the procedure of FMT and its possible side effects on the recipient's body. In addition, we review the role of FMT in the context of its application in various nervous system-related disorders (AD, Parkinson's disease, multiple sclerosis).}, }
@article {pmid34428426, year = {2021}, author = {Jiao, X and Pei, X and Lu, D and Qi, D and Huang, S and He, S and Li, Z}, title = {Microbial Reconstitution Improves Aging-Driven Lacrimal Gland Circadian Dysfunction.}, journal = {The American journal of pathology}, volume = {191}, number = {12}, pages = {2091-2116}, doi = {10.1016/j.ajpath.2021.08.006}, pmid = {34428426}, issn = {1525-2191}, abstract = {Lacrimal glands are highly susceptible to aging and exhibit age-related structural and functional alterations. However, the mechanisms by which aging affects the lacrimal glands are not well-established. The current study explores the crosstalk between the aging process, gut microbiota, and circadian rhythm in age-associated lacrimal gland dysfunction. C57BL/6J mice were divided into young, old, and fecal microbiota transplant (FMT)-treated old groups. The gut bacterial community diversity was analyzed by 16S rRNA sequencing. Exorbital lacrimal glands (ELGs) were collected at 3-hour intervals over a 24-hour circadian cycle, and total RNA was subjected to high-throughput sequencing. Rhythmic transcriptional data were analyzed using the Jonckheere-Terpstra-Kendall algorithm and bioinformatics analysis technology. Immunostaining was used to identify lymphocytic infiltration, lipid deposition, and nerve innervation in the ELGs. Compared with young mice, old mice underwent a significant gut microbial community shift. The rhythmically transcriptomic profile was significantly reprogrammed over a 24-hour cycle in the old ELG group. Intervention with serial FMT from young donors for 1 month rejuvinated the gut microbial community of the old mice. Most alterations in rhythmic transcriptomic profiling were improved. Furthermore, chronic inflammation, lipid deposition, and aberrant neural response of the aging lacrimal glands were significantly reduced. Thus, the study shows that reconstitution of age-associated gut dysbiosis with FMTs from young donors improves aging-driven lacrimal gland circadian dysfunction.}, }
@article {pmid34426641, year = {2021}, author = {Samuelson, DR and Gu, M and Shellito, JE and Molina, PE and Taylor, CM and Luo, M and Welsh, DA}, title = {Pulmonary immune cell trafficking promotes host defense against alcohol-associated Klebsiella pneumonia.}, journal = {Communications biology}, volume = {4}, number = {1}, pages = {997}, pmid = {34426641}, issn = {2399-3642}, support = {R21 AA027199/AA/NIAAA NIH HHS/United States ; K99 AA026336/AA/NIAAA NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; P60 AA009803/AA/NIAAA NIH HHS/United States ; P50 AA009803/AA/NIAAA NIH HHS/United States ; R00 AA026336/AA/NIAAA NIH HHS/United States ; }, abstract = {The intestinal microbiota generates many different metabolites which are critical for the regulation of host signaling pathways. In fact, a wide-range of diseases are associated with increased levels of local or systemic microbe-derived metabolites. In contrast, certain bacterial metabolites, such as tryptophan metabolites, are known to contribute to both local and systemic homeostasis. Chronic alcohol consumption is accompanied by alterations to intestinal microbial communities, and their functional capacities. However, little is known about the role of alcohol-associated dysbiosis on host defense against bacterial pneumonia. Our previous work using fecal transplantation demonstrated that alcohol-associated intestinal dysbiosis, independent of ethanol consumption, increased susceptibility to Klebsiella pneumonia. Here, we demonstrate that intestinal microbiota treatments mitigate the increased risk of alcohol-associated pneumonia. Treatment with the microbial metabolite indole or with probiotics reduced pulmonary and extrapulmonary bacterial burden, restored immune responses, and improved cellular trafficking required for host defense. Protective effects were, in part, mediated by aryl hydrocarbon receptors (AhR), as inhibition of AhR diminished the protective effects. Thus, alcohol appears to impair the production/processing of tryptophan catabolites resulting in immune dysregulation and impaired cellular trafficking. These data support microbiota therapeutics as novel strategies to mitigate the increased risk for alcohol-associated bacterial pneumonia.}, }
@article {pmid34424831, year = {2021}, author = {de Wouters d'Oplinter, A and Rastelli, M and Van Hul, M and Delzenne, NM and Cani, PD and Everard, A}, title = {Gut microbes participate in food preference alterations during obesity.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1959242}, pmid = {34424831}, issn = {1949-0984}, abstract = {Hypothalamic regulations of food intake are altered during obesity. The dopaminergic mesocorticolimbic system, responsible for the hedonic response to food intake, is also affected. Gut microbes are other key players involved in obesity. Therefore, we investigated whether the gut microbiota plays a causal role in hedonic food intake alterations contributing to obesity. We transferred fecal material from lean or diet-induced obese mice into recipient mice and evaluated the hedonic food intake using a food preference test comparing the intake of control and palatable diets (HFHS, High-Fat High-Sucrose) in donor and recipient mice. Obese mice ate 58% less HFHS during the food preference test (p < 0.0001) than the lean donors, suggesting a dysregulation of the hedonic food intake during obesity. Strikingly, the reduction of the pleasure induced by eating during obesity was transferable through gut microbiota transplantation since obese gut microbiota recipient mice exhibited similar reduction in HFHS intake during the food preference test (40% reduction as compared to lean gut microbiota recipient mice, p < 0.01). This effect was associated with a consistent trend in modifications of dopaminergic markers expression in the striatum. We also pinpointed a highly positive correlation between HFHS intake and Parabacteroides (p < 0.0001), which could represent a potential actor involved in hedonic feeding probably through the gut-to-brain axis. We further demonstrated the key roles played by gut microbes in this paradigm since depletion of gut microbiota using broad-spectrum antibiotics also altered HFHS intake during food preference test in lean mice. In conclusion, we discovered that gut microbes regulate hedonic aspects of food intake. Our data demonstrate that gut microbiota modifications associated with obesity participate in dysregulations of the reward and hedonic components of the food intake. These data provide evidence that gut microbes could be an interesting therapeutic target to tackle hedonic disorders related to obesity.}, }
@article {pmid34424357, year = {2021}, author = {Schiereck, T and Yeldan, S and Kranz, J and Schneidewind, L and Wagenlehner, F and Wieters, I and Vehreschild, MJGT and Otto, T and Barski, D}, title = {[Urinary bladder microbiome analysis and probiotic treatment options for women with recurrent urinary tract infections].}, journal = {Der Urologe. Ausg. A}, volume = {}, number = {}, pages = {}, pmid = {34424357}, issn = {1433-0563}, abstract = {Novel preventive measures and therapeutic approaches are needed to reduce the frequency of recurrent urinary tract infections (rUTI) and the associated emergence of multidrug-resistant uropathogens. The aim of this review is to systematically present the available evidence on the urinary bladder microbiome of healthy women and those with rUTIs. In addition, relevant studies on the efficacy of probiotics in rUTIs are presented in a structured manner. This will provide an overview on the current state of research and an outlook on treatment strategies beyond the usual antimicrobial options.}, }
@article {pmid34419965, year = {2021}, author = {Kullberg, RFJ and Wiersinga, WJ and Haak, BW}, title = {Gut microbiota and sepsis: from pathogenesis to novel treatments.}, journal = {Current opinion in gastroenterology}, volume = {37}, number = {6}, pages = {578-585}, doi = {10.1097/MOG.0000000000000781}, pmid = {34419965}, issn = {1531-7056}, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Probiotics/therapeutic use ; *Sepsis/therapy ; }, abstract = {PURPOSE OF REVIEW: This review summarizes recent progress in our understanding of the role of the gut microbiota in sepsis pathogenesis and outlines the potential role of microbiota-targeted therapies.<br><br>RECENT FINDINGS: The composition of the gut microbiome is profoundly distorted during sepsis, with a loss of commensal bacteria and an overgrowth of potential pathogenic micro-organisms. These alterations also extend to nonbacterial intestinal inhabitants. Disruptions of these intestinal communities are associated with both an increased susceptibility to develop sepsis, as well as a higher risk of adverse outcomes. Preclinical studies have characterized the effects of several microbiota-derived metabolites (such as D-lactate, butyrate, and deoxycholic acid) on enhancing the host immune response during critical illness. Microbiota-targeted therapies (e.g. probiotics or fecal microbiota transplantation) might be of benefit, but can also be associated with increased risks of bloodstream infections.<br><br>SUMMARY: Emerging evidence display an important role of gut micro-organisms (including bacteria, fungi, eukaryotic viruses, and bacteriophages) and their derived metabolites in both the susceptibility to, as well as outcomes of sepsis. Despite recent progress in the mechanistic understanding of microbiota-mediated protection, clinical breakthroughs in the development of microbiota-based prognostic tools or therapies are thus far lacking in the field of sepsis.}, }
@article {pmid34419770, year = {2021}, author = {Cheraghmakani, H and Rezai, MS and Valadan, R and Rahimzadeh, G and Moradi, M and Jahanfekr, V and Moosazadeh, M and Tabrizi, N}, title = {Ciprofloxacin for treatment of drug-resistant epilepsy.}, journal = {Epilepsy research}, volume = {176}, number = {}, pages = {106742}, doi = {10.1016/j.eplepsyres.2021.106742}, pmid = {34419770}, issn = {1872-6844}, abstract = {PURPOSE: To investigate the efficacy of short-term treatment with ciprofloxacin in alteration of gut microbiota pattern and reduction of seizure frequency in adult patients with drug-resistant epilepsy.<br><br>METHODS: In a prospective study, we investigated the effect of a 5-day course of treatment with ciprofloxacin on gut microbiota pattern and seizure frequency of 23 adults with drug-resistant epilepsy. Fecal samples were collected before and after treatment and were analyzed for microbial load and species. Changes in seizure frequency were registered for 12 weeks. Responders were defined as patients who experienced ≥50 % seizure reduction in comparison to baseline. Outcome measures were specified as alteration in fecal microbial burden in days 5-7 and responder rate in 4th and 12th weeks.<br><br>RESULTS: The mean baseline frequency of seizures was5.6 ±7.7 per week. All patients were on polytherapy with a mean of 3 ± 1.2 anti-seizure medications. Microbial analysis showed a considerable increase in Bacteroidetes/Firmicutes ratio after treatment. Seizure frequency significantly decreased at the end of first week and the therapeutic effect continued to week 12 (P < 0.001). The responder rate at 4th and 12th weeks were 69.6 % and 73.9 % respectively with a more prominent response in patients with symptomatic generalized epilepsy (P:0.06).<br><br>CONCLUSION: Alteration of abnormal gut microbiota pattern by methods such as short-course antibiotic therapy, prescription of probiotics and fecal microbiota transplant might be effective in treatment of drug-resistant epilepsy.}, }
@article {pmid34416751, year = {2021}, author = {Cao, M and Peng, Y and Lu, Y and Zou, Z and Chen, J and Bottino, R and Knoll, M and Zhang, H and Lin, S and Pu, Z and Sun, L and Fang, Z and Qiu, C and Dai, Y and Cai, Z and Mou, L}, title = {Controls of Hyperglycemia Improves Dysregulated Microbiota in Diabetic Mice.}, journal = {Transplantation}, volume = {105}, number = {9}, pages = {1980-1988}, pmid = {34416751}, issn = {1534-6080}, mesh = {Animals ; Bacteria/classification/genetics/*growth &amp; development ; Biomarkers/blood ; Blood Glucose/*drug effects/metabolism ; Diabetes Mellitus, Experimental/blood/chemically induced/microbiology/*therapy ; Diabetes Mellitus, Type 1/blood/chemically induced/microbiology/*therapy ; Dysbiosis ; Feces/microbiology ; *Gastrointestinal Microbiome ; *Glycemic Control ; Hypoglycemic Agents/*pharmacology ; Insulin/*pharmacology ; Islets of Langerhans Transplantation ; Male ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Ribotyping ; Streptozocin ; Tissue Culture Techniques ; }, abstract = {BACKGROUND: Type 1 diabetes (T1DM) is a chronic autoimmune disease characterized by T-cell-mediated destruction of insulin-producing beta cells. Evidence shows that patients with T1DM and mice used in specific diabetic models both exhibit changes in their intestinal microbiota and dysregulated microbiota contributes to the pathogenesis of T1DM. Islet transplantation (Tx) is poised to play an important role in the treatment of T1DM. However, whether treatment of T1DM with islet Tx can rescue dysregulated microbiota remains unclear.<br><br>METHODS: In this study, we induced diabetic C57BL/6 mice with streptozotocin. Then treatment with either insulin administration, or homogenic or allogenic islet Tx was performed to the diabetic mice. Total DNA was isolated from fecal pellets and high-throughput 16S rRNA sequencing was used to investigate intestinal microbiota composition.<br><br>RESULTS: The overall microbial diversity was comparable between control (nonstreptozotocin treated) and diabetic mice. Our results showed the ratio of the Bacteroidetes: Firmicutes between nondiabetic and diabetic mice was significant different. Treatment with islet Tx or insulin partially corrects the dysregulated bacterial composition. At the genus level, Bacteroides, Odoribacter, and Alistipes were associated with the progression and treatment efficacy of the disease, which may be used as a biomarker to predict curative effect of treatment for patients with T1DM.<br><br>CONCLUSIONS: Collectively, our results indicate that diabetic mice show changed microbiota composition and that treatment with insulin and islet Tx can partially correct the dysregulated microbiota.}, }
@article {pmid34416387, year = {2021}, author = {An, L and Wuri, J and Zheng, Z and Li, W and Yan, T}, title = {Microbiota modulate Doxorubicin induced cardiotoxicity.}, journal = {European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences}, volume = {166}, number = {}, pages = {105977}, doi = {10.1016/j.ejps.2021.105977}, pmid = {34416387}, issn = {1879-0720}, mesh = {Animals ; Cardiotoxicity ; Doxorubicin/toxicity ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; Stroke Volume ; Ventricular Function, Left ; }, abstract = {Chemotherapy has several adverse effects to patients, some of which are life-threatening. We hypothesized that Doxorubicin induced microbiome imbalance and intestinal damage may contribute to Doxorubicin induced cardiac dysfunction. Male adult (2-3 months) C57BL/6 mice were administered 3 mg/kg, 5 mg/kg, 7.5 mg/kg,15 mg/kg, 20 mg/kg doses of Doxorubicin. Echocardiography was performed at 7 and 14 days after Doxorubicin administration. 16S rRNA amplicon sequencing was used to characterize microbiome changes. Fecal microbiota transplantation (FMT) was performed to evaluate the role of the microbiota on Doxorubicin induced cardiac dysfunction. Doxorubicin dose dependently increases mortality rate and induces cardiac dysfunction. 5 mg/kg-Doxorubicin significantly induces decreased left ventricular ejection fraction (LVEF) and fraction shortening (FS) as well as increased cardiac fibrosis, inflammation and oxidative stress respond without increasing mortality. 5 mg/kg-Doxorubicin induces significant decreased colorectum length, increased loss of goblet cells, numbers of ulcers and infiltration of lymphocyte clusters and decreased tight junction protein ZO-1, as well as increased plasma endotoxin level measured by ELISA assay. 16S rRNA microbiota analysis shows that Doxorubicin-induced microbiota dysbiosis with decreased community richness compared with normal control mice. FMT to Doxorubicin-5 mg treated mice significantly improved cardiac function by increasing LVEF and FS as well as decreased perivascular and interstitial fibrosis; increased colorectum length, decreased the loss of goblet cells,infiltration of lymphocyte clusters,the number of ulcers and plasma endotoxin level; improved microbiota composition, function and diversity with increased abundance of Alloprevotella, Prevotellaceae_UCG-001 and Rikenellaceae_RC9_gut_group. We find that normal fecal transplantation improves cardiac function, decreases gut damage and alter microbiota composition induced by Doxorubicin. The microbiota appears to contribute to heart-gut interaction.}, }
@article {pmid34410652, year = {2021}, author = {Zhu, Z and Kaiser, T and Staley, C}, title = {Antibiotic Conditioning and Single Gavage Allows Stable Engraftment of Human Microbiota in Mice.}, journal = {Methods in molecular biology (Clifton, N.J.)}, volume = {2327}, number = {}, pages = {281-291}, pmid = {34410652}, issn = {1940-6029}, abstract = {Mice transplanted with human microbiota are essential tools for studying the role of microbiota in health and disease, striving for the development of microbiota-modulating therapeutics. Traditionally, germ-free mice have been the principal option for establishing human microbiota-associated (HMA) mouse models, leading to significant insights into the composition and function of the human microbiota. However, there are limitations in using germ-free mice as recipients of human microbiota, including considerable resource allocation to establish and maintain the model and incomplete development of their immune system and physiological functions. Thus, antibiotic-treated, non-germ-free mice have been developed as an alternative to satisfy the growing demand for an accessible HMA mouse model. Several methods have been described for creating "humanized" mice. These protocols vary in their key components, mainly antibiotic conditioning and frequency of oral gavage. To address this practical challenge and formulate a simple and repeatable protocol, we established a HMA mouse model with antibiotic-treated conventional and specific-pathogen free (SPF) C57BL/6J mice, revealing that a single oral gavage allows stable engraftment of the human microbiota. In this chapter, we present our simple protocol for antibiotic conditioning to prepare mice for stable engraftment of human gut microbiota.}, }
@article {pmid34409064, year = {2021}, author = {Yu, X and Zuo, T}, title = {Editorial: Food Additives, Cooking and Processing: Impact on the Microbiome.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {731040}, pmid = {34409064}, issn = {2296-861X}, }
@article {pmid34408753, year = {2021}, author = {Varricchi, G and Poto, R and Ianiro, G and Punziano, A and Marone, G and Gasbarrini, A and Spadaro, G}, title = {Gut Microbiome and Common Variable Immunodeficiency: Few Certainties and Many Outstanding Questions.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {712915}, pmid = {34408753}, issn = {1664-3224}, abstract = {Common variable immunodeficiency (CVID) is the most common symptomatic primary antibody immunodeficiency, characterized by reduced serum levels of IgG, IgA, and/or IgM. The vast majority of CVID patients have polygenic inheritance. Immune dysfunction in CVID can frequently involve the gastrointestinal tract and lung. Few studies have started to investigate the gut microbiota profile in CVID patients. Overall, the results suggest that in CVID patients there is a reduction of alpha and beta diversity compared to controls. In addition, these patients can exhibit increased plasma levels of lipopolysaccharide (LPS) and markers (sCD14 and sCD25) of systemic immune cell activation. CVID patients with enteropathy exhibit decreased IgA expression in duodenal tissue. Mouse models for CVID unsatisfactorily recapitulate the polygenic causes of human CVID. The molecular pathways by which gut microbiota contribute to systemic inflammation and possibly tumorigenesis in CVID patients remain poorly understood. Several fundamental questions concerning the relationships between gut microbiota and the development of chronic inflammatory conditions, autoimmune disorders or cancer in CVID patients remain unanswered. Moreover, it is unknown whether it is possible to modify the microbiome and the outcome of CVID patients through specific therapeutic interventions.}, }
@article {pmid34403877, year = {2021}, author = {Chen, L and Kan, J and Zheng, N and Li, B and Hong, Y and Yan, J and Tao, X and Wu, G and Ma, J and Zhu, W and Sheng, L and Chen, L and Li, B and Zhong, J and Du, J and Li, H}, title = {A botanical dietary supplement from white peony and licorice attenuates nonalcoholic fatty liver disease by modulating gut microbiota and reducing inflammation.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {91}, number = {}, pages = {153693}, doi = {10.1016/j.phymed.2021.153693}, pmid = {34403877}, issn = {1618-095X}, mesh = {Animals ; Diet, High-Fat/adverse effects ; *Dietary Supplements ; *Gastrointestinal Microbiome/drug effects ; *Glycyrrhiza/chemistry ; Inflammation/drug therapy ; Liver ; Mice ; Mice, Inbred C57BL ; *Non-alcoholic Fatty Liver Disease/drug therapy ; *Paeonia/chemistry ; *Plant Extracts/pharmacology ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related metabolic disease that is highly associated with gut dysbiosis and inflammation. A botanical dietary supplement, mainly containing an herbal pair of white peony root and licorice as well as grape seeds and broccoli extracts (WLT), exerts auxiliary protection against chemical liver injury. However, it is unclear whether WLT protects against the development of NAFLD induced by a high energy diet.<br><br>PURPOSE: To investigate the protective role of WLT against NAFLD development induced by a high-fat and high-sucrose (HFHS) diet and its mechanism of action.<br><br>METHODS: We investigated the anti-NAFLD effects of WLT on a HFHS diet-induced NAFLD C57BL/6J mouse model by detecting the hepatic triglyceride (TG) level, performing histological examination of the liver tissue, and evaluating glucose tolerance and systemic inflammation. Then, we analyzed the impact of WLT on gut microbiota by 16S rRNA gene sequencing, followed by fecal microbiota transplantation. Furthermore, we performed hepatic transcriptomic analysis of mice with or without WLT treatment using the RNA sequencing approach.<br><br>RESULTS: Our results showed that WLT supplement attenuated body weight gain, hepatic steatosis, glucose tolerance, and systemic inflammation in HFHS-fed mice. Moreover, WLT supplement altered the composition of gut microbiota, which contributed at least in part, to the anti-NAFLD effect. Meanwhile, WLT improved the intestinal integrity and comprehensively modulated the expression of hepatic genes in HFHS mice, particularly reducing the expression of genes in the toll-like receptor-mediated inflammatory pathway.<br><br>CONCLUSION: WLT is protective against NAFLD formation induced by an HFHS diet, and its effect is associated with the modulation of gut microbiota and inflammation, highlighting the potential of WLT to reduce the risk of metabolic disorders as a functional dietary supplement.}, }
@article {pmid34403381, year = {2021}, author = {Yao, ZW and Yang, X and Zhao, BC and Deng, F and Jiang, YM and Pan, WY and Chen, XD and Zhou, BW and Zhang, WJ and Hu, JJ and Zhu, L and Liu, KX}, title = {Predictive and Preventive Potential of Preoperative Gut Microbiota in Chronic Postoperative Pain in Breast Cancer Survivors.}, journal = {Anesthesia and analgesia}, volume = {}, number = {}, pages = {}, doi = {10.1213/ANE.0000000000005713}, pmid = {34403381}, issn = {1526-7598}, abstract = {BACKGROUND: Evidence suggests a potential relationship between gut microbiota and chronic postoperative pain (CPP). This study aimed to explore the predictive and preventive potential of preoperative gut microbiota in CPP in breast cancer survivors.<br><br>METHODS: In the clinical experiments, we designed a nested case-control study to compared preoperative gut microbiota of breast cancer survivors with and without CPP using 16s rRNA sequencing. The primary outcome was clinically meaningful pain in or around the operative area 3 months after surgery. Logistic prediction models based on previously identified risk factors for CPP in breast cancer survivors were tested with and without differential bacteria to evaluate the model's potential for improvement with the addition of gut microbiota information. In the animal experiments, preoperative fecal microbiota was transplanted from patients with and without CPP to mice, and a spared nerve injury (SNI) model was used to mimic neuropathic pain in CPP. Mechanical hyperalgesia and the expression of markers of spinal microglia and peroxisome proliferator-activated receptor-γ (PPAR-γ) were assessed.<br><br>RESULTS: Sixty-six CPP patients and 66 matched controls were analyzed. Preoperative gut microbiota composition was significantly different in the 2 groups at phylus, family, and genera levels. The discrimination of the clinical prediction model (determined by area under the receiver operating characteristic curve) improved by 0.039 and 0.099 after the involvement of differential gut microbiota at the family and genus levels, respectively. After fecal microbiota transplantation (FMT), "CPP microbiota" recipient mice exhibited significantly increased mechanical hyperalgesia and decreased expression of Ppar-γ and arginase-1 (Arg-1) in the spinal cord.<br><br>CONCLUSIONS: Preoperative gut microbiota has the potential to predict and prevent the development of CPP and plays a causal role in its development via the PPAR-γ-microglia pathway in the spinal cord. Thus, it could be targeted to develop a prevention strategy for CPP in breast cancer survivors.}, }
@article {pmid34402648, year = {2021}, author = {Olekhnovich, EI and Ivanov, AB and Ulyantsev, VI and Ilina, EN}, title = {Separation of Donor and Recipient Microbial Diversity Allows Determination of Taxonomic and Functional Features of Gut Microbiota Restructuring following Fecal Transplantation.}, journal = {mSystems}, volume = {6}, number = {4}, pages = {e0081121}, pmid = {34402648}, issn = {2379-5077}, abstract = {Fecal microbiota transplantation (FMT) is currently used in medicine to treat recurrent clostridial colitis and other intestinal diseases. However, neither the therapeutic mechanism of FMT nor the mechanism that allows the donor bacteria to colonize the intestine of the recipient has yet been clearly described. From a biological point of view, FMT can be considered a useful model for studying the ecology of host-associated microbial communities. FMT experiments can shed light on the relationship features between the host and its gut microbiota. This creates the need for experimentation with approaches to metagenomic data analysis which may be useful for the interpretation of observed biological phenomena. Here, the recipient intestine colonization analysis tool (RECAST) novel computational approach is presented, which is based on the metagenomic read sorting process per their origin in the recipient's post-FMT stool metagenome. Using the RECAST algorithm, taxonomic/functional annotation, and machine learning approaches, the metagenomes from three FMT studies, including healthy volunteers, patients with clostridial colitis, and patients with metabolic syndrome, were analyzed. Using our computational pipeline, the donor-derived and recipient-derived microbes which formed the recipient post-FMT stool metagenomes (successful microbes) were identified. Their presence is well explained by a higher relative abundance in donor/pre-FMT recipient metagenomes or other metagenomes from the human population. In addition, successful microbes are enriched with gene groups potentially related to antibiotic resistance, including antimicrobial peptides. Interestingly, the observed reorganization features are universal and independent of the disease. IMPORTANCE We assumed that the enrichment of successful gut microbes by lantibiotic/antibiotic resistance genes can be related to gut microbiota colonization resistance by third-party microbe phenomena and resistance to bacterium-derived or host-derived antimicrobial substances. According to this assumption, competition between the donor-derived and recipient-derived microbes as well as host immunity may play a key role in the FMT-related colonization and redistribution of recipient gut microbiota structure.}, }
@article {pmid34400407, year = {2021}, author = {Derosa, L and Routy, B and Desilets, A and Daillère, R and Terrisse, S and Kroemer, G and Zitvogel, L}, title = {Microbiota-Centered Interventions: The Next Breakthrough in Immuno-Oncology?.}, journal = {Cancer discovery}, volume = {11}, number = {10}, pages = {2396-2412}, doi = {10.1158/2159-8290.CD-21-0236}, pmid = {34400407}, issn = {2159-8290}, abstract = {The cancer-immune dialogue subject to immuno-oncological intervention is profoundly influenced by microenvironmental factors. Indeed, the mucosal microbiota-and more specifically, the intestinal ecosystem-influences the tone of anticancer immune responses and the clinical benefit of immunotherapy. Antibiotics blunt the efficacy of immune checkpoint inhibitors (ICI), and fecal microbial transplantation may restore responsiveness of ICI-resistant melanoma. Here, we review the yin and yang of intestinal bacteria at the crossroads between the intestinal barrier, metabolism, and local or systemic immune responses during anticancer therapies. We discuss diagnostic tools to identify gut dysbiosis and the future prospects of microbiota-based therapeutic interventions. SIGNIFICANCE: Given the recent proof of concept of the potential efficacy of fecal microbial transplantation in patients with melanoma primarily resistant to PD-1 blockade, it is timely to discuss how and why antibiotics compromise the efficacy of cancer immunotherapy, describe the balance between beneficial and harmful microbial species in play during therapies, and introduce the potential for microbiota-centered interventions for the future of immuno-oncology.}, }
@article {pmid34398717, year = {2021}, author = {Saul, S and Fuessel, J and Runde, J}, title = {Pediatric Digestive Health and the Gut Microbiome: Existing Therapies and a Look to the Future.}, journal = {Pediatric annals}, volume = {50}, number = {8}, pages = {e336-e342}, doi = {10.3928/19382359-20210720-01}, pmid = {34398717}, issn = {1938-2359}, mesh = {Child ; Dysbiosis/therapy ; Ecosystem ; *Gastrointestinal Microbiome ; Helicobacter Infections ; Helicobacter pylori ; Humans ; *Probiotics/therapeutic use ; }, abstract = {The human gut is host to trillions of microbes that from birth begin interacting with our immune system. Over time this relationship is thought to shape critical aspects of human function such as metabolism, brain development, immune response, and overall gut health. Recent advances in technology have allowed us to begin understanding this complex relationship and have demonstrated that microbes within the gut ecosystem can be influenced by a variety of factors including mode of delivery, diet, and medication exposure, all of which can impact host health in either positive or detrimental ways. Perturbations of gut homeostasis have been implicated in many forms of digestive disease such as inflammatory bowel disease, irritable bowel syndrome, Helicobacter pylori infection, and even in cases of antibiotic-associated diarrhea. As such, researchers have sought methods to either restore gut homeostasis or prevent dysregulation of the gut community, also known as dysbiosis, through an emerging field known as microbial therapeutics. Examples of existing modalities are reviewed here such as prebiotics, probiotics, fecal microbial transplantation, and dietary therapy. As these therapies become further substantiated through research and increasingly desired by patients and their families, there is a need for providers caring for children to familiarize themselves with the existing data and indications for use. As we look to the future, machine-learning algorithms and more readily available next-generation sequencing of fecal samples may allow us to harness data from a person's gut microbiota to predict response to a particular intervention and tailor therapeutic options with an aim toward precision medicine. [Pediatr Ann. 2021;50(8):e336-e342.].}, }
@article {pmid34397627, year = {2021}, author = {Konopelski, P and Konop, M and Perlejewski, K and Bukowska-Osko, I and Radkowski, M and Onyszkiewicz, M and Jaworska, K and Mogilnicka, I and Samborowska, E and Ufnal, M}, title = {Genetically determined hypertensive phenotype affects gut microbiota composition, but not vice versa.}, journal = {Journal of hypertension}, volume = {39}, number = {9}, pages = {1790-1799}, doi = {10.1097/HJH.0000000000002864}, pmid = {34397627}, issn = {1473-5598}, mesh = {Animals ; Blood Pressure ; *Gastrointestinal Microbiome ; *Hypertension/genetics ; Phenotype ; Rats ; Rats, Inbred SHR ; }, abstract = {OBJECTIVES: Research suggests reciprocal crosstalk between the host and gut bacteria. This study evaluated the interaction between gut microbiota and arterial blood pressure (BP) in rats.<br><br>METHODS: Continuous telemetry recordings of BP were started in 7-week-old normotensive Wistar--Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Two weeks later, half of the WKY and SHR were subjected to cross-transplantation of fecal matter, with stools harvested from either WKY or SHR and BP measurements until the age of 14 weeks. The composition of gut bacteria was assessed through analysis of the bacterial 16S ribosomal RNA gene sequence. The concentration of microbiota-derived metabolites was evaluated using HPLC-MS.<br><br>RESULTS: There was a significant difference between WKY and SHR in the composition of gut bacteria at the start and end of the study. This was accompanied by significant histological differences in the colon. SHR, but not WKY, showed a gradual increase in BP throughout the experiment. For both WKY and SHR, there was no significant difference in BP or metabolic parameters between animals receiving fecal transplantation from either SHR or WKY.<br><br>CONCLUSION: Genetically induced hypertension in SHR is associated with alterations in the composition of gut bacteria and histological morphology of the colon. An inter-strain fecal transplant does not affect BP and does not produce long-term changes in gut bacteria composition. We propose that the impact of the host genotype and/or phenotype on the gut bacteria may be greater than the impact of the gut bacteria on the host BP.}, }
@article {pmid34395484, year = {2021}, author = {Cui, J and Lin, Z and Tian, H and Yang, B and Zhao, D and Ye, C and Li, N and Qin, H and Chen, Q}, title = {Long-Term Follow-Up Results of Fecal Microbiota Transplantation for Irritable Bowel Syndrome: A Single-Center, Retrospective Study.}, journal = {Frontiers in medicine}, volume = {8}, number = {}, pages = {710452}, pmid = {34395484}, issn = {2296-858X}, abstract = {Objective: This study aimed to investigate the long-term efficacy of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS). Study Methods: In this single-center long-term follow-up study, FMT treatment was administered to patients with moderate to severe IBS (IBS severity scoring system (IBS-SSS) > 175). After 1 year of treatment, it was decided whether to repeat FMT based on IBS-SSS score (IBS-SSS > 175). Baseline characteristics before and after FMT and questionnaires were completed at 1, 3, 6, 12, 24, 36, 48, and 60 months after FMT. The study outcomes included treatment efficacy rates, change of IBS-SSS, IBS-specific quality of life and fatigue, effect on stool frequency, Bristol Stool Scale for IBS-C and IBS-D, and side effects. Results: A total of 227 patients (47.58% IBS-C, 39.21% IBS-D, and 13.22% IBS-M) were recruited (142 females and 85 males with a mean age of 41.89 ± 13.57 years). The efficacy rates were 108 (51.92%), 147 (74.62%), 125 (74.41 %), 88 (71.54%), 78 (75.00%), 65 (73.03%), 45 (61.64%), and 37 (62.71%) at different follow-up time points. The total IBS-SSS score was 321.37 ± 73.89 before FMT, which significantly decreased after 1 month. The IBS-specific quality of life (IBS-QoL) score was 40.24 ± 11.34 before FMT, increased gradually, and was significantly higher at 3 months compared to before FMT. The total Fatigue Assessment Scale (FAS) score was 47 ± 8.64 before FMT and was significantly lower at 3 months. During follow-up, 89 (39.21%) side effects occurred that were alleviated by symptomatic treatment, and no serious adverse events were detected. Conclusion: Based on 60 months of long-term follow-up, the safety and efficacy of FMT for IBS was established. However, as the treatment effect declines over time, periodic and repetitive FMT is required for a sustained effect.}, }
@article {pmid34395308, year = {2021}, author = {Jian, Y and Zhang, D and Liu, M and Wang, Y and Xu, ZX}, title = {The Impact of Gut Microbiota on Radiation-Induced Enteritis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {586392}, pmid = {34395308}, issn = {2235-2988}, mesh = {Dysbiosis ; *Enteritis/etiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Intestines ; *Probiotics ; }, abstract = {Radiotherapy is an important treatment for abdominal tumors. A critical side effect for this therapy is enteritis. In this review, we aim to summarize recent findings in radiation enteritis, in particular the role of gut microbiota dysbiosis in the development and therapy of the disease. Gut microbiota dysbiosis plays an important role in the occurrence of various diseases, such as radiation enteritis. Abdominal radiation results in changes in the composition of microbiota and reduces its diversity, which is mainly reflected in the decrease of Lactobacillus spp. and Bifidobacterium spp. and increase of Escherichia coli and Staphylococcus spp. Gut microbiota dysbiosis aggravates radiation enteritis, weakens intestinal epithelial barrier function, and promotes inflammatory factor expression. Pathogenic Escherichia coli induce the rearrangement and redistribution of claudin-1, occludin, and ZO-1 in tight junctions, a critical component in intestinal epithelial barrier. In view of the role that microbiome plays in radiation enteritis, we believe that intestinal flora could be a potential biomarker for the disease. Correction of microbiome by application of probiotics, fecal microbiota transplantation (FMT), and antibiotics could be an effective method for the prevention and treatment of radiation-induced enteritis.}, }
@article {pmid34391441, year = {2021}, author = {Han, SK and Kim, JK and Park, HS and Shin, YJ and Kim, DH}, title = {Chaihu-Shugan-San (Shihosogansan) alleviates restraint stress-generated anxiety and depression in mice by regulating NF-κB-mediated BDNF expression through the modulation of gut microbiota.}, journal = {Chinese medicine}, volume = {16}, number = {1}, pages = {77}, pmid = {34391441}, issn = {1749-8546}, support = {2017R1A5A2014768//National Research Foundation of Korea/ ; }, abstract = {BACKGROUND: Chaihu-Shugan-San (CSS, named Shihosogansan in Korean), a Chinese traditional medicine, is frequently used to treat anxiety and depression. Psychiatric disorders including depression are associated with gut dysbiosis. Therefore, to comprehend gut microbiota-involved anti-depressive effect of CSS, we examined its effect on restraint stress (RS)-induced depression and gut dysbiosis in mice METHODS: CSS was extracted with water in boiling water bath and freeze-dried. Anxiety and depression was induced in C57BL/6 mice by exposure to RS. Anxiety- and depression-like behaviors were measured in the light/dark transition and elevated plus maze tasks, forced swimming test, and tail suspension test. Biomarkers were assayed by using the enzyme-linked immunosorbent assay and immunoblotting. The gut microbiota composition was analyzed by Illumina iSeq sequencer.<br><br>RESULTS: CSS significantly reduced the RS-induced anxiety- and depression-like behaviors in mice. CSS suppressed the RS-induced activation of NF-κB and expression of interleukin (IL)-6 and increased the RS-suppressed expression of brain-derived neurotrophic factor (BDNF). Furthermore, CSS suppressed the RS-induced IL-6 and corticosterone level in the blood and IL-6 expression and myeloperoxidase activity in the colon. CSS decreased the RS-induced γ-Proteobacteria population in gut microbiota, while the RS-suppressed Lactobacillaceae, Prevotellaceae, and AC160630_f populations increased. Fecal transplantation of vehicle-treated control or RS/CSS-treated mice into RS-exposed mice significantly mitigated RS-induced anxity- and depression-like behaviors, suppressed the NF-κB activation in the hippocampus and colon, and reduced the IL-6 and corticosterone levels in the blood. These fecal microbiota transplantations suppressed RS-induced Desulfovibrionaceae and γ-Proteobacteria populations and increased RS-suppressed Lactobacillaceae and Prevotellaceae poulation in the gut microbiota.<br><br>CONCLUSIONS: CSS alleviated anxiety and depression by inducing NF-κB-involved BDNF expression through the regulation of gut inflammation and microbiota.}, }
@article {pmid34383708, year = {2021}, author = {Gholam-Mostafaei, FS and Yadegar, A and Asadzadeh Aghdaei, H and Shahrokh, S and Ebrahimi Daryani, N and Zali, MR}, title = {Fecal microbiota transplantation for recurrent Clostridioides difficile infection in patients with concurrent ulcerative colitis.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {}, number = {}, pages = {}, doi = {10.1556/030.2021.01498}, pmid = {34383708}, issn = {1588-2640}, abstract = {Treatment of recurrent Clostridioides difficile infection (rCDI) has emerged as an important management dilemma particularly in patients with underlying inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) has been used as a safe and highly effective treatment option for rCDI refractory to standard antibiotic therapies. The aim of this study was to report the efficacy of FMT in Iranian rCDI patients with concurrent IBD. A total of seven consecutive patients with ulcerative colitis (UC) who had experienced 3 episodes of rCDI were enrolled in this study. All patients received at least a single FMT administered during colonoscopy by direct infusion of minimally processed donor stool. Patients were followed for a minimum of 6 months for assessment of treatment efficacy and adverse events (AEs) attributable to FMT. All 7 UC patients (100%) experienced a durable clinical response to a single FMT following 2 months after the procedure. One patient received a second FMT in which a successful resolution of rCDI was ultimately achieved. No serious AEs from FMT were noted. FMT through colonoscopy was a safe, simple and effective alternative treatment approach for rCDI in patients with underlying IBD. However, its use and efficacy should be pursued in long-term prospective controlled trials.}, }
@article {pmid34382390, year = {2021}, author = {Zhao, Y and Liu, S and Tang, Y and You, T and Xu, H}, title = {Lactobacillus rhamnosus GG Ameliorated Long-Term Exposure to TiO2 Nanoparticles Induced Microbiota-Mediated Liver and Colon Inflammation and Fructose-Caused Metabolic Abnormality in Metabolism Syndrome Mice.}, journal = {Journal of agricultural and food chemistry}, volume = {69}, number = {34}, pages = {9788-9799}, doi = {10.1021/acs.jafc.1c03301}, pmid = {34382390}, issn = {1520-5118}, mesh = {Animals ; Colon ; Fructose ; Inflammation ; *Lactobacillus rhamnosus ; Liver ; Mice ; *Microbiota ; *Nanoparticles ; *Probiotics ; Titanium ; }, abstract = {A huge number of titanium dioxide nanoparticles (TiO2 NPs) exist in confectionery foods, which is a high-risk factor for development of diet-induced metabolism syndrome (MetS). In this study, we built a high fructose drinking-induced MetS mouse model, and oral intake of 20 mg/kg TiO2 NPs was administered for 8 weeks. Significant pathological changes and inflammatory factors of overproduction were detected in the liver and colon. The 16S rDNA sequencing analysis results indicated that TiO2 NPs evidently and further perturbed the gut microbiota diversity, compositions, and KEGG pathways in MetS mice. Fecal microbiota transplant experiment proved that TiO2 NPs-altered gut microbiota drives liver and colon inflammation damage. More importantly, oral supplementation of Lactobacillus rhamnosus GG (LGG) ameliorated not only the TiO2 NPs-induced inflammation but also the fructose-caused metabolic abnormality. LGG recovered the gut dysbiosis and decreased the abundance of inflammation-related bacteria (Desulfovibrionaceae, Clostridia, and Proteobacteria), thereby protecting against TiO2 NPs-induced severe inflammation damage. Our study suggests the necessity of assessing the toxic effects of foodborne nanoparticles on the chronic disease population and potential usefulness of probiotics as prophylactic and therapeutic.}, }
@article {pmid34381207, year = {2021}, author = {Fremin, BJ and Nicolaou, C and Bhatt, AS}, title = {Simultaneous ribosome profiling of hundreds of microbes from the human microbiome.}, journal = {Nature protocols}, volume = {16}, number = {10}, pages = {4676-4691}, pmid = {34381207}, issn = {1750-2799}, support = {P30 AG047366//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; P30 CA124435/CA/NCI NIH HHS/United States ; R01 AI148623/AI/NIAID NIH HHS/United States ; R01 AI143757/AI/NIAID NIH HHS/United States ; }, mesh = {Feces ; Humans ; *Microbiota ; *Ribosomes ; Sequence Analysis, RNA ; }, abstract = {Ribosome profiling enables sequencing of ribosome-bound fragments of RNA, revealing which transcripts are being translated as well as the position of ribosomes along mRNAs. Although ribosome profiling has been applied to cultured bacterial isolates, its application to uncultured, mixed communities has been challenging. We present MetaRibo-Seq, a protocol that enables the application of ribosome profiling directly to the human fecal microbiome. MetaRibo-Seq is a benchmarked method that includes several modifications to existing ribosome profiling protocols, specifically addressing challenges involving fecal sample storage, purity and input requirements. We also provide a computational workflow to quality control and trim reads, de novo assemble a reference metagenome with metagenomic reads, align MetaRibo-Seq reads to the reference, and assess MetaRibo-Seq library quality (https://github.com/bhattlab/bhattlab_workflows/tree/master/metariboseq). This MetaRibo-Seq protocol enables researchers in standard molecular biology laboratories to study translation in the fecal microbiome in ~5 d.}, }
@article {pmid34381040, year = {2021}, author = {Wang, H and Yang, F and Zhang, S and Xin, R and Sun, Y}, title = {Genetic and environmental factors in Alzheimer's and Parkinson's diseases and promising therapeutic intervention via fecal microbiota transplantation.}, journal = {NPJ Parkinson's disease}, volume = {7}, number = {1}, pages = {70}, pmid = {34381040}, issn = {2373-8057}, abstract = {Neurodegenerative diseases are characterized by neuronal impairment and loss of function, and with the major shared histopathological hallmarks of misfolding and aggregation of specific proteins inside or outside cells. Some genetic and environmental factors contribute to the promotion of the development and progression of neurodegenerative diseases. Currently, there are no effective treatments for neurodegenerative diseases. It has been revealed that bidirectional communication exists between the brain and the gut. The gut microbiota is a changeable and experience-dependent ecosystem and can be modified by genetic and environmental factors. The gut microbiota provides potential therapeutic targets that can be regulated as new interventions for neurodegenerative diseases. In this review, we discuss genetic and environmental risk factors for neurodegenerative diseases, summarize the communication among the components of the microbiota-gut-brain axis, and discuss the treatment strategy of fecal microbiota transplantation (FMT). FMT is a promising treatment for neurodegenerative diseases, and restoration of the gut microbiota to a premorbid state is a novel goal for prevention and treatment strategies.}, }
@article {pmid34378656, year = {2021}, author = {Liaqat, I and Ali, NM and Arshad, N and Sajjad, S and Rashid, F and Hanif, U and Ara, C and Ulfat, M and Andleeb, S and Awan, UF and Bibi, A and Mubin, M and Ali, S and Tahir, HM and Ul-Haq, I}, title = {Gut dysbiosis, inflammation and type 2 diabetes in mice using synthetic gut microbiota from diabetic humans.}, journal = {Brazilian journal of biology = Revista brasleira de biologia}, volume = {83}, number = {}, pages = {e242818}, doi = {10.1590/1519-6984.242818}, pmid = {34378656}, issn = {1678-4375}, mesh = {Animals ; Bacteroides ; Bacteroidetes ; *Diabetes Mellitus, Type 2 ; Diet, High-Fat/adverse effects ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; Mice ; Mice, Inbred C57BL ; Prevotella ; RNA, Ribosomal, 16S/genetics ; Ruminococcus ; }, abstract = {The study was aimed to assess impact of high fat diet (HFD) and synthetic human gut microbiota (GM) combined with HFD and chow diet (CD) in inducing type-2 diabetes (T2D) using mice model. To our knowledge, this is the first study using selected human GM transplantation via culture based method coupled dietary modulation in mice for in vivo establishment of inflammation leading to T2D and gut dysbiosis. Twenty bacteria (T2D1-T2D20) from stool samples of confirmed T2D subjects were found to be morphologically different and subjected to purification on different media both aerobically and anerobically, which revealed seven bacteria more common among 20 isolates on the basis of biochemical characterization. On the basis of 16S rRNA gene sequencing, these seven isolates were identified as Bacteroides stercoris (MT152636), Lactobacillus acidophilus (MT152637), Lactobacillus salivarius (MT152638), Ruminococcus bromii (MT152639), Klebsiella aerogenes (MT152640), Bacteroides fragilis (MT152909), Clostridium botulinum (MT152910). The seven isolates were subsequently used as synthetic gut microbiome (GM) for their role in inducing T2D in mice. Inbred strains of albino mice were divided into four groups and were fed with CD, HFD, GM+HFD and GM+CD. Mice receiving HFD and GM+modified diet (CD/HFD) showed highly significant (P<0.05) increase in weight and blood glucose concentration as well as elevated level of inflammatory cytokines (TNF-α, IL-6, and MCP-1) compared to mice receiving CD only. The 16S rRNA gene sequencing of 11 fecal bacteria obtained from three randomly selected animals from each group revealed gut dysbiosis in animals receiving GM. Bacterial strains including Bacteroides gallinarum (MT152630), Ruminococcus bromii (MT152631), Lactobacillus acidophilus (MT152632), Parabacteroides gordonii (MT152633), Prevotella copri (MT152634) and Lactobacillus gasseri (MT152635) were isolated from mice treated with GM+modified diet (HFD/CD) compared to strains Akkermansia muciniphila (MT152625), Bacteriodes sp. (MT152626), Bacteroides faecis (MT152627), Bacteroides vulgatus (MT152628), Lactobacillus plantarum (MT152629) which were isolated from mice receiving CD/HFD. In conclusion, these findings suggest that constitution of GM and diet plays significant role in inflammation leading to onset or/and possibly progression of T2D. .}, }
