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Bibliography on: Fecal Transplantation

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Robert J. Robbins is a biologist, an educator, a science administrator, a publisher, an information technologist, and an IT leader and manager who specializes in advancing biomedical knowledge and supporting education through the application of information technology. More About:  RJR | OUR TEAM | OUR SERVICES | THIS WEBSITE

RJR: Recommended Bibliography 26 Jan 2022 at 01:33 Created: 

Fecal Transplantation

Fecal Transplantion is a procedure in which fecal matter is collected from a tested donor, mixed with a saline or other solution, strained, and placed in a patient, by colonoscopy, endoscopy, sigmoidoscopy, or enema. The theory behind the procedure is that a normal gut microbial ecosystem is required for good health and that sometimes a benefucuial ecosystem can be destroyed, perhaps by antibiotics, allowing other bacteria, specifically Clostridium difficile to over-populate the colon, causing debilitating, sometimes fatal diarrhea. C. diff. is on the rise throughout the world. The CDC reports that approximately 347,000 people in the U.S. alone were diagnosed with this infection in 2012. Of those, at least 14,000 died. Fecal transplant has also had promising results with many other digestive or auto-immune diseases, including Irritable Bowel Syndrome, Crohn's Disease, and Ulcerative Colitis. It has also been used around the world to treat other conditions, although more research in other areas is needed. Fecal transplant was first documented in 4th century China, where the treatment was known as yellow soup.

Created with PubMed® Query: "(fecal OR faecal) (transplant OR transplantation)" OR "fecal microbiota transplant" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2022-01-20

Beran A, Sharma S, Ghazaleh S, et al (2022)

Predictors of Fecal Microbiota Transplant Failure in Clostridioides difficile Infection: An Updated Meta-analysis.

Journal of clinical gastroenterology pii:00004836-900000000-97321 [Epub ahead of print].

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.

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.

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.

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.

RevDate: 2022-01-20

Qiao Y, Zhang Z, Zhai Y, et al (2021)

Apigenin Alleviates Obesity-Associated Metabolic Syndrome by Regulating the Composition of the Gut Microbiome.

Frontiers in microbiology, 12:805827.

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.

RevDate: 2022-01-20

Kang SH, Gweon TG, Hwang H, et al (2022)

A Case of Ischemic Colitis Complicated by Clostridioides Difficile Infection Treated with Fecal Microbiota Transplantation.

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.

RevDate: 2022-01-20
CmpDate: 2022-01-20

Li X, Khan I, Xia W, et al (2021)

Icariin enhances youth-like features by attenuating the declined gut microbiota in the aged mice.

Pharmacological research, 168:105587.

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 & 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.

RevDate: 2022-01-19

Huang G, Wang L, Li J, et al (2022)

Seasonal shift of the gut microbiome synchronizes host peripheral circadian rhythm for physiological adaptation to a low-fat diet in the giant panda.

Cell reports, 38(3):110203.

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.

RevDate: 2022-01-18

Wang Y, Cui B, F Zhang (2022)

Refractory ulcerative colitis stabilized by interval washed microbiota transplantation: less is more.

Current medical research and opinion [Epub ahead of print].

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.

RevDate: 2022-01-18

Larussa T, Abenavoli L, Fabiano G, et al (2021)

Gut microbiota in inflammatory bowel disease: a target for therapy not to be missed.

Minerva gastroenterology, 67(4):357-368.

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.

RevDate: 2022-01-17

Benech N, Legendre P, Radoszycki L, et al (2022)

Patient knowledge of gut microbiota and acceptability of fecal microbiota transplantation in various diseases.

Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society [Epub ahead of print].

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.

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.

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]).

CONCLUSION AND INFERENCES: Knowledge of gut microbiota is still limited in patients' communities and mainly developed by patients themselves, impacting FMT acceptability.

RevDate: 2022-01-18
CmpDate: 2022-01-18

van de Guchte M, Mondot S, J Doré (2021)

Dynamic Properties of the Intestinal Ecosystem Call for Combination Therapies, Targeting Inflammation and Microbiota, in Ulcerative Colitis.

Gastroenterology, 161(6):1969-1981.e12.

