@article {pmid31440436, year = {2019}, author = {Hasan, N and Yang, H}, title = {Factors affecting the composition of the gut microbiota, and its modulation.}, journal = {PeerJ}, volume = {7}, number = {}, pages = {e7502}, doi = {10.7717/peerj.7502}, pmid = {31440436}, issn = {2167-8359}, abstract = {Gut microbiota have important functions in the body, and imbalances in the composition and diversity of those microbiota can cause several diseases. The host fosters favorable microbiota by releasing specific factors, such as microRNAs, and nonspecific factors, such as antimicrobial peptides, mucus and immunoglobulin A that encourage the growth of specific types of bacteria and inhibit the growth of others. Diet, antibiotics, and age can change gut microbiota, and many studies have shown the relationship between disorders of the microbiota and several diseases and reported some ways to modulate that balance. In this review, we highlight how the host shapes its gut microbiota via specific and nonspecific factors, how environmental and nutritional factors affect it, and how to modulate it using prebiotics, probiotics, and fecal microbiota transplantation.}, }
@article {pmid31439031, year = {2019}, author = {Zhang, Y and Huang, R and Cheng, M and Wang, L and Chao, J and Li, J and Zheng, P and Xie, P and Zhang, Z and Yao, H}, title = {Gut microbiota from NLRP3-deficient mice ameliorates depressive-like behaviors by regulating astrocyte dysfunction via circHIPK2.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {116}, doi = {10.1186/s40168-019-0733-3}, pmid = {31439031}, issn = {2049-2618}, abstract = {BACKGROUND: Inflammasomes have been found to interact with the gut microbiota, and this effect is associated with depression, but the mechanisms underlying this interaction have not been elucidated in detail.<br><br>RESULTS: The locomotor activity of NLRP3 KO mice was significantly greater than that of their WT littermates, while cohousing and transplantation of the NLRP3 KO gut microbiota avoid the effects of NLRP3 KO on the general locomotor activity at baseline. Meanwhile, transplantation of the NLRP3 KO microbiota alleviated the CUS-induced depressive-like behaviors. The compositions of the gut microbiota in NLRP3 KO mice and WT mice were significantly different in terms of the relative abundance of Firmicutes, Proteobacteria, and Bacteroidetes. Fecal microbiota transplantation (FMT) from NLRP3 KO mice significantly ameliorated the depressive-like behavior induced by chronic unpredictable stress (CUS) in recipient mice. Given the correlation between circular RNA HIPK2 (circHIPK2) and depression and the observation that the level of circHIPK2 expression was significantly increased in CUS-treated mice compared with that in the control group, further experiments were performed. FMT significantly ameliorated astrocyte dysfunction in recipient mice treated with CUS via inhibition of circHIPK2 expression.<br><br>CONCLUSIONS: Our study illustrates the involvement of the gut microbiota-circHIPK2-astrocyte axis in depression, providing translational evidence that transplantation of the gut microbiota from NLRP3 KO mice may serve as a novel therapeutic strategy for depression.}, }
@article {pmid31434568, year = {2019}, author = {Chang, CS and Kao, CY}, title = {Current understanding of the gut microbiota shaping mechanisms.}, journal = {Journal of biomedical science}, volume = {26}, number = {1}, pages = {59}, doi = {10.1186/s12929-019-0554-5}, pmid = {31434568}, issn = {1423-0127}, support = {IM-107-PP-04//National Health Research Institutes/ ; 104-2320-B-400-019-MY3//Ministry of Science and Technology, Taiwan/ ; 106-2628-B-400-001-MY3//Ministry of Science and Technology, Taiwan/ ; 108-2321-B-400-011-//Ministry of Science and Technology, Taiwan/ ; }, abstract = {Increasing evidences have shown strong associations between gut microbiota and many human diseases, and understanding the dynamic crosstalks of host-microbe interaction in the gut has become necessary for the detection, prevention, or therapy of diseases. Many reports have showed that diet, nutrient, pharmacologic factors and many other stimuli play dominant roles in the modulation of gut microbial compositions. However, it is inappropriate to neglect the impact of host factors on shaping the gut microbiota. In this review, we highlighted the current findings of the host factors that could modulate the gut microbiota. Particularly the epithelium-associated factors, including the innate immune sensors, anti-microbial peptides, mucus barrier, secretory IgAs, epithelial microvilli, epithelial tight junctions, epithelium metabolism, oxygen barrier, and even the microRNAs are discussed in the context of the microbiota shaping. With these shaping factors, the gut epithelial cells could select the residing microbes and affect the microbial composition. This knowledge not only could provide the opportunities to better control many diseases, but may also be used for predicting the success of fecal microbiota transplantation clinically.}, }