@article {pmid34376591, year = {2021}, author = {Kurokawa, S}, title = {[The Link Between Gut Microbiota and Cerebral Functions: An Update on the Pathogenesis and Treatment of Functional Gastrointestinal Disorders].}, journal = {Brain and nerve = Shinkei kenkyu no shinpo}, volume = {73}, number = {8}, pages = {857-862}, doi = {10.11477/mf.1416201852}, pmid = {34376591}, issn = {1881-6096}, mesh = {Dysbiosis/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Diseases/therapy ; *Gastrointestinal Microbiome ; Humans ; *Probiotics/therapeutic use ; }, abstract = {Recent studies have focused on the mechanism of brain effects on functional gastrointestinal disorders, through dysbiosis of the gut microbiota. Herein, we summarize the known pathogeneses of various functional gastrointestinal disorders relative to the gut microbiota, and discuss future gut microbiota-focused interventions for restoring dysbiosis, including probiotics and fecal microbiota transplantation.}, }
@article {pmid34368762, year = {2021}, author = {Puca, P and Petito, V and Laterza, L and Lopetuso, LR and Neri, M and Del Chierico, F and Boskoski, I and Gasbarrini, A and Scaldaferri, F}, title = {Bariatric procedures and microbiota: patient selection and outcome prediction.}, journal = {Therapeutic advances in gastrointestinal endoscopy}, volume = {14}, number = {}, pages = {26317745211014746}, pmid = {34368762}, issn = {2631-7745}, abstract = {Obesity is a major health issue throughout the world and bariatric surgery plays a key role in its management and treatment. The role of microbiota in determining the pathogenesis of obesity has been widely studied, while its role in determining the outcome of bariatric surgery is an emerging issue that will be an outcome in near future studies. Studies on mice first showed the key role of microbiota in determining obesity, highlighting the fat mass increase in mice transplanted with microbiota from fat individuals, as well as the different microbiota composition between mice undergone to low-fat or high-fat diets. This led to characterize the asset of microbiota composition in obesity: increased abundance of Firmicutes, reduced abundance of Bacteroidetes and other taxonomical features. Variations on the composition of gut microbiome have been detected in patients undergone to diet and/or bariatric surgery procedures. Patients undergone to restricting diets showed lower level of trimethylamine N-oxide and other metabolites strictly associated to microbiome, as well as patients treated with bariatric surgery showed, after the procedure, changes in the relative abundance of Bacteroidetes, Firmicutes and other phyla with a role in the pathogenesis of obesity. Eventually, studies have been led about the effects that the modification of microbiota could have on obesity itself, mainly focusing on elements like fecal microbiota transplantation and probiotics such as inulin. This series of studies and considerations represent the first step in order to select patients eligible to bariatric surgery and to predict their outcome.}, }
@article {pmid34367617, year = {2021}, author = {Manzoor, SE and Zaman, S and Whalley, C and Inglis, D and Bosworth, A and Kidd, M and Shabir, S and Quraishi, N and Green, CA and Iqbal, T and Beggs, AD}, title = {Multi-modality detection of SARS-CoV-2 in faecal donor samples for transplantation and in asymptomatic emergency surgical admissions.}, journal = {F1000Research}, volume = {10}, number = {}, pages = {373}, pmid = {34367617}, issn = {2046-1402}, mesh = {*COVID-19 ; Fecal Microbiota Transplantation ; Humans ; RNA, Viral/genetics ; Real-Time Polymerase Chain Reaction ; *SARS-CoV-2 ; }, abstract = {Background: Faecal transplantation is an evidence-based treatment for Clostridioides difficile. Patients infected with SARS-CoV-2 have been shown to shed the virus in stool for up to 33 days, well beyond the average clearance time for upper respiratory tract shedding. We carried out an analytical and clinical validation of reverse-transcriptase quantitative (RT-qPCR) as well as LAMP, LamPORE and droplet digital PCR in the detection of SARS-CoV-2 RNA in stool from donated samples for faecal microbiota transplantation (FMT), spiked samples and asymptomatic inpatients in an acute surgical unit. Methods: Killed SARS-CoV-2 viral lysate and extracted RNA was spiked into donor stool &amp; FMT and a linear dilution series from 10 -1 to 10 -5 and tested via RT-qPCR, LAMP, LamPORE and ddPCR against SARS-CoV-2. Patients admitted to the critical care unit with symptomatic SARS-CoV-2 and sequential asymptomatic patients from acute presentation to an acute surgical unit were also tested. Results: In a linear dilution series, detection of the lowest dilution series was found to be 8 copies per microlitre of sample. Spiked lysate samples down to 10 -2 dilution were detected in FMT samples using RTQPCR, LamPORE and ddPCR and down to 10 -1 with LAMP. In symptomatic patients 5/12 had detectable SARS-CoV-2 in stool via RT-qPCR and 6/12 via LamPORE, and in 1/97 asymptomatic patients via RT-qPCR. Conclusion: RT-qPCR can be detected in FMT donor samples using RT-qPCR, LamPORE and ddPCR to low levels using validated pathways. As previously demonstrated, nearly half of symptomatic and less than one percent of asymptomatic patients had detectable SARS-CoV-2 in stool.}, }
@article {pmid34367139, year = {2021}, author = {Qu, Y and Li, X and Xu, F and Zhao, S and Wu, X and Wang, Y and Xie, J}, title = {Kaempferol Alleviates Murine Experimental Colitis by Restoring Gut Microbiota and Inhibiting the LPS-TLR4-NF-κB Axis.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {679897}, pmid = {34367139}, issn = {1664-3224}, mesh = {Animals ; Anti-Inflammatory Agents/*pharmacology ; Biomarkers ; Colitis/etiology/*metabolism/pathology/therapy ; Dextran Sulfate/adverse effects ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects ; Intestinal Mucosa/metabolism/microbiology ; Kaempferols/*pharmacology ; Lipopolysaccharides/adverse effects ; Mice ; NF-kappa B/*metabolism ; Permeability ; RNA, Ribosomal, 16S ; Signal Transduction/*drug effects ; Toll-Like Receptor 4/*metabolism ; }, abstract = {Intestinal microbiota dysbiosis is an established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an attractive alternative UC treatment strategy, considering the potential adverse effects of synthetic drugs used to treat UC. Kaempferol (Kae) is an anti-inflammatory and antioxidant flavonoid derived from a variety of medicinal plants. In this study, we determined the efficacy and mechanism of action of Kae as an anti-UC agent in dextran sulfate sodium (DSS)-induced colitis mice. DSS challenge in a mouse model of UC led to weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by pretreatment with Kae. In addition, intestinal permeability was shown to improve using fluorescein isothiocyanate (FITC)-dextran administration. DSS-induced destruction of the intestinal barrier was also significantly prevented by Kae administration via increases in the levels of ZO-1, occludin, and claudin-1. Furthermore, Kae pretreatment decreased the levels of IL-1β, IL-6, and TNF-α and downregulated transcription of an array of inflammatory signaling molecules, while it increased IL-10 mRNA expression. Notably, Kae reshaped the intestinal microbiome by elevating the Firmicutes to Bacteroidetes ratio; increasing the linear discriminant analysis scores of beneficial bacteria, such as Prevotellaceae and Ruminococcaceae; and reducing the richness of Proteobacteria in DSS-challenged mice. There was also an evident shift in the profile of fecal metabolites in the Kae treatment group. Serum LPS levels and downstream TLR4-NF-κB signaling were downregulated by Kae supplementation. Moreover, fecal microbiota transplantation from Kae-treated mice to the DSS-induced mice confirmed the effects of Kae on modulating the gut microbiota to alleviate UC. Therefore, Kae may exert protective effects against colitis mice through regulating the gut microbiota and TLR4-related signaling pathways. This study demonstrates the anti-UC effects of Kae and its potential therapeutic mechanisms, and offers novel insights into the prevention of inflammatory diseases using natural products.}, }
@article {pmid34364884, year = {2021}, author = {McCarthy, S and Barrett, M and Kirthi, S and Pellanda, P and Vlckova, K and Tobin, AM and Murphy, M and Shanahan, F and O'Toole, PW}, title = {Altered Skin and Gut Microbiome in Hidradenitis Suppurativa.}, journal = {The Journal of investigative dermatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jid.2021.05.036}, pmid = {34364884}, issn = {1523-1747}, abstract = {Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by the formation of nodules, abscesses, and fistula at intertriginous sites. The skin-gut axis is an area of emerging research in inflammatory skin disease and is a potential contributory factor to the pathogenesis of HS. 59 patients with HS provided fecal samples, nasal and skin swabs of affected sites for analysis. 30 healthy controls provided fecal samples and 20 healthy controls provided nasal and skin swabs. We performed bacterial 16S rRNA gene amplicon sequencing on total DNA derived from the samples. Microbiome alpha diversity was significantly lower in the fecal, skin and nasal samples of individuals with HS which may be secondary to disease biology or related to antibiotic usage. Ruminococcus gnavus was more abundant in the fecal microbiome of individuals with HS, which is also reported in Crohn's disease (CD), suggesting comorbidity due to shared gut microbiota alterations. Finegoldia magna was over-abundant in HS skin samples relative to healthy controls. It is possible local inflammation is driven by F. magna through promoting the formation of neutrophil extracellular traps (NET). These alterations in both the gut and skin microbiome in HS warrant further exploration, and therapeutic strategies including fecal microbiota transplant (FMT) or bacteriotherapy could be of benefit.}, }
@article {pmid34362925, year = {2021}, author = {Zhang, AN and Gaston, JM and Dai, CL and Zhao, S and Poyet, M and Groussin, M and Yin, X and Li, LG and van Loosdrecht, MCM and Topp, E and Gillings, MR and Hanage, WP and Tiedje, JM and Moniz, K and Alm, EJ and Zhang, T}, title = {An omics-based framework for assessing the health risk of antimicrobial resistance genes.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {4765}, pmid = {34362925}, issn = {2041-1723}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacteria/drug effects/genetics ; Databases, Factual ; Drug Resistance, Bacterial/*drug effects/*genetics ; Gastrointestinal Microbiome/drug effects ; Genes, Bacterial/drug effects ; Genome ; Humans ; Metagenome ; Plasmids ; }, abstract = {Antibiotic resistance genes (ARGs) are widespread among bacteria. However, not all ARGs pose serious threats to public health, highlighting the importance of identifying those that are high-risk. Here, we developed an 'omics-based' framework to evaluate ARG risk considering human-associated-enrichment, gene mobility, and host pathogenicity. Our framework classifies human-associated, mobile ARGs (3.6% of all ARGs) as the highest risk, which we further differentiate as 'current threats' (Rank I; 3%) - already present among pathogens - and 'future threats' (Rank II; 0.6%) - novel resistance emerging from non-pathogens. Our framework identified 73 'current threat' ARG families. Of these, 35 were among the 37 high-risk ARGs proposed by the World Health Organization and other literature; the remaining 38 were significantly enriched in hospital plasmids. By evaluating all pathogen genomes released since framework construction, we confirmed that ARGs that recently transferred into pathogens were significantly enriched in Rank II ('future threats'). Lastly, we applied the framework to gut microbiome genomes from fecal microbiota transplantation donors. We found that although ARGs were widespread (73% of genomes), only 8.9% of genomes contained high-risk ARGs. Our framework provides an easy-to-implement approach to identify current and future antimicrobial resistance threats, with potential clinical applications including reducing risk of microbiome-based interventions.}, }
@article {pmid34359902, year = {2021}, author = {Palma Albornoz, SP and Fraga-Silva, TFC and Gembre, AF and de Oliveira, RS and de Souza, FM and Rodrigues, TS and Kettelhut, IDC and Manca, CS and Jordao, AA and Ramalho, LNZ and Ribolla, PEM and Carlos, D and Bonato, VLD}, title = {Obesity-Induced Dysbiosis Exacerbates IFN-γ Production and Pulmonary Inflammation in the Mycobacterium tuberculosis Infection.}, journal = {Cells}, volume = {10}, number = {7}, pages = {}, pmid = {34359902}, issn = {2073-4409}, support = {2017/21629-5//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, mesh = {Adaptive Immunity ; Animals ; Bacterial Load ; Disease Susceptibility ; Dysbiosis/*etiology/immunology/*microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Interferon-gamma/*biosynthesis ; Leukocytes/metabolism ; Lung/immunology/microbiology/pathology ; Mice, Inbred C57BL ; Microbiota ; Obesity/*complications/immunology/*microbiology ; Pneumonia/immunology/*microbiology ; Tuberculosis/*complications/immunology ; }, abstract = {The microbiota of the gut-lung axis affects local and far-reaching immune responses and might also trigger chronic and inflammatory diseases. We hypothesized that gut dysbiosis induced by obesity, which coexists in countries with a high tuberculosis burden, aggravates the host susceptibility and the pulmonary damage tolerance. To assess our hypothesis, we used a model of high-fat diet (HFD)-induced obesity, followed by infection of C57BL/6 mice with Mycobacterium tuberculosis. We showed that obesity increased the susceptibility, the pulmonary inflammation and IFN-γ levels in M. tuberculosis-infected mice. During the comorbidity obesity and tuberculosis, there is an increase of Bacteroidetes and Firmicutes in the lungs, and an increase of Firmicutes and butyrate in the feces. Depletion of gut microbiota by antibiotic treatment in the obese infected mice reduced the frequencies of CD4+IFN-γ+IL-17- cells and IFN-γ levels in the lungs, associated with an increase of Lactobacillus. Our findings reinforce the role of the gut-lung axis in chronic infections and suggest that the gut microbiota modulation may be a potential host-directed therapy as an adjuvant to treat TB in the context of IFN-γ-mediated immunopathology.}, }
@article {pmid34359501, year = {2021}, author = {Lee, BH and Hsu, WH and Chien, HY and Hou, CY and Hsu, YT and Chen, YZ and Wu, SC}, title = {Applications of Lactobacillus acidophilus-Fermented Mango Protected Clostridioides difficile Infection and Developed as an Innovative Probiotic Jam.}, journal = {Foods (Basel, Switzerland)}, volume = {10}, number = {7}, pages = {}, pmid = {34359501}, issn = {2304-8158}, abstract = {Clostridioides difficile infection (CDI) is a large intestine disease caused by toxins produced by the spore-forming bacterium C. difficile, which belongs to Gram-positive bacillus. Using antibiotics treatment disturbances in the gut microbiota and toxins produced by C. difficile disrupt the intestinal barrier. Some evidence indicates fecal microbiota transplantation and probiotics may decrease the risk of CDI recurrence. This study aimed to evaluate the efficacy of fermented mango by using the lactic acid bacteria Lactobacillus acidophilus and develop innovative products in the form of fermented mango jam. L. acidophilus-fermented mango products inhibited the growth of C. difficile while promoting the growth of next-generation probiotic Faecalibacterium prausnitzii. Both supernatant and precipitate of mango-fermented products prevented cell death in gut enterocyte-like Caco-2 cells against C. difficile infection. Mango-fermented products also protected gut barrier function by elevating the expression of tight junction proteins. Moreover, L. acidophilus-fermented mango jam with high hydrostatic pressure treatment had favorable textural characteristics and sensory quality.}, }
@article {pmid34356911, year = {2021}, author = {Gozalbo-Rovira, R and Santiso-Bellón, C and Buesa, J and Rubio-Del-Campo, A and Vila-Vicent, S and Muñoz, C and Yebra, MJ and Monedero, V and Rodríguez-Díaz, J}, title = {Microbiota Depletion Promotes Human Rotavirus Replication in an Adult Mouse Model.}, journal = {Biomedicines}, volume = {9}, number = {7}, pages = {}, pmid = {34356911}, issn = {2227-9059}, support = {AGL2017-84165-C2-1-R//Ministerio de Ciencia y Tecnología/ ; AGL2017-84165-C2-2-R//Ministerio de Ciencia y Tecnología/ ; }, abstract = {Intestinal microbiota-virus-host interaction has emerged as a key factor in mediating enteric virus pathogenicity. With the aim of analyzing whether human gut bacteria improve the inefficient replication of human rotavirus in mice, we performed fecal microbiota transplant (FMT) with healthy infants as donors in antibiotic-treated mice. We showed that a simple antibiotic treatment, irrespective of FMT, resulted in viral shedding for 6 days after challenge with the human rotavirus G1P[8] genotype Wa strain (RVwa). Rotavirus titers in feces were also significantly higher in antibiotic-treated animals with or without FMT but they were decreased in animals subject to self-FMT, where a partial re-establishment of specific bacterial taxons was evidenced. Microbial composition analysis revealed profound changes in the intestinal microbiota of antibiotic-treated animals, whereas some bacterial groups, including members of Lactobacillus, Bilophila, Mucispirillum, and Oscillospira, recovered after self-FMT. In antibiotic-treated and FMT animals where the virus replicated more efficiently, differences were observed in gene expression of immune mediators, such as IL1β and CXCL15, as well as in the fucosyltransferase FUT2, responsible for H-type antigen synthesis in the small intestine. Collectively, our results suggest that antibiotic-induced microbiota depletion eradicates the microbial taxa that restrict human rotavirus infectivity in mice.}, }
@article {pmid34355542, year = {2021}, author = {Lee, MH}, title = {Harness the functions of gut microbiome in tumorigenesis for cancer treatment.}, journal = {Cancer communications (London, England)}, volume = {41}, number = {10}, pages = {937-967}, pmid = {34355542}, issn = {2523-3548}, support = {2020YFA0803300//National key research and development program/ ; 2018YFC0910300//National key research and development program/ ; 81630072//National Natural Science Foundation of China/ ; KQTD20170810160226082//Shenzhen Municipal Government of China/ ; 2018YFC0910300//China Association for Science and Technology/ ; 2020YFA0803300//China Association for Science and Technology/ ; }, mesh = {Carcinogenesis/genetics ; *Gastrointestinal Microbiome/genetics ; Humans ; *Neoplasms/genetics/therapy ; }, abstract = {It has been shown that gut microbiota dysbiosis leads to physiological changes and links to a number of diseases, including cancers. Thus, many cancer categories and treatment regimens should be investigated in the context of the microbiome. Owing to the availability of metagenome sequencing and multiomics studies, analyses of species characterization, host genetic changes, and metabolic profile of gut microbiota have become feasible, which has facilitated an exponential knowledge gain about microbiota composition, taxonomic alterations, and host interactions during tumorigenesis. However, the complexity of the gut microbiota, with a plethora of uncharacterized host-microbe, microbe-microbe, and environmental interactions, still contributes to the challenge of advancing our knowledge of the microbiota-cancer interactions. These interactions manifest in signaling relay, metabolism, immunity, tumor development, genetic instability, sensitivity to cancer chemotherapy and immunotherapy. This review summarizes current studies/molecular mechanisms regarding the association between the gut microbiota and the development of cancers, which provides insights into the therapeutic strategies that could be harnessed for cancer diagnosis, treatment, or prevention.}, }
@article {pmid34354704, year = {2021}, author = {Wang, D and Shao, S and Zhang, Y and Zhao, D and Wang, M}, title = {Insight Into Polysaccharides From Panax ginseng C. A. Meyer in Improving Intestinal Inflammation: Modulating Intestinal Microbiota and Autophagy.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {683911}, pmid = {34354704}, issn = {1664-3224}, mesh = {Animals ; Autophagy/*drug effects ; Colitis/chemically induced/microbiology/pathology/*therapy ; Cytokines/metabolism ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects ; HT29 Cells ; Humans ; Intestinal Mucosa/metabolism ; Male ; Oxidative Stress/drug effects ; Panax/*chemistry ; Plant Extracts/pharmacology ; Polysaccharides/*pharmacology ; Rats ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {Polysaccharides from Panax ginseng C. A. Meyer (P. ginseng) are the main active component of P. ginseng and exhibit significant intestinal anti-inflammatory activity. However, the therapeutic mechanism of the ginseng polysaccharide is unclear, and this hinders the application for medicine or functional food. In this study, a polysaccharide was isolated from P. ginseng (GP). The primary structure and morphology of the GP were studied by HPLC, FT-IR spectroscopy, and scanning electron microscopy (SEM). Further, its intestinal anti-inflammatory activity and its mechanism of function were evaluated in experimental systems using DSS-induced rats, fecal microbiota transplantation (FMT), and LPS-stimulated HT-29 cells. Results showed that GP modulated the structure of gut microbiota and restored mTOR-dependent autophagic dysfunction. Consequently, active autophagy suppressed inflammation through the inhibition of NF-κB, oxidative stress, and the release of cytokines. Therefore, our research provides a rationale for future investigations into the relationship between microbiota and autophagy and revealed the therapeutic potential of GP for inflammatory bowel disease.}, }
@article {pmid34349661, year = {2021}, author = {Choi, YJ and Kim, JE and Lee, SJ and Gong, JE and Son, HJ and Hong, JT and Hwang, DY}, title = {Dysbiosis of Fecal Microbiota From Complement 3 Knockout Mice With Constipation Phenotypes Contributes to Development of Defecation Delay.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {650789}, pmid = {34349661}, issn = {1664-042X}, abstract = {Significant phenotypes for constipation were detected in complement 3 (C3) knockout (KO) mice, although no research has been conducted on an association with alteration of gut microbiota. To investigate the effects of dysbiosis on fecal microbiota from C3 KO mice with constipation, the composition of fecal microbiota was characterized in mid-colons of 16-week-old C3 KO mice, and their function for defecation delay development was examined after fecal microbiota transplantation (FMT) of C3 KO mice. Some significant alterations in constipation phenotypes, including stool parameters and histopathological structure, were detected in 16-week-old C3 KO mice compared to those of wild-type (WT) mice. Fecal microbiota of C3 KO mice exhibited decreases in Anaerocolumna, Caecibacterium, Christensenella, Kineothrix, and Oscillibacter populations and increases in Prevotellamassilia, Reuthenibacterium, Prevotella, Eubacterium, Culturomica, Bacteroides, and Muribaculum populations. In FMT study, key stool parameters, including weight and water content, were remarkably declined in a transplanted KO (KFMT) group of antibiotics-induced depletion of microbiota (AiDM)-WT and AiDM-KO mice, and a similar change was observed in fecal morphology. However, intestine length decreased in only the KFMT group of AiDM-WT mice compared with that of AiDM-KO mice. The mucosal layer and muscle thickness were commonly decreased in the KFMT group of AiDM-WT and AiDM-KO mice, and significant alterations in the crypt structure of Lieberkuhn and molecular regulators, including AQP8, C-kit, and 5-HT, were observed in the same group. Taken together, results of the present study indicate that dysbiosis of fecal microbiota from C3 KO mice with constipation phenotypes has a key role in the induction and regulation of defecation delay.}, }
@article {pmid34347266, year = {2021}, author = {Zhong, Z and Chen, W and Gao, H and Che, N and Xu, M and Yang, L and Zhang, Y and Ye, M}, title = {Fecal Microbiota Transplantation Exerts a Protective Role in MPTP-Induced Parkinson's Disease via the TLR4/PI3K/AKT/NF-κB Pathway Stimulated by α-Synuclein.}, journal = {Neurochemical research}, volume = {46}, number = {11}, pages = {3050-3058}, pmid = {34347266}, issn = {1573-6903}, abstract = {Gut microbiota is closely related to the Parkinson's disease (PD) pathogenesis. Additionally, aggregation of α-synuclein (α-syn) is central to PD pathogenesis. Here we identified the further mechanisms of gut microbiota in PD. A mouse model with PD was established via injection of MPTP. Normal or MPTP-induced PD like animals were treated with FMT from healthy normal mice. Pole test and traction test were performed to examine the effects of FMT on motor function of PD mice. Fecal SCFAs were assessed by gas chromatography-mass spectrometry. The α-syn level in the substantia nigra pars compacta (SN) of mice was measured using western blot. Dopaminergic neurons and microglial activation in the SN were analyzed by immunohistochemistry (IHC) and immunofluorescence (IF) staining. FMT alleviated physical impairment, decreased fecal SCFAs in a mouse model of PD. Additionally, FMT decreased the expression of α-syn, as well as inhibited the activation of microglia in the SN, and blocked the TLR4/PI3K/AKT/NF-κB signaling in the SN and striatum. FMT could protect mice against PD via suppressing α-syn expression and inactivating the TLR4/PI3K/AKT/NF-κB signaling.}, }
@article {pmid34346283, year = {2021}, author = {Bajaj, JS and Shamsaddini, A and Fagan, A and McGeorge, S and Gavis, E and Sikaroodi, M and Brenner, LA and Wade, JB and Gillevet, PM}, title = {Distinct gut microbial compositional and functional changes associated with impaired inhibitory control in patients with cirrhosis.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1953247}, pmid = {34346283}, issn = {1949-0984}, support = {I01 CX001076/CX/CSRD VA/United States ; R01 HS025412/HS/AHRQ HHS/United States ; R21 TR002024/TR/NCATS NIH HHS/United States ; R21 TR003095/TR/NCATS NIH HHS/United States ; }, abstract = {Most cirrhosis etiologies, such as alcohol, hepatitis C, and obesity, involve behavior that require the loss of inhibitory control. Once cirrhosis develops, patients can also develop cognitive impairment due to minimal hepatic encephalopathy (MHE). Both processes could have distinct imprints on the gut-liver-brain axis. Determine the impact of inhibitory control versus traditional cirrhosis-related cognitive performance on gut microbial composition and function. Outpatients with cirrhosis underwent two tests for MHE: inhibitory control test (MHEICT, computerized associated with response inhibition) and psychometric hepatic encephalopathy score (MHEPHES, paper-pencil HE-specific associated with subcortical impairment) along with stool collection for metagenomics. MHEICT/not, MHEPHES/not, and discordant (positive on one test but negative on the other) were analyzed for demographics, bacterial species, and gut-brain modules (GBM) using multi-variable analyses. Ninety-seven patients [47 (49%) MHEPHES, 76 (78%) MHEICT, 41 discordant] were enrolled. MHEPHES/not: Cirrhosis severity was worse in MHEPHES without differences in alpha/beta diversity on bacterial species or GBMs. Pathobionts (Enterobacteriaceae) and γ-amino-butryic acid (GABA) synthesis GBM were higher in MHEPHES. MHEICT/not: We found similar cirrhosis severity and metagenomic alpha/beta diversity in MHEICT versus not. However, alpha/beta diversity of GBMs were different in MHEICT versus No-MHE patients. Alistipes ihumii, Prevotella copri, and Eubacterium spp. were higher, while Enterococcus spp. were uniquely lower in MHEICT versus no-MHE and discordant comparisons. GBMs belonging to tryptophan, menaquinone, GABA, glutamate, and short-chain fatty acid synthesis were also unique to MHEICT. Gut microbial signature of impaired inhibitory control, which is associated with addictive disorders that can lead to cirrhosis, is distinct from cirrhosis-related cognitive impairment.}, }
@article {pmid34343321, year = {2021}, author = {Conrad, MA and Kelsen, JR}, title = {Clostridioides difficile Infection in Pediatric Inflammatory Bowel Disease: A Clinician's Dilemma.}, journal = {Journal of the Pediatric Infectious Diseases Society}, volume = {10}, number = {Supplement_3}, pages = {S41-S45}, pmid = {34343321}, issn = {2048-7207}, support = {K23 DK119585/DK/NIDDK NIH HHS/United States ; }, mesh = {Child ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/complications/diagnosis ; Humans ; *Inflammatory Bowel Diseases/complications/diagnosis ; Treatment Outcome ; }, abstract = {Clostridioides difficile infection (CDI) in children with inflammatory bowel disease (IBD) can present and manifest differently from the general population with CDI, and it can worsen the underlying disease course. Furthermore, current clinical assays used to test for CDI do not accurately distinguish between true CDI or colonization. This uncertainty leads to difficulty in identifying the etiology and therapy for symptomatic patients with IBD. Improved diagnostic tests, biomarkers, and safe and effective treatment options are greatly needed for this vulnerable population.}, }
@article {pmid34341834, year = {2021}, author = {Zhang, M and Hong, Y and Wu, W and Li, N and Liu, B and Sun, J and Cao, X and Ye, T and Zhou, L and Liu, C and Yang, C and Zhang, X}, title = {Pivotal role of the gut microbiota in congenital insensitivity to pain with anhidrosis.}, journal = {Psychopharmacology}, volume = {238}, number = {11}, pages = {3131-3142}, pmid = {34341834}, issn = {1432-2072}, support = {81974171//Natural Science Foundation Project of China/ ; }, mesh = {Animals ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; *Hereditary Sensory and Autonomic Neuropathies ; Humans ; Mice ; }, abstract = {BACKGROUND: Increasing evidence has shown that the occurrence and development of various human diseases are closely related to the gut microbiota. We compared the gut microbial communities of human subjects with congenital insensitivity to pain with anhidrosis (CIPA) and healthy controls (HCs) to assess whether fecal microbiota transplantation (FMT) into germ-free mice and mice in acute pain influenced the behaviors of the host.<br><br>METHODS: We utilized 16 s rRNA analysis to compare the gut microbial communities of CIPA subjects and HCs and assessed whether FMT into germ-free mice and mice in acute pain influenced the behaviors of the host.<br><br>RESULTS: In a 16 s RNA analysis, the CIPA group had significant decreases in the relative abundance of 11 bacteria, whereas 7 bacteria were significantly increased. In further animal experiments, the transplantation of fecal samples from CIPA patients to healthy mice significantly increased their scores on both the mechanical withdrawal test and the tail flick test; in an acute plantar incision model, scores were also significantly increased on the mechanical withdrawal test at 4 and 5 days after the operation. Moreover, pseudo-germ-free mice receiving fecal bacteria from patients with CIPA took significantly longer to escape and had a significantly longer path length on training days 1, 2, and 5 and also had fewer platform crossings and spent less time in the target quadrant in the probe trial.<br><br>CONCLUSIONS: Our results suggest that the gut microbiota in CIPA subjects plays a key role in behaviors. Therapeutic strategies for improving the gut microbiota might alleviate CIPA symptoms.}, }
@article {pmid34335628, year = {2021}, author = {Brosseau, C and Selle, A and Duval, A and Misme-Aucouturier, B and Chesneau, M and Brouard, S and Cherbuy, C and Cariou, V and Bouchaud, G and Mincham, KT and Strickland, DH and Barbarot, S and Bodinier, M}, title = {Prebiotic Supplementation During Pregnancy Modifies the Gut Microbiota and Increases Metabolites in Amniotic Fluid, Driving a Tolerogenic Environment In Utero.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {712614}, pmid = {34335628}, issn = {1664-3224}, abstract = {The gut microbiota is influenced by environmental factors such as food. Maternal diet during pregnancy modifies the gut microbiota composition and function, leading to the production of specific compounds that are transferred to the fetus and enhance the ontogeny and maturation of the immune system. Prebiotics are fermented by gut bacteria, leading to the release of short-chain fatty acids that can specifically interact with the immune system, inducing a switch toward tolerogenic populations and therefore conferring health benefits. In this study, pregnant BALB/cJRj mice were fed either a control diet or a diet enriched in prebiotics (Galacto-oligosaccharides/Inulin). We hypothesized that galacto-oligosaccharides/inulin supplementation during gestation could modify the maternal microbiota, favoring healthy immune imprinting in the fetus. Galacto-oligosaccharides/inulin supplementation during gestation increases the abundance of Bacteroidetes and decreases that of Firmicutes in the gut microbiota, leading to increased production of fecal acetate, which was found for the first time in amniotic fluid. Prebiotic supplementation increased the abundance of regulatory B and T cells in gestational tissues and in the fetus. Interestingly, these regulatory cells remained later in life. In conclusion, prebiotic supplementation during pregnancy leads to the transmission of specific microbial and immune factors from mother to child, allowing the establishment of tolerogenic immune imprinting in the fetus that may be beneficial for infant health outcomes.}, }
@article {pmid34335508, year = {2021}, author = {Zhu, F and Ke, Y and Luo, Y and Wu, J and Wu, P and Ma, F and Liu, Y}, title = {Effects of Different Treatment of Fecal Microbiota Transplantation Techniques on Treatment of Ulcerative Colitis in Rats.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {683234}, pmid = {34335508}, issn = {1664-302X}, abstract = {Background: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease with abdominal pain, mucus, pus and blood in the stool as the main clinical manifestations. The pathogenesis of UC is still not completely clear, and multiple factors, such as genetic susceptibility, immune response, intestinal microecological changes and environmental factors, together lead to the onset of UC. In recent years, the role of intestinal microbiota disturbances on the pathogenesis of UC has received widespread attention. Therefore, fecal microbiota transplantation (FMT), which changes the intestinal microecological environment of UC patients by transplantation of normal fecal bacteria, has attracted increasing attention from researchers. However, there are no guidelines to recommend fresh FMT or frozen FMT in the treatment of UC, and there are few studies on this. Therefore, the purpose of this study was to explore the effects of fresh and frozen FMT methods on the treatment of experimental UC models in rats. Results: Compared with the model control group, all FMT groups achieved better efficacy, mainly manifested as weight gain by the rats, improvements in fecal characteristics and blood stools, reduced inflammatory factors and normal bacterial microbiota. The efficacy of the frozen FMT group was better than that of the fresh FMT group in terms of behavior and colon length. Conclusion: FMT method supplements the gut microbiota with beneficial bacteria, such as short-chain fatty acid-producing bacteria. These bacteria can regulate intestinal function, protect the mucosal barrier and reduce harmful bacteria, thus mitigating the damage to the intestinal barrier and the associated inflammatory response, resulting in UC remission. FMT is a feasible method for treating UC, with frozen FMT having a superior therapeutic effect than that of fresh FMT.}, }
@article {pmid34332209, year = {2021}, author = {Corrie, L and Gulati, M and Vishwas, S and Kapoor, B and Singh, SK and Awasthi, A and Khursheed, R}, title = {Combination therapy of curcumin and fecal microbiota transplant: Potential treatment of polycystic ovarian syndrome.}, journal = {Medical hypotheses}, volume = {154}, number = {}, pages = {110644}, doi = {10.1016/j.mehy.2021.110644}, pmid = {34332209}, issn = {1532-2777}, mesh = {*Curcumin/therapeutic use ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; Female ; Humans ; *Microbiota ; *Polycystic Ovary Syndrome/therapy ; }, abstract = {Polycystic ovarian syndrome (PCOS) is a combination of various symptoms like anovulation, hirsutism, chronic amenorrhea, infertility, obesity and polycystic ovaries. It affects over 7 million women worldwide. The current strategy to treat this disorder is based on the use of drugs that provide symptomatic relief. Most of these, however, exhibit numerous side effects and are not able to ameliorate all the signs and symptoms of PCOS. As dysbiosis is considered as one of the prime underlying causes of PCOS, restoration of eubiosis was considered as a plausible way to treat it. Bacteriotherpeutics like probiotics, synbiotics and even fecal microbiota transplant (FMT) have shown considerable effectiveness in PCOS. Of these baceteriotherapeutic options, FMT is considered to be the most holistic as it encompasses the bacteriome, virome, fungome, archaeome and even parasitome while both probiotics as well as synbiotics mainly comprise bacteria. Repeated FMT, however, is not a pragmatic option because of its inconvenience, lack of standardization, involved risk and scepticism amongst patients and physicians. If the eubiosis ushered by FMT is sustained for a long time, the repeated administrations of FMT can be avoided and maintenance therapy with any agent that can maintain the eubiotic condition can be adopted. Role of curcumin on gut microbiota is widely known. It is largely attributed to the ability of certain microbes to consume polyphenols as substrates and its positive effect on bacterial consumption of nutrients such as sugars. Based on various mechanisms and studies, a new hypothesis is being proposed wherein FMT and curcumin combination is predicted to be an effective and sustained treatment of PCOS with much lower rates of remission.}, }
@article {pmid34330600, year = {2021}, author = {Ji, Y and Tao, T and Zhang, J and Su, A and Zhao, L and Chen, H and Hu, Q}, title = {Comparison of effects on colitis-associated tumorigenesis and gut microbiota in mice between Ophiocordyceps sinensis and Cordyceps militaris.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {90}, number = {}, pages = {153653}, doi = {10.1016/j.phymed.2021.153653}, pmid = {34330600}, issn = {1618-095X}, mesh = {Animals ; Bacteroidetes ; Bifidobacterium ; Carcinogenesis ; *Colitis/chemically induced/drug therapy ; *Cordyceps/chemistry ; Dextran Sulfate ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Male ; Mice ; Mice, Inbred C57BL ; Probiotics ; }, abstract = {BACKGROUND: Gut microbiota plays an indispensable role in the treatment of inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). As traditional medicinal fungi, previous studies have shown that Ophiocordyceps sinensis could better maintain intestinal health via promoting the growth of probiotics in vitro compared with Cordyceps militaris. However, the detailed pharmacological activities and clinical efficacy of O. sinensis and C. militaris are still elusive.<br><br>PURPOSE: We aimed to evaluate the different actions of O. sinensis and C. militaris on colitis-associated tumorigenesis in Azoxymethane (AOM)/Dextran Sulfate Sodium (DSS)-treated mice and explore the potential gut microbiota-dependent mechanisms.<br><br>METHODS: C57BL/6 mice (Male, 4 weeks old) were used to construct the AOM/DSS-induced CAC mice model. The mice were administered with 0.6 mg/g/d O. sinensis or C. militaris for 12 weeks. It's worth noting that fecal microbiota transplantation (FMT) and antibiotic treatment were used to investigated the complex interactions between the medicinal fungi, gut microbiota and colonic tumorigenesis.<br><br>RESULTS: O. sinensis treatment significantly increased the body weight and survival rate, reduced the number of colon tumors, improved the damage of colon epithelial tissue, restored the crypt structure and alleviate the colonic inflammation in AOM/DSS-treated mice. RT-qPCR results indicated that O. sinensis partly regulated the Wnt/β-catenin signaling via alleviating the overexpression of β-catenin, TCF4 and c-Myc genes in adjacent noncancerous tissues. Compared with C. militaris, O. sinensis showed better anti-tumor activity. Gut microbiota analysis revealed that O. sinensis reversed the decline of gut microbiota diversity and the structural disorder induced by AOM/DSS. Spearman's correlation analysis showed that O. sinensis promoted the growth of Parabacteroides goldsteinii and Bifidobacterium pseudolongum PV8-2, which were positively correlated with the anti-tumor activity and the production of SCFAs. FMT combined with antibiotic treatment showed that horizontal fecal transfer derived from O. sinensis-treated mice improved the intestinal inflammation and alleviated the colitis-associated tumorigenesis, which was consistent with the direct ingestion of O. sinensis.<br><br>CONCLUSION: O. sinensis could better attenuate colitis-associated tumorigenesis compared with C. militaris. These effects might be at least partially due to the increased abundance of probiotics, especially P. goldsteinii and B. pseudolongum PV8-2.}, }
@article {pmid34329563, year = {2021}, author = {Sehgal, K and Khanna, S}, title = {Gut microbiota: a target for intervention in obesity.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {15}, number = {10}, pages = {1169-1179}, doi = {10.1080/17474124.2021.1963232}, pmid = {34329563}, issn = {1747-4132}, abstract = {INTRODUCTION: Obesity is a major public health concern with an increasing prevalence. Recent studies suggest an influence of gastrointestinal microbiota on obesity. Consequently, microbiota restoration therapies are being considered as potential management. We present data on microbiome markers and the future of microbiota therapeutics for obesity.<br><br>AREAS COVERED: We summarize the pathogenesis of obesity, relationship between gut microbiota and obesity, use of microbiota-based therapies. Data were gathered by a literature search of articles in PubMed from the date of inception till August 2020. Keywords used were 'gut microbiota,' 'gut microbiome,' 'microbiota,' 'microbiome,' 'obesity,' and 'obesity and fecal microbiota transplantation' as MeSH terms.<br><br>EXPERT OPINION: The direct relationship of gut microbiota in causing obesity needs exploration. Because of the scarcity of human studies, the utility of microbiota-based therapies as treatment remains uncertain and the use of microbiome restoration for obesity should be restricted to research settings. To evaluate the efficacy of microbiota restoration, studies using these therapies as an adjunct with diet and lifestyle should be conducted. Once relationships between bacterial strains and the human metabolic profile are determined, these strains could be cultured for transfer to obese patients. Such advancement could help in tailoring personalized therapies for obese persons.}, }
@article {pmid34328191, year = {2021}, author = {Nishikawa, H and Fukunishi, S and Asai, A and Yokohama, K and Ohama, H and Nishiguchi, S and Higuchi, K}, title = {Dysbiosis and liver diseases (Review).}, journal = {International journal of molecular medicine}, volume = {48}, number = {3}, pages = {}, doi = {10.3892/ijmm.2021.5016}, pmid = {34328191}, issn = {1791-244X}, abstract = {Dysbiosis, a qualitative and quantitative aberrancy of gut microbiota, has attracted marked attention. At present, advances in molecular biological techniques have made it possible to analyze gut microbiota at the DNA and RNA levels without culturing, and methods such as 16S ribosomal RNA targeting analysis and metagenomic analysis using next‑generation sequencers have been developed. The relationship between gut microbiota and various diseases has been extensively examined. Gut microbiota are essential for the immune system, energy intake and fat storage, and humans use them to build complex immune regulatory mechanisms and to obtain energy from food. The liver is the first organ to be nourished by the portal blood flow of intestinal origin, and liver diseases can be strongly influenced by various factors of intestinal origin, such as intestinal bacteria, bacterial components, and intestinal bacterial metabolites. Rigorous research has revealed that the composition of the gut microbiota is altered and the diversity of bacteria is reduced in liver diseases. Significance of various factors transported to the liver by portal vein blood flow from the intestine has been extensively investigated. Gut microbiota in liver disease can be associated with disease progression regardless of disease etiology and even with carcinogenesis. The relationship between gut microbiota and liver diseases (hepatitis virus‑related diseases, autoimmune liver diseases, alcoholic liver disease, non‑alcoholic fatty liver disease, non‑alcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma) and the treatments of dysbiosis (antibiotics, prebiotics, probiotics and fecal microbiota transplantation) in liver disease are outlined based on the current evidence.}, }
@article {pmid34328058, year = {2021}, author = {Gheorghe, CE and Ritz, NL and Martin, JA and Wardill, HR and Cryan, JF and Clarke, G}, title = {Investigating causality with fecal microbiota transplantation in rodents: applications, recommendations and pitfalls.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1941711}, pmid = {34328058}, issn = {1949-0984}, abstract = {In recent years, studies investigating the role of the gut microbiota in health and diseases have increased enormously - making it essential to deepen and question the research methodology employed. Fecal microbiota transplantation (FMT) in rodent studies (either from human or animal donors) allows us to better understand the causal role of the intestinal microbiota across multiple fields. However, this technique lacks standardization and requires careful experimental design in order to obtain optimal results. By comparing several studies in which rodents are the final recipients of FMT, we summarize the common practices employed. In this review, we document the limitations of this method and highlight different parameters to be considered while designing FMT Studies. Standardizing this method is challenging, as it differs according to the research topic, but avoiding common pitfalls is feasible. Several methodological questions remain unanswered to this day and we offer a discussion on issues to be explored in future studies.}, }
@article {pmid34324703, year = {2021}, author = {Mengoni, F and Salari, V and Kosenkova, I and Tsenov, G and Donadelli, M and Malerba, G and Bertini, G and Del Gallo, F and Fabene, PF}, title = {Gut microbiota modulates seizure susceptibility.}, journal = {Epilepsia}, volume = {62}, number = {9}, pages = {e153-e157}, pmid = {34324703}, issn = {1528-1167}, abstract = {A bulk of data suggest that the gut microbiota plays a role in a broad range of diseases, including those affecting the central nervous system. Recently, significant differences in the intestinal microbiota of patients with epilepsy, compared to healthy volunteers, have been reported in an observational study. However, an active role of the intestinal microbiota in the pathogenesis of epilepsy, through the so-called "gut-brain axis," has yet to be demonstrated. In this study, we evaluated the direct impact of microbiota transplanted from epileptic animals to healthy recipient animals, to clarify whether the microbiota from animals with epilepsy can affect the excitability of the recipients' brain by lowering seizure thresholds. Our results provide the first evidence that mice who received microbiota from epileptic animals are more prone to develop status epilepticus, compared to recipients of "healthy" microbiota, after a subclinical dose of pilocarpine, indicating a higher susceptibility to seizures. The lower thresholds for seizure activity found in this study support the hypothesis that the microbiota, through the gut-brain axis, is able to affect neuronal excitability in the brain.}, }
@article {pmid34321175, year = {2020}, author = {Yang, F and Chen, H and Gao, Y and An, N and Li, X and Pan, X and Yang, X and Tian, L and Sun, J and Xiong, X and Xing, Y}, title = {Gut microbiota-derived short-chain fatty acids and hypertension: Mechanism and treatment.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {130}, number = {}, pages = {110503}, doi = {10.1016/j.biopha.2020.110503}, pmid = {34321175}, issn = {1950-6007}, mesh = {Animals ; Disease Management ; Disease Susceptibility ; Dysbiosis ; Fatty Acids, Volatile/*metabolism ; *Gastrointestinal Microbiome ; Gene Expression Regulation ; Histones/metabolism ; Host-Pathogen Interactions ; Humans ; Hypertension/diagnosis/*etiology/*metabolism/therapy ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; }, abstract = {Hypertension (HTN) is an growing emerging health issue around across the world. In recent years, increasing attention has been paid to the role of dysbacteriosis in HTN and its underlying mechanism. Short-chain fatty acids (SCFAs), which are novel metabolites of intestinal flora, exert substantial regulatory effects on HTN, providing an exciting avenue for novel therapies for this disease. They function primarily by activating transmembrane G protein-coupled receptors and inhibiting histone acetylation. In this review, we discuss the mechanisms underlying the complex interaction between SCFAs and gut microbiota composition to lower blood pressure by regulating the brain-gut and kidney-gut axes, and the role of high-salt diet, immune system, oxidative stress, and inflammatory mechanism in the development of HTN. Furthermore, we also discuss the various treatment strategies for HTN, including diet, antibiotics, probiotics, fecal microflora transplantation, and traditional Chinese medicine. In conclusion, manipulation of SCFAs opens new avenues to improve treatment of HTN.}, }