BACKGROUND & 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).

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).

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.

CONCLUSIONS: Our observations strongly suggest that inflammation suppression should be combined with microbiota management where possible to improve the efficacy of UC treatment.

RevDate: 2022-01-15

Messaoudene M, Pidgeon R, Richard C, et al (2022)

A natural polyphenol exerts antitumor activity and circumvents anti-PD-1 resistance through effects on the gut microbiota.

Cancer discovery pii:2159-8290.CD-21-0808 [Epub ahead of print].

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.

RevDate: 2022-01-14

Blake SJ, James J, Ryan FJ, et al (2021)

The immunotoxicity, but not anti-tumor efficacy, of anti-CD40 and anti-CD137 immunotherapies is dependent on the gut microbiota.

Cell reports. Medicine, 2(12):100464 pii:S2666-3791(21)00336-0.

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.

RevDate: 2022-01-14
CmpDate: 2022-01-14

Spencer CN, McQuade JL, Gopalakrishnan V, et al (2021)

Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response.

Science (New York, N.Y.), 374(6575):1632-1640.

[Figure: see text].

RevDate: 2022-01-13

Wang Y, Tang J, Lv Q, et al (2022)

Establishment and resilience of transplanted gut microbiota in aged mice.

iScience, 25(1):103654 pii:S2589-0042(21)01624-2.

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.

RevDate: 2022-01-13

Azimirad M, Jo Y, Kim MS, et al (2022)

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 of inflammation research, 15:105-116 pii:338212.

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.

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.

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.

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.

RevDate: 2022-01-13
CmpDate: 2022-01-13

Zhang C, Xiong B, Chen L, et al (2021)

Rescue of male fertility following faecal microbiota transplantation from alginate oligosaccharide-dosed mice.

Gut, 70(11):2213-2215.

RevDate: 2022-01-12

Hu H, Shao W, Liu Q, et al (2022)

Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion.

Nature communications, 13(1):252.

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.

RevDate: 2022-01-12
CmpDate: 2022-01-12

Reigadas E, van Prehn J, Falcone M, et al (2021)

How to: prophylactic interventions for prevention of Clostridioides difficile infection.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 27(12):1777-1783.

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.

OBJECTIVES: We aim to review CDI prophylactic treatment strategies and their implementation in clinical practice.

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.

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.

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.

RevDate: 2022-01-12
CmpDate: 2022-01-12

Arnoriaga-Rodríguez M, Mayneris-Perxachs J, Contreras-Rodríguez O, et al (2021)

Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways.

Gut, 70(12):2283-2296.

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.

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.

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.

CONCLUSION: These results highlight the importance of targeting obesity-related impulsive behaviour through the induction of gut microbiota shifts.

RevDate: 2022-01-11

Singh P, Alm EJ, Kelley JM, et al (2022)

Effect of antibiotic pretreatment on bacterial engraftment after Fecal Microbiota Transplant (FMT) in IBS-D.

Gut microbes, 14(1):2020067.

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.

RevDate: 2022-01-11

Chen S, Luo S, C Yan (2021)

Gut Microbiota Implications for Health and Welfare in Farm Animals: A Review.

Animals : an open access journal from MDPI, 12(1): pii:ani12010093.

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.

RevDate: 2022-01-11

Iatcu CO, Steen A, M Covasa (2021)

Gut Microbiota and Complications of Type-2 Diabetes.

Nutrients, 14(1): pii:nu14010166.

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.

RevDate: 2022-01-11

Liu P, Zhou W, Xu W, et al (2021)

The Main Anthocyanin Monomer from Lycium ruthenicum Murray Fruit Mediates Obesity via Modulating the Gut Microbiota and Improving the Intestinal Barrier.

Foods (Basel, Switzerland), 11(1): pii:foods11010098.

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.

RevDate: 2022-01-11

Sevcikova A, Izoldova N, Stevurkova V, et al (2022)

The Impact of the Microbiome on Resistance to Cancer Treatment with Chemotherapeutic Agents and Immunotherapy.

International journal of molecular sciences, 23(1): pii:ijms23010488.

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.