@article {pmid31431428, year = {2019}, author = {Guery, B and Galperine, T and Barbut, F}, title = {Clostridioides difficile: diagnosis and treatments.}, journal = {BMJ (Clinical research ed.)}, volume = {366}, number = {}, pages = {l4609}, doi = {10.1136/bmj.l4609}, pmid = {31431428}, issn = {1756-1833}, mesh = {Algorithms ; Anti-Bacterial Agents/therapeutic use ; Bacterial Vaccines ; Biomarkers/analysis ; Clostridium difficile/immunology/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/*diagnosis/epidemiology/*therapy ; Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Recurrence ; }, abstract = {Clostridioides difficile (formerly Clostridium) is a major cause of healthcare associated diarrhea, and is increasingly present in the community. Historically, C difficile infection was considered easy to diagnose and treat. Over the past two decades, however, diagnostic techniques have changed in line with a greater understanding of the physiopathology of C difficile infection and the use of new therapeutic molecules. The evolution of diagnosis showed there was an important under- and misdiagnosis of C difficile infection, emphasizing the importance of algorithms recommended by European and North American infectious diseases societies to obtain a reliable diagnosis. Previously, metronidazole was considered the reference drug to treat C difficile infection, but more recently vancomycin and other newer drugs are shown to have higher cure rates. Recurrence of infection represents a key parameter in the evaluation of new drugs, and the challenge is to target the right population with the adapted therapeutic molecule. In multiple recurrences, fecal microbiota transplantation is recommended. New approaches, including antibodies, vaccines, and new molecules are already available or in the pipeline, but more data are needed to support the inclusion of these in practice guidelines. This review aims to provide a baseline for clinicians to understand and stratify their choice in the diagnosis and treatment of C difficile infection based on the most recent data available.}, }
@article {pmid29514066, year = {2018}, author = {Bauer, PV and Duca, FA and Waise, TMZ and Dranse, HJ and Rasmussen, BA and Puri, A and Rasti, M and O'Brien, CA and Lam, TKT}, title = {Lactobacillus gasseri in the Upper Small Intestine Impacts an ACSL3-Dependent Fatty Acid-Sensing Pathway Regulating Whole-Body Glucose Homeostasis.}, journal = {Cell metabolism}, volume = {27}, number = {3}, pages = {572-587.e6}, doi = {10.1016/j.cmet.2018.01.013}, pmid = {29514066}, issn = {1932-7420}, support = {FDN-143204//CIHR/Canada ; }, mesh = {Animals ; Diet, High-Fat/methods ; Emulsions/metabolism ; Fatty Acids/*metabolism ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Glucose/*metabolism ; Homeostasis ; Intestine, Small/*metabolism/*microbiology ; Lactobacillus gasseri/*metabolism ; Linoleic Acid/metabolism ; Mice, Inbred C57BL ; Oleic Acid/metabolism ; Phospholipids/metabolism ; Rats, Sprague-Dawley ; Soybean Oil/metabolism ; }, abstract = {Long-chain acyl-CoA synthetase (ACSL)-dependent upper small intestinal lipid metabolism activates pre-absorptive pathways to regulate metabolic homeostasis, but whether changes in the upper small intestinal microbiota alter specific fatty acid-dependent pathways to impact glucose homeostasis remains unknown. We here first find that upper small intestinal infusion of Intralipid, oleic acid, or linoleic acid pre-absorptively increases glucose tolerance and lowers glucose production in rodents. High-fat feeding impairs pre-absorptive fatty acid sensing and reduces upper small intestinal Lactobacillus gasseri levels and ACSL3 expression. Transplantation of healthy upper small intestinal microbiota to high-fat-fed rodents restores L. gasseri levels and fatty acid sensing via increased ACSL3 expression, while L. gasseri probiotic administration to non-transplanted high-fat-fed rodents is sufficient to restore upper small intestinal ACSL3 expression and fatty acid sensing. In summary, we unveil a glucoregulatory role of upper small intestinal L. gasseri that impacts an ACSL3-dependent glucoregulatory fatty acid-sensing pathway.}, }
@article {pmid31425750, year = {2019}, author = {Chen, R and Xu, Y and Wu, P and Zhou, H and Lasanajak, Y and Fang, Y and Tang, L and Ye, L and Li, X and Cai, Z and Zhao, J}, title = {Transplantation of Fecal Microbiota Rich in Short Chain Fatty Acids and Butyric Acid Treat Cerebral Ischemic Stroke by Regulating Gut Microbiota.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {104403}, doi = {10.1016/j.phrs.2019.104403}, pmid = {31425750}, issn = {1096-1186}, abstract = {The gut microbiota and its short chain fatty acid (SCFA) metabolites have been established to play an important protective role against neurodegenerative diseases. Our previous study demonstrated that cerebral ischemic stroke triggers dysfunctional gut microbiota and increased intestinal permeability. In this study, we aimed to clarify the mechanism by which gut microbiota and SCFAs can treat cerebral ischemic stroke in rat middle cerebral artery occlusion models and use the information to develop new therapies. Our results show that oral administration of non-absorbable antibiotics reduced neurological impairment and the cerebral infarct volume, relieved cerebral edemas, and decreased blood lipid levels by altering the gut microbiota. We also found that ischemic stroke decreased intestinal levels of SCFAs. And that transplanting fecal microbiota rich in these metabolites was an effective means of treating the condition. Compared with other SCFAs, butyric acid showed the highest negative correlation with ischemic stroke. Supplementation with butyric acid treated models of ischemic stroke effectively by remodeling the gut microbiota, enriching the beneficial Lactobacillus, and repairing the leaky gut. In conclusion, interfering with the gut microbiota by transplanting fecal bacteria rich in SCFAs and supplementing with butyric acid were found to be effective treatments for cerebral ischemic stroke.}, }