@article {pmid34320242, year = {2021}, author = {Li, Y and Dong, J and Xiao, H and Wang, B and Chen, Z and Zhang, S and Jin, Y and Li, Y and Fan, S and Cui, M}, title = {Caloric restriction alleviates radiation injuries in a sex-dependent fashion.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {35}, number = {8}, pages = {e21787}, doi = {10.1096/fj.202100351RR}, pmid = {34320242}, issn = {1530-6860}, mesh = {Animals ; *Caloric Restriction ; Feces/microbiology ; Female ; Gastrointestinal Diseases/therapy ; *Gastrointestinal Microbiome ; Hematopoiesis/*radiation effects ; Inflammation/therapy ; Male ; Mice ; Mice, Inbred C57BL ; Radiation Injuries/*complications/*therapy ; Sex Factors ; Specific Pathogen-Free Organisms ; }, abstract = {Safe and effective regimens are still needed given the risk of radiation toxicity from iatrogenic irradiation. The gut microbiota plays an important role in radiation damage. Diet has emerged as a key determinant of the intestinal microbiome signature and function. In this report, we investigated whether a 30% caloric restriction (CR) diet may ameliorate radiation enteritis and hematopoietic toxicity. Experimental mice were either fed ad libitum (AL) or subjected to CR preconditioning for 10 days and then exposed to total body irradiation (TBI) or total abdominal irradiation (TAI). Gross examinations showed that short-term CR pretreatment restored hematogenic organs and improved the intestinal architecture in both male and female mice. Intriguingly, CR preconditioning mitigated radiation-induced systemic and enteric inflammation in female mice, while gut barrier function improved in irradiated males. 16S rRNA high-throughput sequencing showed that the frequency of pro-inflammatory microbes, including Helicobacter and Desulfovibrionaceae, was reduced in female mice after 10 days of CR preconditioning, while an enrichment of short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibaculum, Clostridiales, and Lactobacillus, was observed in males. Using fecal microbiota transplantation (FMT) or antibiotic administration to alter the gut microbiota counteracted the short-term CR-elicited radiation tolerance of both male and female mice, further indicating that the radioprotection of a 30% CR diet depends on altering the gut microbiota. Together, our findings provide new insights into CR in clinical applications and indicate that a short-term CR diet prior to radiation modulates sex-specific gut microbiota configurations, protecting male and female mice against the side effects caused by radiation challenge.}, }
@article {pmid34319520, year = {2021}, author = {El-Sayed, A and Aleya, L and Kamel, M}, title = {Microbiota and epigenetics: promising therapeutic approaches?.}, journal = {Environmental science and pollution research international}, volume = {28}, number = {36}, pages = {49343-49361}, doi = {10.1007/s11356-021-15623-6}, pmid = {34319520}, issn = {1614-7499}, mesh = {Fecal Microbiota Transplantation ; *Microbiota ; Prebiotics ; *Probiotics ; *Synbiotics ; }, abstract = {The direct/indirect responsibility of the gut microbiome in disease induction in and outside the digestive tract is well studied. These results are usually from the overpopulation of certain species on the cost of others, interaction with beneficial microflora, interference with normal epigenetic control mechanisms, or suppression of the immune system. Consequently, it is theoretically possible to cure such disorders by rebalancing the microbiome inside our bodies. This can be achieved by changing the lifestyle pattern and diet or by supplementation with beneficial bacteria or their metabolites. Various approaches have been explored to manipulate the normal microbial inhabitants, including nutraceutical, supplementations with prebiotics, probiotics, postbiotics, synbiotics, and antibiotics, or through microbiome transplantation (fecal, skin, or vaginal microbiome transplantation). In the present review, the interaction between the microbiome and epigenetics and their role in disease induction is discussed. Possible future therapeutic approaches via the reestablishment of equilibrium in our internal micro-ecosystem are also highlighted.}, }
@article {pmid34313540, year = {2021}, author = {Trikha, SRJ and Lee, DM and Ecton, KE and Wrigley, SD and Vazquez, AR and Litwin, NS and Thomas, KN and Wei, Y and Battson, ML and Johnson, SA and Kuhn, KA and Colgan, SP and Gentile, CL and Weir, TL}, title = {Transplantation of an obesity-associated human gut microbiota to mice induces vascular dysfunction and glucose intolerance.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1940791}, pmid = {34313540}, issn = {1949-0984}, support = {R01 DK104713/DK/NIDDK NIH HHS/United States ; R01 HL144611/HL/NHLBI NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; }, abstract = {Recent preclinical data suggest that alterations in the gut microbiota may be an important factor linking obesity to vascular dysfunction, an early sign of cardiovascular disease. The purpose of this study was to begin translation of these preclinical data by examining whether vascular phenotypes in humans are transmissible through the gut microbiota. We hypothesized that germ-free mice colonized with gut microbiota from obese individuals would display diminished vascular function compared to germ-free mice receiving microbiota from lean individuals.We transplanted fecal material from obese and lean age-and sex-matched participants with disparate vascular function to germ-free mice. Using Principle Component Analysis, the microbiota of colonized mice separated by donor group along the first principle component, accounting for between 70-93% of the total variability in the dataset. The microbiota of mice receiving transplants from lean individuals was also characterized by increased alpha diversity, as well as increased relative abundance of potentially beneficial bacteria, including Bifidobacterium, Lactobacillus, and Bacteroides ovatis. Endothelium-dependent dilation, aortic pulse wave velocity and glucose tolerance were significantly altered in mice receiving microbiota from the obese donor relative to those receiving microbiota from the lean donor or those remaining germ-free.These data indicate that the obesity-associated human gut microbiota is sufficient to alter the vascular phenotype in germ-free mice in the absence of differences in body weight or dietary manipulation, and provide justification for future clinical trials to test the efficacy of microbiota-targeted therapies in the prevention or treatment of cardiovascular disease.}, }
@article {pmid34312355, year = {2021}, author = {Jo, HG and Seo, GS}, title = {[Efficacy and Safety of Fecal Microbiota Transplantation and Prospect of Microbe-based Therapies for Inflammatory Bowel Disease].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {78}, number = {1}, pages = {31-36}, doi = {10.4166/kjg.2021.089}, pmid = {34312355}, issn = {2233-6869}, mesh = {Clostridium Infections ; Dysbiosis/therapy ; *Fecal Microbiota Transplantation ; Feces ; Humans ; *Inflammatory Bowel Diseases/therapy ; Prospective Studies ; }, abstract = {The use of 5-ASA, immunomodulators, biologics, and small molecule drugs are the main treatment for inflammatory bowel disease (IBD), however, fecal microbiota transplantation (FMT) is also drawing attention as a treatment to improve intestinal dysbiosis by transplantaing normal human stool into patients with IBD. FMT demonstrates relatively good effects in inducing clinical remission in IBD, but unlike Clostridium difficile infection, multiple FMT can enhance the clinical effect. There are no reports of the long-term effectiveness and safety of FMT conducted in IBD yet, therefore, well-designed, prospective studies will be needed. Gut microbiota can affect inflammatory response, intestinal barrier function, and host metabolism, so microbe-based therapies are likely to be a new treatment option for IBD. The deeper the understanding of microbe products or effectors, the more likely it is to provide personalized therapy in IBD.}, }
@article {pmid34308364, year = {2020}, author = {Huang, YW and Pan, P and Echeveste, CE and Wang, HT and Oshima, K and Lin, CW and Yearsley, M and Xiao, J and Chen, J and Sun, C and Yu, J and Wang, LS}, title = {Transplanting fecal material from wild-type mice fed black raspberries alters the immune system of recipient mice.}, journal = {Food frontiers}, volume = {1}, number = {3}, pages = {253-259}, pmid = {34308364}, issn = {2643-8429}, support = {R01 CA148818/CA/NCI NIH HHS/United States ; }, abstract = {By constantly stimulating intestinal immunity, gut microbes play important regulatory roles, and their possible involvement in human physical and mental disorders beyond intestinal diseases suggests the importance of maintaining homeostasis in the gut microbiota. Both transplantation of fecal microbiota and dietary interventions have been shown to restore microbial homeostasis in recipients. In the current study with wild-type mice, we combined these two approaches to determine if transplanting fecal material from mice fed black raspberries (BRB, 5%) altered recipients' immune system. The donors received a control or 5% BRB diet, and fecal transplantation was performed every other day 15 times into recipients fed control diet. Afterward, we used flow cytometry to analyze populations of CD3+ T, CD4+ T, CD8+ T cells, and NK cells among bone marrow cells, splenocytes, and peripheral blood mononuclear cells (PBMCs) collected from the recipients. We found that BRB-fecal material that contained both fecal microbiota and their metabolites increased NK cell populations among bone marrow cells, splenocytes, and PBMCs, and raised levels of CD8+ T cells in splenocytes. Our findings suggest that fecal transplantation can modulate the immune system and might therefore be valuable for managing a range of physical and mental disorders.}, }
@article {pmid34305883, year = {2021}, author = {Malczewski, AB and Ketheesan, N and Coward, JIG and Navarro, S}, title = {Enhancing Checkpoint Inhibitor Therapy in Solid Tissue Cancers: The Role of Diet, the Microbiome &amp; Microbiome-Derived Metabolites.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {624434}, pmid = {34305883}, issn = {1664-3224}, mesh = {Animals ; Bacteria/metabolism ; Diet/adverse effects/*methods ; Dysbiosis/complications ; Gastrointestinal Microbiome/*drug effects/immunology ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; Immunomodulation ; Life Style ; Metabolome/drug effects/*immunology ; Mice ; Neoplasms/*drug therapy/immunology ; }, abstract = {Host immunity plays a central role in the regulation of anti-tumour responses during checkpoint inhibitor therapy (CIT). The mechanisms involved in long lasting remission remain unclear. Animal studies have revealed that the microbiome influences the host immune response. This is supported by human studies linking a higher microbial richness and diversity with enhanced responses to CIT. This review focuses on the role of diet, the microbiome and the microbiome-derived metabolome in enhancing responses to current CIT in solid tissue cancers. The Western diet has been associated with dysbiosis, inflammation and numerous metabolic disorders. There is preliminary evidence that lifestyle factors including a high fibre diet are associated with improved responses to CIT via a potential effect on the microbiota. The mechanisms through which the microbiota may regulate long-term immunotherapy responses have yet to be determined, although bacterial-metabolites including short chain fatty acids (SCFAs) are recognized to have an impact on T cell differentiation, and may affect T effector/regulatory T cell balance. SCFAs were also shown to enhance the memory potential of activated CD8 T cells. Many therapeutic approaches including dietary manipulation and fecal transplantation are currently being explored in order to enhance immunotherapy responses. The microbiome-derived metabolome may be one means through which bacterial metabolic products can be monitored from the start of treatment and could be used to identify patients at risk of poor immunotherapy responses. The current review will discuss recent advances and bring together literature from related fields in nutrition, oncology and immunology to discuss possible means of modulating immunity to improve responses to current CIT.}, }
@article {pmid34304786, year = {2021}, author = {Singh, P and Lembo, A}, title = {Emerging Role of the Gut Microbiome in Irritable Bowel Syndrome.}, journal = {Gastroenterology clinics of North America}, volume = {50}, number = {3}, pages = {523-545}, doi = {10.1016/j.gtc.2021.03.003}, pmid = {34304786}, issn = {1558-1942}, mesh = {Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; *Microbiota ; *Probiotics/therapeutic use ; }, abstract = {Advances in bioinformatics have facilitated investigation of the role of gut microbiota in patients with irritable bowel syndrome (IBS). This article describes the evidence from epidemiologic and clinical observational studies highlighting the link between IBS and gut microbiome by investigating postinfection IBS, small intestinal bacterial overgrowth, and microbial dysbiosis. It highlights the effects of gut microbiota on mechanisms implicated in the pathophysiology of IBS, including gut-brain axis, visceral hypersensitivity, motility, epithelial barrier, and immune activation. In addition, it summarizes the current evidence on microbiome-guided therapies in IBS, including probiotics, antibiotics, diet, and fecal microbiota transplant.}, }
@article {pmid34301806, year = {2021}, author = {Xie, Y and Song, L and Yang, J and Tao, T and Yu, J and Shi, J and Jin, X}, title = {Small intestinal flora graft alters fecal flora, stool, cytokines and mood status in healthy mice.}, journal = {Life science alliance}, volume = {4}, number = {9}, pages = {}, pmid = {34301806}, issn = {2575-1077}, abstract = {Fecal microbiota transplantation is widely used. Large intestinal microbiota (LIM) is more similar to fecal microbiota than small intestinal microbiota (SIM). The SIM communities are very different from those of LIM. Therefore, SIM transplantation (SIMT) and LIM transplantation (LIMT) might exert different influences. Here, healthy adult male C57Bl/6 mice received intragastric SIMT, LIMT, or sterile PBS administration. Microbiota graft samples were collected from small/large intestine of healthy mice of the same age, sex, and strain background. Compared with PBS treatment, SIMT increased pellet number, stool wet weight, and stool water percentage; induced a fecal microbiota profile shift toward the microbial composition of the SIM graft; induced a systemic anti-inflammatory cytokines profile; and ameliorated depressive-like behaviors in recipients. LIMT, however, induced merely a slight alteration in fecal microbial composition and no significant influence on the other aspects. In sum, SIMT, rather than LIMT, affected defecation features, fecal microbial composition, cytokines profile, and depressive-like behaviors in healthy mice. This study reveals the different effects of SIMT and LIMT, providing an interesting clue for further researches involving gut microbial composition change.}, }
@article {pmid34301274, year = {2021}, author = {Lin, X and Liu, Y and Ma, L and Ma, X and Shen, L and Ma, X and Chen, Z and Chen, H and Li, D and Su, Z and Chen, X}, title = {Constipation induced gut microbiota dysbiosis exacerbates experimental autoimmune encephalomyelitis in C57BL/6 mice.}, journal = {Journal of translational medicine}, volume = {19}, number = {1}, pages = {317}, pmid = {34301274}, issn = {1479-5876}, mesh = {Animals ; Constipation ; Cytokines ; Dysbiosis/complications ; *Encephalomyelitis, Autoimmune, Experimental/complications ; Female ; *Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Quality of Life ; Th17 Cells ; }, abstract = {BACKGROUND: Constipation is a common gastrointestinal dysfunction which has a potential impact on people's immune state and their quality of life. Here we investigated the effects of constipation on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS).<br><br>METHODS: Constipation was induced by loperamide in female C57BL/6 mice. The alternations of gut microbiota, permeability of intestinal barrier and blood-brain barrier, and histopathology of colon were assessed after constipation induction. EAE was induced in the constipation mice. Fecal microbiota transplantation (FMT) was performed from constipation mice into microbiota-depleted mice. Clinical scores, histopathology of inflammation and demyelination, Treg/Th17 and Treg17/Teff17 imbalance both in the peripheral lymphatic organs and central nervous system, cytokines include TGF-β, GM-CSF, IL-10, IL-17A, IL-17F, IL-21, IL-22, and IL-23 in serum were assessed in different groups.<br><br>RESULTS: Compared with the vehicle group, the constipation mice showed gut microbiota dysbiosis, colon inflammation and injury, and increased permeability of intestinal barrier and blood-brain barrier. We found that the clinical and pathological scores of the constipation EAE mice were severer than that of the EAE mice. Compared with the EAE mice, the constipation EAE mice showed reduced percentage of Treg and Treg17 cells, increased percentage of Th17 and Teff17 cells, and decreased ratio of Treg/Th17 and Treg17/Teff17 in the spleen, inguinal lymph nodes, brain, and spinal cord. Moreover, the serum levels of TGF-β, IL-10, and IL-21 were decreased while the GM-CSF, IL-17A, IL-17F, IL-22, and IL-23 were increased in the constipation EAE mice. In addition, these pathological processes could be transferred via their gut microbiota.<br><br>CONCLUSIONS: Our results verified that constipation induced gut microbiota dysbiosis exacerbated EAE via aggravating Treg/Th17 and Treg17/Teff17 imbalance and cytokines disturbance in C57BL/6 mice.}, }
@article {pmid34295835, year = {2021}, author = {Wang, X and Tang, Q and Hou, H and Zhang, W and Li, M and Chen, D and Gu, Y and Wang, B and Hou, J and Liu, Y and Cao, H}, title = {Gut Microbiota in NSAID Enteropathy: New Insights From Inside.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {679396}, pmid = {34295835}, issn = {2235-2988}, mesh = {Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; *Gastrointestinal Microbiome ; Humans ; *Intestinal Diseases/chemically induced ; Intestinal Mucosa ; *Microbiota ; *Probiotics ; }, abstract = {As a class of the commonly used drugs in clinical practice, non-steroidal anti-inflammatory drugs (NSAIDs) can cause a series of adverse events including gastrointestinal injuries. Besides upper gastrointestinal injuries, NSAID enteropathy also attracts attention with the introduction of capsule endoscopy and double balloon enteroscopy. However, the pathogenesis of NSAID enteropathy remains to be entirely clarified. Growing evidence from basic and clinical studies presents that gut microbiota is a critical factor in NSAID enteropathy progress. We have reviewed the recent data about the interplay between gut microbiota dysbiosis and NSAID enteropathy. The chronic medication of NSAIDs could change the composition of the intestinal bacteria and aggravate bile acids cytotoxicity. Meanwhile, NSAIDs impair the intestinal barrier by inhibiting cyclooxygenase and destroying mitochondria. Subsequently, intestinal bacteria translocate into the mucosa, and then lipopolysaccharide released from gut microbiota combines to Toll-like receptor 4 and induce excessive production of nitric oxide and pro-inflammatory cytokines. Intestinal injuries present in the condition of intestinal inflammation and oxidative stress. In this paper, we also have reviewed the possible strategies of regulating gut microbiota for the management of NSAID enteropathy, including antibiotics, probiotics, prebiotics, mucosal protective agents, and fecal microbiota transplant, and we emphasized the adverse effects of proton pump inhibitors on NSAID enteropathy. Therefore, this review will provide new insights into a better understanding of gut microbiota in NSAID enteropathy.}, }
@article {pmid34289768, year = {2021}, author = {Park, SH and Lee, JH and Shin, J and Kim, JS and Cha, B and Lee, S and Kwon, KS and Shin, YW and Choi, SH}, title = {Cognitive function improvement after fecal microbiota transplantation in Alzheimer's dementia patient: a case report.}, journal = {Current medical research and opinion}, volume = {37}, number = {10}, pages = {1739-1744}, doi = {10.1080/03007995.2021.1957807}, pmid = {34289768}, issn = {1473-4877}, mesh = {Aged, 80 and over ; *Alzheimer Disease/therapy ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Cognition ; Fecal Microbiota Transplantation ; Feces ; Female ; Humans ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; }, abstract = {After fecal microbiota transplantation (FMT) to treat Clostridioides difficile infection (CDI), cognitive improvement is noticeable, suggesting an essential association between the gut microbiome and neural function. Although it is known that the gut microbiome is linked with cognitive function, whether FMT may lead to cognitive improvement in patients with neurodegenerative disorders remains to be elucidated. We present the case of a 90-year-old woman with Alzheimer's dementia and severe CDI who underwent FMT. Cognitive function testing (Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating assessment) was performed one month before FMT and one week and one month after FMT. We collected the patients' fecal samples before FMT and 3 weeks after FMT to compare the microbiota composition. The 16S rRNA gene amplicons were analyzed using the QIIME2 platform (version 2020.2) and the Phyloseq R package. The linear discriminant analysis effect size was performed to determine the taxonomic difference between pre- and post-FMT. Functional biomarker analysis using the Kruskal-Wallis H test was performed between the pre- and post-FMT. The cognitive function tests after FMT showed an improvement compared to the tests before the procedure. FMT changed the microbiota composition in recipient feces. We found that the genera were reported to be associated with cognitive function. In addition, short-chain fatty acids were found to be significantly different between before and after FMT. This finding suggests the presence of an association between the gut microbiome and cognitive function. Further, it emphasizes the need for clinical awareness regarding the effect of FMT on the brain-gut-microbiome axis and its potential as a therapy for patients with dementia.}, }
@article {pmid34289209, year = {2021}, author = {Ding, G and Gong, Q and Ma, J and Liu, X and Wang, Y and Cheng, X}, title = {Immunosuppressive activity is attenuated by Astragalus polysaccharides through remodeling the gut microenvironment in melanoma mice.}, journal = {Cancer science}, volume = {112}, number = {10}, pages = {4050-4063}, pmid = {34289209}, issn = {1349-7006}, support = {19401901600//the Shanghai Science and Technology Action Innovation Plan/ ; 81973543//National Natural Science Foundation of China/ ; YB-20-08//the Education and Scientific Research Projects of 2021 in the 14th Five Year Plan of National Higher Education of Traditional Chinese Medicine/ ; }, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Arginase/drug effects/metabolism ; Astragalus Plant/*chemistry ; Bifidobacterium/drug effects/metabolism ; CD8-Positive T-Lymphocytes/*immunology ; Drug Combinations ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects/genetics/immunology/physiology ; Immune Tolerance ; Interleukin-10/metabolism ; Interleukin-1beta/blood ; Interleukin-6/blood ; Lactobacillus/drug effects ; Male ; Melanoma/*drug therapy/immunology/pathology ; Mice ; Mice, Inbred C57BL ; Myeloid-Derived Suppressor Cells/*drug effects/immunology/metabolism ; Polysaccharides/*pharmacology ; RNA, Ribosomal, 16S/analysis ; Transforming Growth Factor beta/drug effects/metabolism ; Tumor Microenvironment/immunology ; }, abstract = {Astragalus polysaccharides (APS), the main effective component of Astragalus membranaceus, can inhibit tumor growth, but the underlying mechanisms remain unclear. Previous studies have suggested that APS can regulate the gut microenvironment, including the gut microbiota and fecal metabolites. In this work, our results showed that APS could control tumor growth in melanoma-bearing mice. It could reduce the number of myeloid-derived suppressor cells (MDSC), as well as the expression of MDSC-related molecule Arg-1 and cytokines IL-10 and TGF-β, so that CD8+ T cells could kill tumor cells more effectively. However, while APS were administered with an antibiotic cocktail (ABX), MDSC could not be reduced, and the growth rate of tumors was accelerated. Consistent with the changes in MDSC, the serum levels of IL-6 and IL-1β were lowest in the APS group. Meanwhile, we found that fecal suspension from mice in the APS group could also reduce the number of MDSC in tumor tissues. These results revealed that APS regulated the immune function in tumor-bearing mice through remodeling the gut microbiota. Next, we focused on the results of 16S rRNA, which showed that APS significantly regulated most microorganisms, such as Bifidobacterium pseudolongum, Lactobacillus johnsonii and Lactobacillus. According to the Spearman analysis, the changes in abundance of these microorganisms were related to the increase of metabolites like glutamate and creatine, which could control tumor growth. The present study demonstrates that APS attenuate the immunosuppressive activity of MDSC in melanoma-bearing mice by remodeling the gut microbiota and fecal metabolites. Our findings reveal the therapeutic potential of APS to control tumor growth.}, }
@article {pmid34286501, year = {2021}, author = {de Belvis, AG and Fratini, A and Angioletti, C and Morsella, A and Ruggeri, R and Pepe, G and Ianiro, G and Settanni, C and Gasbarrini, A and Cammarota, G}, title = {How to define a quadruple aim framework to assess value in critical pathway of the patients with Clostridioides difficile infection.}, journal = {European review for medical and pharmacological sciences}, volume = {25}, number = {13}, pages = {4597-4610}, doi = {10.26355/eurrev_202107_26252}, pmid = {34286501}, issn = {2284-0729}, abstract = {OBJECTIVE: The study aims to define the set of Key Performance Indicators (KPIs) required to assess the Value delivered by managing patients with Clostridioides difficile infection through a Critical Pathway. We used the quadruple aim Value-Based approach, and we validated the set of KPIs with the Delphi method.<br><br>MATERIALS AND METHODS: The study focuses on patients on board a Critical Pathway on Clostridioides difficile Infection and targeted towards a Fecal Microbiota Transplantation (FMT). FMT has been used to successfully treat recurrent Clostridium difficile infection. A two-round e-Delphi survey collecting data was conducted in 2019-2020 to validate the Value-Based evaluation tool. The Value-Based criteria taken into account are Clinical Outcomes, Experience of Care, Per-capita cost, Physician's burnout.<br><br>RESULTS: The two rounds led to the validation of 50 items, and four primary clinical outcomes (Mortality rate, length of stay, readmission and complications related to the illness).<br><br>CONCLUSIONS: The evaluation tool included is validated in its totality and can provide a comprehensive overview of the Value created by the Critical pathway for patients with Clostridioides difficile. We can extend the approach illustrated in this study can also to evaluate other Critical pathways.}, }
@article {pmid34282272, year = {2021}, author = {Malard, F and Lavelle, A and Battipaglia, G and Gaugler, B and Dulery, R and Brissot, E and Mediavilla, C and Jegou, S and Rolhion, N and Ledraa, T and Mohty, R and Sokol, H and Mohty, M}, title = {Impact of gut fungal and bacterial communities on the outcome of allogeneic hematopoietic cell transplantation.}, journal = {Mucosal immunology}, volume = {14}, number = {5}, pages = {1127-1132}, pmid = {34282272}, issn = {1935-3456}, abstract = {Patients receiving allogeneic hematopoietic cell transplantation (alloHCT) were previously shown to display a bacterial gut dysbiosis; however, limited data are available regarding the role of fungal microbiota in these patients. We evaluated the bacterial and fungal composition of the fecal microbiota at day 0 of alloHCT. Higher bacterial diversity was associated with an improved overall survival (OS) and disease-free survival (DFS). While fungal diversity had no impact on patient outcomes, we observed that high versus low relative abundance of Candida albicans in alloHCT patients at day 0 was associated with a significantly lower OS, DFS and graft-versus-host-free, relapse-free survival (GRFS) (p = 0.0008, p = 0.0064 and p = 0.026, respectively). While these results are limited by low patient numbers and low fungal read counts in some samples, they suggest a potentially important role for C albicans in alloHCT.}, }
@article {pmid34281401, year = {2021}, author = {Chu, ND and Crothers, JW and Nguyen, LTT and Kearney, SM and Smith, MB and Kassam, Z and Collins, C and Xavier, R and Moses, PL and Alm, EJ}, title = {Dynamic Colonization of Microbes and Their Functions after Fecal Microbiota Transplantation for Inflammatory Bowel Disease.}, journal = {mBio}, volume = {12}, number = {4}, pages = {e0097521}, pmid = {34281401}, issn = {2150-7511}, abstract = {For fecal microbiota transplantation (FMT) to be successful in immune diseases like inflammatory bowel disease, it is assumed that therapeutic microbes and their beneficial functions and immune interactions must colonize a recipient patient and persist in sufficient quantity and for a sufficient period of time to produce a clinical benefit. Few studies, however, have comprehensively profiled the colonization and persistence of transferred microbes along with the transfer of their microbial functions and interactions with the host immune system. Using 16S, metagenomic, and immunoglobulin A (IgA) sequencing, we analyzed hundreds of longitudinal microbiome samples from a randomized controlled trial of 12 patients with ulcerative colitis who received fecal transplant or placebo for 12 weeks. We uncovered diverse competitive dynamics among donor and patient strains, showing that persistence of transferred microbes is far from static. Indeed, one patient experienced a dramatic loss of donor bacteria 10 weeks into the trial, coinciding with a bloom of pathogenic bacteria and worsening symptoms. We evaluated the transfer of microbial functions, including desired ones, such as butyrate production, and unintended ones, such as antibiotic resistance. By profiling bacteria coated with IgA, we identified bacteria associated with inflammation and found that microbial interactions with the host immune system can be transferred across people, which could play a role in gut microbiome therapeutics for immune-related diseases. Our findings shed light on the colonization dynamics of gut microbes and their functions in the context of FMT to treat a complex disease-information that may provide a foundation for developing more-targeted therapeutics. IMPORTANCE Fecal microbiota transplantation (FMT)-transferring fecal microbes from a healthy donor to a sick patient-has shown promise for gut diseases such as inflammatory bowel disease. Unlike pharmaceuticals, however, fecal transplants are complex mixtures of living organisms, which must then interact with the microbes and immune system of the recipient. We sought to understand these interactions by tracking the microbes of 12 inflammatory bowel disease patients who received fecal transplants for 12 weeks. We uncovered a range of dynamics. For example, one patient experienced successful transfer of donor bacteria, only to lose them after 10 weeks. We similarly evaluated transfer of microbial functions, including how they interacted with the recipient's immune system. Our findings shed light on the colonization dynamics of gut microbes, as well as their functions in the context of FMT-information that may provide a critical foundation for the development of more-targeted therapeutics.}, }
@article {pmid34276224, year = {2021}, author = {Yu, C and Zhu, X and Zheng, C and Luo, Y and Wang, F and Gao, Y and Wu, H and Sun, X and Kong, X}, title = {Methyl Diet Enhanced Sepsis-Induced Mortality Through Altering Gut Microbiota.}, journal = {Journal of inflammation research}, volume = {14}, number = {}, pages = {3107-3121}, pmid = {34276224}, issn = {1178-7031}, abstract = {Introduction: Mortality of sepsis is caused by an inappropriately amplified systemic inflammatory response and bacteremia. Methyl diet has been shown to associate with greater inflammation response in different diseases. This study aimed to determine whether dietary supplementation with methyl donors affects the inflammation response and mortality in sepsis and to investigate the underlying mechanisms.<br><br>Methods: Four-week-old male C57BL/6 mice were fed with a high-methyl diet (HMD) or a regulator diet (RD) till the experiment time. Mice septic model was induced by Cecal ligation and puncture (CLP), lipopolysaccharide (LPS), or E.coli. Inflammatory cytokine was analyzed by ELISA and qRT-PCR. Immune cell infiltration was evaluated by H&amp;E and IHC. The composition of gut microbiota was determined by 16S rRNA sequencing. The effect of gut microbiota on sepsis was further verified by fecal microbiome transplantation.<br><br>Results: Our results showed that the diet riches in methyl donors exacerbated mortality, organ injury, and circulating levels of inflammatory mediators in CLP-induced septic mice model, compared to the control diet group. However, no significant differences have been observed in the inflammatory responses in the LPS-induced septic model and macrophages activation between the two groups of mice. There was a higher bacterial burden in CLP-induced HMD mice suggested that methyl diet might modulate gut microbiota. Bacterial 16S rRNA sequencing results showed that the composition of gut microbiota was altered. The high methyl donor diet reduced the abundance of Akkermansia and Lachnospiraceae, which were associated with protective effects in sepsis, in the gut. Moreover, fecal microbiome transplantation experiment showed that the transfer of feces, which obtained from high methyl diet mice, aggravated the mortality and inflammation responses in recipient mice.<br><br>Discussion: Methyl diet enhanced CLP-induced septic mortality and inflammatory responses through altering the composition of gut microbiota. This result indicated that diet-based gut microbiota may be a new therapeutic strategy for sepsis patients.}, }
@article {pmid34275058, year = {2021}, author = {Feuerstadt, P and Aroniadis, OC and Svedlund, FL and Garcia, M and Stong, L and Boules, M and Khanna, S}, title = {Heterogeneity of Randomized Controlled Trials of Fecal Microbiota Transplantation in Recurrent Clostridioides difficile Infection.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {34275058}, issn = {1573-2568}, abstract = {INTRODUCTION: Clinical trials have demonstrated the efficacy of FMT for reduction in CDI recurrences (rCDI), but this treatment and its reporting in the literature has significant heterogeneity. Recent publications (e.g., Ramai et al. in Dig Dis Sci 2020. https://doi.org/10.1007/s10620-020-06185-7) present the clinical outcomes for different FMT methodologies. However, to understand, compare, and contextualize outcomes, this heterogeneity in methods and reporting must be understood.<br><br>METHODS: We performed a literature review of randomized controlled trials (RCTs) of FMT for rCDI to evaluate heterogeneity among trials. A methodical search between January 2010 and May 2019 of Medline, Embase, and Cochrane was conducted for studies investigating FMT in adults with rCDI. RCTs were evaluated for a variety of methodological and reporting criteria.<br><br>RESULTS: Eight RCTs were identified, wherein 14 different FMT preparations were considered (each with distinct protocols for processing, storage, administration, and dosing). Sample sizes were generally small, with only two studies performing FMT in more than 100 patients. Three studies used non-FMT controls (vancomycin), while the remaining compared FMT with differing routes of administration or formulations. Across the identified studies, there was no standardized manner for reporting the timing of the FMT procedure. All studies tracked adverse events; however, follow-up periods were limited.<br><br>CONCLUSIONS: Considerable variability exists among RCTs, with marked differences in study design, control groups, and outcome assessment. Lack of a standard-of-care control in many trials may impact reproducibility of FMT trial outcomes in patients with rCDI. Widespread use of FMT for rCDI is still investigational; therefore, these foundational studies provide opportunities to optimize future trials.}, }
@article {pmid34273490, year = {2021}, author = {Dong, S and Zhu, M and Wang, K and Zhao, X and Hu, L and Jing, W and Lu, H and Wang, S}, title = {Dihydromyricetin improves DSS-induced colitis in mice via modulation of fecal-bacteria-related bile acid metabolism.}, journal = {Pharmacological research}, volume = {171}, number = {}, pages = {105767}, doi = {10.1016/j.phrs.2021.105767}, pmid = {34273490}, issn = {1096-1186}, abstract = {Recent studies show that the nutraceutical supplement dihydromyricetin (DHM) can alleviate IBD in murine models by downregulating the inflammatory pathways. However, the molecular mechanistic link between the therapeutic efficiency of DHM, gut microbiota, and the metabolism of microbial BAs remains elusive. In this study, we explored the improvement of DHM on the dysregulated gut microbiota of mice with dextran sulfate sodium (DSS)-induced colitis. We found that DHM could markedly improve colitis symptoms, gut barrier disruption, and colonic inflammation in DSS-treated mice. In addition, bacterial 16S rDNA sequencing assay demonstrated that DHM could alleviate gut dysbiosis in mice with colitis. Furthermore, antibiotic-mediated depletion of the gut microflora and fecal microbiome transplantation (FMT) demonstrated that the therapeutic efficiency of DHM was closely associated with gut microbiota. BA-targeted metabolomics analysis revealed that DHM restored the metabolism of microbial BAs in the gastrointestinal tract during the development of colitis. DHM significantly enriched the proportion of the beneficial Lactobacillus and Akkermansia genera, which were correlated with increased gastrointestinal levels of unconjugated BAs involving chenodeoxycholic acid and lithocholic acid, enabling the BAs to activate specific receptors, such as FXR and TGR5, and maintaining intestinal integrity. Taken together, DHM could alleviate DSS-induced colitis in mice by restoring the dysregulated gut microbiota and BA metabolism, leading to improvements in intestinal barrier function and colonic inflammation. Increased microbiota-BAs-FXR/TGR5 signaling may be the potential targets of DHM in colitis. Therefore, our findings provide novel insights into the development of novel DHM-derived drugs for the management of IBD.}, }
@article {pmid34270674, year = {2021}, author = {Cappetto, CM}, title = {Correction NoticeErratum to: Successful use of early, repeat fecal microbiota transplantation for initial treatment of severe, refractory Clostridioides difficile colitis.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {}, number = {}, pages = {}, doi = {10.1093/ajhp/zxab273}, pmid = {34270674}, issn = {1535-2900}, }
@article {pmid34267748, year = {2021}, author = {Wu, J and Wang, S and Zheng, B and Qiu, X and Wang, H and Chen, L}, title = {Modulation of Gut Microbiota to Enhance Effect of Checkpoint Inhibitor Immunotherapy.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {669150}, pmid = {34267748}, issn = {1664-3224}, mesh = {Adaptive Immunity ; Animals ; Bacteria/*immunology ; Dysbiosis ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Host-Pathogen Interactions ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; Immunity, Innate ; *Immunotherapy ; Neoplasms/diet therapy/*drug therapy/immunology/microbiology ; Probiotics/therapeutic use ; Treatment Outcome ; Tumor Microenvironment/*immunology ; }, abstract = {Accumulating evidence demonstrated the crucial role of gut microbiota in many human diseases, including cancer. Checkpoint inhibitor therapy has emerged as a novel treatment and has been clinically accepted as a major therapeutic strategy for cancer. Gut microbiota is related to cancer and the effect of immune checkpoint inhibitors (ICIs), and supplement with specific bacterial species can restore or enhance the responses to the ICIs. Namely, specified bacteria can serve as the biomarkers for distinguishing the patient who will respond to ICIs and determine the effectiveness of ICIs, as well as predicting the efficacy of checkpoint inhibitor immunotherapy. Regardless of the significant findings, the relationship between gut microbiota and the effect of ICIs treatment needs a more thorough understanding to provide more effective therapeutic plans and reduce treatment complication. In this review, we summarized the role of gut microbiota played in immune system and cancer. We mainly focus on the relationship between gut microbiota and the checkpoint inhibitor immunotherapy.}, }
@article {pmid34267502, year = {2021}, author = {Wang, R and Chen, T and Wang, Q and Yuan, XM and Duan, ZL and Feng, ZY and Ding, Y and Bu, F and Shi, GP and Chen, YG}, title = {Total Flavone of Abelmoschus manihot Ameliorates Stress-Induced Microbial Alterations Drive Intestinal Barrier Injury in DSS Colitis.}, journal = {Drug design, development and therapy}, volume = {15}, number = {}, pages = {2999-3016}, pmid = {34267502}, issn = {1177-8881}, abstract = {Purpose: Total flavone of Abelmoschus manihot (TFA), the effective constituents extracted from Flos Abelmoschus Manihot, has been reported to inhibit inflammation. However, the effect of TFA on ulcerative colitis (UC) progression in patients with depression is unknown. The purpose of our research was to explore the anti-UC effects of TFA in the context of depression in mice with UC by regulating the gut microbiota to drive the intestinal barrier.<br><br>Methods: In this study, chronic stress (CS) and dextran sodium sulfate (DSS) were used to induce depression and UC, respectively, in C57BL/6J mice. Fecal microbiota transplantation (FMT) was used to evaluate how treating mice modeling UC and depression with TFA effected their gut microbiota.<br><br>Results: Our results showed that TFA effectively improved UC aggravated by CS. In addition, TFA treatment improved the depression-like phenotype, the disturbed gut microbiota, and the intestinal barrier function in CS mice. It is worth noting that FMT from the CS mice to the receptor group further aggravated the damage of the intestinal barrier and the disturbance of the gut microbiota in the recipient DSS mice, thus further aggravating UC, however, treatment of the intervention of TFA in the CS fecal microbiota transplant with TFA also played its therapeutic outcome.<br><br>Conclusion: Taken together, our results show that CS disrupts the gut microbiota, triggers intestinal barrier injury and aggravates DSS colitis, while TFA is a promising drug for the treatment of UC in patients with depression.}, }
@article {pmid34267042, year = {2021}, author = {Jacob, JS and Ahmed, A and Cholankeril, G}, title = {The impact of alteration in gut microbiome in the pathogenesis of nonalcoholic fatty liver disease.}, journal = {Current opinion in infectious diseases}, volume = {34}, number = {5}, pages = {477-482}, pmid = {34267042}, issn = {1473-6527}, abstract = {PURPOSE OF REVIEW: We have increasing evidence that alterations of the intestinal microbiome have a strong influence on human health. Previous work has demonstrated the association between changes in the microbiome and metabolic risk factors. One related area of interest is the relationship between dysbiosis and nonalcoholic fatty liver disease (NAFLD), as the global prevalence of NAFLD, and its resultant complications, increases.<br><br>RECENT FINDINGS: In this review, we summarize the hypothesized pathophysiology of dysbiosis-mediated progression of NAFLD, including promotion of an inflammatory intestinal environment, increased intestinal permeability, endogenous ethanol production, short-chain fatty acid production, secondary bile acid metabolism, and choline depletion. We also review potential therapeutic interventions of the microbiome to slow or prevent NAFLD progression, including antibiotics, probiotics, prebiotics, fecal microbiota transplant, and farnesoid × receptor agonism.<br><br>SUMMARY: Much of the evidence supporting dysbiosis-mediated NAFLD progression has been gathered in high-quality animal trials. There remains a need for additional observational and randomized controlled trials in humans to establish causality between the suspected factors and pathogenesis of NAFLD.}, }
@article {pmid34265528, year = {2021}, author = {Yang, J and Chen, W and Sun, Y and Liu, J and Zhang, W}, title = {Effects of cadmium on organ function, gut microbiota and its metabolomics profile in adolescent rats.}, journal = {Ecotoxicology and environmental safety}, volume = {222}, number = {}, pages = {112501}, doi = {10.1016/j.ecoenv.2021.112501}, pmid = {34265528}, issn = {1090-2414}, mesh = {Animals ; Cadmium/toxicity ; Feces ; Female ; *Gastrointestinal Microbiome ; Metabolomics ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Cadmium (Cd) exposure in adult animals can result in multi-organ damages and gut microbiota disturbance. However, Cd's consequences on health and gut microbiota during adolescence are obscure. In the present study, three-week-old SD rats were exposed to Cd at doses of 0, 0.25, 1, and 4 mg/kg body weight for eight weeks, and the changes of liver, kidney, and ovary function, as well as gut microbiota and its metabolomics profile, were analyzed. After transplantation of fecal bacteria from the 4 mg/kg Cd-treated group into age-matched rats (4 mg/kg-Cd recipients), the organ function and inflammatory reaction were evaluated. The results indicated that Cd perturbed gut microbiota composition, significantly decreased the abundance of Prevotella and Lachnoclostridium but increased Escherichia coli_Shigella. The fecal metabolome profile was altered and was closely correlated with some specific genera. These changes were accompanied by the inflammatory response, dyslipidemia, kidney dysfunction, and abnormal estrogen level. In 4 mg/kg-Cd recipients, the serum triglyceride (TG), lipopolysaccharide (LPS), and inflammatory cytokines were increased with the expressions of IL-1β, IL-6, TNF-α genes up-regulated in liver and kidney. Overall, this study demonstrated that Cd exposure during adolescence could cause disturbance of gut microbiota, dysfunction of liver, kidney, and ovary, which may be correlated with the activation of Cd-induced inflammatory response.}, }
@article {pmid34263258, year = {2021}, author = {Shin, JH and Hays, RA and Warren, CA}, title = {Hospitalized Older Patients with Clostridioides difficile Infection Refractory to Conventional Antibiotic Therapy Benefit from Fecal Microbiota Transplant.}, journal = {Advances in geriatric medicine and research}, volume = {3}, number = {2}, pages = {}, pmid = {34263258}, support = {K08 AG064151/AG/NIA NIH HHS/United States ; R01 AI145322/AI/NIAID NIH HHS/United States ; }, abstract = {Background: Options for Clostridioides difficile infection (CDI) refractory to conventional therapy are limited. Fecal microbiota transplant (FMT) is considered safe and effective treatment for recurrent CDI and could be a treatment option for refractory CDI. We investigated the efficacy and safety of FMT in hospitalized patients who were not responding to standard treatments for CDI.<br><br>Methods: Electronic medical records of patients who received FMT inpatient for refractory CDI were reviewed as part of quality improvement efforts to evaluate safety and efficacy of FMT in inpatient setting.<br><br>Results: Between July 2014 and December 2019, 9 patients (age 60-96) received FMT for CDI as inpatient for refractory or fulminant CDI. Most (7 of 9) of these patients had pseudomembranous colitis and underwent multiple FMTs (mean 2.15, range 1 to 3). Five patients had complete resolution and one patient had diarrhea that was C. difficile-negative. There was one recurrent CDI and two deaths, one of which may have been related to FMT or CDI. Compared to recurrent CDI at diagnosis, patients with refractory CDI had higher WBC and neutrophil counts, which decreased after FMT. The overall cure rate of FMT in refractory cases was 66.7%.<br><br>Conclusions: This study shows moderate efficacy of FMT for treatment of refractory CDI although multiple FMT treatment may need to be administered in the presence of pseudomembranous colitis. Inpatient FMT may be an alternative strategy for managing refractory CDI in this population of patients who may not have any effective medical treatment available.}, }
@article {pmid34262484, year = {2021}, author = {Song, W and Sun, LY and Zhu, ZJ and Wei, L and Qu, W and Zeng, ZG and Yang, YS}, title = {Characteristics of Gut Microbiota in Children With Biliary Atresia After Liver Transplantation.}, journal = {Frontiers in physiology}, volume = {12}, number = {}, pages = {704313}, pmid = {34262484}, issn = {1664-042X}, abstract = {Background and Aims: Biliary atresia (BA) is an idiopathic neonatal cholestasis and is the most common indication in pediatric liver transplantation (LT). Previous studies have suggested that the gut microbiota (GM) in BA is disordered. However, the effect of LT on gut dysbiosis in patients with BA has not yet been elucidated.<br><br>Methods: Patients with BA (n = 16) and healthy controls (n = 10) were recruited. In the early life of children with BA, Kasai surgery is a typical procedure for restoring bile flow. According to whether BA patients had previously undergone Kasai surgery, we divided the post-LT patients into the with-Kasai group (n = 8) and non-Kasai group (n = 8). Fecal samples were collected in both the BA and the control group; among BA patients, samples were obtained again 6 months after LT. A total of 40 fecal samples were collected, of which 16 were pre-LT, 14 were post-LT (8 were with-Kasai, 6 were non-Kasai), and 10 were from the control group. Metagenomic sequencing was performed to evaluate the GM.<br><br>Results: The Kruskal-Wallis test showed a statistically significant difference in the number of genes between the pre-LT and the control group, the pre-LT and the post-LT group (P < 0.05), but no statistical difference between the post-LT and the control group. Principal coordinate analysis also showed that the microbiome structure was similar between the post-LT and control group (P > 0.05). Analysis of the GM composition showed a significant decrease in Serratia, Enterobacter, Morganella, Skunalikevirus, and Phifllikevirus while short chain fatty acid (SCFA)-producing bacteria such as Roseburia, Blautia, Clostridium, Akkermansia, and Ruminococcus were increased after LT (linear discriminant analysis > 2, P < 0.05). However, they still did not reach the normal control level. Concerning functional profiles, lipopolysaccharide metabolism, multidrug resistance, polyamine biosynthesis, GABA biosynthesis, and EHEC/EPEC pathogenicity signature were more enriched in the post-LT group compared with the control group. Prior Kasai surgery had a specific influence on the postoperative GM.<br><br>Conclusion: LT partly improved the GM in patients with BA, which provided new insight into understanding the role of LT in BA.}, }