RevDate: 2022-01-11
CmpDate: 2022-01-11

Bhattacharjee A, Dubey S, S Sharma (2022)

Storage of soil microbiome for application in sustainable agriculture: prospects and challenges.

Environmental science and pollution research international, 29(3):3171-3183.

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.

RevDate: 2022-01-10

Wang H, Wang H, Sun Y, et al (2021)

Potential Associations Between Microbiome and COVID-19.

Frontiers in medicine, 8:785496.

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.

RevDate: 2022-01-10

Yuan B, Lu XJ, Q Wu (2021)

Gut Microbiota and Acute Central Nervous System Injury: A New Target for Therapeutic Intervention.

Frontiers in immunology, 12:800796.

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.

RevDate: 2022-01-09

Suchman K, Luo Y, A Grinspan (2022)

Fecal Microbiota Transplant for Clostridioides Difficile Infection Is Safe and Efficacious in an Immunocompromised Cohort.

Digestive diseases and sciences [Epub ahead of print].

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.

AIMS: To examine the outcomes of FMT for CDI in a diverse cohort of immunocompromised patients stratified by medication class.

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.

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.

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.

RevDate: 2022-01-10
CmpDate: 2022-01-10

Gao A, Su J, Liu R, et al (2021)

Sexual dimorphism in glucose metabolism is shaped by androgen-driven gut microbiome.

Nature communications, 12(1):7080.

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.

RevDate: 2022-01-10
CmpDate: 2022-01-10

Pradhan S, Ray P, P Aich (2022)

Microbiota transplantation from younger to older mice could restore lost immunity to effectively clear salmonella infection in Th2-biased BALB/c mice.

Life sciences, 288:120201.

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.

MATERIALS AND METHODS: In this study, older BALB/c mice (23 weeks) received CMT from younger BALB/c mice (3 weeks).

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.

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.

RevDate: 2022-01-10
CmpDate: 2022-01-10

Chen L, Li R, Wang Z, et al (2022)

Lactate-utilizing bacteria ameliorates DSS-induced colitis in mice.

Life sciences, 288:120179.

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.

RevDate: 2022-01-10
CmpDate: 2022-01-10

Wuethrich I, W Pelzer B, Khodamoradi Y, et al (2021)

The role of the human gut microbiota in colonization and infection with multidrug-resistant bacteria.

Gut microbes, 13(1):1-13.

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.

RevDate: 2022-01-03
CmpDate: 2022-01-03

Liwinski T, Leshem A, E Elinav (2021)

Breakthroughs and Bottlenecks in Microbiome Research.

Trends in molecular medicine, 27(4):298-301.

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.

RevDate: 2021-12-23
CmpDate: 2021-12-23

Haifer C, Saikal A, Paramsothy R, et al (2021)

Response to faecal microbiota transplantation in ulcerative colitis is not sustained long term following induction therapy.

Gut, 70(11):2210-2211.

RevDate: 2022-01-07

Sandhu A, T Chopra (2021)

Fecal microbiota transplantation for recurrent Clostridioides difficile, safety, and pitfalls.

Therapeutic advances in gastroenterology, 14:17562848211053105 pii:10.1177_17562848211053105.

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.

RevDate: 2022-01-07

Lai J, Zhang P, Jiang J, et al (2021)

New Evidence of Gut Microbiota Involvement in the Neuropathogenesis of Bipolar Depression by TRANK1 Modulation: Joint Clinical and Animal Data.

Frontiers in immunology, 12:789647.

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.

RevDate: 2022-01-07
CmpDate: 2022-01-07

Wu LH, Ye ZN, Peng P, et al (2021)

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.

Current medical science, 41(6):1087-1095.

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.

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.

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.

CONCLUSION: The findings from this study may offer a new approach for the prevention and treatment of COVID-19 patients suspected of having GMD.

RevDate: 2022-01-07
CmpDate: 2022-01-07

Wolter M, Grant ET, Boudaud M, et al (2021)

Leveraging diet to engineer the gut microbiome.

Nature reviews. Gastroenterology & hepatology, 18(12):885-902.

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.

RevDate: 2022-01-07
CmpDate: 2022-01-07

Lau HC, Ng SC, J Yu (2022)

Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?.