@article {pmid29851107, year = {2018}, author = {Ianiro, G and Masucci, L and Quaranta, G and Simonelli, C and Lopetuso, LR and Sanguinetti, M and Gasbarrini, A and Cammarota, G}, title = {Randomised clinical trial: faecal microbiota transplantation by colonoscopy plus vancomycin for the treatment of severe refractory Clostridium difficile infection-single versus multiple infusions.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {48}, number = {2}, pages = {152-159}, doi = {10.1111/apt.14816}, pmid = {29851107}, issn = {1365-2036}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Clostridium Infections/microbiology/*therapy ; Clostridium difficile/drug effects ; Colonoscopy/*methods ; Combined Modality Therapy ; *Drug Resistance, Bacterial ; Enterocolitis, Pseudomembranous/microbiology/therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Humans ; Male ; Middle Aged ; Severity of Illness Index ; Treatment Outcome ; Vancomycin/*therapeutic use ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridium difficile infection. Far less evidence exists on the efficacy of FMT in treating severe Clostridium difficile infection refractory to antibiotics.<br><br>AIM: To compare the efficacy of two FMT-based protocols associated with vancomycin in curing subjects with severe Clostridium difficile infection refractory to antibiotics.<br><br>METHODS: Subjects with severe Clostridium difficile infection refractory to antibiotics were randomly assigned to one of the two following treatment arms: (1) FMT-S, including a single faecal infusion via colonoscopy followed by a 14-day vancomycin course, (2) FMT-M, including multiple faecal infusions plus a 14-day vancomycin course. In the FMT-M group, all subjects received at least two infusions, while those with pseudomembranous colitis underwent further infusions until the disappearance of pseudomembranes. The primary outcome was the cure of refractory severe Clostridium difficile infection.<br><br>RESULTS: Fifty six subjects, 28 in each treatment arm, were enrolled. Twenty one patients in the FMT-S group and 28 patients in the FMT-M group were cured (75% vs 100%, respectively, both in per protocol and intention-to-treat analyses; P = 0.01). No serious adverse events associated with any of the two treatment protocols were observed.<br><br>CONCLUSIONS: A pseudomembrane-driven FMT protocol consisting of multiple faecal infusions and concomitant vancomycin was significantly more effective than a single faecal transplant followed by vancomycin in curing severe Clostridium difficile infection refractory to antibiotics. Clinical-Trials.gov registration number: NCT03427229.}, }
@article {pmid31419514, year = {2019}, author = {Mouries, J and Brescia, P and Silvestri, A and Spadoni, I and Sorribas, M and Wiest, R and Mileti, E and Galbiati, M and Invernizzi, P and Adorini, L and Penna, G and Rescigno, M}, title = {Microbiota-driven gut vascular barrier disruption is a prerequisite for non-alcoholic steatohepatitis development.}, journal = {Journal of hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhep.2019.08.005}, pmid = {31419514}, issn = {1600-0641}, abstract = {BACKGROUND AND AIMS: Fatty liver disease, including nonalcoholic fatty liver (NAFLD) and steatohepatitis (NASH), has been associated with increased intestinal barrier permeability and translocation of bacteria or bacterial products into the blood circulation. In this study we aim to unravel the role of both intestinal barriers integrity and microbiota in NAFDL/NASH development.<br><br>METHODS: C57BL/6J mice were fed with High Fat Diet (HFD) or Methionine Choline Deficient Diet for one week or longer to recapitulate NASH disease aspects (steatosis, inflammation, insulin resistance). Genetic and pharmacological strategies have been used to modulate the intestinal barriers integrity.<br><br>RESULTS: We show that disruption of intestinal epithelial barrier and gut vascular barrier (GVB) are early events in NASH pathogenesis. Mice fed a HFD for only one week undergo a diet-induced dysbiosis that drives GVB damage and bacteria translocation into the liver. Fecal microbiota transplantation from HFD-fed mice into specific pathogen-free recipients induces GVB damage and epidydimal adipose tissue enlargement. GVB disruption depends on interference with the WNT/β-catenin signaling pathway, as shown by genetic intervention driving β-catenin activation only in endothelial cells, preventing GVB disruption and NASH development. The bile acid analogue and farnesoid X receptor agonist obeticholic acid drives β-catenin activation in endothelial cells. Accordingly, pharmacologic intervention with OCA protects against GVB disruption, both as preventive and therapeutic agent. Importantly, we found upregulation of the GVB leakage marker in the colon of NASH patients.<br><br>CONCLUSIONS: We have identified a new player in NASH development, the GVB, whose damage leads to bacteria or bacterial product translocation into the blood circulation. Treatment aimed at restoring β-catenin activation in endothelial cells, such as administration of OCA, protects against GVB damage and NASH development.<br><br>LAY SUMMARY: Fatty liver disease incidence is reaching epidemic in USA, with more than 30% of adults having NAFLD (nonalcoholic fatty liver disease). NAFLD can develop into NASH (steatohepatitis), a more severe stage, that can ultimately turn into cirrhosis and hepatocellularcarcinoma. There is a known link between increased intestinal permeability and the development of the disease, however there is no clear description of the initiation of NASH, i.e. if it is a cause or a consequence of NASH. Here, we demonstrate for the first time that high fat diet induces changes in the microbiota, that will in turn disrupt the intestinal barrier. Indeed, there exist two layers of barrier that are sequentially disrupted when microbiota changes following high fat diet consumption. This disruption allows bacteria from the intestine to reach the blood stream and disseminate to the liver fostering the development of a fatty liver. When using a genetically modified mouse model, or a drug (OCA) that protects against barrier disruption, there is no development of the disease. This clearly shows that barrier disruption is a prerequisite for the disease to develop. Finally, we also found indication of barrier disruption in human samples from NASH patients, supporting the idea of a general mechanism. Altogether, these data clearly decipher the very first steps of fatty liver disease onset, and lead the way for a treatment using OCA to block barrier disruption.}, }