@article {pmid34261526, year = {2021}, author = {Cooke, NCA and Bala, A and Allard, JP and Hota, S and Poutanen, S and Taylor, VH}, title = {The safety and efficacy of fecal microbiota transplantation in a population with bipolar disorder during depressive episodes: study protocol for a pilot randomized controlled trial.}, journal = {Pilot and feasibility studies}, volume = {7}, number = {1}, pages = {142}, pmid = {34261526}, issn = {2055-5784}, support = {15T-009//Stanley Medical Research Institute/ ; }, abstract = {BACKGROUND: Bipolar disorder (BD) is a chronic, debilitating illness with significant medical morbidity, often secondary to current treatments, and a high recurrence rate. This burden of disease reflects limitations in the tolerability and efficacy of current treatments. There is a compelling body of evidence linking the gut microbiota to mental illness, and while microbial manipulation via probiotic use has been studied as a therapeutic in BD, targeted trials of fecal microbiota transplantation (FMT) have not been conducted in this population.<br><br>METHODS AND DESIGN: We describe a pilot randomized controlled trial of FMT in participants with BD depression to assess the feasibility, efficacy, safety, and tolerability of this intervention. Individuals between 18 and 65 years of age will be enrolled in the study if they meet diagnostic criteria for a major depressive episode of at least moderate severity in the context of a BD diagnosis and have not responded to treatment for BD. Participants will be randomized 1:1 to receive either screened and processed donor stool (allogenic FMT) or their own stool (autologous FMT) via colonoscopy and monitored for 24 weeks post intervention. Depressive and manic symptoms, treatment acceptability, and gastrointestinal and other side effects are assessed at baseline (prior to randomization) and weekly. Stool samples to assess microbiome composition are obtained at baseline and 3 and 6 months.<br><br>DISCUSSION: Currently, FMT represents a novel therapeutic option for treating BD depression. This protocol allows for the assessment of the feasibility, efficacy, acceptability, and safety of an intervention aimed at changing the microbiome in those with BD. Results from this pilot study will guide the development of larger trials of FMT for BD depression and may give more insight into how the gut microbiome are altered in those with BD depression.<br><br>TRIAL REGISTRATION: Clinical Trials Gov NCT03279224.}, }
@article {pmid34261379, year = {2021}, author = {Baunwall, SMD and Dahlerup, JF and Engberg, JH and Erikstrup, C and Helms, M and Juel, MA and Kjeldsen, J and Nielsen, HL and Nilsson, AC and Rode, AA and Vinter-Jensen, L and Hvas, CL}, title = {Danish national guideline for the treatment of Clostridioides difficile infection and use of faecal microbiota transplantation (FMT).}, journal = {Scandinavian journal of gastroenterology}, volume = {56}, number = {9}, pages = {1056-1077}, doi = {10.1080/00365521.2021.1922749}, pmid = {34261379}, issn = {1502-7708}, mesh = {Adult ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Denmark ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {Aim: This Danish national guideline describes the treatment of adult patients with Clostridioides (formerly Clostridium) difficile (CD) infection and the use of faecal microbiota transplantation (FMT). It suggests minimum standard for implementing an FMT service.Method: Four scientific societies appointed members for a working group which conducted a systematic literature review and agreed on the text and recommendations. All clinical recommendations were evalluated for evidence level and grade of recommendation.Results: In CD infection, the use of marketed and experimental antibiotics as well as microbiota-based therapies including FMT are described. An algorithm for evaluating treatment effect is suggested. The organisation of FMT, donor recruitment and screening, laboratory preparation, clinical application and follow-up are described.Conclusion: Updated evidence for the treatment of CD infection and the use of FMT is provided.}, }
@article {pmid34261137, year = {2021}, author = {Gu, X and Lu, Q and Zhang, C and Tang, Z and Chu, L}, title = {Clinical Application and Progress of Fecal Microbiota Transplantation in Liver Diseases: A Review.}, journal = {Seminars in liver disease}, volume = {41}, number = {4}, pages = {495-506}, pmid = {34261137}, issn = {1098-8971}, support = {National Natural Science Foundation of China//81904129/ ; College Student Innovation Funds Project for the Hebei University of Chinese Medicine//31800952/ ; College Student Innovation Funds Project for the Hebei University of Chinese Medicine//202014432203/ ; Fundamental Research Funds for the Southeast University//3218006405/ ; Fundamental Research Funds for the Southeast University//2242019s10024/ ; }, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Liver Cirrhosis ; *Microbiota ; }, abstract = {The human gut harbors a dense and highly diverse microbiota of approximately 1,000 bacterial species. The interaction between the host and gut bacteria strongly influences human health. Numerous evidence suggest that intestinal flora imbalance is closely associated with the development and treatment of liver diseases, including acute liver injury and chronic liver diseases (cirrhosis, autoimmune liver disease, and fatty liver). Therefore, regulating the gut microbiota is expected to be a new method for the adjuvant treatment of liver diseases. Fecal microbiota transplantation (FMT) is defined as the transplantation of gut microbiota from healthy donors to sick patients via the upper or lower gastrointestinal route to restore the normal intestinal balance. In this study, we briefly review the current research on the gut microbiota and its link to liver diseases and then summarize the evidence to elucidate the clinical application and development of FMT in liver disease treatment.}, }
@article {pmid34258417, year = {2021}, author = {Zhou, H and Sun, J and Yu, B and Liu, Z and Chen, H and He, J and Mao, X and Zheng, P and Yu, J and Luo, J and Luo, Y and Yan, H and Ge, L and Chen, D}, title = {Gut microbiota absence and transplantation affect growth and intestinal functions: An investigation in a germ-free pig model.}, journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)}, volume = {7}, number = {2}, pages = {295-304}, pmid = {34258417}, issn = {2405-6383}, abstract = {This study was conducted to investigate host-microbiota interactions and explore the effects of maternal gut microbiota transplantation on the growth and intestinal functions of newborns in a germ-free (GF) pig model. Twelve hysterectomy-derived GF Bama piglets were reared in 6 sterile isolators. Among them, 6 were considered as the GF group, and the other 6 were orally inoculated with healthy sow fecal suspension as fecal microbiota transplanted (FMT) group. Another 6 piglets from natural birth were regarded as the conventional (CV) group. The GF and FMT groups were hand-fed with Co60-γ-irradiated sterile milk powder, while the CV group was reared by lactating Bama sows. All groups were fed for 21 days. Then, all piglets and then were switched to sterile feed for another 21 days. Results showed that the growth performance, nutrient digestibility, and concentrations of short-chain fatty acids in the GF group decreased (P < 0.05). Meanwhile, the serum urea nitrogen concentration and digesta pH values in the GF group increased compared with those in the FMT and CV groups (P < 0.05). Compared with the CV group, the GF group demonstrated upregulation in the mRNA expression levels of intestinal barrier function-related genes in the small intestine (P < 0.05). In addition, the mRNA abundances of intestinal development and absorption-related genes in the small intestine and colon were higher in the GF group than in the CV and FMT groups (P < 0.05). The FMT group exhibited greater growth performance, lipase activity, and nutrient digestibility (P < 0.05), higher mRNA expression levels of intestinal development and barrier-related genes in the small intestine (P < 0.05), and lower mRNA abundances of pro-inflammatory factor in the colon and jejunum (P < 0.05) than the CV group. In conclusion, the absence of gut microbes impaired the growth and nutrient digestibility, and healthy sow gut microbiota transplantation increased the growth and nutrient digestibility and improved the intestinal development and barrier function of newborn piglets, indicating the importance of intestinal microbes for intestinal development and functions.}, }
@article {pmid34258416, year = {2021}, author = {Peng, J and Tang, Y and Huang, Y}, title = {Gut health: The results of microbial and mucosal immune interactions in pigs.}, journal = {Animal nutrition (Zhongguo xu mu shou yi xue hui)}, volume = {7}, number = {2}, pages = {282-294}, pmid = {34258416}, issn = {2405-6383}, abstract = {There are a large number of microorganisms in the porcine intestinal tract. These microorganisms and their metabolites contribute to intestinal mucosal immunity, which is of great importance to the health of the host. The host immune system can regulate the distribution and composition of intestinal microorganisms and regulate the homeostasis of intestinal flora by secreting a variety of immune effector factors, such as mucin, secretory immunoglobulin A (sIgA), regenerating islet-derived III (RegIII)γ, and defensin. Conversely, intestinal microorganisms can also promote the differentiation of immune cells including regulatory T cells (Treg) and Th17 cells through their specific components or metabolites. Studies have shown that imbalances in the intestinal flora can lead to bacterial translocation and compromised intestinal barrier function, affecting the health of the body. This review focuses on the composition of the pig intestinal flora and the characteristics of intestinal mucosal immunity, discusses the interaction mechanism between the flora and intestinal mucosal immunity, as well as the regulation through fecal microbiota transplantation (FMT), dietary nutritional composition, probiotics and prebiotics of pig intestinal microecology. Finally, this review provides insights into the relationship between intestinal microorganisms and the mucosal immune system.}, }
@article {pmid34257825, year = {2021}, author = {Gao, T and Wang, Z and Cao, J and Dong, Y and Chen, Y}, title = {Melatonin Ameliorates Corticosterone-Mediated Oxidative Stress-Induced Colitis in Sleep-Deprived Mice Involving Gut Microbiota.}, journal = {Oxidative medicine and cellular longevity}, volume = {2021}, number = {}, pages = {9981480}, pmid = {34257825}, issn = {1942-0994}, abstract = {Background: Inflammatory bowel disease (IBD) is a result of a complex interplay, making development of a specific treatment a challenging task. Corticosterone was considered a risk factor of stress relative enteritis. Our previous studies found that melatonin exerts an improvement effect in sleep deprivation (SD)- induced corticosterone overproduction and colitis. A present study further explored the mechanism whereby melatonin prevented corticosterone-mediated SD-induced colitis.<br><br>Methods: A 72-hour SD mouse model with or without melatonin supplementation and fecal microbiota transplantation (FMT) to investigate the core role of corticosterone in melatonin-mediated gut microbiota improving SD-induced colitis. Further, corticosterone-treated mice were assessed to the effect of melatonin on corticosterone-mediated gut microbiota dysbiosis-induced colitis. Meanwhile, an in vitro test studied modulatory mechanism of metabolite melatonin.<br><br>Results: SD caused an excessive corticosterone, gut microbiota disorder and colitis phenotype. Similarly, corticosterone-supplemented mice also exhibited gut microbiota dysbiosis and colitis, and the FMT from SD-mice to normal mice could restore the SD-like colitis, but no change in the corticosterone level, which suggested that corticosterone-mediated intestinal microbiota imbalance plays a central role in SD-induced colitis. Further, we demonstrated melatonin-mediated MT2 weakened GR feedback, suppressed oxidative stress, restored the intestinal microbiota and its metabolites homeostasis, and inactivated the STAT3/AP-1/NF-κB pathway-induced inflammatory response in vivo and in vitro.<br><br>Conclusions: We revealed that excessive corticosterone is a core risk factor for SD-induced colitis and provided a better understanding of the effects of melatonin, expected to be a personalized targeted therapy drug, on corticosterone-mediated gut microbiota inducing colitis.}, }
@article {pmid34252410, year = {2021}, author = {Ianiro, G and Gasbarrini, A and Cammarota, G}, title = {Evaluating donor microbiome before fecal microbiota transplantation.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2021.07.003}, pmid = {34252410}, issn = {1528-0012}, }
@article {pmid34252073, year = {2021}, author = {Verma, S and Dutta, SK and Firnberg, E and Phillips, L and Vinayek, R and Nair, PP}, title = {Identification and engraftment of new bacterial strains by shotgun metagenomic sequence analysis in patients with recurrent Clostridioides difficile infection before and after fecal microbiota transplantation and in healthy human subjects.}, journal = {PloS one}, volume = {16}, number = {7}, pages = {e0251590}, pmid = {34252073}, issn = {1932-6203}, mesh = {Adult ; Clostridioides/*physiology ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/genetics ; *Healthy Volunteers ; Humans ; Male ; *Metagenome ; Middle Aged ; Sequence Analysis ; }, abstract = {BACKGROUND: Recurrent Clostridioides diffícile infection (RCDI) is associated with major bacterial dysbiosis and colitis. Fecal microbiota transplantation (FMT) is a highly effective therapeutic modality for RCDI. While several studies have identified bacterial species associated with resolution of symptoms in patients, characterization of the fecal microbiome at the bacterial strain level in RCDI patients before and after FMT and healthy donors, has been lacking. The aim of this study was to examine the ability of bacterial strains from healthy donors to engraft in the gastrointestinal tract of patients with RCDI following FMT.<br><br>METHODS: Fecal samples were collected from 22 patients with RCDI before and after FMT and their corresponding healthy donors. Total DNA was extracted from each sample and analyzed by shotgun metagenomic sequencing. The Cosmos-ID analysis platform was used for taxonomic assignment of sequences and calculation of the relative abundance (RA) of bacterial species and strains. From these data, the total number of bacterial strains (BSI), Shannon diversity index, dysbiosis index (DI), and bacterial engraftment factor, were calculated for each strain.<br><br>FINDINGS: A marked reduction (p<0·0001) in the RA of total and specific bacterial strains, especially from phylum Firmicutes, was observed in RCDI patients prior to FMT. This change was associated with an increase in the DI (p<0·0001) and in pathobiont bacterial strains from phylum Proteobacteria, such as Escherichia coli O157:H7 and Klebsiella pneumoniae UCI 34. BSI was significantly lower in this group of patients as compared to healthy donors and correlated with the Shannon Index. (p<0·0001). Identification and engraftment of bacterial strains from healthy donors revealed a greater diversity and higher relative abundance of short-chain fatty acid (SCFA)-producing bacterial strains, including Lachnospiraceae bacterium 5_1_63FAA_u_t, Dorea formicigenerans ATCC 27755, Anaerostipes hadrusand others, in RCDI patients after FMT.<br><br>INTERPRETATION: These observations identify a group of SCFA-producing bacterial strains from healthy donors that engraft well in patients with RCDI following FMT and are associated with complete resolution of clinical symptoms and bacterial dysbiosis.}, }
@article {pmid34250000, year = {2021}, author = {Tokuhara, D}, title = {Role of the Gut Microbiota in Regulating Non-alcoholic Fatty Liver Disease in Children and Adolescents.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {700058}, pmid = {34250000}, issn = {2296-861X}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in children and adolescents. Although obesity is the leading cause of NAFLD, the etiologies of NAFLD are multifactorial (e.g., high-fat diet, a lack of exercise, gender, maternal obesity, the antibiotic use), and each of these factors leads to dysbiosis of the gut microbiota community. The gut microbiota is a key player in the development and regulation of the gut mucosal immune system as well as the regulation of both NAFLD and obesity. Dysbiosis of the gut microbiota promotes the development of NAFLD via alteration of gut-liver homeostasis, including disruption of the gut barrier, portal transport of bacterial endotoxin (lipopolysaccharide) to the liver, altered bile acid profiles, and decreased concentrations of short-chain fatty acids. In terms of prevention and treatment, conventional approaches (e.g., dietary and exercise interventions) against obesity and NAFLD have been confirmed to recover the dysbiosis and dysbiosis-mediated altered metabolism. In addition, increased understanding of the importance of gut microbiota-mediated homeostasis in the prevention of NAFLD suggests the potential effectiveness of gut microbiota-targeted preventive and therapeutic strategies (e.g., probiotics and fecal transplantation) against NAFLD in children and adolescents. This review comprehensively summarizes our current knowledge of the gut microbiota, focusing on its interaction with NAFLD and its potential therapeutic role in obese children and adolescents with this disorder.}, }
@article {pmid34249452, year = {2021}, author = {Matsukawa, H and Iida, N and Kitamura, K and Terashima, T and Seishima, J and Makino, I and Kannon, T and Hosomichi, K and Yamashita, T and Sakai, Y and Honda, M and Yamashita, T and Mizukoshi, E and Kaneko, S}, title = {Dysbiotic gut microbiota in pancreatic cancer patients form correlation networks with the oral microbiota and prognostic factors.}, journal = {American journal of cancer research}, volume = {11}, number = {6}, pages = {3163-3175}, pmid = {34249452}, issn = {2156-6976}, abstract = {Microbiota in the gut and oral cavities of pancreatic cancer (PC) patients differ from those of healthy persons, and bacteria in PC tissues are associated with patients' prognoses. However, the species-level relationship between a dysbiotic gut, oral and cancerous microbiota, and prognostic factors remains unknown. Whole-genome sequencing was performed with fecal DNA from 24 PC patients and 18 healthy persons (HD). Microbial taxonomies, metabolic pathways, and viral presence were determined. DNA was sequenced from saliva and PC tissues, and the association between the gut, oral, and cancer microbiota and prognostic factors in PC patients was analyzed. The PC microbiota were altered from those of the healthy microbiota in terms of microbial taxonomy, pathways and viral presence. Twenty-six species differed significantly between the PC and HD microbiota. Six fecal microbes, including Klebsiella pneumoniae, were associated with an increased hazard of death. In the co-occurrence network, microbes that were abundant in PC patients were plotted close together and formed clusters with prognosis-associated microbes, including K. pneumoniae. Multiple salivary microbes were present in the co-occurrence network. Microbacterium and Stenotrophomonas were detected in the PC tissues and formed a network with the fecal and salivary microbes. The dysbiotic gut microbiota in the PC patients formed a complex network with the oral and cancerous microbiota, and gut microbes abundant in the PC patients were closely linked with poor prognostic factors in the network.}, }
@article {pmid34246956, year = {2021}, author = {Deng, L and Shi, Y and Liu, P and Wu, S and Lv, Y and Xu, H and Chen, X}, title = {GeGen QinLian decoction alleviate influenza virus infectious pneumonia through intestinal flora.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {141}, number = {}, pages = {111896}, doi = {10.1016/j.biopha.2021.111896}, pmid = {34246956}, issn = {1950-6007}, abstract = {Influenza in humans is often accompanied by gastroenteritis-like symptoms. GeGen QinLian decoction (GQD), a Chinese herb formula, has been widely used to treat infectious diarrhea for centuries and has the effect of restoring intestinal flora. Studies have also reported that GQD were used to treat patients with influenza. However, whether regulating the intestinal flora is one of the ways GQD treats influenza has not been confirmed. In present research, we conducted a systemic pharmacological study, and the results showed that GQD may acts through multiple targets and pathways. In influenza-infected mice, GQD treatment reduced mortality and lung inflammation. Most importantly, the mortality and lung inflammation were also reduced in influenza-infected mice that have undergone fecal microbiota transplantation (FMT) from GQD (FMT-GQD) treated mice. GQD treatment or FMT-GQD treatment restores the intestinal flora, resulting in an increase in Akkermansia_muciniphila, Desulfovibrio_C21_c20 and Lactobacillus_salivarius, and a decrease in Escherichia_coli. FMT-GQD treatment inhibited the NOD/RIP2/NF-κB signaling pathway in the intestine and affected the expression of downstream related inflammatory cytokines in mesenteric lymph nodes (mLNs) and serum. In addition, FMT-GQD treatment showed systemic protection by restraining the inflammatory differentiation of CD4+ T cells. In conclusion, our study shows that GQD can affect systemic immunity, at least in part, through the intestinal flora, thereby protect the mice against influenza virus infectious pneumonia.}, }
@article {pmid34238831, year = {2021}, author = {Hourigan, SK and Nicholson, MR and Kahn, SA and Kellermayer, R}, title = {Updates and Challenges in Fecal Microbiota Transplantation for Clostridioides difficile Infection in Children.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {73}, number = {4}, pages = {430-432}, pmid = {34238831}, issn = {1536-4801}, support = {K23 AI156132/AI/NIAID NIH HHS/United States ; K23 HD099240/HD/NICHD NIH HHS/United States ; }, mesh = {Adult ; *COVID-19 ; Child ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; Recurrence ; SARS-CoV-2 ; Treatment Outcome ; }, abstract = {ABSTRACT: Fecal microbiota transplantation (FMT) is currently the most effective but loosely regulated therapy, for recurrent Clostridioides difficile infection (rCDI) in pediatrics. Over the last 2 years, there have been mounting challenges in the ability to provide FMT to pediatric patients. Firstly, an Food and Drug Administration (FDA) safety alert in 2019 reported transmission of a multidrug resistant organism from FMT donor to recipient resulting in the death of 1 patient. Secondly, the coronavirus disease 2019 (COVID-19) pandemic induced further safety and regulatory challenges. Biotherapeutics are promising and more readily regulated treatment options for rCDI, which may replace FMT in the near future for adults upon regulatory agency approvals. Such approvals, however, are expected to be significantly delayed for children, raising concerns for limited access to effective treatment for children with rCDI. In this commentary, we discuss the recent challenges and future directions of FMT and microbial therapeutics in children with rCDI.}, }
@article {pmid34238386, year = {2021}, author = {Bermudez-Martin, P and Becker, JAJ and Caramello, N and Fernandez, SP and Costa-Campos, R and Canaguier, J and Barbosa, S and Martinez-Gili, L and Myridakis, A and Dumas, ME and Bruneau, A and Cherbuy, C and Langella, P and Callebert, J and Launay, JM and Chabry, J and Barik, J and Le Merrer, J and Glaichenhaus, N and Davidovic, L}, title = {The microbial metabolite p-Cresol induces autistic-like behaviors in mice by remodeling the gut microbiota.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {157}, pmid = {34238386}, issn = {2049-2618}, support = {291840//EraNet NEURON/ ; MR/M50197/1/MRC_/Medical Research Council/United Kingdom ; ARD2020 Biomédicaments GPCRAb//Région Centre Val-de-Loire/ ; MabImprove//Labex/ ; MicrobiAutism//Agence Nationale de la Recherche (FR)/ ; }, mesh = {Animals ; *Autism Spectrum Disorder ; *Autistic Disorder/etiology ; Cresols ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Mice ; }, abstract = {BACKGROUND: Autism spectrum disorders (ASD) are associated with dysregulation of the microbiota-gut-brain axis, changes in microbiota composition as well as in the fecal, serum, and urine levels of microbial metabolites. Yet a causal relationship between dysregulation of the microbiota-gut-brain axis and ASD remains to be demonstrated. Here, we hypothesized that the microbial metabolite p-Cresol, which is more abundant in ASD patients compared to neurotypical individuals, could induce ASD-like behavior in mice.<br><br>RESULTS: Mice exposed to p-Cresol for 4 weeks in drinking water presented social behavior deficits, stereotypies, and perseverative behaviors, but no changes in anxiety, locomotion, or cognition. Abnormal social behavior induced by p-Cresol was associated with decreased activity of central dopamine neurons involved in the social reward circuit. Further, p-Cresol induced changes in microbiota composition and social behavior deficits could be transferred from p-Cresol-treated mice to control mice by fecal microbiota transplantation (FMT). We also showed that mice transplanted with the microbiota of p-Cresol-treated mice exhibited increased fecal p-Cresol excretion, compared to mice transplanted with the microbiota of control mice. In addition, we identified possible p-Cresol bacterial producers. Lastly, the microbiota of control mice rescued social interactions, dopamine neurons excitability, and fecal p-Cresol levels when transplanted to p-Cresol-treated mice.<br><br>CONCLUSIONS: The microbial metabolite p-Cresol induces selectively ASD core behavioral symptoms in mice. Social behavior deficits induced by p-Cresol are dependant on changes in microbiota composition. Our study paves the way for therapeutic interventions targeting the microbiota and p-Cresol production to treat patients with ASD. Video abstract.}, }
@article {pmid34238227, year = {2021}, author = {Crothers, JW and Chu, ND and Nguyen, LTT and Phillips, M and Collins, C and Fortner, K and Del Rio-Guerra, R and Lavoie, B and Callas, P and Velez, M and Cohn, A and Elliott, RJ and Wong, WF and Vo, E and Wilcox, R and Smith, M and Kassam, Z and Budd, R and Alm, EJ and Mawe, GM and Moses, PL}, title = {Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study.}, journal = {BMC gastroenterology}, volume = {21}, number = {1}, pages = {281}, pmid = {34238227}, issn = {1471-230X}, support = {R01 DK113800/DK/NIDDK NIH HHS/United States ; P30GM118228/NH/NIH HHS/United States ; DK113800/NH/NIH HHS/United States ; }, mesh = {*Colitis, Ulcerative/therapy ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Pilot Projects ; Prospective Studies ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a promising new strategy in the treatment of Inflammatory Bowel Disease, but long-term delivery systems are lacking. This randomized study was designed as a safety and feasibility study of long-term FMT in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT).<br><br>METHODS: Subjects were randomized 1:1 to receive FMT induction by colonoscopy, followed by 12 weeks of daily oral administration of frozen encapsulated cFMT or sham therpay. Subjects were followed for 36 weeks and longitudenal clinical assessments included multiple subjective and objective markers of disease severity. Ribosomal 16S bacterial sequencing was used to assess donor-induced changes in the gut microbiota. Changes in T regulatory (Treg) and mucosal associated invariant T (MAIT) cell populations were evaluated by flow cytometry as an exploratory endpoint.<br><br>RESULTS: Twelve subjects with active UC were randomized: 6 subjects completed the full 12-week course of FMT plus cFMT, and 6 subjects received sham treatment by colonic installation and longitudinal oral placebo capules. Chronic administration of cFMT was found to be safe and well-tolerated but home storage concerns exist. Protocol adherence was high, and none of the study subjects experienced FMT-associated treatment emergent adverse events. Two subjects that received cFMT achieved clinical remission versus none in the placebo group (95% CI = 0.38-infinity, p = 0.45). cFMT was associated with sustained donor-induced shifts in fecal microbial composition. Changes in MAIT cell cytokine production were observed in cFMT recipients and correlated with treatment response.<br><br>CONCLUSION: These pilot data suggest that daily encapsulated cFMT may extend the durability of index FMT-induced changes in gut bacterial community structure and that an association between MAIT cell cytokine production and clinical response to FMT may exist in UC populations. Oral frozen encapsulated cFMT is a promising FMT delivery system and may be preferred for longterm treatment strategies in UC and other chronic diseases but further evaluations will have to address home storage concerns. Larger trials should be done to explore the benefits of cFMT and to determine its long-term impacts on the colonic microbiome.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov (NCT02390726). Registered 17 March 2015, https://clinicaltrials.gov/ct2/show/NCT02390726?term=NCT02390726&amp;draw=2&amp;rank=1 .}, }
@article {pmid34237681, year = {2021}, author = {Segal, A and Zlotnik, Y and Moyal-Atias, K and Abuhasira, R and Ifergane, G}, title = {Fecal microbiota transplant as a potential treatment for Parkinson's disease - A case series.}, journal = {Clinical neurology and neurosurgery}, volume = {207}, number = {}, pages = {106791}, doi = {10.1016/j.clineuro.2021.106791}, pmid = {34237681}, issn = {1872-6968}, abstract = {OBJECTIVE: We aimed to determine whether fecal microbiota transplant (FMT) is safe and possibly efficacious in treating constipation, motor, and non-motor symptoms in Parkinson's disease (PD) patients.<br><br>METHODS: Patients with PD, constipation and an indication for screening colonoscopy were treated with FMT. The study was conducted from December 2017 to November 2019, and clinical outcomes assessing motor, non-motor and constipation symptoms were compared at baseline (week 0) and at 2, 4, 8, 12, 16, 20, and 24 weeks after the FMT.<br><br>RESULTS: Six patients (3 men, age range 47-73, median age 52) were treated with FMT. Four weeks following the FMT, motor, non-motor and constipation scores were improved in 5 of 6 patients. At week 24, compared to before the FMT, the changes in motor scores ranged from - 13-7 points, in non-motor scores from - 2 to - 45 points, and in constipation scores from - 12-1 point. One patient had a serious adverse event requiring admission for observation only, and no adverse events were observed in all other patients.<br><br>CONCLUSIONS: In this preliminary uncontrolled case series of 6 PD patients, a treatment with donor FMT infused via colonoscopy, was safe and resulted in improvement of PD motor and non-motor symptoms, including constipation, at 6 months. Further research is needed to assess longer-term maintenance of efficacy and safety, including in large scale randomized controlled trials.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov - NCT03876327.}, }
@article {pmid34236740, year = {2021}, author = {El-Salhy, M and Hausken, T and Hatlebakk, JG}, title = {Current status of fecal microbiota transplantation for irritable bowel syndrome.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {33}, number = {11}, pages = {e14157}, doi = {10.1111/nmo.14157}, pmid = {34236740}, issn = {1365-2982}, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) is a common gastrointestinal functional disorder. Although IBS is a benign condition, it reduces the quality of life considerably. While there is currently no effective treatment for this disorder, fecal microbiota transplantation (FMT) seems to be promising.<br><br>PURPOSE: The aim of this review was to analysis possible factors affecting the success or failure of the randomized controlled trials (RCTs) of FMT for IBS and highlighting the gaps in our knowledge that need to be filled and of sketching a possible model for successful FMT in IBS patients.<br><br>METHODS: A systematic search was conducted of literature published in English from January 2015 to December 2020 using the keywords: fecal microbiota transplantation, randomized trials, and IBS.<br><br>KEY RESULTS: Seven randomized controlled trials (RCTs) on the efficacy of FMT for IBS were found in the literature. Four of the seven RCTs found various positive effects, while the other three did not find any effect.<br><br>CONCLUSIONS AND INFERENCES: The efficacy of FMT for IBS appears to be donor-dependent. The effective (super) donor would need to have a favorable microbiota signature, and 11 clinical criteria that are known to be associated with a favorable microbiota have been suggested for selecting FMT donors for IBS. Comparing the microbiota of the effective donors with those of healthy subjects would reveal the favorable microbiota signature required for a super-donor. However, the studies reviewed were not designed to compare efficacy of different donor types. The dose of the fecal transplant is also an important factor influencing the outcome of FMT for IBS. However, further studies designed to test the effect of fecal transplant dose are needed to answer this question. Administering the fecal transplant to either the small or large intestine seems to be effective, but the optimal route of administration remains to be determined. Moreover, whether single or repeated FMT is more effective is also still unclear. A 1-year follow-up of IBS patients who received FMT showed that adverse events of abdominal pain, diarrhea, and constipation were both mild and self-limiting.}, }
@article {pmid34232990, year = {2021}, author = {Li, Y and Honda, K}, title = {Toward the development of defined microbial therapeutics.}, journal = {International immunology}, volume = {33}, number = {12}, pages = {761-766}, doi = {10.1093/intimm/dxab038}, pmid = {34232990}, issn = {1460-2377}, support = {JP20gm0010003//Japan Agency for Medical Research and Development/ ; 20H05627//Japan Society for the Promotion of Science/ ; //Cabinet Office of the Government of Japan/ ; //Naito Foundation/ ; //Takeda Science Foundation/ ; //RIKEN Special Postdoctoral Researcher/ ; }, abstract = {The collection of micro-organisms living in the mammalian gastrointestinal tract, termed the gut microbiota, has been shown to have profound impacts on host health and increasingly is regarded as a viable therapeutic target. Clinical studies of fecal microbiota transplantation have demonstrated potential efficacy of microbiota-based therapies for diseases including Clostridioides difficile infections, inflammatory bowel disease, graft-versus-host disease and cancer. However, the lack of understanding of the active ingredients and potential risks of such therapies pose challenges for clinical application. Meanwhile, efforts are being made to identify effector microbes directly associated with a given phenotype, to establish causality and to devise well-characterized microbial therapeutics for clinical use. Strategies based on defined microbial components will likely enhance the potential of microbiota-targeted therapies.}, }
@article {pmid34232137, year = {2021}, author = {Kociolek, LK and Crews, JD and Schwenk, HT}, title = {Recent advances in Clostridioides difficile infection epidemiology, diagnosis and treatment in children.}, journal = {Current opinion in infectious diseases}, volume = {34}, number = {5}, pages = {527-532}, doi = {10.1097/QCO.0000000000000753}, pmid = {34232137}, issn = {1473-6527}, abstract = {PURPOSE OF REVIEW: The US Centers for Disease Control and Prevention (CDC) classified Clostridioides difficile as an 'urgent' public health threat that requires 'urgent and aggressive action'. This call to action has led to new discoveries that have advanced C. difficile infection (CDI) epidemiology, diagnosis and treatment, albeit predominantly in adults. In 2017, the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America published clinical practice guidelines for both adults and children. At that time, recommendations in children were generally limited to relatively low-quality evidence.<br><br>RECENT FINDINGS: Since publication of this guidance, there have been many advancements in the understanding of CDI in children. These include better understanding of healthcare settings as uncommon sources of C. difficile acquisition in children; risk factors for recurrent and community-associated CDI; performance of diagnostic tests in children and strategies for optimizing their use; and a more rigorous evidence base for CDI treatment in children, including the first-ever randomized controlled trial of CDI treatment in children and the largest study of fecal microbiota transplantation in children.<br><br>SUMMARY: This review highlights the most recent salient advancements in paediatric CDI knowledge and practice that supplement published clinical guidance provided prior to these advancements.}, }
@article {pmid34226737, year = {2021}, author = {Mocanu, V and Zhang, Z and Deehan, EC and Kao, DH and Hotte, N and Karmali, S and Birch, DW and Samarasinghe, KK and Walter, J and Madsen, KL}, title = {Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial.}, journal = {Nature medicine}, volume = {27}, number = {7}, pages = {1272-1279}, pmid = {34226737}, issn = {1546-170X}, support = {//CIHR/Canada ; }, mesh = {Dietary Fiber/*therapeutic use ; Dietary Supplements ; Double-Blind Method ; Fecal Microbiota Transplantation/*methods ; Female ; Fermentation/physiology ; Gastrointestinal Microbiome/physiology ; Humans ; Insulin Resistance/*physiology ; Male ; Metabolic Syndrome/*therapy ; Middle Aged ; Obesity, Morbid/*therapy ; Proof of Concept Study ; }, abstract = {Fecal microbial transplantation (FMT) from lean donors to patients with obesity has been associated with metabolic benefits, yet results so far have been inconsistent. In this study, we tested the application of daily fiber supplementation as an adjunct to FMT therapy to modulate cardiometabolic outcomes. We performed a double-blind randomized trial in patients with severe obesity and metabolic syndrome receiving oral FMT, to test high-fermentable (HF) and low-fermentable (LF) fiber supplements (NCT03477916). Seventy participants were randomized to the FMT-HF (n = 17), FMT-LF (n = 17), HF (n = 17) and LF (n = 19) groups. The primary outcome was the assessment of change in insulin sensitivity from baseline to 6 weeks using the homeostatic model assessment (HOMA2-IR/IS). After 6 weeks, only patients in the FMT-LF group had significant improvements in HOMA2-IR (3.16 ± 3.01 at 6 weeks versus 3.77 ± 3.57 at baseline; P = 0.02). No difference in HOMA2-IR was observed over this period for those in the FMT-HF group (3.25 ± 1.70 at 6 weeks versus 3.17 ± 1.72 at baseline; P = 0.8), the HF group (3.49 ± 1.43 at 6 weeks versus 3.26 ± 1.33 at baseline; P = 0.8) or the LF group (3.76 ± 2.01 at 6 weeks versus 3.56 ± 1.81 at baseline; P = 0.8). Interventions were safe and well-tolerated with no treatment-attributed serious adverse events. We provide proof of concept for the use of a single-dose oral FMT combined with daily low-fermentable fiber supplementation to improve insulin sensitivity in patients with severe obesity and metabolic syndrome.}, }
@article {pmid34226711, year = {2021}, author = {Montassier, E and Valdés-Mas, R and Batard, E and Zmora, N and Dori-Bachash, M and Suez, J and Elinav, E}, title = {Probiotics impact the antibiotic resistance gene reservoir along the human GI tract in a person-specific and antibiotic-dependent manner.}, journal = {Nature microbiology}, volume = {6}, number = {8}, pages = {1043-1054}, pmid = {34226711}, issn = {2058-5276}, support = {/WT_/Wellcome Trust/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adult ; Anti-Bacterial Agents/*administration &amp; dosage ; Bacteria/classification/*drug effects/*genetics/isolation &amp; purification ; Bacterial Proteins/*genetics/metabolism ; Cohort Studies ; *Drug Resistance, Bacterial ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Gastrointestinal Tract/microbiology ; Humans ; Male ; Metagenome/drug effects ; Middle Aged ; Probiotics/*administration &amp; dosage ; Young Adult ; }, abstract = {Antimicrobial resistance poses a substantial threat to human health. The gut microbiome is considered a reservoir for potential spread of resistance genes from commensals to pathogens, termed the gut resistome. The impact of probiotics, commonly consumed by many in health or in conjunction with the administration of antibiotics, on the gut resistome is elusive. Reanalysis of gut metagenomes from healthy antibiotics-naïve humans supplemented with an 11-probiotic-strain preparation, allowing direct assessment of the gut resistome in situ along the gastrointestinal (GI) tract, demonstrated that probiotics reduce the number of antibiotic resistance genes exclusively in the gut of colonization-permissive individuals. In mice and in a separate cohort of humans, a course of antibiotics resulted in expansion of the lower GI tract resistome, which was mitigated by autologous faecal microbiome transplantation or during spontaneous recovery. In contrast, probiotics further exacerbated resistome expansion in the GI mucosa by supporting the bloom of strains carrying vancomycin resistance genes but not resistance genes encoded by the probiotic strains. Importantly, the aforementioned effects were not reflected in stool samples, highlighting the importance of direct sampling to analyse the effect of probiotics and antibiotics on the gut resistome. Analysing antibiotic resistance gene content in additional published clinical trials with probiotics further highlighted the importance of person-specific metagenomics-based profiling of the gut resistome using direct sampling. Collectively, these findings suggest opposing person-specific and antibiotic-dependent effects of probiotics on the resistome, whose contribution to the spread of antimicrobial resistance genes along the human GI tract merit further studies.}, }
@article {pmid34225483, year = {2021}, author = {Matsui, M and Fukunishi, S and Nakano, T and Ueno, T and Higuchi, K and Asai, A}, title = {Ileal Bile Acid Transporter Inhibitor Improves Hepatic Steatosis by Ameliorating Gut Microbiota Dysbiosis in NAFLD Model Mice.}, journal = {mBio}, volume = {12}, number = {4}, pages = {e0115521}, pmid = {34225483}, issn = {2150-7511}, abstract = {Nonalcoholic fatty liver disease (NAFLD), characterized by excessive fat deposition in the liver unrelated to alcohol consumption, is highly prevalent worldwide. However, effective therapeutic agents approved for NAFLD treatment are lacking. An ileal bile acid transporter inhibitor (IBATi), which represents a new mode of treatment of chronic idiopathic constipation, leads to increased delivery of bile acids to the colon. We investigated the effect of IBATi against NAFLD through modification of the gut microbiota in mice. IBATi treatment significantly suppressed body weight gain, liver dysfunction, and serum low-density lipoprotein levels and significantly decreased NAFLD activity scores in high-fat diet (HFD) mice. Treatment with IBATi ameliorated the decreased hepatic cholesterol 7-a-monooxygenase (Cyp7a1) and increased ileal fibroblast growth factor 15 (Fgf15) mRNA expression in HFD mice. Further, IBATi treatment changed the α-diversity in the gut microbiota reduced by HFD, which was analyzed in feces using 16S rRNA sequencing. To establish the mechanism underlying improvement in NAFLD induced by IBATi, we recolonized antibiotic solution-treated mice by fecal microbiome transplantation (FMT) using stool from HFD or HFD plus IBATi mice. This is the first report that fecally transplanted gut microbiota from HFD plus IBATi mice prevented hepatic steatosis caused by HFD. In conclusion, IBATi improved hepatic steatosis by ameliorating gut microbiota dysbiosis in NAFLD model mice, suggesting a potential therapeutic agent for NAFLD treatment. IMPORTANCE NAFLD is an increasingly recognized condition that may progress to liver cirrhosis and hepatocellular carcinoma, and community surveys have assessed that the prevalence is 14 to 32% worldwide. The first line of treatment for NAFLD is lifestyle modification to achieve weight reduction, particularly through diet and exercise. However, weight reduction is difficult to achieve and maintain, and pharmacological agents approved for the treatment of NAFLD are lacking. This study investigated the influence of the gut microbiota and the effect of an IBATi on NAFLD using a murine model. Treatment with IBATi significantly improved NAFLD in HFD mice. Further, fecal microbiome transplantation using stool from HFD plus IBATi mice prevented hepatic steatosis caused by HFD. Our study makes a significant contribution to the literature because the study findings suggest a potential treatment strategy for NAFLD patients by ameliorating gut microbiota dysbiosis.}, }
@article {pmid34222037, year = {2021}, author = {Tan, R and Dong, H and Chen, Z and Jin, M and Yin, J and Li, H and Shi, D and Shao, Y and Wang, H and Chen, T and Yang, D and Li, J}, title = {Intestinal Microbiota Mediates High-Fructose and High-Fat Diets to Induce Chronic Intestinal Inflammation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {654074}, pmid = {34222037}, issn = {2235-2988}, mesh = {Animals ; *Diet, High-Fat/adverse effects ; Firmicutes ; Fructose ; *Gastrointestinal Microbiome ; Inflammation ; Mice ; Mice, Inbred C57BL ; }, abstract = {An unhealthy diet has been linked to increased incidence of chronic diseases. To investigate the relationship between diet and intestinal inflammation, mice in two experimental groups were fed on a high-fat diet or high-fructose diet, respectively. The result showed that the defecation volume of the experimental groups was significantly reduced compared with that of the control group, and the levels of pro-inflammatory cytokines (interleukin (IL)-1β and IL-6) and IgG in serum were increased significantly. In addition, inflammatory cell infiltration was observed in intestinal tissue, indicating that a high-fructose or high-fat diet can lead to constipation and inflammation. Further analysis showed that the microbial composition of the experimental groups changed significantly, including a decrease of the Bacteroidetes/Firmicutes ratio and increased levels of Bacteroides, Akkermansia, Lactobacillus, and Ruminococcus, which might be associated with inflammation. The results of pro-inflammatory metabolites analysis showed that the levels of arachidonic acid, stearic acid, and indoxylsulfuric acid were significantly increased in the experimental groups, which were related significantly to Bacteroides, Enterococcus, and Akkermansia. Meanwhile, the content of 5-hydroxytryptamine (5-HT) was significantly decreased, which might cause constipation by reducing intestinal peristalsis. Moreover, transplantation of fecal bacteria from inflammatory mice caused constipation and inflammation in normal mice, which could be relieved by feeding a normal diet. The results of the present study indicated that changes in intestinal microbiota and microbial metabolites may underlie chronic intestinal inflammation and constipation caused by high-fructose and high-fat diets.}, }
@article {pmid34221998, year = {2021}, author = {Liu, Y and Yang, C and Zhang, Z and Jiang, H}, title = {Gut Microbiota Dysbiosis Accelerates Prostate Cancer Progression Through Increased LPCAT1 Expression and Enhanced DNA Repair Pathways.}, journal = {Frontiers in oncology}, volume = {11}, number = {}, pages = {679712}, pmid = {34221998}, issn = {2234-943X}, abstract = {Gut microbiota dysbiosis is related to cancer development and progression. Our previous study showed that Ruminococcus was more abundant in CRPC (Castration-resistant prostate cancer) than HSPC (Hormone-sensitive prostate cancer) individuals. Here, we determined the potential mechanism of microbiota dysbiosis in prostate cancer (PCa) progression. Metagenomics was used to verify the gut microbial discrepancies between CRPC and HSPC individuals. Fecal microbiota transplantation (FMT) was performed by transferring the fecal suspension of CRPC or HSPC individuals to TRAMP mice. Afterwards, the mice's prostate histopathology and gut microbiota composition were determined. Since Ruminococcus was demonstrated to correlate with phospholipid metabolism, we used lipidomics to examine the mice's fecal lipid profiles. The expression of LPCAT1 the key enzyme for phospholipid remodeling in mice prostate was also examined. Meanwhile, both microbial functions prediction and LPCAT1 GSEA analysis (Gene Set Enrichment Analysis) indicated DNA repair pathways, we further determined the expressions of RAD51 and DNA-PKcs in mice prostate. The results showed that gut Ruminococcus was significantly more abundant in CRPC individuals. FMT using CRPC feces accelerated mice's PCa progression and increased their gut Ruminococcus abundance. Majority of fecal lipids including lysophosphatidylcholine and phosphatidylcholine were upregulated in CRPC FMT treated mice, accompanied with enhanced expressions of LPCAT1, RAD51, and DNA-PKcs in mice prostate. We reported an abundant colonization of Ruminococcus in the gut of CRPC individuals and mice receiving their fecal suspensions, and revealed the promotive capability of Ruminococcus in PCa progression via upregulating LPCAT1 and DNA repair protein expressions. The bacterium and its downstream pathways may become the targets of therapies for PCa in the future.}, }
@article {pmid34220825, year = {2021}, author = {Zhao, Y and Li, X and Zhou, Y and Gao, J and Jiao, Y and Zhu, B and Wu, D and Qi, X}, title = {Safety and Efficacy of Fecal Microbiota Transplantation for Grade IV Steroid Refractory GI-GvHD Patients: Interim Results From FMT2017002 Trial.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {678476}, pmid = {34220825}, issn = {1664-3224}, mesh = {Adolescent ; Adult ; Clinical Decision-Making ; Disease Management ; Disease Susceptibility ; Drug Resistance ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Gastrointestinal Diseases/*diagnosis/etiology/*therapy ; Graft vs Host Disease/*diagnosis/etiology/*therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunosuppressive Agents/therapeutic use ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Severity of Illness Index ; Steroids/therapeutic use ; Treatment Outcome ; Young Adult ; }, abstract = {Gastrointestinal (GI) tract graft-versus-host disease (GvHD) is a major cause of post-allo-HSCT (hematopoietic stem cell transplantation) morbidity and mortality. Patients with steroid-refractory GI-GvHD have a poor prognosis and limited therapeutic options. FMT2017002 trial (#NCT03148743) was a non-randomized, open-label, phase I/II clinical study of FMT for treating patients with grade IV steroid-refractory GI-GvHD. A total of 55 patients with steroid-refractory GI-GvHD were enrolled in this study. Forty-one patients with grade IV steroid-refractory GI-GvHD were included in the final statistical analysis. Of them, 23 patients and 18 patients were assigned to the FMT group and the control group, respectively. On days 14 and 21 after FMT, clinical remission was significantly greater in the FMT group than in the control group. Within a follow-up period of 90 days, the FMT group showed a better overall survival (OS). At the end of the study, the median survival time was >539 days in the FMT group and 107 days in the control group (HR=3.51; 95% CI, 1.21-10.17; p=0.021). Both the event-free survival time (EFS) (HR=2.3, 95% CI, 0.99-5.4; p=0.08) and OS (HR=4.4, 95% CI, 1.5-13.04; p=0.008) were higher in the FMT group during the follow-up period. Overall, the mortality rate was lower in the FMT group (HR=3.97; 95% CI, 1.34-11.75; p=0.013). No differences in the occurrence of any other side effects were observed. Our data suggest that the diversity of the intestinal microbiota could be affected by allo-HSCT. Although its effectiveness and safety need further evaluation, FMT may serve as a therapeutic option for grade IV steroid-refractory GI-GvHD.<br><br>Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT03148743].}, }