Gastroenterology, 162(1):9-16.

RevDate: 2022-01-07
CmpDate: 2022-01-07

Farshbafnadi M, Agah E, N Rezaei (2021)

The second brain: The connection between gut microbiota composition and multiple sclerosis.

Journal of neuroimmunology, 360:577700.

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.

RevDate: 2022-01-07
CmpDate: 2022-01-07

Glenny EM, Fouladi F, Thomas SA, et al (2021)

Gut microbial communities from patients with anorexia nervosa do not influence body weight in recipient germ-free mice.

Gut microbes, 13(1):1-15.

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.

RevDate: 2022-01-07
CmpDate: 2022-01-07

Meng Q, Ma M, Zhang W, et al (2021)

The gut microbiota during the progression of atherosclerosis in the perimenopausal period shows specific compositional changes and significant correlations with circulating lipid metabolites.

Gut microbes, 13(1):1-27.

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.

RevDate: 2022-01-06

Aaldijk E, Y Vermeiren (2022)

The role of serotonin within the microbiota-gut-brain axis in the development of Alzheimer's disease: a narrative review.

Ageing research reviews pii:S1568-1637(21)00303-2 [Epub ahead of print].

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.

RevDate: 2022-01-06

Spindelboeck W, Halwachs B, Bayer N, et al (2021)

Antibiotic use and ileocolonic immune cells in patients receiving fecal microbiota transplantation for refractory intestinal GvHD: a prospective cohort study.

Therapeutic advances in hematology, 12:20406207211058333 pii:10.1177_20406207211058333.

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.

Methods: Consecutive patients with treatment-refractory GI-GvHD were treated with up to six endoscopically applied FMTs.

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.

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.

RevDate: 2022-01-06

D'Amico F, Barone M, Tavella T, et al (2022)

Host microbiomes in tumor precision medicine: how far are we?.

Current medicinal chemistry pii:CMC-EPUB-119988 [Epub ahead of print].

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.

RevDate: 2022-01-06
CmpDate: 2022-01-06

Koo H, CD Morrow (2021)

Incongruence between dominant commensal donor microbes in recipient feces post fecal transplant and response to anti-PD-1 immunotherapy.

BMC microbiology, 21(1):251.

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.

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.

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.

RevDate: 2022-01-06
CmpDate: 2022-01-06

Han X, Wang Y, Zhang P, et al (2021)

Kazak faecal microbiota transplantation induces short-chain fatty acids that promote glucagon-like peptide-1 secretion by regulating gut microbiota in db/db mice.

Pharmaceutical biology, 59(1):1077-1087.

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.

OBJECTIVE: To study the mechanism of improved glycolipid disorders in db/db mice by FMT from a KNGT donor.

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.

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).

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.

RevDate: 2022-01-05

Szychowiak P, Villageois-Tran K, Patrier J, et al (2022)

The role of the microbiota in the management of intensive care patients.

Annals of intensive care, 12(1):3.

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.

RevDate: 2022-01-05

Sorboni SG, Moghaddam HS, Jafarzadeh-Esfehani R, et al (2022)

A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders.

Clinical microbiology reviews [Epub ahead of print].

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.

RevDate: 2022-01-04

Gweon TG, Lee YJ, Kim KO, et al (2022)

Clinical Practice Guidelines for Fecal Microbiota Transplantation in Korea.

Journal of neurogastroenterology and motility, 28(1):28-42.

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.

RevDate: 2022-01-04

Chen Y, Liu Y, Wang Y, et al (2022)

Prevotellaceae produces butyrate to alleviate PD-1/PD-L1 inhibitor-related cardiotoxicity via PPARα-CYP4X1 axis in colonic macrophages.

Journal of experimental & clinical cancer research : CR, 41(1):1.

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.

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.

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.

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.

RevDate: 2022-01-04

Pan B, Liu X, Shi J, et al (2021)

A Meta-Analysis of Microbial Therapy Against Metabolic Syndrome: Evidence From Randomized Controlled Trials.

Frontiers in nutrition, 8:775216.

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%.