@article {pmid31414930, year = {2019}, author = {Rosenbaum, JT}, title = {Just another crappy commentary: the future of fecal microbiota transplantation.}, journal = {Expert review of clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1080/1744666X.2019.1656528}, pmid = {31414930}, issn = {1744-8409}, }
@article {pmid31412603, year = {2019}, author = {Khan, I and Ullah, N and Zha, L and Bai, Y and Khan, A and Zhao, T and Che, T and Zhang, C}, title = {Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome.}, journal = {Pathogens (Basel, Switzerland)}, volume = {8}, number = {3}, pages = {}, doi = {10.3390/pathogens8030126}, pmid = {31412603}, issn = {2076-0817}, support = {(No. BA2016036)//Jiangsu Science and Technology Major Project/ ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic complex inflammatory gut pathological condition, examples of which include Crohn's disease (CD) and ulcerative colitis (UC), which is associated with significant morbidity. Although the etiology of IBD is unknown, gut microbiota alteration (dysbiosis) is considered a novel factor involved in the pathogenesis of IBD. The gut microbiota acts as a metabolic organ and contributes to human health by performing various physiological functions; deviation in the gut flora composition is involved in various disease pathologies, including IBD. This review aims to summarize the current knowledge of gut microbiota alteration in IBD and how this contributes to intestinal inflammation, as well as explore the potential role of gut microbiota-based treatment approaches for the prevention and treatment of IBD. The current literature has clearly demonstrated a perturbation of the gut microbiota in IBD patients and mice colitis models, but a clear causal link of cause and effect has not yet been presented. In addition, gut microbiota-based therapeutic approaches have also shown good evidence of their effects in the amelioration of colitis in animal models (mice) and IBD patients, which indicates that gut flora might be a new promising therapeutic target for the treatment of IBD. However, insufficient data and confusing results from previous studies have led to a failure to define a core microbiome associated with IBD and the hidden mechanism of pathogenesis, which suggests that well-designed randomized control trials and mouse models are required for further research. In addition, a better understanding of this ecosystem will also determine the role of prebiotics and probiotics as therapeutic agents in the management of IBD.}, }
@article {pmid31411909, year = {2019}, author = {Yang, J and Yang, H}, title = {Non-antibiotic therapy for Clostridioides difficile infection: A review.}, journal = {Critical reviews in clinical laboratory sciences}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/10408363.2019.1648377}, pmid = {31411909}, issn = {1549-781X}, abstract = {Clostridioides difficile infection (CDI) is a common infectious disease that is mainly caused by antibiotics. Antibiotic therapy is still the dominant treatment for CDI, although it is accompanied by side effects. Probiotics, fecal microbiota transplantation (FMT), engineered microorganisms, bacteriophages, diet, natural active substances, nanoparticles and compounds are examples of emerging non-antibiotic therapies that have received a great amount of attention. In this review, we collected data about different non-antibiotic therapies for CDI and provided a comprehensive analysis and detailed comparison of these therapies. The mechanism of action, therapeutic efficacy, and the strengths and weaknesses of these non-antibiotic therapies have been investigated to provide a basis for the reasonable alternative of non-antibiotic therapies for CDI. In summary, probiotics and FMT are currently the best choice for non-antibiotic therapy for CDI.}, }
@article {pmid30419580, year = {2018}, author = {Stallmach, A and Reuken, PA and Teich, N}, title = {[Advances in the diagnosis and treatment of Clostridioides [Clostridium] difficile infections in inflammatory bowel disease].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {56}, number = {11}, pages = {1369-1377}, doi = {10.1055/a-0729-3168}, pmid = {30419580}, issn = {1439-7803}, mesh = {*Clostridium Infections/complications/diagnosis/therapy ; *Clostridium difficile ; *Fecal Microbiota Transplantation/adverse effects ; Feces ; Humans ; *Inflammatory Bowel Diseases/complications ; Intestines ; }, abstract = {Patients with chronic inflammatory bowel disease (IBD) have a significantly increased risk of clinically relevant clostridial infection (CDI). In turn, CDI can increase IBD activity. Therefore, rapid diagnosis and therapy is required. Many diagnostic and treatment studies on patients with CDI without inflammatory bowel disease are not congruent with IBD patients. This overview summarizes the everyday data of recent years and condenses these into four guiding principles. 1) patients with IBD present a risk population for a CDI. A CDI not only worsens the disease activity in the short term, but also causes increased morbidity and mortality in the long term. 2) If a CDI is suspected, glutamate-dehydrogenase (GDH) detection should be carried out quickly. If this is positive, and the disease activity is high, a therapy against C. difficile already may be initiated and-if necessary-terminated in cases of negative confirmation tests. 3) IBD patients with a proven CDI should be treated primarily with vancomycin. 4) In a relapsing CDI, fecal microbiome transfer is an effective therapeutic measure. However, activation of the IBD must be expected in about 15 % of cases. Consistent adherence to these guidelines may help treat a CDI in IBD patients.}, }