@article {pmid34219519, year = {2021}, author = {Gallop, A and Weagley, J and Paracha, SU and Grossberg, G}, title = {The Role of The Gut Microbiome in Parkinson's Disease.}, journal = {Journal of geriatric psychiatry and neurology}, volume = {34}, number = {4}, pages = {253-262}, doi = {10.1177/08919887211018268}, pmid = {34219519}, issn = {0891-9887}, mesh = {Disease Progression ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Inflammation ; *Parkinson Disease ; }, abstract = {The gut microbiota is known to play a role in various disease states through inflammatory, immune and endocrinologic response. Parkinson's Disease is of particular interest as gastrointestinal involvement is one of the earlier features seen in this disease. This paper examines the relationship between gut microbiota and Parkinson's Disease, which has a growing body of literature. Inflammation caused by gut dysbiosis is thought to increase a-synuclein aggregation and worsen motor and neurologic symptoms of Parkinson's disease. We discuss potential treatment and supplementation to modify the microbiota. Some of these treatments require further research before recommendations can be made, such as cord blood transplant, antibiotic use, immunomodulation and fecal microbiota transplant. Other interventions, such as increasing dietary fiber, polyphenol and fermented food intake, can be made with few risks and may have some benefit for symptom relief and speed of disease progression.}, }
@article {pmid34213510, year = {2021}, author = {Dhere, T and Tager, D and Kilakkathi, SP and Woodworth, MH and Kraft, CS}, title = {Earlier use of fecal transplant administration during hospitalization for Clostridioides difficile infectionmay improve outcome.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {33}, number = {8}, pages = {1132-1133}, doi = {10.1097/MEG.0000000000002159}, pmid = {34213510}, issn = {1473-5687}, mesh = {Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/therapy ; Fecal Microbiota Transplantation ; Hospitalization ; Humans ; }, }
@article {pmid34212214, year = {2021}, author = {Gupta, M and Krishan, P and Kaur, A and Arora, S and Trehanpati, N and Singh, TG and Bedi, O}, title = {Mechanistic and physiological approaches of fecal microbiota transplantation in the management of NAFLD.}, journal = {Inflammation research : official journal of the European Histamine Research Society ... [et al.]}, volume = {70}, number = {7}, pages = {765-776}, pmid = {34212214}, issn = {1420-908X}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a multifaceted disease allied with various metabolic disorders, obesity and dysbiosis. Gut microbiota plays an influential role in the pathogenesis of NAFLD and other metabolic disorders. However, recent scientific upsurge emphasizes on the utility of beneficial gut microbiota and bacteriotherapy in the management of NAFLD. Fecal microbiota transplantation (FMT) is the contemporary therapeutic approach with state-of-the-art methods for the treatment of NAFLD. Other potential therapies include probiotics and prebiotics supplements which are based on alteration of gut microbes to treat NAFLD. In this review, our major focus is on the pathological association of gut microbiota with progression of NAFLD, historical aspects and recent advances in FMT with possible intervention to combat NAFLD and its associated metabolic dysfunctions.}, }
@article {pmid34209573, year = {2021}, author = {Gopalakrishnan, V and Dozier, EA and Glover, MS and Novick, S and Ford, M and Morehouse, C and Warrener, P and Caceres, C and Hess, S and Sellman, BR and Cohen, TS}, title = {Engraftment of Bacteria after Fecal Microbiota Transplantation Is Dependent on Both Frequency of Dosing and Duration of Preparative Antibiotic Regimen.}, journal = {Microorganisms}, volume = {9}, number = {7}, pages = {}, pmid = {34209573}, issn = {2076-2607}, abstract = {The gut microbiota has emerged as a key mediator of human physiology, and germ-free mice have been essential in demonstrating a role for the microbiome in disease. Preclinical models using conventional mice offer the advantage of working with a mature immune system. However, optimal protocols for fecal microbiota transplant (FMT) engraftment in conventional mice are yet to be established. Conventional BALB/c mice were randomized to receive 3-day (3d) or 3-week (3w) antibiotic (ABX) regimen in their drinking water followed by 1 or 5-daily FMTs from a human donor. Fecal samples were collected longitudinally and characterized using 16S ribosomal RNA (rRNA) sequencing. Semi-targeted metabolomic profiling of fecal samples was also done with liquid chromatography-mass spectrometry (LC-MS). Lastly, we sought to confirm our findings in BKS mice. Recovery of baseline diversity scores were greatest in the 3d groups, driven by re-emergence of mouse commensal microbiota, whereas the most resemblance to donor microbiota was seen in the 3w + 5-FMT group. Amplicon sequence variants (ASVs) that were linked to the input material (human ASVs) engrafted to a significantly greater extent when compared to mouse ASVs in the 3-week groups but not the 3-day groups. Lastly, comparison of metabolomic profiles revealed distinct functional profiles by ABX regimen. These results indicate successful model optimization and emphasize the importance of ABX duration and frequency of FMT dosing; the most stable and reliable colonization by donor ASVs was seen in the 3wk + 5-FMT group.}, }
@article {pmid34204748, year = {2021}, author = {Paratore, M and Santopaolo, F and Cammarota, G and Pompili, M and Gasbarrini, A and Ponziani, FR}, title = {Fecal Microbiota Transplantation in Patients with HBV Infection or Other Chronic Liver Diseases: Update on Current Knowledge and Future Perspectives.}, journal = {Journal of clinical medicine}, volume = {10}, number = {12}, pages = {}, pmid = {34204748}, issn = {2077-0383}, abstract = {Liver disease and gut dysbiosis are strictly associated, and the pathophysiology of this bidirectional relationship has recently been the subject of several investigations. Growing evidence highlights the link between gut microbiota composition, impairment of the gut-liver axis, and the development or progression of liver disease. Therefore, the modulation of gut microbiota to maintain homeostasis of the gut-liver axis could represent a potential instrument to halt liver damage, modify the course of liver disease, and improve clinical outcomes. Among all the methods available to achieve this purpose, fecal microbiota transplantation (FMT) is one of the most promising, being able to directly reshape the recipient's gut microbial communities. In this review, we report the main characteristics of gut dysbiosis and its pathogenetic consequences in cirrhotic patients, discussing the emerging data on the application of FMT for liver disease in different clinical settings.}, }
@article {pmid34204274, year = {2021}, author = {Fianchi, F and Liguori, A and Gasbarrini, A and Grieco, A and Miele, L}, title = {Nonalcoholic Fatty Liver Disease (NAFLD) as Model of Gut-Liver Axis Interaction: From Pathophysiology to Potential Target of Treatment for Personalized Therapy.}, journal = {International journal of molecular sciences}, volume = {22}, number = {12}, pages = {}, pmid = {34204274}, issn = {1422-0067}, mesh = {Bile Acids and Salts/metabolism ; Biomarkers ; Disease Management ; *Disease Susceptibility ; Energy Metabolism ; Gastrointestinal Microbiome ; Gastrointestinal Tract/*metabolism/microbiology ; Humans ; Liver/*metabolism/pathology ; Non-alcoholic Fatty Liver Disease/*etiology/*metabolism/pathology/therapy ; Permeability ; Precision Medicine/methods ; *Signal Transduction ; }, abstract = {Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide, affecting both adults and children and will result, in the near future, as the leading cause of end-stage liver disease. Indeed, its prevalence is rapidly increasing, and NAFLD is becoming a major public health concern. For this reason, great efforts are needed to identify its pathogenetic factors and new therapeutic approaches. In the past decade, enormous advances understanding the gut-liver axis-the complex network of cross-talking between the gut, microbiome and liver through the portal circulation-have elucidated its role as one of the main actors in the pathogenesis of NAFLD. Indeed, evidence shows that gut microbiota is involved in the development and progression of liver steatosis, inflammation and fibrosis seen in the context of NAFLD, as well as in the process of hepatocarcinogenesis. As a result, gut microbiota is currently emerging as a non-invasive biomarker for the diagnosis of disease and for the assessment of its severity. Additionally, to its enormous diagnostic potential, gut microbiota is currently studied as a therapeutic target in NAFLD: several different approaches targeting the gut homeostasis such as antibiotics, prebiotics, probiotics, symbiotics, adsorbents, bariatric surgery and fecal microbiota transplantation are emerging as promising therapeutic options.}, }
@article {pmid34204263, year = {2021}, author = {Vacca, M and Celano, G and Lenucci, MS and Fontana, S and Forgia, FM and Minervini, F and Scarano, A and Santino, A and Dalfino, G and Gesualdo, L and De Angelis, M}, title = {In Vitro Selection of Probiotics, Prebiotics, and Antioxidants to Develop an Innovative Synbiotic (NatuREN G) and Testing Its Effect in Reducing Uremic Toxins in Fecal Batches from CKD Patients.}, journal = {Microorganisms}, volume = {9}, number = {6}, pages = {}, pmid = {34204263}, issn = {2076-2607}, support = {XUANRO4//Regione Puglia/ ; }, abstract = {We aimed to develop an innovative synbiotic formulation for use in reducing dysbiosis, uremic toxins (e.g., p-cresol and indoxyl sulfate), and, consequently, the pathognomonic features of patients with chronic kidney disease (CKD). Twenty-five probiotic strains, belonging to lactobacilli and Bifidobacterium, were tested for their ability to grow in co-culture with different vegetable (pomegranate, tomato, and grapes) sources of antioxidants and prebiotics (inulin, fructo-oligosaccharides, and β-glucans). Probiotics were selected based on the acidification rates and viable cell counts. Inulin and fructo-oligosaccharides reported the best prebiotic activity, while a pomegranate seed extract was initially chosen as antioxidant source. The investigation was also conducted in fecal batches from healthy and CKD subjects, on which metabolomic analyses (profiling volatile organic compounds and total free amino acids) were conducted. Two out of twenty-five probiotics were finally selected. After the stability tests, the selective innovative synbiotic formulation (named NatuREN G) comprised Bifidobacterium animalis BLC1, Lacticaseibacillus casei LC4P1, fructo-oligosaccharides, inulin, quercetin, resveratrol, and proanthocyanidins. Finally, NatuREN G was evaluated on fecal batches collected from CKD in which modified the viable cell densities of some cultivable bacterial patterns, increased the concentration of acetic acid and decane, while reduced the concentration of nonanoic acid, dimethyl trisulfide, and indoxyl sulfate.}, }
@article {pmid34203609, year = {2021}, author = {Pavel, FM and Vesa, CM and Gheorghe, G and Diaconu, CC and Stoicescu, M and Munteanu, MA and Babes, EE and Tit, DM and Toma, MM and Bungau, S}, title = {Highlighting the Relevance of Gut Microbiota Manipulation in Inflammatory Bowel Disease.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {11}, number = {6}, pages = {}, pmid = {34203609}, issn = {2075-4418}, abstract = {Two different conditions are included in inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), being distinguished by chronic recurrence of gut inflammation in persons that are genetically predisposed and subjected to environmental causative factors. The normal structure of the gut microbiome and its alterations in IBD were defined in several microbial studies. An important factor in the prolonged inflammatory process in IBD is the impaired microbiome or "dysbiosis". Thus, gut microbiome management is likely to be an objective in IBD treatment. In this review, we analyzed the existing data regarding the pathophysiological/therapeutic implications of intestinal microflora in the development and evolution of IBD. Furthermore, the main effects generated by the administration of probiotics, prebiotics, fecal transplantation, and phytochemicals supplementation were analyzed regarding their potential roles in improving the clinical and biochemical status of patients suffering from Crohn's disease (CD) and ulcerative colitis (UC), and are depicted in the sections/subsections of the present paper. Data from the literature give evidence in support of probiotic and prebiotic therapy, showing effects such as improving remission rate, improving macroscopic and microscopic aspects of IBD, reducing the pro-inflammatory cytokines and interleukins, and improving the disease activity index. Therefore, the additional benefits of these therapies should not be ignored as adjuvants to medical therapy.}, }
@article {pmid34203536, year = {2021}, author = {Özdirik, B and Müller, T and Wree, A and Tacke, F and Sigal, M}, title = {The Role of Microbiota in Primary Sclerosing Cholangitis and Related Biliary Malignancies.}, journal = {International journal of molecular sciences}, volume = {22}, number = {13}, pages = {}, pmid = {34203536}, issn = {1422-0067}, support = {1983 4/1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; Bile Duct Neoplasms/genetics/*metabolism ; Cholangiocarcinoma/genetics/metabolism ; Cholangitis, Sclerosing/genetics/*metabolism ; Gastrointestinal Microbiome/genetics/*physiology ; Humans ; Inflammatory Bowel Diseases/genetics/metabolism ; Mice ; }, abstract = {Primary sclerosing cholangitis (PSC) is an immune-related cholangiopathy characterized by biliary inflammation, cholestasis, and multifocal bile duct strictures. It is associated with high rates of progression to end-stage liver disease as well as a significant risk of cholangiocarcinoma (CCA), gallbladder cancer, and colorectal carcinoma. Currently, no effective medical treatment with an impact on the overall survival is available, and liver transplantation is the only curative treatment option. Emerging evidence indicates that gut microbiota is associated with disease pathogenesis. Several studies analyzing fecal and mucosal samples demonstrate a distinct gut microbiome in individuals with PSC compared to healthy controls and individuals with inflammatory bowel disease (IBD) without PSC. Experimental mouse and observational human data suggest that a diverse set of microbial functions may be relevant, including microbial metabolites and bacterial processing of pharmacological agents, bile acids, or dietary compounds, altogether driving the intrahepatic inflammation. Despite critical progress in this field over the past years, further functional characterization of the role of the microbiota in PSC and related malignancies is needed. In this review, we discuss the available data on the role of the gut microbiome and elucidate important insights into underlying pathogenic mechanisms and possible microbe-altering interventions.}, }
@article {pmid34203292, year = {2021}, author = {Szczyrek, M and Bitkowska, P and Chunowski, P and Czuchryta, P and Krawczyk, P and Milanowski, J}, title = {Diet, Microbiome, and Cancer Immunotherapy-A Comprehensive Review.}, journal = {Nutrients}, volume = {13}, number = {7}, pages = {}, pmid = {34203292}, issn = {2072-6643}, mesh = {Animals ; Anti-Bacterial Agents ; Antibodies, Monoclonal, Humanized ; Bacteria/immunology ; Diet/*methods ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunotherapy/*methods ; Neoplasms/*therapy ; Obesity ; Probiotics/therapeutic use ; Thiamine ; Vitamin D ; }, abstract = {The immune system plays a key role in cancer suppression. Immunotherapy is widely used as a treatment method in patients with various types of cancer. Immune checkpoint blockade using antibodies, such as anti-PD-1, anti-PD-L1, and anti-CTLA-4, is currently gaining popularity. A systematic literature search was executed, and all available data was summarized. This review shows that specific dietary patterns (such as, e.g., animal-based, vegetarian, or Mediterranean diet) alter the gut microbiome's composition. An appropriate intestinal microbiota structure might modulate the function of human immune system, which affects the bodily anti-cancer response. This paper shows also that specific bacteria species inhabiting the gastrointestinal tract can have a beneficial influence on the efficacy of immunotherapy. Antibiotics weaken gut bacteria and worsen the immune checkpoint blockers' efficacy, whereas a faecal microbiota transplant or probiotics supplementation may help restore bacterial balance in the intestine. Other factors (like vitamins, glucose, or BMI) change the cancer treatment response, as well. This review demonstrates that there is a strong association between one's diet, gut microbiome composition, and the outcome of immunotherapy. However, further investigation on this subject is required.}, }
@article {pmid34202257, year = {2021}, author = {Kao, TW and Huang, CC}, title = {Recent Progress in Metabolic Syndrome Research and Therapeutics.}, journal = {International journal of molecular sciences}, volume = {22}, number = {13}, pages = {}, pmid = {34202257}, issn = {1422-0067}, support = {V109C-076//Taipei Veterans General Hospital/ ; MOST 108-2314-B-075-062-MY3//Ministry of Science and Technology, Taiwan/ ; }, mesh = {Animals ; COVID-19/pathology/virology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Metabolic Syndrome/metabolism/pathology/*therapy ; Metabolomics ; Precision Medicine ; Proteomics ; SARS-CoV-2/isolation &amp; purification ; }, abstract = {Metabolic syndrome (MetS) is a well-defined yet difficult-to-manage disease entity. Both the precipitous rise in its incidence due to contemporary lifestyles and the growing heterogeneity among affected populations present unprecedented challenges. Moreover, the predisposed risk for developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in populations with MetS, and the viral impacts on host metabolic parameters, underscores the need to investigate this mechanism thoroughly. Recent investigations of metabolomics and proteomics have revealed not only differentially expressed substances in MetS, but also the consequences of diet consumption and physical activity on energy metabolism. These variations in metabolites, as well as protein products, also influence a wide spectrum of host characteristics, from cellular behavior to phenotype. Research on the dysregulation of gut microbiota and the resultant inflammatory status has also contributed to our understanding of the underlying pathogenic mechanisms. As for state-of-the-art therapies, advancing depictions of the bio-molecular landscape of MetS have emerged and now play a key role in individualized precision medicine. Fecal microbiota transplantation, aiming to restore the host's homeostasis, and targeting of the bile acid signaling pathway are two approaches to combatting MetS. Comprehensive molecular inquiries about MetS by omics measures are mandatory to facilitate the development of novel therapeutic modalities.}, }
@article {pmid34202210, year = {2021}, author = {Villoslada-Blanco, P and Pérez-Matute, P and Oteo, JA}, title = {Lights and Shadows of Microbiota Modulation and Cardiovascular Risk in HIV Patients.}, journal = {International journal of environmental research and public health}, volume = {18}, number = {13}, pages = {}, pmid = {34202210}, issn = {1660-4601}, mesh = {*Cardiovascular Diseases/epidemiology/prevention &amp; control ; *HIV Infections ; Heart Disease Risk Factors ; Humans ; *Microbiota ; Risk Factors ; }, abstract = {Human immunodeficiency virus (HIV) infection is associated with premature aging and the development of aging-related comorbidities, such as cardiovascular disease (CVD). Gut microbiota (GM) disturbance is involved in these comorbidities and there is currently interest in strategies focused on modulating GM composition and/or functionality. Scientific evidence based on well-designed clinical trials is needed to support the use of prebiotics, probiotics, symbiotics, and fecal transplantation (FT) to modify the GM and reduce the incidence of CVD in HIV-infected patients. We reviewed the data obtained from three clinical trials focused on prebiotics, 25 trials using probiotics, six using symbiotics, and four using FT. None of the trials investigated whether these compounds could reduce CVD in HIV patients. The huge variability observed in the type of compound as well as the dose and duration of administration makes it difficult to adopt general recommendations and raise serious questions about their application in clinical practice.}, }
@article {pmid34199428, year = {2021}, author = {Akutko, K and Stawarski, A}, title = {Probiotics, Prebiotics and Synbiotics in Inflammatory Bowel Diseases.}, journal = {Journal of clinical medicine}, volume = {10}, number = {11}, pages = {}, pmid = {34199428}, issn = {2077-0383}, abstract = {Inflammatory bowel diseases (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory diseases of the digestive tract with periods of remission and relapses. The etiopathogenesis of IBD is multifactorial and has not been fully understood. Hence, only symptomatic treatment of these diseases is possible. The current pharmacological treatment has variable efficacy and is associated with the risk of significant side effects. Therefore, there is a constant need to search for new types of therapies with a high safety profile. Considering that the qualitative and quantitative profile of the gastrointestinal microbiome is often different in patients with IBD than in healthy individuals, there is a need for looking for therapies aimed at restoring intestinal microbiome homeostasis. Thus, the use of strictly defined probiotics, prebiotics and synbiotics may become an alternative form of IBD therapy. There is evidence that treatment with certain probiotic strains, e.g., VSL#3 and Escherischia coli Nissle 1917, is an effective form of therapy to induce remission in patients with mild to moderate UC. So far, the effectiveness of the use of probiotics, prebiotics and synbiotics in inducing or maintaining remission in patients with CD has not been confirmed. There are also reports of possible beneficial effects of fecal microbiota transplantation (FMT) on the course of IBD, especially UC. Further, well-planned studies on a large group of patients are needed to determine the role of specific probiotic strains, prebiotics, synbiotics and FMT in the treatment of IBD in adults and in children.}, }
@article {pmid34196310, year = {2021}, author = {Ghezzi, L and Cantoni, C and Pinget, GV and Zhou, Y and Piccio, L}, title = {Targeting the gut to treat multiple sclerosis.}, journal = {The Journal of clinical investigation}, volume = {131}, number = {13}, pages = {}, pmid = {34196310}, issn = {1558-8238}, support = {R01 NS102633/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Autoimmunity ; Disease Models, Animal ; Dysbiosis/immunology/physiopathology ; Endocrine System/immunology/physiopathology ; Enteric Nervous System/immunology/microbiology/physiopathology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects/immunology/physiology ; Humans ; Intestinal Mucosa/immunology/microbiology/physiopathology ; Models, Neurological ; Multiple Sclerosis/etiology/microbiology/*therapy ; Neuroimmunomodulation ; Probiotics/therapeutic use ; }, abstract = {The gut-brain axis (GBA) refers to the complex interactions between the gut microbiota and the nervous, immune, and endocrine systems, together linking brain and gut functions. Perturbations of the GBA have been reported in people with multiple sclerosis (pwMS), suggesting a possible role in disease pathogenesis and making it a potential therapeutic target. While research in the area is still in its infancy, a number of studies revealed that pwMS are more likely to exhibit altered microbiota, altered levels of short chain fatty acids and secondary bile products, and increased intestinal permeability. However, specific microbes and metabolites identified across studies and cohorts vary greatly. Small clinical and preclinical trials in pwMS and mouse models, in which microbial composition was manipulated through the use of antibiotics, fecal microbiota transplantation, and probiotic supplements, have provided promising outcomes in preventing CNS inflammation. However, results are not always consistent, and large-scale randomized controlled trials are lacking. Herein, we give an overview of how the GBA could contribute to MS pathogenesis, examine the different approaches tested to modulate the GBA, and discuss how they may impact neuroinflammation and demyelination in the CNS.}, }
@article {pmid34196224, year = {2021}, author = {Long, D and Merlin, D}, title = {Micro- and nanotechnological delivery platforms for treatment of dysbiosis-related inflammatory bowel disease.}, journal = {Nanomedicine (London, England)}, volume = {16}, number = {20}, pages = {1741-1745}, pmid = {34196224}, issn = {1748-6963}, support = {BX002526, BX004476//U.S. Department of Veterans Affairs/ ; I01 BX002526/BX/BLRD VA/United States ; R01 DK107739/DK/NIDDK NIH HHS/United States ; #689659//Research Fellowship Award from the Crohn's and Colitis Foundation of America/ ; IK6 BX004476/BX/BLRD VA/United States ; RO1-DK-107739, RO1-DK-116306/DK/NIDDK NIH HHS/United States ; R01 DK116306/DK/NIDDK NIH HHS/United States ; }, mesh = {*Colitis ; Dysbiosis/drug therapy ; Humans ; *Inflammatory Bowel Diseases/drug therapy ; }, }
@article {pmid34191698, year = {2021}, author = {Wang, X and Liang, Z and Wang, S and Ma, D and Zhu, M and Feng, J}, title = {Role of Gut Microbiota in Multiple Sclerosis and Potential Therapeutic Implications.}, journal = {Current neuropharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/1570159X19666210629145351}, pmid = {34191698}, issn = {1875-6190}, abstract = {The role of gut microbiota in health and diseases has been receiving increased attention recently. Emerging evidence from previous studies on the gut-microbiota-brain axis highlighted the importance of gut microbiota in neurological disorders. Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) resulting from T-cell-driven, myelin-directed autoimmunity. The dysbiosis of gut microbiota in MS patients has been reported in published research studies, indicating that gut microbiota plays an important role in the pathogenesis of MS. Gut microbiota has also been reported to influence the initiation of disease and severity of experimental autoimmune encephalomyelitis, which is the animal model of MS. However, the underlying mechanisms of gut microbiota involvement in the pathogenesis of MS remain unclear. Therefore, in this review, we summerized the potential mechanisms for gut microbiota involvement in the pathogenesis of MS, including increasing the permeability of the intestinal barrier, initiating an autoimmune response, disrupting the blood-brain barrier integrity, and contributing to chronic inflammation. The possibility for gut microbiota as a target for MS therapy has also been discussed. This review provides new insight into understanding the role of gut microbiota in neurological and inflammatory diseases.}, }
@article {pmid34190675, year = {2021}, author = {Bibbò, S and Ianiro, G and Giambò, F and Settanni, CR and Cammarota, G and Gasbarrini, A}, title = {Role of gut microbiome on immunotherapy efficacy in melanoma.}, journal = {Human vaccines &amp; immunotherapeutics}, volume = {}, number = {}, pages = {1-6}, doi = {10.1080/21645515.2021.1926759}, pmid = {34190675}, issn = {2164-554X}, abstract = {The gut microbiota is considered a key component in many aspects of cancer pathophysiology and response to therapy. In particular, in recent years intriguing evidences has been emerging regarding the role of the intestinal microbiota in the response to immunotherapy and in promoting the development of adverse events, such as colitis. For this reason, studies are being carried out both on pre-clinical models and on humans to study how to predict the response to immunotherapy through the study of the microbiota or how to improve its clinical response through modulation. Promising data have recently been reported through modulation by probiotics or prebiotics, and in particular by fecal microbiota transplantation. The aim of this review is to analyze the evidence regarding the role of the microbiota in immunotherapy with a particular focus on melanoma.}, }
@article {pmid34186487, year = {2021}, author = {Wilson, BC and Butler, ÉM and Grigg, CP and Derraik, JGB and Chiavaroli, V and Walker, N and Thampi, S and Creagh, C and Reynolds, AJ and Vatanen, T and O'Sullivan, JM and Cutfield, WS}, title = {Oral administration of maternal vaginal microbes at birth to restore gut microbiome development in infants born by caesarean section: A pilot randomised placebo-controlled trial.}, journal = {EBioMedicine}, volume = {69}, number = {}, pages = {103443}, doi = {10.1016/j.ebiom.2021.103443}, pmid = {34186487}, issn = {2352-3964}, mesh = {Administration, Oral ; Adult ; Bacteroides/pathogenicity ; Cesarean Section/*adverse effects ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; *Gastrointestinal Microbiome ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases/etiology/*microbiology/prevention &amp; control ; Male ; Vagina/*microbiology ; }, abstract = {BACKGROUND: Birth by caesarean section (CS) is associated with aberrant gut microbiome development and greater disease susceptibility later in life. We investigated whether oral administration of maternal vaginal microbiota to infants born by CS could restore their gut microbiome development in a pilot single-blinded, randomised placebo-controlled trial (Australian New Zealand Clinical Trials Registry, ACTRN12618000339257).<br><br>METHODS: Pregnant women scheduled for a CS underwent comprehensive antenatal pathogen screening. At birth, healthy neonates were randomised to receive a 3 ml solution of either maternal vaginal microbes (CS-seeded, n = 12) or sterile water (CS-placebo, n = 13). Vaginally-born neonates were used as the reference control (VB, n = 22). Clinical assessments occurred within the first 2 h of birth, and at 1 month and 3 months of age. Infant stool samples and maternal vaginal extracts from CS women underwent shotgun metagenomic sequencing. The primary outcome was gut microbiome composition at 1 month of age. Secondary outcomes included maternal strain engraftment, functional potential of the gut microbiome, anthropometry, body composition, and adverse events.<br><br>FINDINGS: Despite the presence of viable microbial cells within transplant solutions, there were no observed differences in gut microbiome composition or functional potential between CS-seeded and CS-placebo infants at 1 month or 3 months of age. Both CS groups displayed the characteristic signature of low Bacteroides abundance, which contributed to a number of biosynthesis pathways being underrepresented when compared with VB microbiomes. Maternal vaginal strain engraftment was rare. Vaginal seeding had no observed effects on anthropometry or body composition. There were no serious adverse events associated with treatment.<br><br>INTERPRETATION: Our pilot findings question the value of vaginal seeding given that oral administration of maternal vaginal microbiota did not alter early gut microbiome development in CS-born infants. The limited colonisation of maternal vaginal strains suggest that other maternal sources, such as the perianal area, may play a larger role in seeding the neonatal gut microbiome.<br><br>FUNDING: Health Research Council of New Zealand, A Better Start - National Science Challenge.}, }
@article {pmid34182544, year = {2021}, author = {Liu, M and Song, S and Chen, Q and Sun, J and Chu, W and Zhang, Y and Ji, F}, title = {Gut microbiota mediates cognitive impairment in young mice after multiple neonatal exposures to sevoflurane.}, journal = {Aging}, volume = {13}, number = {12}, pages = {16733-16748}, pmid = {34182544}, issn = {1945-4589}, mesh = {Anesthesia ; Animals ; Anti-Bacterial Agents/pharmacology ; Behavior, Animal ; Cognitive Dysfunction/*microbiology ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/drug effects ; Germ-Free Life ; Mice, Inbred C57BL ; Morris Water Maze Test ; Pregnancy ; Prenatal Exposure Delayed Effects/*microbiology ; Sevoflurane/*adverse effects ; }, abstract = {Multiple exposures to anesthesia may increase the risk of cognitive impairment in young children. However, the mechanisms underlying this neurodevelopmental disorder remain elusive. In this study, we investigated alteration of the gut microbiota after multiple neonatal exposures to the anesthetic sevoflurane and the potential role of microbiota alteration on cognitive impairment using a young mice model. Multiple neonatal sevoflurane exposures resulted in obvious cognitive impairment symptoms and altered gut microbiota composition. Fecal transplantation experiments confirmed that alteration of the microbiota was responsible for the cognitive disorders in young mice. Microbiota profiling analysis identified microbial taxa that showed consistent differential abundance before and after fecal microbiota transplantation. Several of the differentially abundant taxa are associated with memory and/or health of the host, such as species of Streptococcus, Lachnospiraceae, and Pseudoflavonifractor. The results reveal that abnormal composition of the gut microbiota is a risk factor for cognitive impairment in young mice after multiple neonatal exposures to sevoflurane and provide insight into a potential therapeutic strategy for sevoflurane-related neurotoxicity.}, }
@article {pmid34179058, year = {2021}, author = {Yu, Y and Cao, Y and Huang, W and Liu, Y and Lu, Y and Zhao, J}, title = {β-Sitosterol Ameliorates Endometrium Receptivity in PCOS-Like Mice: The Mediation of Gut Microbiota.}, journal = {Frontiers in nutrition}, volume = {8}, number = {}, pages = {667130}, pmid = {34179058}, issn = {2296-861X}, abstract = {Background: Polycystic ovary syndrome (PCOS), one of the most common endocrine diseases in women of childbearing age, has been found to be accompanied by changes in the gut microbiota. The Bu Shen Yang Xue formula (BSYXF) is a traditional Chinese medicine widely used for the treatment of PCOS. This study aimed to investigate whether the protective effects of β-sitosterol, the main active ingredient of BSYXF, on PCOS was mediated by regulating gut microbiota. Methods: The presence of β-sitosterol in BSYXF was detected by liquid chromatography-mass spectrometry. The PCOS-like mouse model was induced by dehydroepiandrosterone. The fecal supernatant of β-sitosterol-treated mice was prepared for fecal microbiota transplantation (FMT). Body weight and wet weight of the uterus and ovary of the mice were recorded for organ index calculation. Hematoxylin and eosin stain was used to assess the endometrial morphology and microenvironment changes. Expression of endometrial receptivity markers cyclooxygenase-2 (COX-2), Integrin ανβ3, leukemia inhibitory factor (LIF), and homeobox A10 (HOXA10) in the endometrium were determined by immunohistochemistry and western blot analysis. Enzyme-linked immunosorbent assay was employed to detect the expression of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), and testosterone (T) in the serum. The diversity of gut microbiota was examined by 16S rDNA gene sequencing. Results: With the treatment of β-sitosterol and β-sitosterol-FMT, the uterine index of PCOS-like mice increased, the ovarian index decreased, levels of COX-2, LH and T decreased, and levels of Integrin ανβ3, LIF, HOXA10, FSH, and P increased. Under β-sitosterol treatment, the structure of the gut microbiota in PCOS-like mice was also changed. Conclusion: β-sitosterol regulates the endometrial receptivity of PCOS and harmonizes the sex hormone balance, which may be related to the changes in the structure and composition of gut microbiota, thus affecting the pathological process of PCOS.}, }
@article {pmid34178927, year = {2021}, author = {Vedala, K and Sobash, P and Shah, P and Kamoga, GR}, title = {Does Fecal Microbiota Transplant Have a Role in Treating Recurrent Clostridioides difficile Infection in Rural Hospitals?.}, journal = {Frontiers in public health}, volume = {9}, number = {}, pages = {670941}, pmid = {34178927}, issn = {2296-2565}, mesh = {Clostridioides ; *Clostridioides difficile ; Hospitals, Rural ; Humans ; *Microbiota ; Recurrence ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Clostridioides difficile infection possesses a significant economical burden, specifically in the inpatient and rural settings. Fecal Microbiota Transplant has been used for treatment of recurrent Clostridioides difficile but its utility is limited by current guidelines and resources. We conducted a retrospective chart review to evaluate the financial benefit of using Fecal Microbiota Transplant after first recurrence of Clostridioides difficile infection. We found that while its use was restricted, on average Fecal Microbiota Transplant can save $11,603.49 per patient. In conclusion, our study shows that using Fecal Microbiota Transplant could prove to be economically beneficial in treating recurrent CDI in rural hospitals.}, }
@article {pmid34177852, year = {2021}, author = {Ma, X and Zhang, Y and Xu, T and Qian, M and Yang, Z and Zhan, X and Han, X}, title = {Early-Life Intervention Using Exogenous Fecal Microbiota Alleviates Gut Injury and Reduce Inflammation Caused by Weaning Stress in Piglets.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {671683}, pmid = {34177852}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) could shape the structure of intestinal microbiota in animals. This study was conducted to explore the changes that happen in the structure and function of microbiota caused by weaning stress, and whether early-life FMT could alleviate weaning stress through modifying intestinal microbiota in weaned piglets. Diarrheal (D) and healthy (H) weaned piglets were observed, and in the same farm, a total of nine litters newborn piglets were randomly allocated to three groups: sucking normally (S), weaned at 21 d (W), and early-life FMT + weaned at 21 d (FW). The results demonstrated that differences of fecal microbiota existed in group D and H. Early-life FMT significantly decreased diarrhea incidence of weaned piglets. Intestinal morphology and integrity were improved in the FW group. Both ZO-1 and occludin (tight junction proteins) of jejunum were greatly enhanced, while the zonulin expression was significantly down-regulated through early-life FMT. The expression of IL-6 and TNF-α (intestinal mucosal inflammatory cytokines) were down-regulated, while IL-10 (anti-inflammatory cytokines) was up-regulated by early-life FMT. In addition, early-life FMT increased the variety of the intestinal microbial population and the relative amounts of some beneficial bacteria such as Spirochaetes, Akkermansia, and Alistipes. Functional alteration of the intestinal microbiota revealed that lipid biosynthesis and aminoacyl-tRNA biosynthesis were enriched in the FW group. These findings suggested that alteration of the microbiota network caused by weaning stress induced diarrhea, and early-life FMT alleviated weaning stress in piglets, which was characterized by decreased diarrhea incidence, improved intestinal morphology, reduced intestinal inflammation, and modified intestinal bacterial composition and function.}, }
@article {pmid34177842, year = {2021}, author = {Koopen, AM and Almeida, EL and Attaye, I and Witjes, JJ and Rampanelli, E and Majait, S and Kemper, M and Levels, JHM and Schimmel, AWM and Herrema, H and Scheithauer, TPM and Frei, W and Dragsted, L and Hartmann, B and Holst, JJ and O'Toole, PW and Groen, AK and Nieuwdorp, M}, title = {Effect of Fecal Microbiota Transplantation Combined With Mediterranean Diet on Insulin Sensitivity in Subjects With Metabolic Syndrome.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {662159}, pmid = {34177842}, issn = {1664-302X}, abstract = {Background: Recent studies demonstrate that a Mediterranean diet has beneficial metabolic effects in metabolic syndrome subjects. Since we have shown that fecal microbiota transplantation (FMT) from lean donors exerts beneficial effects on insulin sensitivity, in the present trial, we investigated the potential synergistic effects on insulin sensitivity of combining a Mediterranean diet with donor FMT in subjects with metabolic syndrome.<br><br>Design: Twenty-four male subjects with metabolic syndrome were put on a Mediterranean diet and after a 2-week run-in phase, the subjects were randomized to either lean donor (n = 12) or autologous (n = 12) FMT. Changes in the gut microbiota composition and bacterial strain engraftment after the 2-week dietary regimens and 6 weeks post-FMT were the primary endpoints. The secondary objectives were changes in glucose fluxes (both hepatic and peripheral insulin sensitivity), postprandial plasma incretin (GLP-1) levels, subcutaneous adipose tissue inflammation, and plasma metabolites.<br><br>Results: Consumption of the Mediterranean diet resulted in a reduction in body weight, HOMA-IR, and lipid levels. However, no large synergistic effects of combining the diet with lean donor FMT were seen on the gut microbiota diversity after 6 weeks. Although we did observe changes in specific bacterial species and plasma metabolites, no significant beneficial effects on glucose fluxes, postprandial incretins, or subcutaneous adipose tissue inflammation were detected.<br><br>Conclusions: In this small pilot randomized controlled trial, no synergistic beneficial metabolic effects of combining a Mediterranean diet with lean donor FMT on glucose metabolism were achieved. However, we observed engraftment of specific bacterial species. Future trials are warranted to test the combination of other microbial interventions and diets in metabolic syndrome.}, }
@article {pmid34176888, year = {2021}, author = {Feng, J and Tang, YN and Zhou, LX and Pan, JS}, title = {Standardized Nursing Procedures for Fecal Microbiota Transplantation via Upper Endoscopy.}, journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates}, volume = {44}, number = {4}, pages = {227-232}, doi = {10.1097/SGA.0000000000000577}, pmid = {34176888}, issn = {1538-9766}, mesh = {*Fecal Microbiota Transplantation ; Feces ; Gastroscopy ; Humans ; *Inflammatory Bowel Diseases ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation is an emerging treatment option that lacks a standardized nursing procedure. In our department, fecal microbiota transplantation has been undertaken to treat chronic hepatitis B and inflammatory bowel diseases since 2015. The fecal microbiota transplantation process involves various nursing measures that are critical for the successful completion of the procedures. In our center, a set of standardized nursing procedures has been established and has proved effective and operable. Standardized nursing procedures enhance the efficacy of fecal microbiota transplantation and alleviate the risk of treatment-related complications.}, }
@article {pmid34175104, year = {2021}, author = {Khanna, S}, title = {My Treatment Approach to Clostridioides difficile Infection.}, journal = {Mayo Clinic proceedings}, volume = {96}, number = {8}, pages = {2192-2204}, doi = {10.1016/j.mayocp.2021.03.033}, pmid = {34175104}, issn = {1942-5546}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridium/*isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; }, abstract = {Clostridioides difficile infection is the most common cause of infectious diarrhea in hospitals with an increasing incidence in the community. Clinical presentation of C difficile infection ranges from diarrhea manageable in the outpatient setting to fulminant infection requiring intensive care admission. There have been significant advances in the management of primary and recurrent C difficile infection including diagnostics, newer antibiotics, antibody treatments, and microbiome restoration therapies. Because of the risk of clinical false-positive results with the polymerase chain reaction test, a two-step assay combining an enzyme immune assay for glutamate dehydrogenase and the C difficile toxin is being used. Cost permitting, I treat a first episode of C difficile infection preferably with fidaxomicin over vancomycin but not metronidazole. The most common complication after C difficile infection is recurrence. I manage a first recurrence with a vancomycin taper and pulse or fidaxomicin and recommend a single dose of intravenous bezlotoxumab (a monoclonal antibody against the toxin B) to reduce recurrence rates for those patients at high risk. Patients with multiply recurrent C difficile infection are managed with a course of antibiotics such as vancomycin or fidaxomicin followed by microbiota restoration. The success of fecal microbiota transplantation is greater than 85%, compared with the 40% to 50% success rate of antibiotics in this situation. Fecal microbiota transplantation is heterogeneous and has rare but serious risks such as transmission of infections. Standardized microbiota restoration therapies are in clinical development and have completed phase III clinical trials. This review answers common clinical questions in the management of C difficile infection.}, }
@article {pmid34173726, year = {2021}, author = {Tan, Q and Orsso, CE and Deehan, EC and Kung, JY and Tun, HM and Wine, E and Madsen, KL and Zwaigenbaum, L and Haqq, AM}, title = {Probiotics, prebiotics, synbiotics, and fecal microbiota transplantation in the treatment of behavioral symptoms of autism spectrum disorder: A systematic review.}, journal = {Autism research : official journal of the International Society for Autism Research}, volume = {14}, number = {9}, pages = {1820-1836}, doi = {10.1002/aur.2560}, pmid = {34173726}, issn = {1939-3806}, mesh = {*Autism Spectrum Disorder/therapy ; Behavioral Symptoms ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; *Probiotics/therapeutic use ; Randomized Controlled Trials as Topic ; *Synbiotics ; }, abstract = {The emerging role of a microbiota-gut-brain axis in autism spectrum disorder (ASD) suggests that modulating gut microbial composition may offer a tractable approach to addressing the lifelong challenges of ASD. The aim of this systematic review was to provide an overview and critically evaluate the current evidence on the efficacy and safety of probiotic, prebiotic, synbiotic, and fecal microbiota transplantation therapies for core and co-occurring behavioral symptoms in individuals with ASD. Comprehensive searches of MEDLINE, EMBASE, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar were performed from inception to March 5, 2020, and two update searches were completed on October 25, 2020, and April 22, 2021, respectively. A total of 4306 publications were identified, of which 14 articles met the inclusion criteria. Data were extracted independently by two reviewers using a preconstructed form. Results of probiotic studies do not confirm the supposed beneficial effect of probiotics on ASD, whereas prebiotics and synbiotic combinations appear to be efficacious in selective behavioral symptoms. Evidence of the efficacy of fecal microbiota transplantation in ASD is still scarce but supports further research. Overall, the current evidence base to suggest beneficial effects of these modalities in ASD is limited and inconclusive. More clinical trials are currently looking at the use of microbial-based therapies in ASD. With a robust double-blind randomized controlled protocol to investigate the efficacy, these trials should provide significant and definitive results. LAY SUMMARY: There is a link between altered gut bacteria and autism spectrum disorder. Some people believe that modulating bacterial composition in the gut may help reduce autism symptoms, but evidence from human studies suggesting beneficial effects of probiotic, prebiotic, and combination thereof as well as fecal transplants in autism spectrum disorder is limited and inconclusive. Current data should not encourage use of these modalities. Further clinical studies are needed.}, }
@article {pmid34172092, year = {2021}, author = {Zheng, H and Xu, P and Jiang, Q and Xu, Q and Zheng, Y and Yan, J and Ji, H and Ning, J and Zhang, X and Li, C and Zhang, L and Li, Y and Li, X and Song, W and Gao, H}, title = {Depletion of acetate-producing bacteria from the gut microbiota facilitates cognitive impairment through the gut-brain neural mechanism in diabetic mice.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {145}, pmid = {34172092}, issn = {2049-2618}, support = {21974096//National Natural Science Foundation of China/ ; 22074106//National Natural Science Foundation of China/ ; 81771386//National Natural Science Foundation of China/ ; 2018R52052//Ten-thousand Talents Program of Zhejiang Province/ ; QJD1802023//Qianjiang Talent Project of Zhejiang Province/ ; SQ2018YFE010015//National Key Research and Development Program/ ; }, mesh = {Acetates/pharmacology ; Animals ; Bacteria/genetics ; Brain ; *Cognitive Dysfunction ; *Diabetes Mellitus, Experimental ; *Gastrointestinal Microbiome ; Mice ; }, abstract = {BACKGROUND: Modification of the gut microbiota has been reported to reduce the incidence of type 1 diabetes mellitus (T1D). We hypothesized that the gut microbiota shifts might also have an effect on cognitive functions in T1D. Herein we used a non-absorbable antibiotic vancomycin to modify the gut microbiota in streptozotocin (STZ)-induced T1D mice and studied the impact of microbial changes on cognitive performances in T1D mice and its potential gut-brain neural mechanism.<br><br>RESULTS: We found that vancomycin exposure disrupted the gut microbiome, altered host metabolic phenotypes, and facilitated cognitive impairment in T1D mice. Long-term acetate deficiency due to depletion of acetate-producing bacteria resulted in the reduction of synaptophysin (SYP) in the hippocampus as well as learning and memory impairments. Exogenous acetate supplement or fecal microbiota transplant recovered hippocampal SYP level in vancomycin-treated T1D mice, and this effect was attenuated by vagal inhibition or vagotomy.<br><br>CONCLUSIONS: Our results demonstrate the protective role of microbiota metabolite acetate in cognitive functions and suggest long-term acetate deficiency as a risk factor of cognitive decline. Video Abstract.}, }
@article {pmid34171951, year = {2021}, author = {Špeciánová, Š}, title = {Legal aspects of intestinal microbiome application.}, journal = {Vnitrni lekarstvi}, volume = {67}, number = {E-3}, pages = {41-46}, pmid = {34171951}, issn = {0042-773X}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Application of intestinal microbiome (Fecal Microbiota Transplantation) is currently discussed treatment procedure which is the subject of professional interest not only when it comes to its medical aspects, but also its legal regulation. The aim of this article is to introduce a legal perspective on this subject matter and outline possible newly regulated areas. The subject matter is linked not only with the legislation contained in the Czech Civil Code in the section devoted to products having its origin in the human body, but also with other laws in the area of medical law. The position of regulatory authorities in the EU is also mentioned. It is apparent that EUs regulatory authorities leave this area for the legislation of individual EU member States.}, }