RevDate: 2022-01-04

Li S, Wei J, T Chen (2021)

Editorial: Gut Microbiota in the Occurrence, Development and Treatment of Gut-Brain Disorders.

Frontiers in cellular and infection microbiology, 11:808454.

RevDate: 2022-01-04

Ye X, Liu Y, Hu J, et al (2021)

Chlorogenic Acid-Induced Gut Microbiota Improves Metabolic Endotoxemia.

Frontiers in endocrinology, 12:762691.

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.

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.

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.

Conclusion: CGA-induced changes in the gut microbiota played an important role in the inhibition of metabolic endotoxemia in HFD-fed mice.

RevDate: 2022-01-01

Gao G, Ma T, Zhang T, et al (2021)

Adjunctive Probiotic Lactobacillus rhamnosus Probio-M9 Administration Enhances the Effect of Anti-PD-1 Antitumor Therapy via Restoring Antibiotic-Disrupted Gut Microbiota.

Frontiers in immunology, 12:772532.

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.

RevDate: 2022-01-03
CmpDate: 2022-01-03

Vuyyuru SK, Kedia S, Kalaivani M, et al (2021)

Efficacy and safety of fecal transplantation versus targeted therapies in ulcerative colitis: network meta-analysis.

Future microbiology, 16:1215-1227.

Aim: We conducted this network meta-analysis to compare the efficacy and safety of targeted pharmacotherapies and fecal microbial transplantation (FMT). Patients & 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.

RevDate: 2022-01-03
CmpDate: 2022-01-03

Zheng W, Duan M, Jia J, et al (2021)

Low-molecular alginate improved diet-induced obesity and metabolic syndrome through modulating the gut microbiota in BALB/c mice.

International journal of biological macromolecules, 187:811-820.

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.

RevDate: 2021-12-31
CmpDate: 2021-12-31

Khoruts A (2021)

Can FMT Cause or Prevent CRC? Maybe, But There Is More to Consider.

Gastroenterology, 161(4):1103-1105.

RevDate: 2021-12-30

Hu Y, Ye Z, Wu M, et al (2021)

The Communication Between Intestinal Microbiota and Ulcerative Colitis: An Exploration of Pathogenesis, Animal Models, and Potential Therapeutic Strategies.

Frontiers in medicine, 8:766126.

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.

RevDate: 2021-12-29

Hiippala K, Khan I, Ronkainen A, et al (2022)

Novel strain of Pseudoruminococcus massiliensis possesses traits important in gut adaptation and host-microbe interactions.

Gut microbes, 14(1):2013761.

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.

RevDate: 2021-12-29

Lin H, Guo Q, Wen Z, et al (2021)

The multiple effects of fecal microbiota transplantation on diarrhea-predominant irritable bowel syndrome (IBS-D) patients with anxiety and depression behaviors.

Microbial cell factories, 20(1):233.

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.

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".

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 .

RevDate: 2021-12-29
CmpDate: 2021-12-29

Tu T, C Zhao (2021)

Treating autism spectrum disorder by intervening with gut microbiota.

Journal of medical microbiology, 70(12):.

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.

RevDate: 2021-12-28

Jang S, Kim Y, Lee C, et al (2021)

The Effect of Formula-based Nutritional Treatment on Colitis in a Murine Model.

Journal of Korean medical science, 36(50):e342 pii:36.e342.

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.

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.

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.

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.

RevDate: 2021-12-28

Chernikova MA, Flores GD, Kilroy E, et al (2021)

The Brain-Gut-Microbiome System: Pathways and Implications for Autism Spectrum Disorder.

Nutrients, 13(12): pii:nu13124497.

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.

RevDate: 2021-12-28

Sobocki BK, Kaźmierczak-Siedlecka K, Folwarski M, et al (2021)

Pancreatic Cancer and Gut Microbiome-Related Aspects: A Comprehensive Review and Dietary Recommendations.

Nutrients, 13(12): pii:nu13124425.

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.

RevDate: 2021-12-28

Pane S, Ristori MV, Gardini S, et al (2021)

Clinical Parasitology and Parasitome Maps as Old and New Tools to Improve Clinical Microbiomics.