@article {pmid30126889, year = {2019}, author = {Milliken, EJT}, title = {Fifty years of faecal microbiota transplant in Central Australia.}, journal = {Gut}, volume = {68}, number = {8}, pages = {1536}, doi = {10.1136/gutjnl-2018-317235}, pmid = {30126889}, issn = {1468-3288}, mesh = {Australia ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Microbiota ; }, }
@article {pmid31402904, year = {2019}, author = {Gargiullo, L and Del Chierico, F and D'Argenio, P and Putignani, L}, title = {Gut Microbiota Modulation for Multidrug-Resistant Organism Decolonization: Present and Future Perspectives.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1704}, doi = {10.3389/fmicb.2019.01704}, pmid = {31402904}, issn = {1664-302X}, abstract = {The emergence of antimicrobial resistance (AMR) is of great concern to global public health. Treatment of multi-drug resistant (MDR) infections is a major clinical challenge: the increase in antibiotic resistance leads to a greater risk of therapeutic failure, relapses, longer hospitalizations, and worse clinical outcomes. Currently, there are no validated treatments for many MDR or pandrug-resistant (PDR) infections, and preventing the spread of these pathogens through hospital infection control procedures and antimicrobial stewardship programs is often the only tool available to healthcare providers. Therefore, new solutions to control the colonization of MDR pathogens are urgently needed. In this narrative review, we discuss current knowledge of microbiota-mediated mechanisms of AMR and strategies for MDR colonization control. We focus particularly on fecal microbiota transplantation for MDR intestinal decolonization and report updated literature on its current clinical use.}, }
@article {pmid30926290, year = {2019}, author = {Tavoukjian, V}, title = {Faecal microbiota transplantation for the decolonization of antibiotic-resistant bacteria in the gut: a systematic review and meta-analysis.}, journal = {The Journal of hospital infection}, volume = {102}, number = {2}, pages = {174-188}, doi = {10.1016/j.jhin.2019.03.010}, pmid = {30926290}, issn = {1532-2939}, mesh = {Bacterial Infections/microbiology/*therapy ; Carrier State/microbiology/*therapy ; *Drug Resistance, Bacterial ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; ROC Curve ; Treatment Outcome ; }, abstract = {Antibiotic resistance is a growing global problem associated with increased morbidity and mortality, and presents a significant financial and economic burden on healthcare. Faecal microbiota transplantation (FMT) has been proven effective for curing recurrent Clostridium difficile infections, however no systematic review to date has addressed its effectiveness for decolonization of antibiotic-resistant bacteria from the gut. The aim of this study was to establish whether faecal microbiota transplantation decolonizes antibiotic-resistant bacteria from the gut of colonized adults. A systematic review was performed by undertaking a comprehensive search on MEDLINE, Embase, CENTRAL, PubMed and CINAHL databases for evidence up until May 2018. Randomized and non-randomized studies evaluating the effects of FMT on gut colonization of antibiotic-resistant bacteria in adults were eligible. Studies were assessed using the Joanna Briggs Institution critical appraisal checklists. Quality of reporting was assessed using PROCESS and CARE checklists. Data was synthesized narratively, along with a meta-analysis of proportions for the primary outcome. Five studies with a total number of 52 participants were included. Evidence of low quality showed that decolonization was achieved in half of the cases one month after FMT with higher response noted in Pseudomonas aeruginosa, and lower response in Klebsiella pneumoniae with New Delhi metallo-beta-lactamase 1 (NDM-1) and extended-spectrum β-lactamase (ESBL) mechanisms of resistance. In successful cases, 70% of decolonization cases occurred within the first week after FMT. Few temporary adverse events were identified. Despite the limitations of the included studies, evidence from this review indicates a potential benefit of FMT as a decolonization intervention, which can only be confirmed by future well-designed RCTs.}, }