@article {pmid34170204, year = {2021}, author = {Dharmaratne, P and Rahman, N and Leung, A and Ip, M}, title = {Is there a role of faecal microbiota transplantation in reducing antibiotic resistance burden in gut? A systematic review and Meta-analysis.}, journal = {Annals of medicine}, volume = {53}, number = {1}, pages = {662-681}, pmid = {34170204}, issn = {1365-2060}, abstract = {OBJECTIVES: The aim of current systematic review and meta-analysis is to provide insight into the therapeutic efficacy of fecal microbiota transplantation (FMT) for the decolonization of antimicrobial-resistant (AMR) bacteria from the gut.<br><br>METHODS: The protocol for this Systematic Review was prospectively registered with PROSPERO (CRD42020203634). Four databases (EMBASE, MEDLINE, SCOPUS, and WEB of SCIENCE) were consulted up until September 2020. A total of fourteen studies [in vivo (n = 2), case reports (n = 7), case series without control arm (n = 3), randomized clinical trials (RCT, n = 2)], were reviewed. Data were synthesized narratively for the case reports, along with a proportion meta-analysis for the case series studies (n = 102 subjects) without a control arm followed by another meta-analysis for case series studies with a defined control arm (n = 111 subjects) for their primary outcomes.<br><br>RESULTS: Overall, seven non-duplicate case reports (n = 9 participants) were narratively reviewed and found to have broad AMR remission events at the 1-month time point. Proportion meta-analysis of case series studies showed an overall 0.58 (95% CI: 0.42-0.74) AMR remission. Additionally, a significant difference in AMR remission was observed in FMT vs treatment naïve (RR = 0.44; 95% CI: 0.20-0.99) and moderate heterogeneity (I2=65%). A subgroup analysis of RCTs (n = 2) revealed FMT with further benefits of AMR remission with low statistical heterogeneity (RR = 0.37; 95% CI: 0.18-0.79; I2 =23%).<br><br>CONCLUSION: More rigorous RCTs with larger sample size and standardized protocols on FMTs for gut decolonization of AMR organisms are warranted.KEY MESSAGEExisting studies in this subject are limited and of low quality with moderate heterogeneity, and do not allow definitive conclusions to be drawn.More rigorous RCTs with larger sample size and standardized protocols on FMTs for gut decolonization of AMR organisms are warranted.}, }
@article {pmid34169565, year = {2021}, author = {Fehily, SR and Basnayake, C and Wright, EK and Kamm, MA}, title = {Fecal microbiota transplantation therapy in Crohn's disease: Systematic review.}, journal = {Journal of gastroenterology and hepatology}, volume = {36}, number = {10}, pages = {2672-2686}, doi = {10.1111/jgh.15598}, pmid = {34169565}, issn = {1440-1746}, abstract = {BACKGROUND: The gastrointestinal microbiota is the key antigenic drive in the inflammatory bowel diseases. Randomized controlled trials (RCTs) in ulcerative colitis have established fecal microbiota transplantation (FMT) as an effective therapy. We have conducted a systematic review to evaluate the efficacy of FMT in Crohn's disease.<br><br>METHODS: A systematic literature search was performed through to August 2020 (MEDLINE; Embase). Studies were included if they reported FMT administration in patients with Crohn's disease, and reported on clinical outcomes.<br><br>RESULTS: Fifteen studies published between 2014 and 2020, comprising 13 cohort studies and two RCTs, were included in the analysis. The majority of trials evaluated FMT for induction of remission, with follow-up duration varying from 4 to 52 weeks. One RCT in 21 patients, of single-dose FMT versus placebo, following steroid-induced remission, showed a higher rate of steroid-free clinical remission in the FMT group compared to the control group: 87.5% vs 44.4% at week 10 (P = 0.23). Another RCT, two-dose FMT in 31 patients, showed an overall clinical remission rate of 36% at week 8, however, with no difference in clinical or endoscopic endpoints between FMT administered by gastroscopy and colonoscopy. Considering all studies, the clinical response rates in early follow up were higher following multiple FMT than with single FMT. FMT dose did not appear to influence clinical outcomes, nor did whether FMT was fresh or frozen. FMT delivered via upper gastrointestinal route demonstrated higher early efficacy rates of 75 to 100% compared with lower delivery route rates of 30% to 58%, but on follow up beyond 8 weeks, this difference was not maintained. Whether pre-FMT antibiotic administration was beneficial was not able to be determined due to the limited number of patients receiving antibiotics and varying antibiotic regimens. No serious adverse events were reported.<br><br>CONCLUSIONS: Preliminary studies suggest that FMT may be an effective therapy in Crohn's disease. However large controlled trials are needed. No serious safety concerns have been identified.}, }
@article {pmid34168535, year = {2021}, author = {Xu, X and Wang, K and Cao, X and Li, Z and Zhou, Y and Ren, J and Liu, F}, title = {Gut Microbial Metabolite Short-Chain Fatt Acids Partially Reverse Surgery and Anesthesia-Induced Behavior Deficits in C57BL/6J Mice.}, journal = {Frontiers in neuroscience}, volume = {15}, number = {}, pages = {664641}, pmid = {34168535}, issn = {1662-4548}, abstract = {Accumulating evidence has demonstrated that damages of gut microbiota are strongly associated with central nervous system (CNS) diseases, such as perioperative neurocognitive disorders (PND). The present study investigated the role of gut microbial metabolite short-chain fatty acids (SCFAs) in surgery-induced cognitive deficits and neuroinflammation in the hippocampus. Adult male C57BL/6J mice received either SCFA mixture or saline orally for 4 weeks, and then partial hepatectomy was performed. The fecal supernatant of surgical mice was transplanted to normal mice for 3 weeks. The Morris water maze (MWM) and open-field tests were used to evaluate behavioral performance on postoperative or post-transplantation days 3 and 7. In the MWM test, pretreatment with exogenous SCFAs partially reversed surgery-induced impairments in crossing times and the time spent in the target quadrant on postoperative day 3 (p < 0.05, p < 0.05, respectively). In the open-field test, compared with the surgical mice, exogenous SCFA administration prior to surgery partially improved the locomotor activity (p < 0.05) and anxiety-like behavior (p < 0.05) on postoperative day 3. Surgical trauma and anesthesia enhanced ionized calcium-binding adapter molecule 1 (Iba-1) expression (p < 0.001), increased the levels of interleukin (IL)-1β (p < 0.001) and IL-6 (p < 0.001), and inhibited SCFA production (p < 0.001) on postoperative day 3. The expression of the brain-derived neurotrophic factor (BDNF) was also decreased (p < 0.001). Overall, surgical trauma and anesthesia exacerbated cognitive impairment, enhanced neuroinflammatory responses, and inhibited SCFA production. Pretreatment with SCFAs attenuated these effects partially by reversing microglial overactivation, inhibiting neuroinflammatory responses, and enhancing BDNF expression.}, }
@article {pmid34168399, year = {2021}, author = {El-Salhy, M and Patcharatrakul, T and Gonlachanvit, S}, title = {Fecal microbiota transplantation for irritable bowel syndrome: An intervention for the 21st century.}, journal = {World journal of gastroenterology}, volume = {27}, number = {22}, pages = {2921-2943}, pmid = {34168399}, issn = {2219-2840}, mesh = {Diarrhea ; Fatty Acids, Volatile ; Fecal Microbiota Transplantation/adverse effects ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; }, abstract = {Irritable bowel syndrome (IBS) affects about 12% of the global population. Although IBS does not develop into a serious disease or increase mortality, it results in a considerable reduction in the quality of life. The etiology of IBS is not known, but the intestinal microbiota appears to play a pivotal role in its pathophysiology. There is no effective treatment for IBS, and so the applied treatments clinically focus on symptom relief. Fecal microbiota transplantation (FMT), an old Chinese treatment, has been applied to IBS patients in seven randomized controlled trials (RCTs). Positive effects on IBS symptoms in various degrees were obtained in four of these RCTs, while there was no effect in the remaining three. Across the seven RCTs there were marked differences in the selection processes for the donor and treated patients, the transplant dose, the route of administration, and the methods used to measure how the patients responded to FMT. The present frontier discusses these differences and proposes: (1) criteria for selecting an effective donor (superdonor); (2) selection criteria for patients that are suitable for FMT; (3) the optimal FMT dose; and (4) the route of transplant administration. FMT appears to be safe, with only mild, self-limiting side effects of abdominal pain, cramping, tenderness, diarrhea, and constipation. Although it is early to speculate about the mechanisms underlying the effects of FMT, the available data suggest that changes in the intestinal bacteria accompanied by changes in fermentation patterns and fermentation products (specifically short-chain fatty acids) play an important role in improving the IBS symptoms seen after FMT. FMT appears to be a promising treatment for IBS, but further studies are needed before it can be applied in everyday clinical practice.}, }
@article {pmid34168032, year = {2021}, author = {Hoffmann-Vold, AM and Fretheim, HH and Sarna, VK and Barua, I and Carstens, MN and Distler, O and Khanna, D and Volkmann, ER and Midtvedt, Ø and Didriksen, H and Dhainaut, A and Halse, AK and Bakland, G and Pesonen, M and Olsen, I and Molberg, Ø}, title = {Safety and efficacy of faecal microbiota transplantation by Anaerobic Cultivated Human Intestinal Microbiome (ACHIM) in patients with systemic sclerosis: study protocol for the randomised controlled phase II ReSScue trial.}, journal = {BMJ open}, volume = {11}, number = {6}, pages = {e048541}, pmid = {34168032}, issn = {2044-6055}, mesh = {Anaerobiosis ; Clinical Trials, Phase II as Topic ; Double-Blind Method ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Los Angeles ; Multicenter Studies as Topic ; Pilot Projects ; Randomized Controlled Trials as Topic ; *Scleroderma, Systemic/therapy ; Treatment Outcome ; }, abstract = {INTRODUCTION: In the multisystem inflammatory disorder systemic sclerosis (SSc), gastrointestinal tract (GIT) affliction is highly prevalent. There are no known disease modifying therapies and the negative impact is substantial. Aiming for a new therapeutic principle, and inspired by recent work showing associations between gut microbiota changes and GIT symptoms in SSc, we performed a pilot study on faecal microbiota transplantation (FMT) with the single-donor bacterial culture 'Anaerobic Cultivated Human Intestinal Microbiome (ACHIM)'. Motivated by positive pilot study signals, we designed the ReSScue trial as a phase II multicentre, placebo-controlled, randomised 20-week trial to evaluate safety and efficacy on lower GIT symptoms of FMT by ACHIM in SSc.<br><br>METHODS AND ANALYSES: We aim to include 70 SSc participants with moderate to severe lower GIT symptoms, defined by the validated patient-reported University of California Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 2.0 questionnaire. The trial includes three parts. In part A1 (induction phase) lasting from week 0 to week 12, participants will be randomised 1:1 to repeat infusions of 30 mL ACHIM or placebo at week 0 and 2 by gastroduodenoscopy. In part A2, which is an 8-week subsequent maintenance phase, all study participants will receive 30 mL ACHIM at week 12 and followed until week 20 on continued blind. In part B, which will last until the last participant completes part A2, the participants will be followed through a maximum 16-week extended monitoring period, for longer-term data on safety and intervention effects. Primary endpoint is change from baseline to week 12 in UCLA GIT subscale scores of diarrhoea or bloating, depending on the worst symptom at baseline evaluated separately for each patient. Secondary endpoints are safety measures and changes in UCLA GIT scores (total, diarrhoea and bloating).<br><br>ETHICS AND DISSEMINATION: This protocol was approved by the Northern Norwegian Committee for Medical Ethics. Study findings will be published.<br><br>TRIAL REGISTRATION NUMBER: NCT04300426; Pre-results.<br><br>PROTOCOL VERSION: V.3.1.}, }
@article {pmid34163471, year = {2021}, author = {Adda-Rezig, H and Carron, C and Pais de Barros, JP and Choubley, H and Charron, É and Rérole, AL and Laheurte, C and Louvat, P and Gaiffe, É and Simula-Faivre, D and Deckert, V and Lagrost, L and Saas, P and Ducloux, D and Bamoulid, J}, title = {New Insights on End-Stage Renal Disease and Healthy Individual Gut Bacterial Translocation: Different Carbon Composition of Lipopolysaccharides and Different Impact on Monocyte Inflammatory Response.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {658404}, pmid = {34163471}, issn = {1664-3224}, mesh = {Adult ; Aged ; *Bacterial Translocation ; Biomarkers ; Case-Control Studies ; Comorbidity ; Cytokines/blood ; Disease Management ; *Disease Susceptibility/immunology ; Endotoxemia/diagnosis/etiology ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Inflammation Mediators/blood/metabolism ; Kidney Failure, Chronic/complications/diagnosis/*etiology/*therapy ; Kidney Transplantation ; Lipopolysaccharides/immunology/metabolism ; Male ; Middle Aged ; Monocytes/immunology/metabolism ; }, abstract = {Chronic kidney disease induces disruption of the intestinal epithelial barrier, leading to gut bacterial translocation. Here, we appreciated bacterial translocation by analyzing circulating lipopolysaccharides (LPS) using two methods, one measuring only active free LPS, and the other quantifying total LPS as well as LPS lipid A carbon chain length. This was done in end-stage renal disease (ESRD) patients and healthy volunteers (HV). We observed both higher LPS concentration in healthy volunteers and significant differences in composition of translocated LPS based on lipid A carbon chain length. Lower LPS activity to mass ratio and higher concentration of high-density lipoproteins were found in HV, suggesting a better plasma capacity to neutralize LPS activity. Higher serum concentrations of soluble CD14 and pro-inflammatory cytokines in ESRD patients confirmed this hypothesis. To further explore whether chronic inflammation in ESRD patients could be more related to LPS composition rather than its quantity, we tested the effect of HV and patient sera on cytokine secretion in monocyte cultures. Sera with predominance of 14-carbon chain lipid A-LPS induced higher secretion of pro-inflammatory cytokines than those with predominance of 18-carbon chain lipid A-LPS. TLR4 or LPS antagonists decreased LPS-induced cytokine production by monocytes, demonstrating an LPS-specific effect. Thereby, septic inflammation observed in ESRD patients may be not related to higher bacterial translocation, but to reduced LPS neutralization capacity and differences in translocated LPS subtypes.}, }
@article {pmid34163114, year = {2021}, author = {Nishida, A and Nishino, K and Sakai, K and Owaki, Y and Noda, Y and Imaeda, H}, title = {Can control of gut microbiota be a future therapeutic option for inflammatory bowel disease?.}, journal = {World journal of gastroenterology}, volume = {27}, number = {23}, pages = {3317-3326}, pmid = {34163114}, issn = {2219-2840}, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/therapy ; *Microbiota ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract encompassing two main clinical entities, Crohn's disease and ulcerative colitis. Accumulated evidence indicates that an aberrant immune activation caused by the interplay of genetic susceptibility and environmental impact on the gut microbiota may be involved in the pathogenesis of IBD. Rapid advances in next-generation sequencing technology have enabled a number of studies to identify the alteration of the gut microbiota, termed dysbiosis, in IBD. Moreover, the alteration in the metabolites derived from the gut microbiota in IBD has also been described in many studies. Therefore, microbiota-based interventions such as fecal microbiota transplantation (FMT) have attracted attention as a novel therapeutic option in IBD. However, in clinical trials, the efficacy of FMT for IBD remains controversial. Additional basic and clinical studies are required to validate whether FMT can assume a complementary role in the treatment of IBD. The present review provides a synopsis on dysbiosis in IBD and on the association between the gut microbiota and the pathogenesis of IBD. In addition, we summarize the use of probiotics in IBD and the results of current clinical trials of FMT for IBD.}, }
@article {pmid34162429, year = {2021}, author = {Hayase, E and Jenq, RR}, title = {Role of the intestinal microbiome and microbial-derived metabolites in immune checkpoint blockade immunotherapy of cancer.}, journal = {Genome medicine}, volume = {13}, number = {1}, pages = {107}, pmid = {34162429}, issn = {1756-994X}, support = {R01 HL124112/HL/NHLBI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; }, abstract = {Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block immune inhibitory pathways. Administration of ICIs augments T cell-mediated immune responses against tumor, resulting in improved overall survival in cancer patients. It has emerged that the intestinal microbiome can modulate responses to ICIs via the host immune system and that the use of antibiotics can lead to reduced efficacy of ICIs. Recently, reports that fecal microbiota transplantation can lead to ICI therapy responses in patients previously refractory to therapy suggest that targeting the microbiome may be a viable strategy to reprogram the tumor microenvironment and augment ICI therapy. Intestinal microbial metabolites may also be linked to response rates to ICIs. In addition to response rates, certain toxicities that can arise during ICI therapy have also been found to be associated with the intestinal microbiome, including in particular colitis. A key mechanistic question is how certain microbes can enhance anti-tumor responses or, alternatively, predispose to ICI-associated colitis. Evidence has emerged that the intestinal microbiome can modulate outcomes to ICI therapies via two major mechanisms, including those that are antigen-specific and those that are antigen-independent. Antigen-specific mechanisms occur when epitopes are shared between microbial and tumor antigens that could enhance, or, alternatively, reduce anti-tumor immune responses via cross-reactive adaptive immune cells. Antigen-independent mechanisms include modulation of responses to ICIs by engaging innate and/or adaptive immune cells. To establish microbiome-based biomarkers of outcomes and specifically modulate the intestinal microbiome to enhance efficacy of ICIs in cancer immunotherapy, further prospective interventional studies will be required.}, }
@article {pmid34158061, year = {2021}, author = {Patrono, E and Svoboda, J and Stuchlík, A}, title = {Schizophrenia, the gut microbiota, and new opportunities from optogenetic manipulations of the gut-brain axis.}, journal = {Behavioral and brain functions : BBF}, volume = {17}, number = {1}, pages = {7}, pmid = {34158061}, issn = {1744-9081}, support = {CZ.02.2.69/0.0/0.0/19_074/0016409//European Science Foundation/ ; 20-00939S//Grantová Agentura České Republiky/ ; 21-16667K//Grantová Agentura České Republiky/ ; }, abstract = {Schizophrenia research arose in the twentieth century and is currently rapidly developing, focusing on many parallel research pathways and evaluating various concepts of disease etiology. Today, we have relatively good knowledge about the generation of positive and negative symptoms in patients with schizophrenia. However, the neural basis and pathophysiology of schizophrenia, especially cognitive symptoms, are still poorly understood. Finding new methods to uncover the physiological basis of the mental inabilities related to schizophrenia is an urgent task for modern neuroscience because of the lack of specific therapies for cognitive deficits in the disease. Researchers have begun investigating functional crosstalk between NMDARs and GABAergic neurons associated with schizophrenia at different resolutions. In another direction, the gut microbiota is getting increasing interest from neuroscientists. Recent findings have highlighted the role of a gut-brain axis, with the gut microbiota playing a crucial role in several psychopathologies, including schizophrenia and autism.There have also been investigations into potential therapies aimed at normalizing altered microbiota signaling to the enteric nervous system (ENS) and the central nervous system (CNS). Probiotics diets and fecal microbiota transplantation (FMT) are currently the most common therapies. Interestingly, in rodent models of binge feeding, optogenetic applications have been shown to affect gut colony sensitivity, thus increasing colonic transit. Here, we review recent findings on the gut microbiota-schizophrenia relationship using in vivo optogenetics. Moreover, we evaluate if manipulating actors in either the brain or the gut might improve potential treatment research. Such research and techniques will increase our knowledge of how the gut microbiota can manipulate GABA production, and therefore accompany changes in CNS GABAergic activity.}, }
@article {pmid34154439, year = {2021}, author = {Drekonja, DM and Shaukat, A and Zhang, JH and Reinink, AR and Nugent, S and Dominitz, JA and Davis-Karim, A and Gerding, DN and Kyriakides, TC}, title = {Microbiota or placebo after antimicrobial therapy for recurrent Clostridioides difficile at home: A clinical trial with novel home-based enrollment.}, journal = {Clinical trials (London, England)}, volume = {18}, number = {5}, pages = {622-629}, doi = {10.1177/17407745211021198}, pmid = {34154439}, issn = {1740-7753}, mesh = {*Anti-Bacterial Agents/therapeutic use ; COVID-19 ; *Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Microbiota ; Quality of Life ; Recurrence ; Treatment Outcome ; }, abstract = {INTRODUCTION: Clostridiodes difficile infection is the leading cause of infectious diarrhea in the United States, with substantial morbidity and mortality. Recurrent infection is especially challenging, with each recurrence increasing the likelihood of a successive recurrence, leading to cycles of prolonged symptoms, frequent antimicrobial use, and decreased quality of life. Fecal microbiota transplantation to prevent recurrent infection is a promising intervention with a large effect size in observational studies, but with conflicting results from randomized controlled trials. We are conducting a Veterans Affairs-wide randomized controlled trial utilizing centralized case identification, with enrollment and fecal microbiota transplant administration occurring at the participant's home. This type of trial design significantly improves trial efficiency, greatly decreases trial cost, increases consistency of trial administration, and most importantly makes nationwide clinical trials in less-common diseases possible.<br><br>METHODS: This is a randomized comparison of capsule-delivered fecal microbiota transplant for the prevention of recurrent Clostridiodes difficile infection, administered after successful initial treatment of recurrent C. difficile infection with standard therapy. The primary endpoint is the incidence of recurrent C. difficile infection or death. Cases are identified by searching the Veterans Affairs Corporate Data Warehouse, with central study coordinators then reaching out to potential participants. Individuals meeting inclusion criteria and interested in participation are scheduled for in-home consent, randomization, and capsule administration, followed by telephone follow-up for 6 months. To mitigate risks of COVID-19, enrollment via video visits has been implemented.<br><br>RESULTS: A total of 102 participants have been enrolled through January 2021. Centralized case identification and in-home enrollment has facilitated enrollment from 34 unique states, with 38% being from rural or highly rural areas.<br><br>DISCUSSION: Centralized case identification and in-home enrollment is a feasible and innovative method of conducting randomized controlled trials in the Veterans Affairs system, improving access to clinical research for populations who may have difficulty engaging with the traditional model of clinical trials where enrollment is based at large hospitals in major metropolitan areas.}, }
@article {pmid34153321, year = {2021}, author = {Thomaz, AC and Iyer, V and Woodward, TJ and Hohmann, AG}, title = {Fecal microbiota transplantation and antibiotic treatment attenuate naloxone-precipitated opioid withdrawal in morphine-dependent mice.}, journal = {Experimental neurology}, volume = {343}, number = {}, pages = {113787}, pmid = {34153321}, issn = {1090-2430}, support = {R01 DA041229/DA/NIDA NIH HHS/United States ; R01 DA047858/DA/NIDA NIH HHS/United States ; R21 DA042584/DA/NIDA NIH HHS/United States ; T32 DA024628/DA/NIDA NIH HHS/United States ; }, mesh = {Analgesics, Opioid/administration &amp; dosage ; Animals ; Anti-Bacterial Agents/*administration &amp; dosage ; Combined Modality Therapy/methods ; Fecal Microbiota Transplantation/*methods ; Male ; Mice ; Mice, Inbred C57BL ; Morphine Dependence/drug therapy/metabolism/*therapy ; Naloxone/*toxicity ; Narcotic Antagonists/*toxicity ; Probiotics/administration &amp; dosage ; Substance Withdrawal Syndrome/drug therapy/metabolism/*therapy ; }, abstract = {Opioid addiction can produce severe side effects including physical dependence and withdrawal. Perturbations of the gut microbiome have recently been shown to alter opioid-induced side-effects such as addiction, tolerance and dependence. In the present study, we investigated the influence of the gut microbiome on opioid withdrawal by evaluating the effects of fecal microbiota transplantation (FMT), antibiotic and probiotic treatments, and pharmacological inhibition of gut permeability in a mouse model of opioid dependence. Repeated intraperitoneal (i.p.) morphine treatment produced physical dependence that was quantified by measuring somatic signs of withdrawal (i.e. number of jumps) precipitated using the opioid antagonist naloxone. Morphine-dependent mice that received FMT from morphine-treated donor mice exhibited fewer naloxone-precipitated jumps compared to morphine-dependent counterparts receiving FMT from saline-treated donor mice. Microbial contents in the mouse cecum were altered by morphine treatment but were not differentially impacted by FMT. A broad-spectrum antibiotic cocktail (ABX) regimen reduced the bacterial load and attenuated naloxone-precipitated morphine withdrawal in morphine-dependent mice, whereas commercially available probiotic strains did not reliably alter somatic signs of opioid withdrawal. ML-7, a pharmacological inhibitor of gut permeability, reduced the morphine-induced increase in gut permeability in vivo but did not reliably alter somatic signs of naloxone-precipitated opioid withdrawal. Our results suggest that the gut microbiome impacts the development of physical dependence induced by chronic morphine administration, and that therapeutic manipulations of the gut microbiome may reduce opioid withdrawal.}, }
@article {pmid34152776, year = {2021}, author = {Yan, X and Ren, X and Liu, X and Wang, Y and Ma, J and Song, R and Wang, X and Dong, Y and Fan, Q and Wei, J and Yu, A and She, G}, title = {Dietary Ursolic Acid Prevents Alcohol-Induced Liver Injury via Gut-Liver Axis Homeostasis Modulation: The Key Role of Microbiome Manipulation.}, journal = {Journal of agricultural and food chemistry}, volume = {69}, number = {25}, pages = {7074-7083}, doi = {10.1021/acs.jafc.1c02362}, pmid = {34152776}, issn = {1520-5118}, mesh = {Animals ; *Chemical and Drug Induced Liver Injury, Chronic ; *Gastrointestinal Microbiome ; Homeostasis ; Liver ; *Liver Diseases, Alcoholic/drug therapy/prevention &amp; control ; Mice ; *Triterpenes ; }, abstract = {Ursolic acid (UA), a natural triterpenoid widely distributed within fruits and edible plants, has been proven to relieve alcoholic liver disease (ALD). However, the mechanisms involved largely remain unclear. This study investigated whether the beneficial effects of UA on ALD could be related to gut-liver axis (GLA) modulation. Special attention was paid to the contribution of gut microbiome manipulation. UA ameliorated intestinal oxidative stress and barrier dysfunction induced by alcohol. As a consequence of gut leakiness amelioration, the related endotoxemia-mediated liver toll-like receptor 4 pathway induction and the subsequent reactive oxygen species overproduction were reverted. UA also counteracted alcohol-induced gut dysbiosis. A fecal microbiota transplantation study indicated that liver injury as well as ileum oxidative stress and gut barrier dysfunction of recipient mice were partly ameliorated as a result of microbiome remodeling. These results suggest that dietary UA alleviates ALD through GLA homeostasis modulation. Gut microbiome manipulation contributes to the hepatoprotective activity and GLA modulating effect of UA.}, }
@article {pmid34152347, year = {2021}, author = {Deng, L and Zeng, H and Hu, X and Xiao, M and He, D and Zhang, Y and Jin, Y and Hu, Y and Zhu, Y and Gong, L and Wang, Z and Xiang, L and Zhu, R and Zhang, Y and Cheng, Y and Chen, X and Zhang, S and Peng, Y and Cao, K}, title = {Se@Albumin nanoparticles ameliorate intestinal mucositis caused by cisplatin via gut microbiota-targeted regulation.}, journal = {Nanoscale}, volume = {13}, number = {25}, pages = {11250-11261}, doi = {10.1039/d0nr07981b}, pmid = {34152347}, issn = {2040-3372}, mesh = {Albumins ; Animals ; Cisplatin ; Fluorouracil ; *Gastrointestinal Microbiome ; Mice ; *Mucositis ; *Nanoparticles ; }, abstract = {Chemotherapy-associated intestinal mucositis is still one of the major challenges in the first-line clinical cancer treatment. Selenium element has shown health benefits on enteritis upon uptake in trace amounts; however, it was limited because of its narrow safety margin. In this work, a new form of Se@Albumin complex nanoparticles (Se@Albumin NPs) was developed by self-assembly of denatured human serum albumin and selenite salts. Se@Albumin NPs significantly improve intestinal mucositis induced with cisplatin (CDDP) in a mouse model via attenuating the level of intestinal oxidative stress, reducing intestinal permeability, and relieving gastric dysmotility. It is very interesting that the restoration of anti-inflammatory bacteria (Bacteroidetes and Firmicutes) and reduced abundance of proinflammatory bacteria (Escherichia) contributed to the reduction of intestinal mucositis by Se@Albumin NPs in mice. In addition, the fecal microbiota transplantation (FMT) with materials from Se@Albumin NP-treated mice significantly protected pseudo-aseptic mice from CDDP-induced intestinal mucositis. In conclusion, our findings showed that Se@Albumin NPs can significantly improve CDDP-induced intestinal mucositis, and its function may be directly mediated by gut microbiota regulation, which will provide new helpful information for clinical treatment.}, }
@article {pmid34151049, year = {2021}, author = {West, C and McVey Neufeld, KA}, title = {Animal models of visceral pain and the role of the microbiome.}, journal = {Neurobiology of pain (Cambridge, Mass.)}, volume = {10}, number = {}, pages = {100064}, pmid = {34151049}, issn = {2452-073X}, abstract = {Visceral pain refers to pain arising from the internal organs and is distinctly different from the expression and mechanisms of somatic pain. Diseases and disorders with increased visceral pain are associated with significantly reduced quality of life and incur large financial costs due to medical visits and lost work productivity. In spite of the notable burden of illness associated with those disorders involving increased visceral pain, and some knowledge regarding etiology, few successful therapeutics have emerged, and thus increased attention to animal models of visceral hypersensitivity is warranted in order to elucidate new treatment opportunities. Altered microbiota-gut-brain (MGB) axis communication is central to the comorbid gastrointestinal/psychiatric diseases of which increased visceral (intestinal) sensitivity is a hallmark. This has led to a particular focus on intestinal microbiome disruption and its potential role in the etiology of heightened visceral pain. Here we provide a review of studies examining models of heightened visceral pain due to altered bidirectional communication of the MGB axis, many of which are conducted on a background of stress exposure. We discuss work in which the intestinal microbiota has either been directly manipulated (as with germ-free, antibiotic, and fecal microbial transplantation studies) or indirectly affected through early life or adult stress, inflammation, and infection. Animal models of visceral pain alterations with accompanying changes to the intestinal microbiome have the highest face and construct validity to the human condition and are the focus of the current review.}, }
@article {pmid34150673, year = {2021}, author = {Varga, A and Kocsis, B and Sipos, D and Kása, P and Vigvári, S and Pál, S and Dembrovszky, F and Farkas, K and Péterfi, Z}, title = {How to Apply FMT More Effectively, Conveniently and Flexible - A Comparison of FMT Methods.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {657320}, pmid = {34150673}, issn = {2235-2988}, mesh = {*Clostridioides difficile ; *Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Recurrence ; Treatment Outcome ; }, abstract = {Purpose: Metronidazol and vancomycin were long the two best options against Clostridioides (formerly Clostridium) difficile infections (CDI). Now, the cost of new drugs such as fidaxomicin directs us towards alternative treatment options, such as faecal microbiota transplant (FMT). Its effectiveness is similar to fidaxomicin. There are questions regarding its safety, but the biggest challenges are prejudice and inconvenience. Most protocols refer to FMT applied in the form of a solution. We investigated different modalities of FMT.<br><br>Methods: Instead of using nasoenteric tubes or colonoscopy, we place frozen or lyophilised stool in non-coated, size "00", hard gelatine capsules or enterosolvent, size "0" capsules.<br><br>Results: We found that non-coated, size "00", hard gelatine capsules are appropriate for conducting FMT. Capsules containing lyophilised supernatant with a low number of bacteria have been proven to be non-inferior to other FMT modalities. The primary cure rate in the supernatant group was 93.75%, and 66.67% in the sediment group. The overall cure rate was 82.14%. Depending on the protocol, 4-7 capsules are sufficient per patient. Capsules can be stored for up to one year at -20°C.<br><br>Conclusions: FMT is a feasible alternative to antibiotic treatments in CDI. Our method makes the process flexible and less inconvenient to patients. Long storage time allows a consistent supply of capsules, while small volume and formulation make the procedure tolerable.}, }
@article {pmid34149723, year = {2021}, author = {Ponce-Alonso, M and García-Hoz, C and Halperin, A and Nuño, J and Nicolás, P and Martínez-Pérez, A and Ocaña, J and García-Pérez, JC and Guerrero, A and López-Sanromán, A and Cantón, R and Roy, G and Del Campo, R}, title = {An Immunologic Compatibility Testing Was Not Useful for Donor Selection in Fecal Microbiota Transplantation for Ulcerative Colitis.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {683387}, pmid = {34149723}, issn = {1664-3224}, mesh = {Adult ; Aged ; Clinical Decision-Making ; Colitis, Ulcerative/diagnosis/*immunology/*therapy ; Disease Management ; *Donor Selection ; *Fecal Microbiota Transplantation ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is an effective procedure against Clostridioides difficile infection (CDI), with promising but still suboptimal performance in other diseases, such as ulcerative colitis (UC). The recipient's mucosal immune response against the donor's microbiota could be relevant factor in the effectiveness of FMT. Our aim was to design and validate an individualized immune-based test to optimize the fecal donor selection for FMT. First, we performed an in vitro validation of the test by co-culturing lymphocytes obtained from the small intestine mucosa of organ donor cadavers (n=7) and microbe-associated molecular patterns (MAMPs) obtained from the feces of 19 healthy donors. The inflammatory response was determined by interleukin supernatant quantification using the Cytometric Bead Array kit (B&amp;D). We then conducted a clinical pilot study with 4 patients with UC using immunocompetent cells extracted from rectal biopsies and MAMPs from 3 donor candidates. We employed the test results to guide donor selection for FMT, which was performed by colonoscopy followed by 4 booster instillations by enema in the following month. The microbiome engraftment was assessed by 16S rDNA massive sequencing in feces, and the patients were clinically followed-up for 16 weeks. The results demonstrated that IL-6, IL-8, and IL-1ß were the most variable markers, although we observed a general tolerance to the microbial insults. Clinical and colonoscopy remission of the patients with UC was not achieved after 16 weeks, although FMT provoked enrichment of the Bacteroidota phylum and Prevotella genus, with a decrease in the Actinobacteriota phylum and Agathobacter genus. The most relevant result was the lack of Akkermansia engraftment in UC. In summary, the clinical success of FMT in patients with UC appears not to be influenced by donor selection based on the explored recipient's local immunological response to FMT, suggesting that this approach would not be valid for FMT fecal donor optimization in such patients.}, }
@article {pmid34147969, year = {2021}, author = {Wang, S and Ishima, T and Qu, Y and Shan, J and Chang, L and Wei, Y and Zhang, J and Pu, Y and Fujita, Y and Tan, Y and Wang, X and Ma, L and Wan, X and Hammock, BD and Hashimoto, K}, title = {Ingestion of Faecalibaculum rodentium causes depression-like phenotypes in resilient Ephx2 knock-out mice: A role of brain-gut-microbiota axis via the subdiaphragmatic vagus nerve.}, journal = {Journal of affective disorders}, volume = {292}, number = {}, pages = {565-573}, pmid = {34147969}, issn = {1573-2517}, support = {P42 ES004699/ES/NIEHS NIH HHS/United States ; R35 ES030443/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Brain ; *Depression/genetics ; Eating ; Epoxide Hydrolases ; Firmicutes ; *Gastrointestinal Microbiome/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phenotype ; Stress, Psychological ; Vagus Nerve ; }, abstract = {BACKGROUND: The brain-gut-microbiota axis plays a crucial role in the bidirectional interactions between the brain and the gut. Soluble epoxide hydrolase (coded by the Ephx2 gene) plays an important role in inflammation, which has been implicated in stress-related depression. Ephx2 knock-out (KO) mice exposed to chronic social defeat stress (CSDS) did not show depression-like behaviors, indicating stress resilience. Here we examined whether the brain-gut-microbiota axis influences the resilience in Ephx2 KO mice.<br><br>METHODS: Effects of fecal microbiota transplantation (FMT) from CSDS-susceptible (or control) mice in wild-type (WT) mice and Ephx2 KO mice treated with an antibiotic cocktail (ABX) were investigated. Behavioral, biochemical tests and 16S ribosome RNA analysis were performed.<br><br>RESULTS: FMT from CSDS-susceptible mice produced anhedonia-like behavior in ABX-treated WT and Ephx2 KO mice. The 16S ribosome RNA analysis showed that Faecalibaculum rodentium (F. rodentium) may be responsible for the observed anhedonia-like behavior following FMT from CSDS-susceptible mice. Ingestion of F. rodentium for 14 days produced depression- and anhedonia-like behaviors, higher blood levels of interleukin-6, and reduced expression of synaptic proteins in the prefrontal cortex of ABX-treated Ephx2 KO mice. Furthermore, subdiaphragmatic vagotomy blocked the development of these behavioral abnormalities after ingestion of F. rodentium.<br><br>LIMITATIONS: Detailed mechanisms are unclear.<br><br>CONCLUSIONS: These findings suggest that F. rodentium might contribute to the conversion of resilient Ephx2 KO mice into KO mice with depression-like phenotypes. The brain-gut-microbiota axis via the subdiaphragmatic vagus nerve plays a crucial role in susceptibility and resilience to stress.}, }
@article {pmid34145677, year = {2021}, author = {El-Salhy, M and Kristoffersen, AB and Valeur, J and Casen, C and Hatlebakk, JG and Gilja, OH and Hausken, T}, title = {Long-term effects of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {}, number = {}, pages = {e14200}, doi = {10.1111/nmo.14200}, pmid = {34145677}, issn = {1365-2982}, support = {40415//Helse Fonna/ ; }, abstract = {BACKGROUND: We recently found fecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) patients to be an effective and safe treatment after 3 months. The present follow-up study investigated the efficacy and safety of FMT at 1 year after treatment.<br><br>METHODS: This study included 77 of the 91 IBS patients who had responded to FMT in our previous study. Patients provided a fecal sample and completed five questionnaires to assess their symptoms and quality of life at 1 year after FMT. The dysbiosis index (DI) and fecal bacterial profile were analyzed using a 16S rRNA gene-based DNA probe hybridization. The levels of fecal short-chain fatty acids (SCFAs) were determined by gas chromatography.<br><br>RESULTS: There was a persistent response to FMT at 1 year after treatment in 32 (86.5%) and 35 (87.5%) patients who received 30-g and 60-g FMT, respectively. In the 30-g FMT group, 12 (32.4%) and 8 (21.6%) patients showed complete remission at 1 year and 3 months, respectively; the corresponding numbers in the 60-g FMT group were 18 (45%) and 11 (27.5%), respectively. Abdominal symptoms and the quality of life were improved at 1 year compared with after 3 months. These findings were accompanied by comprehensive changes in the fecal bacterial profile and SCFAs.<br><br>CONCLUSIONS: Most of the IBS patients maintained a response at 1 year after FMT. Moreover, the improvements in symptoms and quality of life increased over time. Changes in DI, fecal bacterial profile and SCFAs were more comprehensive at 1 year than after 3 months. www.clinicaltrials.gov (NCT03822299).}, }
@article {pmid34144192, year = {2021}, author = {Tang, B and Zhu, J and Fang, S and Wang, Y and Vinothkumar, R and Li, M and Weng, Q and Zheng, L and Yang, Y and Qiu, R and Xu, M and Zhao, Z and Ji, J}, title = {Pharmacological inhibition of MELK restricts ferroptosis and the inflammatory response in colitis and colitis-propelled carcinogenesis.}, journal = {Free radical biology &amp; medicine}, volume = {172}, number = {}, pages = {312-329}, doi = {10.1016/j.freeradbiomed.2021.06.012}, pmid = {34144192}, issn = {1873-4596}, mesh = {Animals ; Carcinogenesis ; *Colitis/chemically induced/complications/drug therapy ; Dextran Sulfate ; Disease Models, Animal ; *Ferroptosis ; Humans ; Mice ; Protein Serine-Threonine Kinases/metabolism ; Signal Transduction ; }, abstract = {INTRODUCTION: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic recurrent and incurable gastrointestinal diseases with an unknown etiology that leads to a high risk of developing colitis-associated colorectal cancer (CRC).<br><br>OBJECTIVES: In this study, we measured the expression characteristics of MELK in IBD and CRC tissues and explored the regulatory effect of OTSSP167 (a MELK-selective inhibitor) on the mice models of colitis and colitis-associated carcinogenesis and analyzed the specific molecular mechanisms.<br><br>METHODS: DSS-induced colitis and colitis-associated carcinogenesis (CAC) model were treated with MELK inhibitor OTSSP167 then the fight against effect of OTSSP167 in the clinical symptoms of colitis and CAC was measured. In addition, underlying mechanism of OTSSP167 treatment in vitro and vivo including anti-ferroptosis and anti-inflammatory response effect was further explored.<br><br>RESULTS: We found that pharmacological inhibition of MELK was indicated to significantly alleviate the inflammatory response in mice with colitis, reduce intestinal damage, and effectively inhibit the occurrence and progression of colitis-propelled carcinogenesis, which was closely related to the regulation of gut microbial composition, and OTSSP167-mediated fecal microbiota transplantation effectively alleviated DSS-induced colitis. In addition, OTSSP167 treatment obviously inhibited ferroptosis in the intestinal tissue and suppressed macrophage infiltration and M1 polarization, which reduced the secretion of pro-inflammatory factors. Further exploration of the molecular mechanism revealed that OTSSP167 inhibited AKT/IKK/P65 and ERK/IKK/P65 signaling cascades both in vivo and in vitro, which may help alleviate intestinal inflammation and control the occurrence of cancer.<br><br>CONCLUSION: Our findings lay a theoretical foundation for the use of OTSSP167 as a treatment for IBD and its inhibition of the occurrence of colitis-associated carcinogenesis; additionally, MELK may be a potentially effective target molecule, thus providing more options for clinical treatment.}, }
@article {pmid34142885, year = {2021}, author = {Silva, CBP and Elias-Oliveira, J and McCarthy, CG and Wenceslau, CF and Carlos, D and Tostes, RC}, title = {Ethanol: striking the cardiovascular system by harming the gut microbiota.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {321}, number = {2}, pages = {H275-H291}, pmid = {34142885}, issn = {1522-1539}, support = {K99 HL151889/HL/NHLBI NIH HHS/United States ; R00GM118885//Foundation for the National Institutes of Health (FNIH)/ ; R01 HL149762/HL/NHLBI NIH HHS/United States ; R01HL149762//Foundation for the National Institutes of Health (FNIH)/ ; R00 GM118885/GM/NIGMS NIH HHS/United States ; }, mesh = {Alcohol Drinking/immunology/*physiopathology ; Anti-Bacterial Agents/therapeutic use ; Anti-Infective Agents, Local ; Cardiovascular Diseases/immunology/*physiopathology/therapy ; Dysbiosis/immunology/*physiopathology/therapy ; Ethanol ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {Ethanol consumption represents a significant public health problem, and excessive ethanol intake is a risk factor for cardiovascular disease (CVD), one of the leading causes of death and disability worldwide. The mechanisms underlying the effects of ethanol on the cardiovascular system are complex and not fully comprehended. The gut microbiota and their metabolites are indispensable symbionts essential for health and homeostasis and therefore, have emerged as potential contributors to ethanol-induced cardiovascular system dysfunction. By mechanisms that are not completely understood, the gut microbiota modulates the immune system and activates several signaling pathways that stimulate inflammatory responses, which in turn, contribute to the development and progression of CVD. This review summarizes preclinical and clinical evidence on the effects of ethanol in the gut microbiota and discusses the mechanisms by which ethanol-induced gut dysbiosis leads to the activation of the immune system and cardiovascular dysfunction. The cross talk between ethanol consumption and the gut microbiota and its implications are detailed. In summary, an imbalance in the symbiotic relationship between the host and the commensal microbiota in a holobiont, as seen with ethanol consumption, may contribute to CVD. Therefore, manipulating the gut microbiota, by using antibiotics, probiotics, prebiotics, and fecal microbiota transplantation might prove a valuable opportunity to prevent/mitigate the deleterious effects of ethanol and improve cardiovascular health and risk prevention.}, }
@article {pmid34140459, year = {2021}, author = {Nicholson, MR and Hourigan, SK and Conrad, M and Goyal, A and Jensen, K and Kelsen, J and Kennedy, M and Weatherly, M and Kahn, SA}, title = {Current Challenges in Fecal Microbiota Transplantation for Clostridioides difficile Infection in Children.}, journal = {The American journal of gastroenterology}, volume = {116}, number = {9}, pages = {1954-1956}, pmid = {34140459}, issn = {1572-0241}, support = {K23 AI156132/AI/NIAID NIH HHS/United States ; K23 DK119585/DK/NIDDK NIH HHS/United States ; K23 HD099240/HD/NICHD NIH HHS/United States ; UL1 TR000445/TR/NCATS NIH HHS/United States ; }, mesh = {*COVID-19 ; Child ; Clostridium Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; *Practice Patterns, Physicians' ; SARS-CoV-2/*isolation &amp; purification ; Surveys and Questionnaires ; United States ; }, abstract = {INTRODUCTION: The impact of the 2019 US Food and Drug Administration safety alert involving transmission of multidrug resistant organisms through fecal microbiota transplantation (FMT), and the COVID-19 pandemic on the use of FMT in children, is unknown.<br><br>METHODS: A survey of pediatric gastroenterologists performing FMT for Clostridioides difficile infection was conducted.<br><br>RESULTS: Of 36 respondents, 17 (47%) and 30 (83%) changed their FMT practices related to the US Food and Drug Administration safety alert and COVID-19 pandemic, respectively, with 22 (61%) of programs halted.<br><br>DISCUSSION: The US Food and Drug Administration safety alert and COVID-19 pandemic have substantially influenced the availability and access of FMT for children.}, }
@article {pmid34139232, year = {2021}, author = {Chatterjee, S and Bose, D and Seth, R}, title = {Host gut microbiome and potential therapeutics in Gulf War Illness: A short review.}, journal = {Life sciences}, volume = {280}, number = {}, pages = {119717}, doi = {10.1016/j.lfs.2021.119717}, pmid = {34139232}, issn = {1879-0631}, mesh = {Animals ; Dysbiosis/microbiology/therapy/virology ; Fatty Acids, Volatile/therapeutic use ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Persian Gulf Syndrome/microbiology/*therapy/virology ; Phenols/therapeutic use ; Probiotics/therapeutic use ; }, abstract = {AIMS: Since our troops had returned from the first Persian Gulf War in 1990-91, the veterans have reported chronic multisymptomatic illness widely referred to as Gulf War Illness (GWI). We aim to review the current directions of GWI pathology research in the context of chronic multisymptomatic illness and its possible gut microbiome targeted therapies. The veterans of Gulf War show symptoms of chronic fatigue, cognitive deficits, and a subsection report of gastrointestinal complications.<br><br>METHOD: Efforts of finding a suitable treatment regimen and clinical management remain a challenge. More recently, we have shown that the pathology is connected to alterations in the gut microbiome, and efforts of finding a suitable regimen for gut-directed therapeutics are underway. We discuss the various clinical interventions and summarize the possible effectiveness of gut-directed therapies such as the use of short-chain fatty acids (SCFA), phenolic compounds, and their metabolites, use of probiotics, and fecal microbiota transfer.<br><br>SIGNIFICANCE: The short review will be helpful to GWI researchers to expand their studies to the gut and find an effective treatment strategy for chronic multisymptomatic illness.}, }