Pathogens (Basel, Switzerland), 10(12): pii:pathogens10121550.

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.

RevDate: 2021-12-28
CmpDate: 2021-12-28

Liang Y, Cui L, Gao J, et al (2021)

Gut Microbial Metabolites in Parkinson's Disease: Implications of Mitochondrial Dysfunction in the Pathogenesis and Treatment.

Molecular neurobiology, 58(8):3745-3758.

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.

RevDate: 2021-12-27

Bi C, Xiao G, Liu C, et al (2021)

Molecular Immune Mechanism of Intestinal Microbiota and Their Metabolites in the Occurrence and Development of Liver Cancer.

Frontiers in cell and developmental biology, 9:702414 pii:702414.

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.

RevDate: 2021-12-27

Zhao D, Ye C, Zhang S, et al (2021)

Analysis of risk factors for early clinical recurrence of inflammatory bowel disease after fecal microbiota transplantation.

American journal of translational research, 13(11):12875-12886.

OBJECTIVE: To explore the risk factors for early clinical recurrence of inflammatory bowel disease (IBD) after fecal microbiota transplantation (FMT).

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.

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).

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.

RevDate: 2021-12-27

Zhao Z, Guo Z, Yin Z, et al (2021)

Gut Microbiota Was Involved in the Process of Liver Injury During Intra-Abdominal Hypertension.

Frontiers in physiology, 12:790182.

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.

RevDate: 2021-12-27

Aira A, Arajol C, Casals-Pascual C, et al (2021)

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.

Enfermedades infecciosas y microbiologia clinica (English ed.) pii:S2529-993X(21)00241-0 [Epub ahead of print].

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.

RevDate: 2021-12-25

Shaikh DH, Patel H, Munshi R, et al (2021)

Patients with Clostridium difficile infection and prior appendectomy may be prone to worse outcomes.

World journal of gastrointestinal surgery, 13(11):1436-1447.

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.

AIM: To study the impact of prior appendectomy on the severity and outcomes of CDI.

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.

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).

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.

RevDate: 2021-12-25

Xu B, Qin W, Xu Y, et al (2021)

Dietary Quercetin Supplementation Attenuates Diarrhea and Intestinal Damage by Regulating Gut Microbiota in Weanling Piglets.

Oxidative medicine and cellular longevity, 2021:6221012.

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.

RevDate: 2021-12-24

Wu Y, Zhang Y, Xie B, et al (2021)

RhANP attenuates endotoxin-derived cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota-brain axis.

Journal of neuroinflammation, 18(1):300.

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.

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.

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.

CONCLUSIONS: Our results suggest that rhANP could mitigate LPS-induced hippocampal inflammation and cognitive dysfunction through subdiaphragmatic vagus nerve-mediated gut microbiota-brain axis.

RevDate: 2021-12-24

Kosaka S, Nadatani Y, Higashimori A, et al (2021)

Ovariectomy-Induced Dysbiosis May Have a Minor Effect on Bone in Mice.

Microorganisms, 9(12): pii:microorganisms9122563.

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.

RevDate: 2021-12-24

Broecker F, K Moelling (2021)

The Roles of the Virome in Cancer.

Microorganisms, 9(12): pii:microorganisms9122538.

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.

RevDate: 2021-12-24

Popa D, Neamtu B, Mihalache M, et al (2021)

Fecal Microbiota Transplant in Severe and Non-Severe Clostridioides difficile Infection. Is There a Role of FMT in Primary Severe CDI?.

Journal of clinical medicine, 10(24): pii:jcm10245822.

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.

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.

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.

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.

RevDate: 2021-12-24
CmpDate: 2021-12-24

Rolling T, Zhai B, Gjonbalaj M, et al (2021)

Haematopoietic cell transplantation outcomes are linked to intestinal mycobiota dynamics and an expansion of Candida parapsilosis complex species.

Nature microbiology, 6(12):1505-1515.

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.

RevDate: 2021-12-24
CmpDate: 2021-12-24

Fang Y, Zhang J, Zhu S, et al (2021)

Berberine ameliorates ovariectomy-induced anxiety-like behaviors by enrichment in equol generating gut microbiota.