@article {pmid30472293, year = {2019}, author = {Saïdani, N and Lagier, JC and Cassir, N and Million, M and Baron, S and Dubourg, G and Eldin, C and Kerbaj, J and Valles, C and Raoult, D and Brouqui, P}, title = {Faecal microbiota transplantation shortens the colonisation period and allows re-entry of patients carrying carbapenamase-producing bacteria into medical care facilities.}, journal = {International journal of antimicrobial agents}, volume = {53}, number = {4}, pages = {355-361}, doi = {10.1016/j.ijantimicag.2018.11.014}, pmid = {30472293}, issn = {1872-7913}, mesh = {Acinetobacter/*growth &amp; development ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Carbapenem-Resistant Enterobacteriaceae/*growth &amp; development ; Case-Control Studies ; Drug Resistance, Multiple, Bacterial/physiology ; Enterobacteriaceae Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Young Adult ; }, abstract = {BACKGROUND: Colonisation with carbapenemase-producing Enterobacteriaceae or Acinetobacter (CPE/A) is associated with complex medical care requiring implementation of specific isolation policies and limitation of patient discharge to other medical facilities. Faecal microbiota transplantation (FMT) has been proposed in order to reduce the duration of gut colonisation.<br><br>OBJECTIVES: This study investigated whether a dedicated protocol of FMT could reduce the negativation time of CPE/A intestinal carriage in patients whose medical care has been delayed due to such colonisation.<br><br>METHOD: A matched case-control retrospective study between patients who received FMT treatment and those who did not among CPE/A-colonised patients addressed for initial clustering at the current institute. The study adjusted two controls per case based on sex, age, bacterial species, and carbapenemase type. The primary outcome was delay in negativation of rectal-swab cultures.<br><br>RESULTS: At day 14 post FMT, 8/10 (80%) treated patients were cleared for intestinal CPE/A carriage. In the control group, 2/20 (10%) had spontaneous clearance at day 14 after CPE/A diagnosis. Faecal microbiota transplantation led patients to reduce the delay in decolonisation (median 3 days post FMT for treated patients vs. 50.5 days after the first documentation of digestive carriage for control patients) and discharge from hospital (median 19.5 days post FMT for treated patients vs. 41 for control patients).<br><br>CONCLUSION: Faecal microbiota transplantation is a safe and time-saving procedure to discharge CPE/A-colonised patients from the hospital. A standardised protocol, including 5 days of antibiotic treatment, bowel cleansing and systematic indwelling devices removal, should improve protocol effectiveness.}, }
@article {pmid30084095, year = {2019}, author = {Dicks, LMT and Mikkelsen, LS and Brandsborg, E and Marcotte, H}, title = {Clostridium difficile, the Difficult &quot;Kloster&quot; Fuelled by Antibiotics.}, journal = {Current microbiology}, volume = {76}, number = {6}, pages = {774-782}, doi = {10.1007/s00284-018-1543-8}, pmid = {30084095}, issn = {1432-0991}, mesh = {Anti-Bacterial Agents/*adverse effects/therapeutic use ; Clostridium Infections/*microbiology/pathology ; Clostridium difficile/*drug effects/*growth &amp; development ; Colitis/complications/*microbiology/pathology/therapy ; *Drug Resistance, Bacterial ; Dysbiosis/*chemically induced ; Fecal Microbiota Transplantation/methods ; Humans ; Multiple Organ Failure ; Probiotics/administration &amp; dosage ; }, abstract = {Clostridium difficile is normally present in low numbers in a healthy adult gastro-intestinal tract (GIT). Drastic changes in the microbial population, e.g., dysbiosis caused by extensive treatment with antibiotics, stimulates the growth of resistant strains and the onset of C. difficile infection (CDI). Symptoms of infection varies from mild diarrhea to colitis (associated with dehydration and bleeding), pseudomembranous colitis with yellow ulcerations in the mucosa of the colon, to fulminant colitis (perforation of the gut membrane), and multiple organ failure. Inflamed epithelial cells and damaged mucosal tissue predisposes the colon to other opportunistic pathogens such as Clostridium perfringens, Staphylococcus aureus, Klebsiella oxytoca, Candida spp., and Salmonella spp. This may lead to small intestinal bacterial overgrowth (SIBO), sepsis, toxic megacolon, and even colorectal cancer. Many stains of C. difficile are resistant to metronidazole and vancomycin. Vaccination may be an answer to CDI, but requires more research. Success in treatment with probiotics depends on the strains used. Oral or rectal fecal transplants are partly effective, as spores in the small intestine may germinate and colonize the colon. The effect of antibiotics on C. difficile and commensal gut microbiota is summarized and changes in gut physiology are discussed. The need to search for non-antibiotic methods in the treatment of CDI and C. difficile-associated disease (CDAD) is emphasized.}, }
@article {pmid31398337, year = {2019}, author = {Riquelme, E and Zhang, Y and Zhang, L and Montiel, M and Zoltan, M and Dong, W and Quesada, P and Sahin, I and Chandra, V and San Lucas, A and Scheet, P and Xu, H and Hanash, SM and Feng, L and Burks, JK and Do, KA and Peterson, CB and Nejman, D and Tzeng, CD and Kim, MP and Sears, CL and Ajami, N and Petrosino, J and Wood, LD and Maitra, A and Straussman, R and Katz, M and White, JR and Jenq, R and Wargo, J and McAllister, F}, title = {Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes.}, journal = {Cell}, volume = {178}, number = {4}, pages = {795-806.e12}, doi = {10.1016/j.cell.2019.07.008}, pmid = {31398337}, issn = {1097-4172}, abstract = {Most patients diagnosed with resected pancreatic adenocarcinoma (PDAC) survive less than 5 years, but a minor subset survives longer. Here, we dissect the role of the tumor microbiota and the immune system in influencing long-term survival. Using 16S rRNA gene sequencing, we analyzed the tumor microbiome composition in PDAC patients with short-term survival (STS) and long-term survival (LTS). We found higher alpha-diversity in the tumor microbiome of LTS patients and identified an intra-tumoral microbiome signature (Pseudoxanthomonas-Streptomyces-Saccharopolyspora-Bacillus clausii) highly predictive of long-term survivorship in both discovery and validation cohorts. Through human-into-mice fecal microbiota transplantation (FMT) experiments from STS, LTS, or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration. Our study demonstrates that PDAC microbiome composition, which cross-talks to the gut microbiome, influences the host immune response and natural history of the disease.}, }