@article {pmid34139173, year = {2021}, author = {Zhu, W and Romano, KA and Li, L and Buffa, JA and Sangwan, N and Prakash, P and Tittle, AN and Li, XS and Fu, X and Androjna, C and DiDonato, AJ and Brinson, K and Trapp, BD and Fischbach, MA and Rey, FE and Hajjar, AM and DiDonato, JA and Hazen, SL}, title = {Gut microbes impact stroke severity via the trimethylamine N-oxide pathway.}, journal = {Cell host &amp; microbe}, volume = {29}, number = {7}, pages = {1199-1208.e5}, pmid = {34139173}, issn = {1934-6069}, support = {P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; R01 HL150537/HL/NHLBI NIH HHS/United States ; T32 HL134622/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification/*metabolism ; Choline/metabolism ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Methylamines/*metabolism ; Mice ; Mice, Inbred C57BL ; Oxides/*metabolism ; Severity of Illness Index ; Stroke/metabolism/*microbiology/pathology ; }, abstract = {Clinical studies have demonstrated associations between circulating levels of the gut-microbiota-derived metabolite trimethylamine-N-oxide (TMAO) and stroke incident risk. However, a causal role of gut microbes in stroke has not yet been demonstrated. Herein we show that gut microbes, through dietary choline and TMAO generation, directly impact cerebral infarct size and adverse outcomes following stroke. Fecal microbial transplantation from low- versus high-TMAO-producing human subjects into germ-free mice shows that both TMAO generation and stroke severity are transmissible traits. Furthermore, employing multiple murine stroke models and transplantation of defined microbial communities with genetically engineered human commensals into germ-free mice, we demonstrate that the microbial cutC gene (an enzymatic source of choline-to-TMA transformation) is sufficient to transmit TMA/TMAO production, heighten cerebral infarct size, and lead to functional impairment. We thus reveal that gut microbiota in general, specifically the metaorganismal TMAO pathway, directly contributes to stroke severity.}, }
@article {pmid34137411, year = {2021}, author = {Zhao, R and Ji, Y and Chen, X and Hu, Q and Zhao, L}, title = {Polysaccharide from Flammulina velutipes attenuates markers of metabolic syndrome by modulating the gut microbiota and lipid metabolism in high fat diet-fed mice.}, journal = {Food &amp; function}, volume = {12}, number = {15}, pages = {6964-6980}, doi = {10.1039/d1fo00534k}, pmid = {34137411}, issn = {2042-650X}, abstract = {Natural biological macromolecules with putative functions of gut microbiota regulation possess the advantage of improving metabolic syndrome (MS). In this research, we aimed to determine the effects of Flammulina velutipes polysaccharide (FVP) (Expt. 1) and fecal microbiota transplantation (FMT) (Expt. 2) on MS-related disorders, gut microbiota structure changes and their underlying mechanisms in a murine model fed with high-fat diet (HFD). In Expt. 1, six-week-old male C57BL/6J mice were fed with a control diet (10% calories from fat) or a high fat diet (45% calories from fat), administered with saline or FVP (0.4 mg per g b.w.) by gavage over a 12-week period. In Expt. 2, mice were fed with a HFD, administered with fecal supernatants from healthy and FVP-fed donor mice for 12 weeks simultaneously. The body mass, blood lipid levels and blood glucose homeostasis of mice were analyzed, and total RNA from mouse liver and adipose tissue were extracted by TRIzol and the lipid metabolism-related gene expressions were calculated by qRT-PCR. Gut microbiota changes were evaluated by high-throughput sequencing. Results indicated that FVP and FMT supplementations showed an attenuation effect on mouse obesity, hyperlipidemia and insulin resistance. Up-regulated expressions of Ampkα1 and Ppara were found both in FVP and FMT treatment groups. Different changes were found in the gut microbiota caused by FVP and FMT, respectively. PICRUSt analysis indicated that compared with FVP supplementation, FMT showed a significant effect on regulating lipid metabolism in HFD-fed mice. The findings from this study indicated that oral administrations of FVP or FMT could significantly attenuate MS-related obesity, hyperlipidemia and insulin resistance in HFD-fed mice, and the beneficial effects may be mediated through lipid metabolism and gut microbiota regulation in different ways. These results improve the understanding of the functional activity of FVP as prebiotics.}, }
@article {pmid34135557, year = {2021}, author = {Wen, X and Wang, HG and Zhang, MN and Zhang, MH and Wang, H and Yang, XZ}, title = {Fecal microbiota transplantation ameliorates experimental colitis via gut microbiota and T-cell modulation.}, journal = {World journal of gastroenterology}, volume = {27}, number = {21}, pages = {2834-2849}, pmid = {34135557}, issn = {2219-2840}, mesh = {Animals ; CD8-Positive T-Lymphocytes ; *Colitis/chemically induced/therapy ; *Colitis, Ulcerative/chemically induced/therapy ; Colon ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Mice ; }, abstract = {BACKGROUND: Emerging evidence has demonstrated that fecal microbiota transplantation (FMT) has a promising therapeutic effect on mice with experimental colitis and patients with ulcerative colitis (UC), although the mechanism of FMT is unclear.<br><br>AIM: To evaluate the protective effect of FMT on UC and clarify its potential dependence on the gut microbiota, through association analysis of gut microbiota with colon transcriptome in mice.<br><br>METHODS: Dextran sodium sulfate (DSS)-induced experimental colitis was established and fecal microbiota was transplanted by gavage. Severity of colon inflammation was measured by body weight, disease activity index, colon length and histological score. Gut microbiota alteration was analyzed through 16S ribosomal ribonucleic acid sequencing. The differentially expressed genes (DEGs) in the colon were obtained by transcriptome sequencing. The activation status of colonic T lymphocytes in the lamina propria was evaluated by flow cytometry.<br><br>RESULTS: Compared with the DSS group, the weight loss, colon length shortening and inflammation were significantly alleviated in the FMT group. The scores of disease activity index and colon histology decreased obviously after FMT. FMT restored the balance of gut microbiota, especially by upregulating the relative abundance of Lactobacillus and downregulating the relative abundance of Clostridium_sensu_stricto_1 and Turicibacter. In the transcriptomic analysis, 128 DEGs intersected after DSS treatment and FMT. Functional annotation analysis suggested that these DEGs were mainly involved in T-lymphocyte activation. In the DSS group, there was an increase in colonic T helper CD4+ and T cytotoxic CD8+ cells by flow cytometry. FMT selectively downregulated the ratio of colonic CD4+ and CD8+ T cells to maintain intestinal homeostasis. Furthermore, Clostri dium_sensu_stricto_1 was significantly related to inflammation-related genes including REG3G, CCL8 and IDO1.<br><br>CONCLUSION: FMT ameliorated DSS-induced colitis in mice via regulating the gut microbiota and T-cell modulation.}, }
@article {pmid34134605, year = {2021}, author = {Zhao, J and Bai, M and Yang, X and Wang, Y and Li, R and Sun, S}, title = {Alleviation of refractory IgA nephropathy by intensive fecal microbiota transplantation: the first case reports.}, journal = {Renal failure}, volume = {43}, number = {1}, pages = {928-933}, doi = {10.1080/0886022X.2021.1936038}, pmid = {34134605}, issn = {1525-6049}, mesh = {Adult ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/*physiology ; Glomerulonephritis, IGA/*therapy ; Humans ; Middle Aged ; Remission Induction ; Serum Albumin ; }, abstract = {BACKGROUND: Gut dysbiosis may be implicated in the pathogenesis of IgA nephropathy (IgAN) through immune and/or metabolite pathways. Fecal microbiota transplantation (FMT) could reestablish the micro-ecological balance in IgAN, although this has never been attempted before. We explored whether FMT could be efficacious in treating IgAN in two patients with refractory IgAN.<br><br>CASE PRESENTATION: Two Chinese female patients with IgAN failed to achieve clinical remission after receiving several rounds of immunosuppressive therapy and suffered from unbearable adverse effects due to immunosuppressants. Both patients received intensive fresh FMT conducted through transendoscopic enteral tubing (TET) regularly for 6-7 months, and were followed up for a further 6 months. Partial clinical remission was achieved in both patients, evidenced by a decrease in the 24-h urinary protein (24-hUP) to less than half of baseline during FMT treatment or follow-up, along with increased serum albumin (sAlb) and stable kidney function. The gut microbiota of both patients was distorted with lower biodiversity and altered composition, which was reversed following FMT. Phylum Proteobacteria decreased while genus Prevotella increased during and after FMT. The intensive fresh FMT was well-tolerated, and no severe adverse events occurred.<br><br>CONCLUSIONS: Preliminary evidence of the safety and efficacy of FMT for treating refractory IgAN may provide a new direction by which to decipher the pathogenesis of IgAN.}, }
@article {pmid34133889, year = {2021}, author = {Mehta, N and Wang, T and Friedman-Moraco, RJ and Carpentieri, C and Mehta, AK and Rouphael, N and Dhere, T and Larsen, CP and Kraft, CS and Woodworth, MH}, title = {Fecal Microbiota Transplantation Donor Screening Updates and Research Gaps for Solid Organ Transplant Recipients.}, journal = {Journal of clinical microbiology}, volume = {}, number = {}, pages = {JCM0016121}, doi = {10.1128/JCM.00161-21}, pmid = {34133889}, issn = {1098-660X}, abstract = {In this review, we discuss stool donor screening considerations to mitigate potential risks of pathogen transmission through fecal microbiota transplant (FMT) in solid organ transplant (SOT) recipients. SOT recipients have a higher risk for Clostridioides difficile infection (CDI) and are more likely to have severe CDI. FMT has been shown to be a valuable tool in the treatment of recurrent CDI (RCDI), however guidelines for screening for opportunistic infections transmitted through FMT are underdeveloped. We review reported adverse effects of FMT as they pertain to an immunocompromised population and discuss current understanding and recommendations for screening found in the literature while noting gaps in research. We conclude that while FMT is being performed in the SOT population, typically with positive results, there remain many unanswered questions which may have major safety implications and warrant further study.}, }
@article {pmid34133861, year = {2021}, author = {Bajaj, JS and Kamath, PS and Reddy, KR}, title = {The Evolving Challenge of Infections in Cirrhosis.}, journal = {The New England journal of medicine}, volume = {384}, number = {24}, pages = {2317-2330}, doi = {10.1056/NEJMra2021808}, pmid = {34133861}, issn = {1533-4406}, mesh = {Algorithms ; Anti-Bacterial Agents/therapeutic use ; Bacterial Infections/diagnosis/*etiology/therapy ; Candidiasis/etiology ; Chronic Disease ; Cross Infection/etiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Hospital Mortality ; Humans ; Liver Cirrhosis/*complications/immunology/mortality ; Phage Therapy ; Risk Factors ; Sepsis/etiology ; }, }
@article {pmid34126062, year = {2021}, author = {Nooij, S and Ducarmon, QR and Laros, JFJ and Zwittink, RD and Norman, JM and Smits, WK and Verspaget, HW and Keller, JJ and Terveer, EM and Kuijper, EJ and , }, title = {Fecal Microbiota Transplantation Influences Procarcinogenic Escherichia coli in Recipient Recurrent Clostridioides difficile Patients.}, journal = {Gastroenterology}, volume = {161}, number = {4}, pages = {1218-1228.e5}, doi = {10.1053/j.gastro.2021.06.009}, pmid = {34126062}, issn = {1528-0012}, abstract = {BACKGROUND &amp; AIMS: Patients with multiple recurrent Clostridioides difficile infection (rCDI) have a disturbed gut microbiota that can be restored by fecal microbiota transplantation (FMT). Despite extensive screening, healthy feces donors may carry bacteria in their intestinal tract that could have long-term health effects, such as potentially procarcinogenic polyketide synthase-positive (pks+) Escherichia coli. Here, we aim to determine whether the pks abundance and persistence of pks+E coli is influenced by pks status of the donor feces.<br><br>METHODS: In a cohort of 49 patients with rCDI treated with FMT and matching donor samples-the largest cohort of its kind, to our knowledge-we retrospectively screened fecal metagenomes for pks+E coli and compared the presence of pks in patients before and after treatment and to their respective donors.<br><br>RESULTS: The pks island was more prevalent (P = .026) and abundant (P < .001) in patients with rCDI (pre-FMT, 27 of 49 [55%]; median, 0.46 reads per kilobase per million [RPKM] pks) than in healthy donors (3 of 8 donors [37.5%], 11 of 38 samples [29%]; median, 0.01 RPKM pks). The pks status of patients post-FMT depended on the pks status of the donor suspension with which the patient was treated (P = .046). Particularly, persistence (8 of 9 cases) or clearance (13 of 18) of pks+E coli in pks+ patients was correlated to pks in the donor (P = .004).<br><br>CONCLUSIONS: We conclude that FMT contributes to pks+E coli persistence or eradication in patients with rCDI but that donor-to-patient transmission of pks+E coli is unlikely.}, }
@article {pmid34120835, year = {2021}, author = {Biruete, A and Cross, TL and Allen, JM and Kistler, BM and de Loor, H and Evenepoel, P and Fahey, GC and Bauer, L and Swanson, KS and Wilund, KR}, title = {Effect of Dietary Inulin Supplementation on the Gut Microbiota Composition and Derived Metabolites of Individuals Undergoing Hemodialysis: A Pilot Study.}, journal = {Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation}, volume = {31}, number = {5}, pages = {512-522}, pmid = {34120835}, issn = {1532-8503}, support = {T32 DK120524/DK/NIDDK NIH HHS/United States ; }, abstract = {OBJECTIVE: The prebiotic fiber inulin has been studied in individuals undergoing hemodialysis (HD) due to its ability to reduce gut microbiota-derived uremic toxins. However, studies examining the effects of inulin on the gut microbiota and derived metabolites are limited in these patients. We aimed to assess the impact of a 4-week supplementation of inulin on the gut microbiota composition and microbial metabolites of patients on HD.<br><br>DESIGN AND METHODS: In a randomized, double-blind, placebo-controlled, crossover study, twelve HD patients (55 ± 10 y, 50% male, 58% Black American, BMI 31.6 ± 8.9 kg/m2, 33% diabetes mellitus) were randomized to consume inulin [10 g/d for females; 15 g/d for males] or maltodextrin [6 g/d for females; 9 g/d for males] for 4 weeks, with a 4-week washout period. We assessed the fecal microbiota composition, fecal metabolites (short-chain fatty acids (SCFA), phenols, and indoles), and plasma indoxyl sulfate and p-cresyl sulfate.<br><br>RESULTS: At baseline, factors that explained the gut microbiota variability included BMI category and type of phosphate binder prescribed. Inulin increased the relative abundance of the phylum Verrucomicrobia and its genus Akkermansia (P interaction = 0.045). Inulin and maltodextrin resulted in an increased relative abundance of the phylum Bacteroidetes and its genus Bacteroides (P time = 0.04 and 0.03, respectively). Both treatments increased the fecal acetate and propionate (P time = 0.032 and 0.027, respectively), and there was a trend toward increased fecal butyrate (P time = 0.06). Inulin did not reduce fecal p-cresol or indoles, or plasma concentrations of p-cresyl sulfate or indoxyl sulfate.<br><br>CONCLUSIONS: A 4-week supplementation of inulin did not lead to major shifts in the fecal microbiota and gut microbiota-derived metabolites. This may be due to high variability among participants and an unexpected increase in fecal excretion of SCFA with maltodextrin. Larger studies are needed to determine the effects of prebiotic fibers on the gut microbiota and clinical outcomes to justify their use in patients on HD.}, }
@article {pmid34118466, year = {2021}, author = {Yeh, YM and Cheng, HT and Le, PH and Chen, CC and Kuo, CJ and Chen, CL and Chiu, CT and Chiu, CH}, title = {Implementation of fecal microbiota transplantation in a medical center for recurrent or refractory Clostridioides difficile infection and report of preliminary outcome.}, journal = {Biomedical journal}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bj.2021.06.001}, pmid = {34118466}, issn = {2320-2890}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been shown to highly effective in the treatment of recurrent or refractory Clostridioides difficile infection (rCDI) in many countries of the world. Not until 2018, Ministry of Health and Welfare, Taiwan approved the application of FMT for rCDI under a special law. The study reported the first implementation of the technology in the medical center in Taiwan and the preliminary outcome.<br><br>METHODS: FMT was used to treat patients with rCDI in Chang Gung Memorial Hospital. FMT was delivered by gastroenterologists using colonoscope. Strict donor screening was performed according to the guidelines. We followed up the clinical course of patients after FMT. 16S rRNA sequencing of fecal samples for donor, and also recipient before and after FMT was carried out.<br><br>RESULTS: From September 2018 to June 2020, 39 patients with rCDI received FMT, with a successful rate of 89.7%. Two patients died due to causes unrelated to FMT, and two other cases showed no clinical improvement after the procedure. High school and college students showed the best pass rate during donor screening. The presence of multi-drug resistant pathogen was the most common cause for screening failure. We demonstrated in a case the use of rRNA sequencing as a biomarker indicating for the improvement of dysbiosis in a patient after FMT.<br><br>CONCLUSIONS: FMT was successfully implemented in a medical center in Taiwan and showed a comparable successful rate in treating rCDI, compared to other countries. Safety remains the most important issue when applying FMT in the clinical setting.}, }
@article {pmid34118462, year = {2021}, author = {Li, Y and Cao, W and Gao, NL and Zhao, XM and Chen, WH}, title = {Consistent Alterations of Human Fecal Microbes after Transplantation into Germ-free Mice.}, journal = {Genomics, proteomics &amp; bioinformatics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.gpb.2020.06.024}, pmid = {34118462}, issn = {2210-3244}, abstract = {Fecal microbiota transplantation (FMT) of human fecal samples into germ-free (GF) mice is useful for establishing causal relationships between the gut microbiota and human phenotypes. However, due to the intrinsic differences between human and mouse intestines and the different diets of the two organisms, it may not be possible to replicate human phenotypes in mice through FMT; similarly, treatments that are effective in mouse models may not be effective in humans. In this study, we aimed to identify human gut microbes that undergo significant and consistent changes (i.e., in relative abundances) after transplantation into GF mice in multiple experimental settings. We collected 16S rDNA-seq data from four published studies and analyzed the gut microbiota profiles from 1713 human-mouse pairs. Strikingly, on average, we found that only 47% of the human gut microbes could be re-established in mice at the species level, among which more than 1/3 underwent significant changes (referred to as "variable taxa"). Most of the human gut microbes that underwent significant changes were consistent across multiple human-mouse pairs and experimental settings. Consequently, about 1/3 of human samples changed their enterotypes, i.e., significant changes in their leading species after FMT. Mice fed with a controlled diet showed a lower enterotype change rate (23.5%) than those fed with a noncontrolled diet (49.0%), suggesting a possible solution for rescue. Most of the variable taxa have been reported to be implicated in human diseases, with some recognized as the causative species. Our results highlight the challenges of using a mouse model to replicate human gut microbiota-associated phenotypes, provide useful information for researchers using mice in gut microbiota studies, and call for additional validations after FMT. An online database named FMT-DB is publicly available at http://fmt2mice.humangut.info/#/.}, }
@article {pmid34118321, year = {2021}, author = {Núñez F, P and Quera, R and Bay, C and Thomson, P}, title = {Fecal microbiota transplant, its usefulness beyond Clostridioides difficile in gastrointestinal diseases.}, journal = {Gastroenterologia y hepatologia}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.gastrohep.2021.05.009}, pmid = {34118321}, issn = {0210-5705}, abstract = {Fecal microbiota transplant (FMT) is currently recommended for recurrent Clostridioidesdifficile infection. However, it is interesting to acknowledge the potential therapeutic role in other diseases associated with dysbiosis. This review will focus on the current and potential indications of FMT in gastrointestinal diseases, evaluating the available evidence and also exposing the necessary requirements to carry it out.}, }
@article {pmid34116562, year = {2021}, author = {Wu, Y and Chen, Y and Li, Q and Ye, X and Guo, X and Sun, L and Zou, J and Shen, Y and Mao, Y and Li, C and Yang, Y}, title = {Tetrahydrocurcumin alleviates allergic airway inflammation in asthmatic mice by modulating the gut microbiota.}, journal = {Food &amp; function}, volume = {12}, number = {15}, pages = {6830-6840}, doi = {10.1039/d1fo00194a}, pmid = {34116562}, issn = {2042-650X}, abstract = {Dietary factors can reshape the gut microbiota and consequently affect disease progression. We previously reported that tetrahydrocurcumin (THC), the major active metabolite of curcumin (Cur), could ameliorate allergic inflammation in asthmatic mice. Herein, we aimed to investigate whether THC or Cur exerts anti-inflammatory effects on allergic asthma via modulating gut microbiota. Ovalbumin (OVA)-induced asthmatic mice were treated with Cur or THC, and the gut microbiota profiles were analyzed by 16S rRNA sequencing. Fecal microbiota transplantation (FMT) from Cur- or THC-fed donor mice was administered to OVA-induced asthmatic mice. Nasal symptoms and inflammation patterns of lungs and colons were evaluated in control, OVA-induced and Cur-or THC-treated mice. Both Cur and THC treatment could alter the compositions of the gut microbiota in asthmatic mice, characterized by a significant decrease in the ratio of Firmicutes to Bacteroidetes; Cur or THC supplementation also reduced the relative abundances of pro-inflammatory bacteria, e.g., Proteobacteria, Intestinimonas, Unidentified-Ruminococcaceae, and Lachnospiraceae, in OVA-induced mice. The relative abundances of Unidentified-Ruminococcaceae, Romboutsia, Intestinimonas, Akkermansia, and Mucispirillum were positively associated with the levels of Th2-related factors in asthmatic mice upon Cur or THC treatment. Moreover, THC-FMT showed better preventive effects than Cur-FMT on the development of allergic inflammation in OVA-induced mice, resulting in a reduction in symptoms and Th2-mediated inflammation in both lung and colon tissues. The results reveal that Cur- or THC-mediated alleviation of airway allergic inflammation is dependent on gut microbiota modulation. THC-induced gut microbiota may have therapeutic potential for asthma treatment.}, }
@article {pmid34111616, year = {2021}, author = {Shao, S and Jia, R and Zhao, L and Zhang, Y and Guan, Y and Wen, H and Liu, J and Zhao, Y and Feng, Y and Zhang, Z and Ji, Q and Li, Q and Wang, Y}, title = {Xiao-Chai-Hu-Tang ameliorates tumor growth in cancer comorbid depressive symptoms via modulating gut microbiota-mediated TLR4/MyD88/NF-κB signaling pathway.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {88}, number = {}, pages = {153606}, doi = {10.1016/j.phymed.2021.153606}, pmid = {34111616}, issn = {1618-095X}, mesh = {Animals ; Antidepressive Agents/pharmacology ; Antineoplastic Agents/*pharmacology ; Colorectal Neoplasms/*drug therapy/metabolism/pathology ; Comorbidity ; Depression/drug therapy/epidemiology/*pathology ; Drugs, Chinese Herbal/*pharmacology ; Dysbiosis/drug therapy/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Male ; Mice, Inbred C57BL ; Middle Aged ; Myeloid Differentiation Factor 88/metabolism ; NF-kappa B/metabolism ; Toll-Like Receptor 4/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: Depressive symptoms are thought to promote cancer development and depressive remission has been reported to be effective for defeating cancer. The herbal formula Xiao-Chai-Hu-Tang (XCHT), that has an anti-depressive efficacy, has been widely utilized in China. However, its anti-cancer effect and underlying mechanisms remain unclear.<br><br>PURPOSE: The present study aims to investigate the effects of XCHT on the depression-associated tumor and its potential mechanisms.<br><br>METHODS: A placebo-controlled trial was conducted in cancer patients comorbid with depressive symptoms to evaluate the effects of XCHT on depressive scales, tumor-related immune indicators, and gut microbial composition. A xenografted colorectal cancer (CRC) mouse model exposure to chronic restraint stress (CRS) was established to examine XCHT effects on tumorigenesis in vivo. Further, by manipulating gut bacteria with fecal microbial transplantation (FMT) or antibiotics-induced bacterial elimination in CRS-associated xenografted model, gut microbiota-mediated anti-tumor mechanism was explored.<br><br>RESULTS: In cancer patients comorbid with depressive symptoms, XCHT showed substantial effects on improvement of depressive scales, system inflammatory levels and gut dysbiosis. In vivo, XCHT inhibited tumor growth and prolonged survival time in addition to showing anti-depressive effect. Similarly, in our clinical trial, XCHT partially reversed gut dysbiosis, particularly through reducing abundances of Parabacteroides, Blautia and Ruminococcaceae bacterium. Manipulation of gut bacteria in CRS-associated xenografted model further proved that the inhibition of XCHT on tumor progression was mediated by gut microbiota and that the underlying mechanism involves in downregulation of TLR4/MyD88/NF-κB signaling.<br><br>CONCLUSIONS: We demonstrated that gut microbiota mediates the anti-tumor action of the formula XCHT in cancer patients and models that were comorbid with depressive symptoms. This study implies a novel clinical significance of anti-depressive herbal medicine in the cancer treatment and clarifies the important role of gut microbiota in treating cancer accompanied by depressive symptoms.}, }
@article {pmid34111528, year = {2021}, author = {Wang, M and Cao, J and Gong, C and Amakye, WK and Yao, M and Ren, J}, title = {Exploring the microbiota-Alzheimer's disease linkage using short-term antibiotic treatment followed by fecal microbiota transplantation.}, journal = {Brain, behavior, and immunity}, volume = {96}, number = {}, pages = {227-238}, doi = {10.1016/j.bbi.2021.06.003}, pmid = {34111528}, issn = {1090-2139}, mesh = {*Alzheimer Disease/therapy ; Amyloid beta-Peptides ; Animals ; Anti-Bacterial Agents ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Mice ; Mice, Transgenic ; *Microbiota ; }, abstract = {Gut microbiota is proven to be involved in the development of beta amyloid (Aβ) pathology in Alzheimer's disease (AD). Since there are difficulties in translating microbiota findings based on germ-free mice into clinical practice, here, we used short-term antibiotic cocktail treatment to develop a novel model with a near-germ-free status and without impacting Aβ pathology. Three months old APPSWE/PS1ΔE9 mice were fed with antibiotic cocktails for two weeks by gavage to obtain a near "germ-free" status, and then received the donor fecal matter from the 16 months old APPSWE/PS1ΔE9 mice for 7 consecutive days. Fecal pellets were collected prior to antibiotics treatment, following antibiotic exposure, prior to and following fecal microbiota transplantation for gut microbiota analysis. Also, Aβ pathology, astrocyte and microglia morphology were further explored. Pre-antibiotic-treated mice successfully allowed engraftment of gut microbiota following 7 consecutive days gavage with aged APPSWE/PS1ΔE9 mice microbiota. Microbiota reconstitution by transplantation was largely attributable to the donor source (e.g. g_Coriobacteriaceae and g_Clostridium) and led to a significant increase in Aβ plaques. Surprisingly, astrocyte activation around Aβ plaques was suppressed rather than microglia, the well-recognized plaque phagocytic cell type in Aβ clearance, following microbiota engraftment. Our findings provide a novel framework for understanding the mechanisms of AD through the gut-brain axis and the translation of gut microbiota manipulation from bench to clinical practice.}, }
@article {pmid34108292, year = {2021}, author = {Seo, HS and Chin, HS and Kim, YH and Moon, HS and Kim, K and Nguyen, LP and Yong, D}, title = {Laboratory Aspects of Donor Screening for Fecal Microbiota Transplantation at a Korean Fecal Microbiota Bank.}, journal = {Annals of laboratory medicine}, volume = {41}, number = {6}, pages = {612}, doi = {10.3343/alm.2021.41.6.612}, pmid = {34108292}, issn = {2234-3814}, }
@article {pmid34106090, year = {2021}, author = {Babiker, A and Ingersoll, JM and Adelman, MW and Webster, AS and Broder, KJ and Stittleburg, V and Waggoner, JJ and Kraft, CS and Woodworth, MH}, title = {Validation of High-Sensitivity Severe Acute Respiratory Syndrome Coronavirus 2 Testing for Stool-Toward the New Normal for Fecal Microbiota Transplantation.}, journal = {Clinical and translational gastroenterology}, volume = {12}, number = {6}, pages = {e00363}, pmid = {34106090}, issn = {2155-384X}, support = {P30 AI050409/AI/NIAID NIH HHS/United States ; K23 AI144036/AI/NIAID NIH HHS/United States ; }, mesh = {COVID-19/diagnosis/epidemiology/*transmission/virology ; COVID-19 Testing/*methods/statistics &amp; numerical data ; Centers for Disease Control and Prevention, U.S./standards ; Fecal Microbiota Transplantation/*methods/statistics &amp; numerical data ; Feces/*virology ; Humans ; Nasopharynx/virology ; RNA, Viral/genetics ; Reverse Transcriptase Polymerase Chain Reaction/methods ; SARS-CoV-2/*genetics/isolation &amp; purification ; Tissue Donors/supply &amp; distribution ; United States ; }, abstract = {INTRODUCTION: Mounting evidence demonstrates potential for fecal-oral transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The US Food and Drug Administration now requires SARS-CoV-2 testing of potential feces donors before the use of stool manufactured for fecal microbiota transplantation. We sought to develop and validate a high-sensitivity SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) procedure for testing stool specimens.<br><br>METHODS: A modified extraction method was used with an RT-PCR assay adapted from the Centers for Disease Control and Prevention PCR protocol for respiratory specimens. Contrived specimens were created using pre-COVID-19 banked stool specimens and spiking in known concentrations of SARS-CoV-2-specific nucleic acid. The highest transcript concentration at which 2/2 or 1/2 SARS-CoV-2 targets were detected in 9/10 replicates was defined as the dual-target limit and single-target limit of detection, respectively. The clinical performance of the assay was evaluated with stool samples collected from 17 nasopharyngeal swab RT-PCR-positive patients and 14 nasopharyngeal RT-PCR-negative patients.<br><br>RESULTS: The dual-target and single-target limit of detection were 56 copies/μL and 3 copies/μL, respectively. SARS-CoV-2 was detected at concentrations as low as 0.6 copies/μL. Clinical stool samples from known COVID-19-positive patients demonstrated the detection of SARS-CoV-2 in stool up to 29 days from symptom onset with a high agreement with nasopharyngeal swab tests (kappa statistic of 0.95, P value < 0.001).<br><br>DISCUSSION: The described RT-PCR test is a sensitive and flexible approach for the detection of SARS-CoV-2 in stool specimens. We propose an integrated screening approach that incorporates this stool test to support continuation of fecal microbiota transplantation programs.}, }
@article {pmid34104214, year = {2021}, author = {Gupta, A and Ananthakrishnan, AN}, title = {Economic burden and cost-effectiveness of therapies for Clostridiodes difficile infection: a narrative review.}, journal = {Therapeutic advances in gastroenterology}, volume = {14}, number = {}, pages = {17562848211018654}, pmid = {34104214}, issn = {1756-283X}, abstract = {Clostridioides difficile is the most common cause of healthcare-associated diarrhea. Disease complications as well as recurrent infections contribute significantly to morbidity and mortality. Over the past decades, there has been a rapid increase in the incidence of C. difficile infection (CDI), with a rise in the number of community-acquired cases. CDI has a profound economic impact on both the healthcare system and patients, secondary to recurrences, hospitalization, prolonged length of stay, cost of treatment, and indirect societal costs. With emergence of newer treatment options, the standard of care is shifting from metronidazole and vancomycin towards fidaxomicin and fecal microbiota transplantation (FMT), which despite being more expensive, are more efficacious in preventing recurrences and hence overall are more beneficial forms of therapy per cost-effectiveness analyses. Data regarding preferred route of FMT, timing of FMT, and non-conventional therapies such as bezlotoxumab is scant. There is a need for further studies to elucidate the true attributable costs of CDI as well as continued cost-effectiveness research to reduce the economic burden associated with the disease and improve clinical practice.}, }
@article {pmid34101828, year = {2021}, author = {Fillon, M}, title = {Fecal microbiota transplants may aid melanoma immunotherapy resistance.}, journal = {CA: a cancer journal for clinicians}, volume = {71}, number = {4}, pages = {285-286}, doi = {10.3322/caac.21676}, pmid = {34101828}, issn = {1542-4863}, mesh = {Fecal Microbiota Transplantation ; Humans ; Immunotherapy ; *Melanoma/therapy ; *Microbiota ; }, }
@article {pmid34099716, year = {2021}, author = {Choi, BS and Daniel, N and Houde, VP and Ouellette, A and Marcotte, B and Varin, TV and Vors, C and Feutry, P and Ilkayeva, O and Ståhlman, M and St-Pierre, P and Bäckhed, F and Tremblay, A and White, PJ and Marette, A}, title = {Feeding diversified protein sources exacerbates hepatic insulin resistance via increased gut microbial branched-chain fatty acids and mTORC1 signaling in obese mice.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {3377}, pmid = {34099716}, issn = {2041-1723}, support = {FDN-143247//CIHR/Canada ; }, mesh = {Animal Feed/adverse effects ; Animals ; Cell Line, Tumor ; Diet, High-Fat/adverse effects ; Diet, Western/adverse effects ; Dietary Proteins/*adverse effects ; Dietary Sucrose/adverse effects ; Disease Models, Animal ; Fatty Acids/*metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Germ-Free Life ; Gluconeogenesis ; Hepatocytes ; Humans ; *Insulin Resistance ; Liver/metabolism/pathology ; Male ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice ; Obesity/*etiology/metabolism/pathology ; Rats ; Ribosomal Protein S6 Kinases, 90-kDa/metabolism ; Signal Transduction ; }, abstract = {Animal models of human diseases are classically fed purified diets that contain casein as the unique protein source. We show that provision of a mixed protein source mirroring that found in the western diet exacerbates diet-induced obesity and insulin resistance by potentiating hepatic mTORC1/S6K1 signaling as compared to casein alone. These effects involve alterations in gut microbiota as shown by fecal microbiota transplantation studies. The detrimental impact of the mixed protein source is also linked with early changes in microbial production of branched-chain fatty acids (BCFA) and elevated plasma and hepatic acylcarnitines, indicative of aberrant mitochondrial fatty acid oxidation. We further show that the BCFA, isobutyric and isovaleric acid, increase glucose production and activate mTORC1/S6K1 in hepatocytes. Our findings demonstrate that alteration of dietary protein source exerts a rapid and robust impact on gut microbiota and BCFA with significant consequences for the development of obesity and insulin resistance.}, }
@article {pmid34096956, year = {2021}, author = {Han, Z and Yao, L and Zhong, Y and Xiao, Y and Gao, J and Zheng, Z and Fan, S and Zhang, Z and Gong, S and Chang, S and Cui, X and Cai, J}, title = {Gut microbiota mediates the effects of curcumin on enhancing Ucp1-dependent thermogenesis and improving high-fat diet-induced obesity.}, journal = {Food &amp; function}, volume = {12}, number = {14}, pages = {6558-6575}, doi = {10.1039/d1fo00671a}, pmid = {34096956}, issn = {2042-650X}, mesh = {Animals ; Anti-Obesity Agents/pharmacology ; Bile Acids and Salts/metabolism ; Curcumin/*pharmacology ; Diet, High-Fat/adverse effects ; Energy Metabolism/drug effects ; G-Protein-Coupled Receptor Kinase 5/metabolism ; Gastrointestinal Microbiome/*drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/*drug therapy/metabolism ; Thermogenesis/*drug effects ; Uncoupling Protein 1/*metabolism ; Weight Gain/drug effects ; }, abstract = {Due to extremely poor systemic bioavailability, the mechanism by which curcumin increases energy expenditure remains unelucidated. Accumulating evidence suggests a strong association between the gut microbiota (GM) and energy metabolism. We investigated whether the GM mediates the effects of curcumin on improving energy homeostasis. High-fat diet (HFD)-fed wild type, uncoupling protein 1 (Ucp1) knockout and G protein-coupled membrane receptor 5 (TGR5) knockout mice were treated with curcumin (100 mg kg-1 d-1, p.o.). Curcumin-treated HFD-fed mice displayed decreased body weight gain and augmented cold tolerance due to enhanced adaptive thermogenesis as compared with that in control mice. The anti-obesity effects of curcumin were abolished by Ucp1 knockout. 16S ribosomal DNA sequencing analysis revealed that curcumin restructured the GM in HFD-fed mice. Fecal microbiota transplantation (FMT) and endogenous GM depletion indicated that the GM mediated the enhanced effect of curcumin on Ucp1-dependent thermogenesis. Curcumin altered bile acid (BA) metabolism with increased fractions of circulating deoxycholic acid (DCA) and lithocholic acid (LCA), which are the two most potent ligands for TGR5. Consistently, the enhanced effect of curcumin on Ucp1-dependent thermogenesis was eliminated by TGR5 knockout. Curcumin requires the GM and TGR5 to activate the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway in thermogenic adipose tissue. Here, we demonstrated that the GM mediates the effects of curcumin on enhancing Ucp1-dependent thermogenesis and ameliorating HFD-induced obesity by influencing BA metabolism. We disclosed the potential of nutritional and pharmacologic manipulations of the GM to enhance Ucp1-dependent thermogenesis in the prevention and treatment of obesity.}, }
@article {pmid34093740, year = {2021}, author = {Fu, Y and Luo, Y and Grinspan, AM}, title = {Epidemiology of community-acquired and recurrent Clostridioides difficile infection.}, journal = {Therapeutic advances in gastroenterology}, volume = {14}, number = {}, pages = {17562848211016248}, pmid = {34093740}, issn = {1756-283X}, abstract = {Clostridioides difficile infection is a leading cause of healthcare-associated infections with significant morbidity and mortality. For the past decade, the bulk of infection prevention and epidemiologic surveillance efforts have been directed toward mitigating hospital-acquired C. difficile. However, the incidence of community-associated infection is on the rise. Patients with community-associated C. difficile tend to be younger and have lower mortality rate. Rates of recurrent C. difficile infection overall have decreased in the United States, but future research and public health endeavors are needed to standardize and improve disease detection, stratify risk factors in large-scale population studies, and to identify regional and local variations in strain types, reservoirs and transmission routes to help characterize and combat the changing epidemiology of C. difficile.}, }
@article {pmid34092246, year = {2021}, author = {Wu, Y and He, F and Zhang, C and Zhang, Q and Su, X and Zhu, X and Liu, A and Shi, W and Lin, W and Jin, Z and Yang, H and Lin, J}, title = {Melatonin alleviates titanium nanoparticles induced osteolysis via activation of butyrate/GPR109A signaling pathway.}, journal = {Journal of nanobiotechnology}, volume = {19}, number = {1}, pages = {170}, pmid = {34092246}, issn = {1477-3155}, support = {81871789//National Natural Science Foundation of China/ ; 31771063//National Natural Science Foundation of China (CN)/ ; 81802200//National Natural Science Foundation of China (CN)/ ; 82171333//National Natural Science Foundation of China (CN)/ ; 82101033//National Natural Science Foundation of China (CN)/ ; BK20180052//Natural Science Foundation of Jiangsu Province (CN)/ ; GSWS2020023//Gusu Health Talents Program/ ; }, mesh = {Animals ; Butyrates/*metabolism ; Fatty Acids, Volatile ; Feces/microbiology ; Gastrointestinal Microbiome/drug effects ; Homeostasis ; Male ; Melatonin/chemistry/metabolism/*pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Nanoparticles/chemistry/therapeutic use ; Osteolysis/metabolism/pathology/*prevention &amp; control ; RNA, Ribosomal, 16S ; Receptors, G-Protein-Coupled/*genetics/*metabolism ; Signal Transduction/*drug effects ; Titanium/chemistry/metabolism/*pharmacology ; }, abstract = {BACKGROUND: Inflammatory osteolysis after total joint replacement (TJR) may cause implant failure, periprosthetic fractures, and be a severe threat to global public health. Our previous studies demonstrated that melatonin had a therapeutic effect on wear-particles induced osteolysis. Gut microbiota is closely related to bone homeostasis, and has been proven to be affected by melatonin. However, whether melatonin could play its anti-osteolysis effects through reprogramming gut microbiota remains elusive.<br><br>RESULTS: Here, we demonstrated that melatonin could alleviate Ti-particles induced osteolysis, while this therapeutic effect was blocked by antibiotic cocktail treatment. Interestingly, transplantation of fecal microbiota from mice treated with melatonin reappeared the same beneficial effect. Analysis of the 16S rRNA revealed that melatonin could reverse dysbacteriosis triggered by osteolysis, and elevate the relative abundance of some short chain fatty acid (SCFA) producing bacteria. Moreover, butyrate was enriched by exogenous melatonin administration, while acetate and propionate did not show an evident difference. This was consistent with the results of the metagenomic approach (PICRUSt2) analysis, which revealed a general increase in the synthetic enzymes of butyrate. More importantly, direct supplementation of butyrate could also recapitulate the anti-osteolysis effect of melatonin. Further analysis identified that butyrate alleviated osteolysis via activating its receptor GPR109A, and thus to suppress the activation of NLRP3 inflammasome triggered by Ti-particles.<br><br>CONCLUSIONS: Taken together, our results suggested that the benefits of melatonin mainly depend on the ability of modulating gut microbiota and regulating butyrate production.}, }
@article {pmid34090885, year = {2021}, author = {Ianiro, G and Giambò, F and Cammarota, G}, title = {Residual Gastrointestinal Symptoms after Fecal Microbiota Transplantation for Clostridioides difficile Infection: A Matter of Efficacy Rather Than Safety?.}, journal = {Gastroenterology}, volume = {161}, number = {4}, pages = {1344}, doi = {10.1053/j.gastro.2021.06.002}, pmid = {34090885}, issn = {1528-0012}, }
@article {pmid34089791, year = {2021}, author = {Wang, J and Zheng, S and Yang, X and Huazeng, B and Cheng, Q}, title = {Influences of non-IgE-mediated cow's milk protein allergy-associated gut microbial dysbiosis on regulatory T cell-mediated intestinal immune tolerance and homeostasis.}, journal = {Microbial pathogenesis}, volume = {158}, number = {}, pages = {105020}, doi = {10.1016/j.micpath.2021.105020}, pmid = {34089791}, issn = {1096-1208}, mesh = {Animals ; Cattle ; Dysbiosis ; Female ; *Gastrointestinal Microbiome ; Homeostasis ; Immune Tolerance ; Mice ; *Milk Hypersensitivity ; RNA, Ribosomal, 16S/genetics ; T-Lymphocytes, Regulatory ; }, abstract = {Gut microbial dysbiosis is closely associated with cow's milk protein allergy (CMPA) during infancy. Recent research has highlighted the crucial role of the commensal microbiota-induced intestinal regulatory T (Treg) cell response in the development of oral tolerance and protection against IgE-mediated food allergies. However, the influences of CMPA (particularly non-IgE-mediated CMPA)-associated microbial dysbiosis on Treg cell-mediated intestinal immune tolerance and homeostasis remain poorly characterized. To investigate this issue, fecal microbiota from infant donors with food protein-induced allergic proctocolitis (FPIAP) associated with cow's milk, which is the most frequent clinical type of non-IgE-mediated gastrointestinal CMPA, and from age-matched healthy controls were transplanted into germ-free mice in this study. Two weeks post fecal microbiota transplantation, the gut microbiome of the recipient mice was analyzed by 16S rRNA gene sequencing, and the intestinal immunological alterations associated with the Treg cell compartment and intestinal immune homeostasis were detected. The specific gut microbial phylotypes that were potentially responsible for the disruption of intestinal immune homeostasis were also analyzed. We observed that the main characteristics of the gut microbiome in infant donors could be stably maintained in recipient mice. We also found that mice colonized with the gut microbiome from infants with cow's milk-induced FPIAP showed significant deficiencies in the accumulation and function of intestinal Treg cells. Furthermore, these mice showed disrupted intestinal immune homeostasis, which was characterized by an overactivated Th2 biased immune response. We further identified two potentially pathogenic genera that contribute to this disruption. Overall, our results highlight a destructive effect of non-IgE-mediated CMPA-associated microbial dysbiosis on intestinal immune tolerance and homeostasis. We believe these findings will help improve our understanding of the gut microbiota-mediated pathogenesis of non-IgE-mediated CMPA in the future.}, }
@article {pmid34089134, year = {2021}, author = {Mendelsohn, RB and Kaltsas, A and King, S and Hwang, C and Kassam, Z and Abend, AM and Kramer, E and Kamboj, M}, title = {Fecal Microbiota Transplantation Is Safe for Clostridiodies difficile Infection in Patients with Solid Tumors Undergoing Chemotherapy.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {34089134}, issn = {1573-2568}, abstract = {BACKGROUND: Recurrent Clostridiodies difficile infection (CDI) contributes to morbidity and mortality in cancer patients. Fecal microbiota transplantation (FMT) has been proven to be effective in treatment of recurrent CDI, but immunocompromised patients have been excluded from prospective studies due to safety concerns. The aim of this study was to investigate the safety of FMT for recurrent CDI in immunocompromised patients with solid tumor malignancy undergoing chemotherapy.<br><br>METHODS: This was a single center, prospective observational study of patients at a tertiary care cancer center of 10 patients with recurrent CDI who were at least 18 years of age, with a solid tumor malignancy who had received chemotherapy within the previous 6 months. Patients received FMT either by upper endoscopy or colonoscopy and were followed for 6 months. Safety was a primary outcome measured by infections occurring within 2 weeks of FMT. Efficacy of FMT was also evaluated.<br><br>RESULTS: Nineteen patients were evaluated. On applying exclusion criteria, 10 were included in the study. One patient requested to be off study within 2 weeks and was considered a treatment failure. Seven received FMT via upper endoscopy, three via colonoscopy. There were no infectious complications from FMT. Eight patients (80%) were cured after the first FMT. All eight patients went on to restart oncologic treatment with an average of 32.5 days after FMT.<br><br>CONCLUSIONS: FMT is safe and effective for recurrent CDI in solid tumor patients undergoing chemotherapy. Patients can resume oncologic treatment after FMT.}, }
@article {pmid34088413, year = {2021}, author = {Khanna, S and Tande, A and Rubin, DT and Khoruts, A and Kahn, SA and Pardi, DS}, title = {Fecal Microbiota Transplantation for Recurrent C difficile Infection During the COVID-19 Pandemic: Experience and Recommendations.}, journal = {Mayo Clinic proceedings}, volume = {96}, number = {6}, pages = {1418-1425}, pmid = {34088413}, issn = {1942-5546}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R24 AI118629/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; COVID-19/diagnosis/*epidemiology/prevention &amp; control ; *Clostridioides difficile ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; SARS-CoV-2 ; Young Adult ; }, abstract = {OBJECTIVE: To report experience with fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) and provide recommendations for management of rCDI and donor testing during the COVID-19 pandemic.<br><br>METHODS: A retrospective study of patients with rCDI who underwent FMT from May 26, 2020, to September 30, 2020, with stool from well-screened donors with health and infectious screening and a newly implemented strategy for COVID-19 screening with every 2-week bookend testing with stool quarantine. Patients were followed up for development of rCDI and COVID-19.<br><br>RESULTS: Of the 57 patients who underwent FMT for rCDI, 29 were tested for COVID-19 via nasopharyngeal polymerase chain reaction (PCR) and 22 via serology. All results were negative, except for 1 positive serology. Donor testing every 2 weeks for COVID-19 via serology and nasopharyngeal swab PCR was negative, except for 2 donors at 1 center who were excluded. Three patients had rCDI after FMT, and 1 underwent repeat FMT. One patient developed respiratory symptoms suggestive of COVID-19 and tested negative via nasopharyngeal PCR. Eleven patients who underwent COVID-19 testing for elective procedures or hospitalizations tested negative. No SARS-CoV-2 transmission was noted.<br><br>CONCLUSIONS: With appropriate donor screening, FMT can be performed safely for rCDI during the COVID-19 pandemic. Development of a validated stool assay for SARS-CoV-2 will simplify this process further.}, }