Pharmacological research, 165:105439.

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.

RevDate: 2021-12-23

Wang S, Chen H, Wen X, et al (2021)

The Efficacy of Fecal Microbiota Transplantation in Experimental Autoimmune Encephalomyelitis: Transcriptome and Gut Microbiota Profiling.

Journal of immunology research, 2021:4400428.

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.

Method: We measured the severity of disease by clinical EAE scores and H&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.

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.

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.

RevDate: 2021-12-22

Hofmeister M, Clement F, Patten S, et al (2021)

The effect of interventions targeting gut microbiota on depressive symptoms: a systematic review and meta-analysis.

CMAJ open, 9(4):E1195-E1204 pii:9/4/E1195.

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.

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.

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.

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.

STUDY REGISTRATION: PROSPERO no. 143178.

RevDate: 2021-12-23
CmpDate: 2021-12-23

Hofer U (2021)

Faecal phage transplant to the rescue?.

Nature reviews. Microbiology, 19(12):744.

RevDate: 2021-12-20
CmpDate: 2021-12-20

Sasaki K, Sasaki D, Sasaki K, et al (2021)

Growth stimulation of Bifidobacterium from human colon using daikenchuto in an in vitro model of human intestinal microbiota.

Scientific reports, 11(1):4580.

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.

RevDate: 2021-12-21

Chen X, Wu Q, Gao X, et al (2021)

Gut Microbial Dysbiosis Associated with Type 2 Diabetes Aggravates Acute Ischemic Stroke.

mSystems, 6(6):e0130421.

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.

RevDate: 2021-12-21

Mashiah J, Karady T, Fliss-Isakov N, et al (2021)

Clinical efficacy of fecal microbial transplantation treatment in adults with moderate-to-severe atopic dermatitis.

Immunity, inflammation and disease [Epub ahead of print].

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.

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.

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.

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.

RevDate: 2021-12-20

Zhang Y, Xue X, Su S, et al (2021)

Patients and physicians' attitudes change on fecal microbiota transplantation for inflammatory bowel disease over the past 3 years.

Annals of translational medicine, 9(21):1619.

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.

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.

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.

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.

RevDate: 2021-12-20

Pan Q, Guo F, Huang Y, et al (2021)

Gut Microbiota Dysbiosis in Systemic Lupus Erythematosus: Novel Insights into Mechanisms and Promising Therapeutic Strategies.

Frontiers in immunology, 12:799788.

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.

RevDate: 2021-12-20

Guo Q, Lin H, Chen P, et al (2021)

Dynamic changes of intestinal flora in patients with irritable bowel syndrome combined with anxiety and depression after oral administration of enterobacteria capsules.

Bioengineered [Epub ahead of print].

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].

RevDate: 2021-12-19

He Y, Du W, Xiao S, et al (2021)

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 of translational medicine, 19(1):510.

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.

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.

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.

CONCLUSIONS: The microbiota was found to have NEC and the microbial butyrate-Treg axis was identified as a potential mechanism for the observed effects.

RevDate: 2021-12-17

Zhang L, Wang Y, Wu F, et al (2021)

MDG, an Ophiopogon japonicus polysaccharide, inhibits non-alcoholic fatty liver disease by regulating the abundance of Akkermansia muciniphila.

International journal of biological macromolecules pii:S0141-8130(21)02652-0 [Epub ahead of print].

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.

RevDate: 2021-12-20

Qi L, Huang X, He C, et al (2021)

Steroid-resistant intestinal aGVHD and refractory CMV and EBV infections complicated by haplo-HSCT were successfully rescued by FMT and CTL infusion.

The Journal of international medical research, 49(12):3000605211063292.

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.

RevDate: 2021-12-17

Wang Y, Z Xie (2021)

Exploring the role of gut microbiome in male reproduction.

Andrology [Epub ahead of print].

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.

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.

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.

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.

RevDate: 2021-12-20
CmpDate: 2021-12-20

Islam SMS, Ryu HM, Sayeed HM, et al (2021)

Eubacterium rectale Attenuates HSV-1 Induced Systemic Inflammation in Mice by Inhibiting CD83.