@article {pmid31396536, year = {2019}, author = {Zhou, GF and Jiang, YH and Ma, DF and Wang, YC and Yang, JL and Chen, JY and Chi, CY and Han, XW and Li, ZY and Li, X}, title = {Xiao-Qing-Long Tang Prevents Cardiomyocyte Hypertrophy, Fibrosis, and the Development of Heart Failure with Preserved Ejection Faction in Rats by Modulating the Composition of the Gut Microbiota.}, journal = {BioMed research international}, volume = {2019}, number = {}, pages = {9637479}, doi = {10.1155/2019/9637479}, pmid = {31396536}, issn = {2314-6141}, abstract = {Background: Changes in the gut microbiota are associated with cardiovascular disease progression. Xiao-Qing-Long Tang (XQLT), a traditional herbal formula, has an anti-inflammatory effect and regulates the steady state of the immune system, which is also associated with the progression of heart failure with preserved ejection faction (HFpEF). In this study, we investigated whether XQLT could contribute to prevent the development of HFpEF and whether the modulation of the gut microbiota by this herbal formula could be involved in such effect.<br><br>Methods: The gut microbiota, SCFAs, the histology/function of the heart, and systolic blood pressure were examined to evaluate the effect of XQLT on the gut microbiota and the progression of HFpEF after oral administration of XQLT to model rats. Furthermore, we evaluated, through fecal microbiota transplantation experiments, whether the favorable effects of XQLT could be mediated by the gut microbiota.<br><br>Results: Oral administration of XQLT contributed to the reduction of elevated blood pressure, inflammation, and compensatory hypertrophy, features that are associated with the progression of HFpEF. The gut microbiota composition, SCFA levels, and intestinal mucosal histology were improved after treatment with XQLT. Moreover, fecal transfer from XQLT-treated rats was sufficient to prevent the progression of HFpEF.<br><br>Conclusions: These data suggested that XQLT prevented the development of HFpEF in model rats by regulating the composition of the gut microbiota.}, }
@article {pmid31394793, year = {2019}, author = {El-Salhy, M and Hatlebakk, JG and Hausken, T}, title = {Diet in Irritable Bowel Syndrome (IBS): Interaction with Gut Microbiota and Gut Hormones.}, journal = {Nutrients}, volume = {11}, number = {8}, pages = {}, doi = {10.3390/nu11081824}, pmid = {31394793}, issn = {2072-6643}, abstract = {Diet plays an important role not only in the pathophysiology of irritable bowel syndrome (IBS), but also as a tool that improves symptoms and quality of life. The effects of diet seem to be a result of an interaction with the gut bacteria and the gut endocrine cells. The density of gut endocrine cells is low in IBS patients, and it is believed that this abnormality is the direct cause of the symptoms seen in IBS patients. The low density of gut endocrine cells is probably caused by a low number of stem cells and low differentiation progeny toward endocrine cells. A low fermentable oligo-, di-, monosaccharide, and polyol (FODMAP) diet and fecal microbiota transplantation (FMT) restore the gut endocrine cells to the level of healthy subjects. It has been suggested that our diet acts as a prebiotic that favors the growth of a certain types of bacteria. Diet also acts as a substrate for gut bacteria fermentation, which results in several by-products. These by-products might act on the stem cells in such a way that the gut stem cells decrease, and consequently, endocrine cell numbers decrease. Changing to a low-FODMAP diet or changing the gut bacteria through FMT improves IBS symptoms and restores the density of endocrine cells.}, }
@article {pmid29733457, year = {2018}, author = {Spychala, MS and Venna, VR and Jandzinski, M and Doran, SJ and Durgan, DJ and Ganesh, BP and Ajami, NJ and Putluri, N and Graf, J and Bryan, RM and McCullough, LD}, title = {Age-related changes in the gut microbiota influence systemic inflammation and stroke outcome.}, journal = {Annals of neurology}, volume = {84}, number = {1}, pages = {23-36}, pmid = {29733457}, issn = {1531-8249}, support = {R01 NS094543/NS/NINDS NIH HHS/United States ; R01 NS103592/NS/NINDS NIH HHS/United States ; R21 NS094806/NS/NINDS NIH HHS/United States ; R01 NS080531/NS/NINDS NIH HHS/United States ; RF1 AG058463/AG/NIA NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; }, mesh = {Age Factors ; *Aging ; Animals ; Cytokines/metabolism ; Disease Models, Animal ; Exploratory Behavior ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Inflammation/*microbiology/physiopathology ; Mice ; Mice, Inbred C57BL ; Muscle Strength/physiology ; Neurologic Examination ; RNA, Ribosomal, 16S/metabolism ; Stroke/*microbiology/physiopathology ; }, abstract = {OBJECTIVE: Chronic systemic inflammation contributes to the pathogenesis of many age-related diseases. Although not well understood, alterations in the gut microbiota, or dysbiosis, may be responsible for age-related inflammation.<br><br>METHODS: Using stroke as a disease model, we tested the hypothesis that a youthful microbiota, when established in aged mice, produces positive outcomes following ischemic stroke. Conversely, an aged microbiota, when established in young mice, produces negative outcomes after stroke. Young and aged male mice had either a young or an aged microbiota established by fecal transplant gavage (FTG). Mice were subjected to ischemic stroke (middle cerebral artery occlusion; MCAO) or sham surgery. During the subsequent weeks, mice underwent behavioral testing and fecal samples were collected for 16S ribosomal RNA analysis of bacterial content.