@article {pmid34087350, year = {2021}, author = {Li, Q and Cui, Y and Xu, B and Wang, Y and Lv, F and Li, Z and Li, H and Chen, X and Peng, X and Chen, Y and Wu, E and Qu, D and Jian, Y and Si, H}, title = {Main active components of Jiawei Gegen Qinlian decoction protects against ulcerative colitis under different dietary environments in a gut microbiota-dependent manner.}, journal = {Pharmacological research}, volume = {170}, number = {}, pages = {105694}, doi = {10.1016/j.phrs.2021.105694}, pmid = {34087350}, issn = {1096-1186}, abstract = {As an effective drug against acute enteritis diarrhea, Gegen Qinlian decoction (GQD) has a history of 2000 years. However, the potential molecular mechanism through which GQD could protect intestinal barrier from ulcerative colitis (UC) still remains undefined. As an important part of the homeostasis of the colon, gut microbiota is closely related to the dynamic evolution of the surrounding environment and the adjustment of dietary structure. At present, the effectiveness and mechanism of Jiawei Gegen Qinlian decoction against UC in different dietary environments are not clear. Here, the main active components of Jiawei Gegen Qinlian Decoction (PBM), were selected to construct a reasonable and effective compound scheme. We adopted "5% dextran sulfate sodium (DSS)" and "high temperature and humidity + high sugar and high fat + alcohol + 5%DSS" to induce UC rat models in general environment and UC rat models in Lingnan area, respectively. Then, we examined the therapeutic effects of PBM (89.96 mg/kg and 179.92 mg/kg) on two kinds of UC rats. The role of gut microbiota in the anti-UC effect of PBM was identified by intestinal flora consumption and fecal microbiota transplantation (FMT) experiments. Subsequently, we monitored the alterations of gut microbiota and fecal metabolism in the rat colon by 16Sr DNA technique and targeted metabonomics, respectively. The colon inflammation of the PBM-treated and the FMT-treated rats both showed significant relief, as evidenced by a reduction in body weight loss, bloody stool, diarrhea, disease activity index (DAI) score, shortening of colon length as well as decreased colon histology damage. Interestingly enough, the depletion of intestinal flora took away the protective effect of PBM, confirming the importance of intestinal flora in the anti-UC effect of PBM. Then our findings suggested that PBM could not only regulate the gut microbiota by increasing Akkermansia and Romboutsia but also decrease Escherichia-Shigella. More importantly, PBM could increase the production of propionate and total short-chain fatty acids (SCFAs) in colitis rats, regulate medium and long chain fatty acids (M-LCFAs), maintain bile acids (BAs) homeostasis, and regulate amino acids (AAs) metabolism. The transformation of intestinal environment might be related to the upregulation of anti-inflammation, anti-oxidation and tight junction protein expression in colonic mucosa. In summary, PBM showed potential for anti-UC activity through gut microbiota dependence and was expected to be a complementary and alternative medicine herb therapy.}, }
@article {pmid34086219, year = {2021}, author = {Müssig, K}, title = {.}, journal = {MMW Fortschritte der Medizin}, volume = {163}, number = {11}, pages = {26-27}, doi = {10.1007/s15006-021-0069-3}, pmid = {34086219}, issn = {1613-3560}, mesh = {Body Weight ; *Diet ; *Fecal Microbiota Transplantation ; Humans ; Weight Gain ; }, }
@article {pmid34079458, year = {2021}, author = {Li, Q and Ding, X and Liu, Y and Marcella, C and Dai, M and Zhang, T and Bai, J and Xiang, L and Wen, Q and Cui, B and Zhang, F}, title = {Fecal Microbiota Transplantation is a Promising Switch Therapy for Patients with Prior Failure of Infliximab in Crohn's Disease.}, journal = {Frontiers in pharmacology}, volume = {12}, number = {}, pages = {658087}, pmid = {34079458}, issn = {1663-9812}, abstract = {Background: How to handle patients with anti-tumor necrosis factor (anti-TNF) failure was a common challenge to clinicians in Crohn's disease (CD). The present study is dedicated to clarifying whether fecal microbiota transplantation (FMT) could be a switch therapy for patients with prior failure of infiiximab (IFX) in CD in a long-term observation. Methods: Thirty-six patients with CD who had prior failure of IFX were recruited from January 2013 to December 2019. The "one-hour FMT protocol" was followed in all patients. All patients received the first course of FMT through gastroscopy or mid-gut transendoscopic enteral tubing. After April 2014, the methodology of FMT was coined as washed microbiota transplantation (WMT), substituting for the manual methods, which is dependent on the automatic microbiota purification system and the washing process. The primary endpoint of this study was the clinical remission at one month and one year after FMT. The secondary endpoint was the safety of FMT in the short and long term, and clinical factors as predictors for long-term efficacy of FMT. Clinical factors as independent predictors of efficacy from FMT were isolated using univariable and multivariable logistic regression analysis. Results: There was no significant difference in the rates of clinical response and remission between IFX treatment stage and FMT treatment stage (at one month, three months and six months after administration) (p > 0.05). Compared with those of 19 patients who achieved clinical remission at one month after FMT, the rates of clinical relapse were significantly higher in 18 patients who achieved clinical remission at one month after IFX [log-rank test p = 0.0009 HR = 3.081 (95% CI 1.43-6.639)]. Multivariate analysis revealed that the gender of donor (95% CI: 0.001-0.72; p = 0.031) was an independent predictor of efficacy at one year after FMT. No serious adverse events (AEs) associated with FMT were observed during and after FMT. The rate of AEs was significantly lower in group FMT than that in group IFX (p = 0.002). Conclusion: The present findings first time provided the evidence for clinicians to consider FMT into practice as an alternative switch therapy for patients with prior loss of response or intolerance to IFX in CD. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT01793831.}, }
@article {pmid34078971, year = {2021}, author = {Skaarud, KJ and Hov, JR and Hansen, SH and Kummen, M and Valeur, J and Seljeflot, I and Bye, A and Paulsen, V and Lundin, KEA and Trøseid, M and Tjønnfjord, GE and Iversen, PO}, title = {Mortality and microbial diversity after allogeneic hematopoietic stem cell transplantation: secondary analysis of a randomized nutritional intervention trial.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {11593}, pmid = {34078971}, issn = {2045-2322}, mesh = {Adult ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation/mortality ; Humans ; Male ; Middle Aged ; *Nutritional Support ; Transplantation, Homologous ; Young Adult ; }, abstract = {Gut mucosal barrier injury is common following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and associated with poor clinical outcomes. Diet is critical for microbial diversity, but whether nutritional support affects microbiota and outcome after allo-HSCT is unknown. We present a secondary analysis of a randomized controlled nutritional intervention trial during allo-HSCT. We investigated if the intervention influenced gut microbiota, short-chain fatty acids (SCFAs), and markers of gut barrier functions, and if these parameters were associated with clinical outcomes. Fecal specimens were available from 47 recipients, and subjected to 16S rRNA gene sequencing. We found no significant differences between the intervention group and controls in investigated parameters. We observed a major depletion of microbiota, SCFAs, and altered markers of gut barrier function from baseline to 3 weeks post-transplant. One-year mortality was significantly higher in patients with lower diversity at 3 weeks post-HSCT, but not related to diversity at baseline. The relative abundance of Blautia genus at 3 weeks was higher in survivors. Fecal propionic acid was associated with survival. Markers of gut barrier functions were less strongly associated with clinical outcomes. Possibly, other strategies than dietary intervention are needed to prevent negative effects of gut microbiota and clinical outcomes after allo-HSCT.ClinicalTrials.gov (NCT01181076).}, }
@article {pmid34077717, year = {2021}, author = {Hanssen, NMJ and de Vos, WM and Nieuwdorp, M}, title = {Fecal microbiota transplantation in human metabolic diseases: From a murky past to a bright future?.}, journal = {Cell metabolism}, volume = {33}, number = {6}, pages = {1098-1110}, doi = {10.1016/j.cmet.2021.05.005}, pmid = {34077717}, issn = {1932-7420}, abstract = {Fecal microbiota transplantation (FMT) is gaining considerable traction as a therapeutic approach to influence the course of a plethora of chronic conditions, ranging from metabolic syndrome and malignancies to auto-immune and neurological diseases, and helped to establish the contribution of the gut microbiome to these conditions. Although FMT procedures have yielded important mechanistic insights, their use in clinical practice may be limited due to practical objections in the setting of metabolic diseases. While its applicability is established to treat recurrent Clostridiodes difficile, FMT is emerging in ulcerative colitis and various other diseases. A particularly new insight is that FMTs may not only alter insulin sensitivity but may also alter the course of type 1 diabetes by attenuating underlying auto-immunity. In this review, we will outline the major principles and pitfalls of FMT and where optimization of study design and the procedure itself will further advance the field of cardiometabolic medicine.}, }
@article {pmid34074837, year = {2021}, author = {Craven, LJ and Parvathy, SN and Burton, JP and Silverman, MS}, title = {Response to Ianiro et al.}, journal = {The American journal of gastroenterology}, volume = {116}, number = {6}, pages = {1361-1362}, doi = {10.14309/ajg.0000000000001160}, pmid = {34074837}, issn = {1572-0241}, mesh = {Fecal Microbiota Transplantation ; Humans ; *Non-alcoholic Fatty Liver Disease ; Permeability ; }, }
@article {pmid34074836, year = {2021}, author = {Ianiro, G and Porcari, S and Gasbarrini, A and Cammarota, G}, title = {Quantity of Donor Stool for Fecal Microbiota Transplantation: The More, the Better?.}, journal = {The American journal of gastroenterology}, volume = {116}, number = {6}, pages = {1360-1361}, doi = {10.14309/ajg.0000000000001130}, pmid = {34074836}, issn = {1572-0241}, mesh = {*Clostridium Infections ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Non-alcoholic Fatty Liver Disease ; Permeability ; }, }
@article {pmid34074214, year = {2021}, author = {Browne, PD and Cold, F and Petersen, AM and Halkjær, SI and Christensen, AH and Günther, S and Hestbjerg Hansen, L}, title = {Engraftment of strictly anaerobic oxygen-sensitive bacteria in irritable bowel syndrome patients following fecal microbiota transplantation does not improve symptoms.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-16}, pmid = {34074214}, issn = {1949-0984}, mesh = {Bacteria/classification/genetics/growth &amp; development/isolation &amp; purification ; Bacteria, Anaerobic/classification/genetics/isolation &amp; purification/*metabolism ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/*microbiology/*therapy ; Oxygen/*metabolism ; Treatment Outcome ; }, abstract = {Dysbiosis of the gut microbiome has been correlated with irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) is being explored as a therapeutic option. Little is known of the mechanisms of engraftment of microbes following FMT and whether the engraftment of certain microbes correlate with clinical improvement in IBS. Microbiome data, from a previously reported placebo-controlled trial of treatment of IBS with FMT or placebo capsules, were used to investigate microbial engraftment 15 days, 1, 3 and 6 months after treatment through assessment of gains, losses and changes in abundance of amplicon sequence variants (ASVs) and microbial diversity (CHAO-1 richness) between the FMT group and the placebo group. These data were compared to changes in IBS Symptom Severity Scores (IBS-SSS). Twelve days of treatment with 25 daily multi-donor FMT capsules induced significant short- and long-term changes in the recipients' microbiomes for at least 6 months, with persistent engraftment of a variety of anaerobic bacteria from keystone genera, such as Faecalibacterium, Prevotella and Bacteroides and increased microbial diversity, particularly in patients with low initial diversity. FMT recipients lost ASVs after treatment, which was seen to a much lesser extent in the placebo group. No ASVs increased to a greater extent between FMT responders and non-responders following treatment. Major long-term changes, lasting for at least 6 months, in the gut microbiomes of IBS patients are seen following treatment with FMT capsules. None of these changes correlated with clinical improvement. The relationship between the microbiome and the etiology of IBS still remains unsolved.}, }
@article {pmid34073695, year = {2021}, author = {Chiu, CW and Tsai, PJ and Lee, CC and Ko, WC and Hung, YP}, title = {Application of Microbiome Management in Therapy for Clostridioides difficile Infections: From Fecal Microbiota Transplantation to Probiotics to Microbiota-Preserving Antimicrobial Agents.}, journal = {Pathogens (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {}, pmid = {34073695}, issn = {2076-0817}, support = {MOHW105-CDC-C-114-122113//Ministry of Health and Welfare/ ; MOST 108-2321-B-006-004 and 109-2314-B-006-089-MY//Ministry of Science and Technology/ ; NCKUH-11004029//National Cheng Kung University Hospital/ ; }, abstract = {Oral vancomycin and metronidazole, though they are the therapeutic choice for Clostridioides difficile infections (CDIs), also markedly disturb microbiota, leading to a prolonged loss of colonization resistance to C. difficile after therapy; as a result, their use is associated with a high treatment failure rate and high recurrent rate. An alternative for CDIs therapy contains the delivery of beneficial (probiotic) microorganisms into the intestinal tract to restore the microbial balance. Recently, mixture regimens containing Lactobacillus species, Saccharomyces boulardii, or Clostridium butyricum have been extensively studied for the prophylaxis of CDIs. Fecal microbiota transplantation (FMT), the transfer of (processed) fecal material from healthy donors to patients for treating CDIs, combined with vancomycin was recommended as the primary therapy for multiple recurrent CDIs (rCDIs). Either probiotics or FMT have been utilized extensively in preventing or treating CDIs, aiming at less disturbance in the microbiota to prevent rCDIs after therapy cessation. Otherwise, many newly developed therapeutic agents have been developed and aim to preserve microbiota during CDI treatment to prevent disease recurrence and might be useful in clinical patients with rCDIs in the future.}, }
@article {pmid34071229, year = {2021}, author = {Shang, L and Liu, H and Yu, H and Chen, M and Yang, T and Zeng, X and Qiao, S}, title = {Core Altered Microorganisms in Colitis Mouse Model: A Comprehensive Time-Point and Fecal Microbiota Transplantation Analysis.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {10}, number = {6}, pages = {}, pmid = {34071229}, issn = {2079-6382}, support = {2016YFD0501308//National Key Research and Development Program of China/ ; cstc2019ngzx0019//Chongqing Rongchang Agricultural and Animal Husbandry High-tech Industry Research and Development Project/ ; }, abstract = {Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic and relapsing inflammation within the gastrointestinal tract. Antibiotics have been used to treat IBD, primarily utilizing metronidazole. Although there does seem to be a treatment effect, the broad-spectrum antibiotics that have been used to date are crude tools and have many adverse effects. Available evidence suggests that the host microbiome is implicated in the pathogenesis of IBD, though the key bacteria remain unknown. If the bacterial population can be modified appropriately, the use of antibiotics will have a better therapeutic effect. In this study, mice were fed dextran sodium sulfate (DSS) solution for 5 days, followed by 5 days of normal drinking water, to investigate the gut microbiota response to colitis and the initial alteration of microbiota in recovery phase. Day 0 was considered the normal control, while day 5 and day 10 were considered the colitis mouse model progressive phase and recovery phase, respectively. Results showed that inflammation could induce proportional changes in the gut microbiota. Furthermore, transplanting the microbiota in progressive phase to antibiotic-induced microbiota-depleted mice could induce inflammation similar to colitis, which proves the importance of initial alteration of the microbiota for IBD recovery and the potential of the microbiota as a target for the treatment of IBD. Meanwhile, we have also identified three possible target microorganisms in the development of colitis, namely genera Muribaculaceae (negative correlation), Turicibacter (positive correlation) and Lachnospiraceae (negative correlation) in inflammation status through comprehensive analysis.}, }
@article {pmid34071065, year = {2021}, author = {LeBlanc, JF and Segal, JP and de Campos Braz, LM and Hart, AL}, title = {The Microbiome as a Therapy in Pouchitis and Ulcerative Colitis.}, journal = {Nutrients}, volume = {13}, number = {6}, pages = {}, pmid = {34071065}, issn = {2072-6643}, mesh = {Colitis, Ulcerative/microbiology/*therapy ; Diet, Mediterranean ; Fatty Acids, Omega-3/therapeutic use ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/therapy ; Microbiota ; Pouchitis/microbiology/*therapy ; Prebiotics/administration &amp; dosage ; Probiotics/therapeutic use ; }, abstract = {The gut microbiome has been implicated in a range of diseases and there is a rapidly growing understanding of this ecosystem's importance in inflammatory bowel disease. We are yet to identify a single microbe that causes either ulcerative colitis (UC) or pouchitis, however, reduced microbiome diversity is increasingly recognised in active UC. Manipulating the gut microbiome through dietary interventions, prebiotic and probiotic compounds and faecal microbiota transplantation may expand the therapeutic landscape in UC. Specific diets, such as the Mediterranean diet or diet rich in omega-3 fatty acids, may reduce intestinal inflammation or potentially reduce the risk of incident UC. This review summarises our knowledge of gut microbiome therapies in UC and pouchitis.}, }
@article {pmid34068085, year = {2021}, author = {Haindl, R and Engel, J and Kulozik, U}, title = {Establishment of an In Vitro System of the Human Intestinal Microbiota: Effect of Cultivation Conditions and Influence of Three Donor Stool Samples.}, journal = {Microorganisms}, volume = {9}, number = {5}, pages = {}, pmid = {34068085}, issn = {2076-2607}, abstract = {Fecal microbiota transplantation (FMT) is an alternative method for the treatment of gastrointestinal diseases with a high recovery rate. Disadvantages are ethical concerns, high donor requirements and the low storability of stool samples. The cultivation of an in vitro microbiota in a continuous bioreactor was established as an alternative to FMT to overcome these problems. In this study, the influence of the system parameters and donor stool characteristics was investigated. Each continuous colonic fermentation system was inoculated with feces from three different donors until a stable state was established. The influence of the fermentation conditions on the system's behavior regarding cell count, metabolic activity, short-chain fatty acid profile and microbiota composition as well as richness and diversity was assessed. Cultivation conditions were found to affect the microbial system: the number of cells and the production of short-chain fatty acids increased. The abundance of Actinobacteria and Firmicutes decreased, Bacteroidetes increased, while Proteobacteria and Verrucomicrobia remained largely unaffected. Diversity in the in vitro system decreased, but richness was unaffected. The cultivation of stool from different donors revealed that the performance of the created in vitro system was similar and comparable, but unique characteristics of the composition of the original stool remained.}, }
@article {pmid34061595, year = {2021}, author = {Sato, K and Yamazaki, K and Kato, T and Nakanishi, Y and Tsuzuno, T and Yokoji-Takeuchi, M and Yamada-Hara, M and Miura, N and Okuda, S and Ohno, H and Yamazaki, K}, title = {Obesity-Related Gut Microbiota Aggravates Alveolar Bone Destruction in Experimental Periodontitis through Elevation of Uric Acid.}, journal = {mBio}, volume = {12}, number = {3}, pages = {e0077121}, pmid = {34061595}, issn = {2150-7511}, mesh = {Alveolar Bone Loss/*etiology/pathology ; Animals ; Diet, High-Fat ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/complications/*microbiology ; Periodontitis/etiology/*microbiology ; Risk Factors ; Uric Acid/analysis/*metabolism ; }, abstract = {Obesity is a risk factor for periodontal disease (PD). Initiation and progression of PD are modulated by complex interactions between oral dysbiosis and host responses. Although obesity is associated with increased susceptibility to bacterial infection, the detailed mechanisms that connect obesity and susceptibility to PD remain elusive. Using fecal microbiota transplantation and a ligature-induced PD model, we demonstrated that gut dysbiosis-associated metabolites from high-fat diet (HFD)-fed mice worsen alveolar bone destruction. Fecal metabolomics revealed elevated purine degradation pathway activity in HFD-fed mice, and recipient mice had elevated levels of serum uric acid upon PD induction. Furthermore, PD induction caused more severe bone destruction in hyperuricemic than normouricemic mice, and the worsened bone destruction was completely abrogated by allopurinol, a xanthine oxidase inhibitor. Thus, obesity increases the risk of PD by increasing production of uric acid mediated by gut dysbiosis. IMPORTANCE Obesity is an epidemic health issue with a rapid increase worldwide. It increases the risk of various diseases, including periodontal disease, an oral chronic infectious disease. Although obesity increases susceptibility to bacterial infection, the precise biological mechanisms that link obesity and susceptibility to periodontal disease remain elusive. Using fecal microbial transplantation, experimental periodontitis, and metabolomics, our study demonstrates uric acid as a causative substance for greater aggravation of alveolar bone destruction in obesity-related periodontal disease. Gut microbiota from obese mice upregulated the purine degradation pathway, and the resulting elevation of serum uric acid promoted alveolar bone destruction. The effect of uric acid was confirmed by administration of allopurinol, an inhibitor of xanthine oxidase. Overall, our study provides new insights into the pathogenic mechanisms of obesity-associated periodontal disease and the development of new therapeutic options for the disease.}, }
@article {pmid34061001, year = {2021}, author = {Novais, F and Capela, J and Machado, S and Murillo-Rodriguez, E and Telles-Correia, D}, title = {Does Dysbiosis Increase the Risk of Developing Schizophrenia? - A Comprehensive Narrative Review.}, journal = {Current topics in medicinal chemistry}, volume = {21}, number = {11}, pages = {976-984}, doi = {10.2174/1568026621666210521163555}, pmid = {34061001}, issn = {1873-4294}, mesh = {Brain/*metabolism ; Central Nervous System/growth &amp; development/metabolism ; Dysbiosis/*complications/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammation/*metabolism ; Intestines/microbiology ; Prebiotics ; Probiotics/metabolism ; Schizophrenia/*etiology ; }, abstract = {BACKGROUND: There is increasing evidence regarding the influence of the intestinal microbiota on the disease processes of various organs and systems. Dysbiosis, that is, alteration of the composition and function of the microbiota may constitute an important risk factor for the development of mental disorders, namely, schizophrenia.<br><br>OBJECTIVE: This works aims to review current evidence regarding the pathological mechanisms leading from dysbiosis to schizophrenia and in particular the deficit syndrome in schizophrenia.<br><br>METHODS: Scientific articles from PubMed, SCOPUS, EMBASE, and Web of Science Core Collection published between September 2017 and December 2020 were included in this review.<br><br>RESULTS: The commensal intestinal flora plays an important role in neurodevelopment. In the presence of dysbiosis, this maturation gets disturbed, resulting in the modification of brain structures and inflammatory responses at the intestinal, systemic, and Central Nervous System (CNS) levels. These disturbances may be linked to the development of symptoms of the disease. The microbiota exerts its influence on the CNS through several pathways, however, in this paper we focused on the membrane hypothesis and the inflammatory hypothesis. We explored the evidence concerning the use of probiotics, prebiotics, and fecal transplants.<br><br>CONCLUSION: Although there is no consensus regarding the alterations that could constitute a risk factor for schizophrenia, some of the species appear to be more frequently altered, and their relationship with the host is dysregulated in patients at risk and with established schizophrenia, particularly in deficit schizophrenia.}, }
@article {pmid34058102, year = {2021}, author = {Horton, LC and Feuerstein, JD}, title = {In recurrent C difficile infection, oral FMT capsules have a pooled cure rate of 82% (low-quality evidence).}, journal = {Annals of internal medicine}, volume = {174}, number = {6}, pages = {JC65}, doi = {10.7326/ACPJ202106150-065}, pmid = {34058102}, issn = {1539-3704}, mesh = {Capsules ; *Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {SOURCE CITATION: Du C, Luo Y, Walsh S, Grinspan A. Oral fecal microbiota transplant capsules are safe and effective for recurrent Clostridioides difficile infection: a systematic review and meta-analysis. J Clin Gastroenterol. 2021;55:300-8. 33471490.}, }
@article {pmid34055657, year = {2021}, author = {Mazzawi, T and El-Salhy, M and Lied, GA and Hausken, T}, title = {The Effects of Fecal Microbiota Transplantation on the Symptoms and the Duodenal Neurogenin 3, Musashi 1, and Enteroendocrine Cells in Patients With Diarrhea-Predominant Irritable Bowel Syndrome.}, journal = {Frontiers in cellular and infection microbiology}, volume = {11}, number = {}, pages = {524851}, pmid = {34055657}, issn = {2235-2988}, mesh = {Diarrhea ; Duodenum ; Enteroendocrine Cells ; *Fecal Microbiota Transplantation ; Feces ; Female ; Humans ; *Irritable Bowel Syndrome/therapy ; Male ; Norway ; }, abstract = {Introduction: Interactions between the gut microbiota and enteroendocrine cells play important role in irritable bowel syndrome (IBS). Reduced stem cell densities and their differentiation into enteroendocrine cells may cause abnormal densities of the duodenal enteroendocrine cells in IBS patients.<br><br>Materials and Methods: We aimed to investigate the effects of fecal microbiota transplantation (FMT) on stem cell differentiation into enteroendocrine cells as detected by neurogenin 3, stem cells as detected by Musashi 1, and the enteroendocrine cells in the duodenum of IBS patients. The study included 16 IBS patients according to Rome III criteria. Four patients were excluded. The remaining patients (n = 12, four females and eight males) were divided according to the cause of IBS into post-infectious (n = 6) and idiopathic (n = 6) IBS. They completed the following questionnaires before and 3 weeks after FMT: IBS-Symptom Severity Scoring system (IBS-SSS) and IBS-Symptom Questionnaire (IBS-SQ). Feces donated by healthy relatives of the patients were transplanted via gastroscope. Biopsies were taken from the descending part of the duodenum at baseline and 3 weeks after FMT. They were immunostained for neurogenin 3, Musashi 1, and all types of duodenal enteroendocrine cells and quantified by computerized image analysis. Microbiota analyses of feces collected just before and 3 weeks after FMT were performed using GA-map™ Dysbiosis test (Genetic Analysis AS, Oslo, Norway).<br><br>Results: The total scores for IBS-SSS and IBS-SQ were significantly improved 3 weeks after receiving FMT, P = 0.0009 and <0.0001, respectively. The stem cell densities of neurogenin 3 increased significantly following FMT (P = 0.0006) but not for Musashi 1 (P = 0.42). The cell densities of chromogranin A, cholecystokinin, gastric inhibitory peptide, serotonin, and somatostatin, but not for secretin, have significantly changed in both IBS groups after 3 weeks from receiving FMT.<br><br>Conclusion: More than two-thirds of IBS patients experienced improvement in their symptoms parallel to changes in the enteroendocrine cells densities 3 weeks after FMT. The changes in the enteroendocrine cell densities do not appear to be caused by changes in the stem cells or their early progenitors rather by changes in the differentiation progeny as detected by neurogenin 3. The study was retrospectively registered at ClinicalTrials.gov (ID: NCT03333291).<br><br>Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03333291.}, }
@article {pmid34054866, year = {2021}, author = {Yang, M and Yang, Y and He, Q and Zhu, P and Liu, M and Xu, J and Zhao, M}, title = {Intestinal Microbiota-A Promising Target for Antiviral Therapy?.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {676232}, pmid = {34054866}, issn = {1664-3224}, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Antiviral Agents/*therapeutic use ; COVID-19/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Host-Pathogen Interactions ; Humans ; Probiotics/*therapeutic use ; SARS-CoV-2/*physiology ; Virus Diseases/*therapy ; }, abstract = {The intestinal microbiota is thought to be an important biological barrier against enteric pathogens. Its depletion, however, also has curative effects against some viral infections, suggesting that different components of the intestinal microbiota can play both promoting and inhibitory roles depending on the type of viral infection. The two primary mechanisms by which the microbiota facilitates or inhibits viral invasion involve participation in the innate and adaptive immune responses and direct or indirect interaction with the virus, during which the abundance and composition of the intestinal microbiota might be changed by the virus. Oral administration of probiotics, faecal microbiota transplantation (FMT), and antibiotics are major therapeutic strategies for regulating intestinal microbiota balance. However, these three methods have shown limited curative effects in clinical trials. Therefore, the intestinal microbiota might represent a new and promising supplementary antiviral therapeutic target, and more efficient and safer methods for regulating the microbiota require deeper investigation. This review summarizes the latest research on the relationship among the intestinal microbiota, anti-viral immunity and viruses and the most commonly used methods for regulating the intestinal microbiota with the goal of providing new insight into the antiviral effects of the gut microbiota.}, }
@article {pmid34054845, year = {2021}, author = {Bosák, J and Lexa, M and Fiedorová, K and Gadara, DC and Micenková, L and Spacil, Z and Litzman, J and Freiberger, T and Šmajs, D}, title = {Patients With Common Variable Immunodeficiency (CVID) Show Higher Gut Bacterial Diversity and Levels of Low-Abundance Genes Than the Healthy Housemates.}, journal = {Frontiers in immunology}, volume = {12}, number = {}, pages = {671239}, pmid = {34054845}, issn = {1664-3224}, mesh = {Adenosine/metabolism ; Biodiversity ; Clostridiaceae/*physiology ; Common Variable Immunodeficiency/genetics/*microbiology ; Computational Biology/*methods ; Dysbiosis/genetics/*microbiology ; Feces/microbiology ; Gastrointestinal Microbiome/*genetics ; Homeostasis ; Humans ; Metabolomics ; Metagenome ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {Common variable immunodeficiency (CVID) is a clinically and genetically heterogeneous disorder with inadequate antibody responses and low levels of immunoglobulins including IgA that is involved in the maintenance of the intestinal homeostasis. In this study, we analyzed the taxonomical and functional metagenome of the fecal microbiota and stool metabolome in a cohort of six CVID patients without gastroenterological symptomatology and their healthy housemates. The fecal microbiome of CVID patients contained higher numbers of bacterial species and altered abundance of thirty-four species. Hungatella hathewayi was frequent in CVID microbiome and absent in controls. Moreover, the CVID metagenome was enriched for low-abundance genes likely encoding nonessential functions, such as bacterial motility and metabolism of aromatic compounds. Metabolomics revealed dysregulation in several metabolic pathways, mostly associated with decreased levels of adenosine in CVID patients. Identified features have been consistently associated with CVID diagnosis across the patients with various immunological characteristics, length of treatment, and age. Taken together, this initial study revealed expansion of bacterial diversity in the host immunodeficient conditions and suggested several bacterial species and metabolites, which have potential to be diagnostic and/or prognostic CVID markers in the future.}, }
@article {pmid34053243, year = {2021}, author = {Kang, Y and Kang, X and Zhang, H and Liu, Q and Yang, H and Fan, W}, title = {Gut Microbiota and Parkinson's Disease: Implications for Faecal Microbiota Transplantation Therapy.}, journal = {ASN neuro}, volume = {13}, number = {}, pages = {17590914211016217}, pmid = {34053243}, issn = {1759-0914}, mesh = {Animals ; Dysbiosis/diagnosis/*therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Parkinson Disease/diagnosis/microbiology/*therapy ; }, abstract = {Parkinson's disease (PD) ranks the second place among neurodegenerative diseases in terms of its morbidity, which affects 1-2% people aged over 65 years. In addition to genetics, some environmental factors may exert vital parts in PD occurrence as well. At present, more and more studies are conducted to elucidate the association between gut microbial dysbiosis and the incidence of PD. Gut microbial dysbiosis has a certain effect on both the central nervous system (CNS) and the enteric nervous system (ENS), which indicates that there is a gut-microbiota-brain axis that induces CNS disorders. Some gut microbial strains are suggested to suppress or weaken the neuroinflammation- and gut-inflammation-immune responses, which suggests the protective and pathogenic effects of certain gut microbial species on PD progression. Therefore, gut microbiome may contain plenty of targets for preventing and managing PD. Faecal microbiota transplantation (FMT) may serve as a direct and useful treatment for PD in the future. Nonetheless, there is little available scientific research in this field. The present work reviewed the latest research to examine the association of gut microbiota with PD, and the future prospects of FMT treatment.}, }
@article {pmid34051351, year = {2021}, author = {Pandya, G and Kirtonia, A and Singh, A and Goel, A and Mohan, CD and Rangappa, KS and Pandey, AK and Kapoor, S and Tandon, S and Sethi, G and Garg, M}, title = {A comprehensive review of the multifaceted role of the microbiota in human pancreatic carcinoma.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2021.05.027}, pmid = {34051351}, issn = {1096-3650}, abstract = {Pancreatic carcinoma is associated with one of the worst clinical outcomes throughout the globe because of its aggressive, metastatic, and drug-resistant nature. During the past decade, several studies have shown that oral, gut, and tumor microbiota play a critical role in the modulation of metabolism and immune responses. Growing pieces of evidence have proved beyond a doubt that the microbiota has a unique ability to influence the tumor microenvironment as well as the metabolism of chemotherapeutic agents or drugs. Given this, microbiota, known as the ecological community of microorganisms, stands to be an avenue of quality research. In this review, we provide detailed and critical information on the role of oral, gut, and pancreatic microbiota disruptions in the development of pancreatic carcinoma. Moreover, we comprehensively discuss the different types of microbiota, their potential role, and mechanism associated with pancreatic carcinoma. The microbiome provides the unique opportunity to enhance the effectiveness of chemotherapeutic agents and immunotherapies for pancreatic cancer by maintaining the right type of microbiota and holds a promising future to enhance the clinical outcomes of patients with pancreatic carcinoma.}, }
@article {pmid34051218, year = {2021}, author = {Wang, H and Banerjee, N and Liang, Y and Wang, G and Hoffman, KL and Khan, MF}, title = {Gut microbiome-host interactions in driving environmental pollutant trichloroethene-mediated autoimmunity.}, journal = {Toxicology and applied pharmacology}, volume = {424}, number = {}, pages = {115597}, pmid = {34051218}, issn = {1096-0333}, support = {R01 ES016302/ES/NIEHS NIH HHS/United States ; R01 ES026887/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Autoimmunity/*drug effects ; Bacteria/*drug effects ; Drug Administration Schedule ; Environmental Pollutants/*toxicity ; Female ; Gastrointestinal Microbiome/*drug effects/physiology ; Inflammation ; Liver/drug effects ; Mice ; Mice, Inbred Strains ; Oxidative Stress ; Spleen/drug effects ; Trichloroethylene/*toxicity ; }, abstract = {Trichloroethene (TCE), a widely used industrial solvent, is associated with the development of autoimmune diseases (ADs), including systemic lupus erythematosus and autoimmune hepatitis. Increasing evidence support a linkage between altered gut microbiome composition and the onset of ADs. However, it is not clear how gut microbiome contributes to TCE-mediated autoimmunity, and initial triggers for microbiome-host interactions leading to systemic autoimmune responses remain unknown. To achieve this, female MRL+/+ mice were treated with 0.5 mg/ml TCE for 52 weeks and fecal samples were subjected to 16S rRNA sequencing to determine the microbiome composition. TCE exposure resulted in distinct bacterial community revealed by β-diversity analysis. Notably, we observed reduction in Lactobacillaceae, Rikenellaceae and Bifidobacteriaceae families, and enrichment of Akkermansiaceae and Lachnospiraceae families after TCE exposure. We also observed significantly increased colonic oxidative stress and inflammatory markers (CD14 and IL-1β), and decreased tight junction proteins (ZO-2, occludin and claudin-3). These changes were associated with increases in serum antinuclear and anti-smooth muscle antibodies and cytokines (IL-6 and IL-12), together with increased PD1 + CD4+ T cells in TCE-exposed spleen and liver tissues. Importantly, fecal microbiota transplantation (FMT) using feces from TCE-treated mice to antibiotics-treated mice induced increased anti-dsDNA antibodies and hepatic CD4+ T cell infiltration in the recipient mice. Our studies thus delineate how imbalance in gut microbiome and mucosal redox status together with gut inflammatory response and permeability changes could be the key factors in contributing to TCE-mediated ADs. Furthermore, FMT studies provide a solid support to a causal role of microbiome in TCE-mediated autoimmunity.}, }
@article {pmid34049374, year = {2021}, author = {Saha, S and Sehgal, K and Singh, S and Grover, M and Pardi, D and Khanna, S}, title = {Postinfection Irritable Bowel Syndrome Following Clostridioides difficile Infection: A Systematic-review and Meta-analysis.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {34049374}, issn = {1539-2031}, support = {K23 DK103911/DK/NIDDK NIH HHS/United States ; R03 DK120745/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: Postinfection irritable bowel syndrome (PI-IBS) affects ~14% patients after acute bacterial enterocolitis.<br><br>AIM: The aim of this study was to conduct a systematic review and meta-analysis to find the prevalence of PI-IBS following Clostridioides difficile infection (CDI).<br><br>METHODS: We systematically searched Medline, Embase, and Web of Science from inception through January 20, 2020 for cohort studies assessing PI-IBS following CDI. Primary outcome was pooled prevalence calculated using inverse variance heterogeneity model [MetaXL (v. 5.3)]. A priori subgroup analyses were done [by irritable bowel syndrome (IBS) diagnostic criteria-Rome vs. others, time of IBS diagnosis-<6 or >6 mo, exclusion or inclusion of pre-existing IBS and CDI treatment-antibiotic with fecal microbiota transplantation vs. antibiotic only]. Heterogeneity was considered substantial if I2>50%.<br><br>RESULTS: From 2007 to 2019, 15 studies were included (10 prospective, 5 retrospective; 9 full-text, 6 abstracts). Data from 1218 patients were included in the quantitative analysis. Risk of bias was low in 7, medium in 4 and high in 4 studies. Pooled prevalence of PI-IBS was 21.1% (95% confidence interval, 8.2%-35.7%), I2=96%. Common PI-IBS subtypes were diarrhea-predominant in 46.3% (50) patients, and mixed in 33.3% (36) patients. Subgroup analyses by IBS diagnostic criteria, time of IBS diagnosis or CDI treatment did not significantly change the primary outcome (all P>0.05), nor decrease heterogeneity. Funnel plot analysis revealed publication bias.<br><br>CONCLUSIONS: Over 20% of patients develop PI-IBS after CDI. Factors such as diagnostic criteria for IBS and CDI treatment did not affect prevalence, though small numbers limit the confidence in these conclusions. Larger, well conducted studies are needed to study PI-IBS in CDI.}, }
@article {pmid34048223, year = {2021}, author = {Liu, J and Zhao, F and Wang, T and Xu, Y and Qiu, J and Qian, Y}, title = {Host Metabolic Disorders Induced by Alterations in Intestinal Flora under Dietary Pesticide Exposure.}, journal = {Journal of agricultural and food chemistry}, volume = {69}, number = {22}, pages = {6303-6317}, doi = {10.1021/acs.jafc.1c00273}, pmid = {34048223}, issn = {1520-5118}, mesh = {Animals ; Dietary Exposure ; *Gastrointestinal Microbiome ; Liver ; Mice ; Obesity ; *Pesticides/toxicity ; }, abstract = {A dietary pesticide residue causes underestimated influences on body health. In this work, experimental mice were exposed to commonly used pesticides that cause insulin resistance, inflammation, and non-alcoholic fatty liver diseases. Alterations in intestinal flora were detected in the exposure groups. The abundance of the flora causing high endotoxin production was intensively increased and led to body inflammation. High Firmicutes/Bacteroidetes and obesity-related flora characteristics were also found. The metabolisms of intestinal flora and host circulation were investigated through metabolomics. The associations of flora with their metabolites and host circulation were also established. Association analysis can determine the influences of pesticide exposure on such a complex system. The affected metabolic pathways in the liver were also determined to clarify the mechanism underlying the effect of pesticide exposure on host physiology. Interventions with fructooligosaccharides and fecal microbiota transplantation alleviated the metabolic disorders, thus directly confirming that the intestinal flora mediates the effects of pesticide exposure on host circulation. This work elucidated the intestinal-flora-mediated effects of dietary pollutant exposure on body health and provided potential measures for regulating flora and host circulation.}, }
@article {pmid34045661, year = {2021}, author = {Qi, R and Sun, J and Qiu, X and Zhang, Y and Wang, J and Wang, Q and Huang, J and Ge, L and Liu, Z}, title = {The intestinal microbiota contributes to the growth and physiological state of muscle tissue in piglets.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {11237}, pmid = {34045661}, issn = {2045-2322}, mesh = {Animals ; Gastrointestinal Microbiome/*physiology ; Gene Expression Profiling ; Insulin-Like Growth Factor I/metabolism ; Muscle, Skeletal/*physiology ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/physiology ; Swine ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {Although the importance of the intestinal microbiota in host growth and health is well known, the relationship between microbiota colonization and muscle development is unclear. In this study, the direct causal effects of the colonization of gut microorganisms on the muscle tissue of piglets were investigated. The body weight and lean mass of germ-free (GF) piglets were approximately 40% lower than those of normal piglets. The deletion of the intestinal microbiota led to weakened muscle function and a reduction in myogenic regulatory proteins, such as MyoG and MyoD, in GF piglets. In addition, the blinded IGF1/AKT/mTOR pathway in GF piglets caused muscle atrophy and autophagy, which were characterized by the high expression of Murf-1 and KLF15. Gut microbiota introduced to GF piglets via fecal microbiota transplantation not only colonized the gut but also partially restored muscle growth and development. Furthermore, the proportion of slow-twitch muscle fibers was lower in the muscle of GF piglets, which was caused by the reduced short-chain fatty acid content in the circulation and impaired mitochondrial function in muscle. Collectively, these findings suggest that the growth, development and function of skeletal muscle in animals are mediated by the intestinal microbiota.}, }
@article {pmid34044101, year = {2021}, author = {Gonzales-Luna, AJ and Spinler, JK and Oezguen, N and Khan, MAW and Danhof, HA and Endres, BT and Alam, MJ and Begum, K and Lancaster, C and Costa, GP and Savidge, TC and Hurdle, JG and Britton, R and Garey, KW}, title = {Systems biology evaluation of refractory Clostridioides difficile infection including multiple failures of fecal microbiota transplantation.}, journal = {Anaerobe}, volume = {70}, number = {}, pages = {102387}, pmid = {34044101}, issn = {1095-8274}, support = {F32 AI136404/AI/NIAID NIH HHS/United States ; R01 AI139261/AI/NIAID NIH HHS/United States ; U01 AI124290/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) aims to cure Clostridioides difficile infection (CDI) through reestablishing a healthy microbiome and restoring colonization resistance. Although often effective after one infusion, patients with continued microbiome disruptions may require multiple FMTs. In this N-of-1 study, we use a systems biology approach to evaluate CDI in a patient receiving chronic suppressive antibiotics with four failed FMTs over two years.<br><br>METHODS: Seven stool samples were obtained between 2016-18 while the patient underwent five FMTs. Stool samples were cultured for C. difficile and underwent microbial characterization and functional gene analysis using shotgun metagenomics. C. difficile isolates were characterized through ribotyping, whole genome sequencing, metabolic pathway analysis, and minimum inhibitory concentration (MIC) determinations.<br><br>RESULTS: Growing ten strains from each sample, the index and first four recurrent cultures were single strain ribotype F078-126, the fifth was a mixed culture of ribotypes F002 and F054, and the final culture was ribotype F002. One single nucleotide polymorphism (SNP) variant was identified in the RNA polymerase (RNAP) β-subunit RpoB in the final isolated F078-126 strain when compared to previous F078-126 isolates. This SNV was associated with metabolic shifts but phenotypic differences in fidaxomicin MIC were not observed. Microbiome differences were observed over time during vancomycin therapy and after failed FMTs.<br><br>CONCLUSION: This study highlights the importance of antimicrobial stewardship in patients receiving FMT. Continued antibiotics play a destructive role on a transplanted microbiome and applies selection pressure for resistance to the few antibiotics available to treat CDI.}, }
@article {pmid34035760, year = {2021}, author = {Allegretti, JR}, title = {Update on Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease.}, journal = {Gastroenterology &amp; hepatology}, volume = {17}, number = {1}, pages = {31-34}, pmid = {34035760}, issn = {1554-7914}, }
@article {pmid34035290, year = {2021}, author = {Malard, F and Vekhoff, A and Lapusan, S and Isnard, F and D'incan-Corda, E and Rey, J and Saillard, C and Thomas, X and Ducastelle-Lepretre, S and Paubelle, E and Larcher, MV and Rocher, C and Recher, C and Tavitian, S and Bertoli, S and Michallet, AS and Gilis, L and Peterlin, P and Chevallier, P and Nguyen, S and Plantamura, E and Boucinha, L and Gasc, C and Michallet, M and Dore, J and Legrand, O and Mohty, M}, title = {Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {3084}, pmid = {34035290}, issn = {2041-1723}, mesh = {Acute Disease ; Adult ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bacteria/classification/drug effects/genetics ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects/genetics ; Humans ; Leukemia, Myeloid/*drug therapy/microbiology ; Male ; Middle Aged ; Prospective Studies ; Transplantation, Autologous ; Treatment Outcome ; Young Adult ; }, abstract = {Acute myeloid leukemia (AML) intensive chemotherapy combined with broad-spectrum antibiotics, leads to gut microbiota dysbiosis promoting pathological conditions and an increased incidence of complications. Here we report findings from a phase II single-arm, multicenter study evaluating autologous fecal microbiota transfer (AFMT) in 25 AML patients treated with intensive chemotherapy and antibiotics (ClinicalTrials.gov number: NCT02928523). The co-primary outcomes of the study are to evaluate the efficacy of AFMT in dysbiosis correction and multidrug-resistant bacteria eradication. The main secondary outcomes are to define a dysbiosis biosignature, to evaluate the effect of dysbiosis correction on patient clinical status, to assess the short and mid-term safety of AFMT in this immunocompromised population, and to evaluate the feasibility of the AFMT procedure and acceptability by the patient. Intensive induction chemotherapy induces a dramatic decrease of α-diversity indices, and a microbial dysbiosis with a significant shift of the microbial communities and domination of pro-inflammatory families. After AFMT treatment, α-diversity indices return to their initial mean levels and the similarity index shows the restoration of microbial communities. The trial meets pre-specified endpoints. AFMT appears to be safe and may be effective for gut microbiota restoration in AML patients receiving intensive chemotherapy and antibiotics, with an excellent gut microbiota reconstruction based on both richness and diversity indices at the species level.}, }
@article {pmid34030988, year = {2021}, author = {Ianiro, G and Porcari, S and Bibbò, S and Giambò, F and Quaranta, G and Masucci, L and Sanguinetti, M and Gasbarrini, A and Cammarota, G}, title = {Donor program for fecal microbiota transplantation: A 3-year experience of a large-volume Italian stool bank.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {53}, number = {11}, pages = {1428-1432}, doi = {10.1016/j.dld.2021.04.009}, pmid = {34030988}, issn = {1878-3562}, mesh = {Adult ; *Biological Specimen Banks/organization &amp; administration/statistics &amp; numerical data ; Donor Selection/*methods/organization &amp; administration/statistics &amp; numerical data ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; Infection Control/methods ; Italy ; Male ; Program Evaluation ; Prospective Studies ; }, abstract = {BACKGROUND: Due to the increasing rise of C. difficile infection, stool banks and donor programs have been launched to grant access to fecal microbiota transplantation (FMT). Our aim is to describe characteristics and outcomes of the donor program at our stool bank.<br><br>METHODS: Donor candidates underwent a four-step selection process, including a clinical interview, blood and stool testing, a further question