Frontiers in immunology, 12:712312.

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.

RevDate: 2021-12-20
CmpDate: 2021-12-20

Bozward AG, Ronca V, Osei-Bordom D, et al (2021)

Gut-Liver Immune Traffic: Deciphering Immune-Pathogenesis to Underpin Translational Therapy.

Frontiers in immunology, 12:711217.

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.

RevDate: 2021-12-20
CmpDate: 2021-12-20

Zhou CB, Zhou YL, JY Fang (2021)

Gut Microbiota in Cancer Immune Response and Immunotherapy.

Trends in cancer, 7(7):647-660.

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.

RevDate: 2021-12-16

Hollingshead C, Ciricillo J, J Kammeyer (2021)

Ethical Implications of the Fecal Microbiota Transplantation: Disclosure of a False-Positive HIV Test.

Case reports in infectious diseases, 2021:6696542.

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.

RevDate: 2021-12-16

Liang M, Liwen Z, Jianguo S, et al (2021)

Fecal Microbiota Transplantation Controls Progression of Experimental Autoimmune Hepatitis in Mice by Modulating the TFR/TFH Immune Imbalance and Intestinal Microbiota Composition.

Frontiers in immunology, 12:728723.

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.

RevDate: 2021-12-16
CmpDate: 2021-12-16

Lee KA, Luong MK, Shaw H, et al (2021)

The gut microbiome: what the oncologist ought to know.

British journal of cancer, 125(9):1197-1209.

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.

RevDate: 2021-12-14

Zhao Y, Chen X, Shen J, et al (2021)

Black Tea Alleviates Particulate Matter-Induced Lung Injury via the Gut-Lung Axis in Mice.

Journal of agricultural and food chemistry [Epub ahead of print].

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.

RevDate: 2021-12-13

de Souza JB, Brelaz-de-Castro MCA, IMF Cavalcanti (2021)

Strategies for the treatment of colorectal cancer caused by gut microbiota.

Life sciences pii:S0024-3205(21)01189-9 [Epub ahead of print].

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.

RevDate: 2021-12-14
CmpDate: 2021-12-07

Greathouse KL, AJ Johnson (2021)

Does caloric restriction prime the microbiome for pathogenic bacteria?.

Cell host & microbe, 29(8):1209-1211.

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.

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RJR Experience and Expertise

Researcher

Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.

Educator

Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.

Administrator

Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.

Technologist

Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.

Publisher

While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.

Speaker

Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.

Facilitator

Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.

Designer

Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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A practical handbook on fecal microbiota transplantation (FMT) for physicians, nurses, physician assistants, students, residents, and fellows, The 6 Ds of Fecal Microbiota Transplantation: A Primer from Decision to Discharge and Beyond provides a clinical framework to understand and administer this treatment. FMT has emerged as a promising treatment for C. difficile infection (CDI), and there is a major need for educational resources on the topic. Drs. Jessica Allegretti, Zain Kassam, and their expert contributors are leaders in the field and have collectively cared for thousands of patients suffering from recurrent CDI who have benefitted from FMT. This guide provides practical tools, clinical pearls, and answers to frequently asked questions. Beginning with introductory information on the microbiome and exploring the history of FMT, The 6 Ds of Fecal Microbiota Transplantation outlines a step-by-step checklist for administering FMT: Decision: Who is the right CDI patient to receive FMT? What clinical questions should you ask patients in your FMT clinical assessment?; Donor: How do you select and screen a donor for FMT?; Discussion: What are the risks, benefits, and alternatives that need to be discussed with patients?; Delivery: What is the best delivery method for FMT-colonoscopy, nasogastric tube, enema, or capsules?; Discharge and follow-up: What is the ideal post-FMT care? How should you council patients following FMT?; and Discovery: What are the most promising emerging clinical applications for FMT? What is the evidence for FMT in obesity, autism, irritable bowel syndrome, inflammatory bowel disease, antibiotic resistant bacteria, and liver disease? Arming healthcare professionals with the ability to answer questions from patients regarding FMT and the microbiome, The 6 Ds of Fecal Microbiota Transplantation provides a pragmatic guide for this exciting treatment.

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Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

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Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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