<br><br>RESULTS: We found that the microbiota is altered after experimental stroke in young mice and resembles the biome of uninjured aged mice. In aged mice, the ratio of Firmicutes to Bacteroidetes (F:B), two main bacterial phyla in gut microbiota, increased ∼9-fold (p < 0.001) compared to young. This increased F:B ratio in aged mice is indicative of dysbiosis. Altering the microbiota in young by fecal gavage to resemble that of aged mice (∼6-fold increase in F:B ratio, p < 0.001) increased mortality following MCAO, decreased performance in behavioral testing, and increased cytokine levels. Conversely, altering the microbiota in aged to resemble that of young (∼9-fold decrease in F:B ratio, p < 0.001) increased survival and improved recovery following MCAO.<br><br>INTERPRETATION: Aged biome increased the levels of systemic proinflammatory cytokines. We conclude that the gut microbiota can be modified to positively impact outcomes from age-related diseases. Ann Neurol 2018;83:23-36.}, }
@article {pmid31391921, year = {2019}, author = {Muscogiuri, G and Cantone, E and Cassarano, S and Tuccinardi, D and Barrea, L and Savastano, S and Colao, A and , }, title = {Gut microbiota: a new path to treat obesity.}, journal = {International journal of obesity supplements}, volume = {9}, number = {1}, pages = {10-19}, doi = {10.1038/s41367-019-0011-7}, pmid = {31391921}, issn = {2046-2166}, abstract = {Obesity is a multifactorial disease resulting in excessive accumulation of adipose tissue. Over the last decade, growing evidence has identified the gut microbiota as a potential factor in the pathophysiology of both obesity and the related metabolic disorders. The gut microbiota is known to protect gastrointestinal mucosa permeability and to regulate the fermentation and absorption of dietary polysaccharides, perhaps explaining its importance in the regulation of fat accumulation and the resultant obesity. The proposed mechanisms by which the gut microbiota could contribute to the pathogenesis of obesity and the related metabolic diseases include: (a) a high abundance of bacteria that ferment carbohydrates, leading to increased rates of short-chain fatty acid (SCFA) biosynthesis, providing an extra source of energy for the host, that is eventually stored as lipids or glucose; (b) increased intestinal permeability to bacterial lipopolysaccharides (LPS), resulting in elevated systemic LPS levels that aggravate low-grade inflammation and insulin resistance; (c) increased activity of the gut endocannabinoid system. Fecal transplantation studies in germ-free mice have provided crucial insights into the potential causative role of the gut microbiota in the development of obesity and obesity-related disorders. Diet +/- bariatric surgery have been reported to modulate the gut microbiota, leading to lean host phenotype body composition. This review aims to report clinical evidence for a link of the gut microbiota with human obesity and obesity-related diseases, to provide molecular insights into these associations, and to address the effect of diet and bariatric surgery on the gut microbiota, including colonic microbiota, as a potential mechanism for promoting weight loss.}, }
@article {pmid31391545, year = {2019}, author = {Zhu, F and Guo, R and Wang, W and Ju, Y and Wang, Q and Ma, Q and Sun, Q and Fan, Y and Xie, Y and Yang, Z and Jie, Z and Zhao, B and Xiao, L and Yang, L and Zhang, T and Liu, B and Guo, L and He, X and Chen, Y and Chen, C and Gao, C and Xu, X and Yang, H and Wang, J and Dang, Y and Madsen, L and Brix, S and Kristiansen, K and Jia, H and Ma, X}, title = {Transplantation of microbiota from drug-free patients with schizophrenia causes schizophrenia-like abnormal behaviors and dysregulated kynurenine metabolism in mice.}, journal = {Molecular psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41380-019-0475-4}, pmid = {31391545}, issn = {1476-5578}, abstract = {Accumulating evidence suggests that gut microbiota plays a role in the pathogenesis of schizophrenia via the microbiota-gut-brain axis. This study sought to investigate whether transplantation of fecal microbiota from drug-free patients with schizophrenia into specific pathogen-free mice could cause schizophrenia-like behavioral abnormalities. The results revealed that transplantation of fecal microbiota from schizophrenic patients into antibiotic-treated mice caused behavioral abnormalities such as psychomotor hyperactivity, impaired learning and memory in the recipient animals. These mice also showed elevation of the kynurenine-kynurenic acid pathway of tryptophan degradation in both periphery and brain, as well as increased basal extracellular dopamine in prefrontal cortex and 5-hydroxytryptamine in hippocampus, compared with their counterparts receiving feces from healthy controls. Furthermore, colonic luminal filtrates from the mice transplanted with patients' fecal microbiota increased both kynurenic acid synthesis and kynurenine aminotransferase II activity in cultured hepatocytes and forebrain cortical slices. Sixty species of donor-derived bacteria showed significant difference between the mice colonized with the patients' and the controls' fecal microbiota, highlighting 78 differentially enriched functional modules including tryptophan biosynthesis function. In conclusion, our study suggests that the abnormalities in the composition of gut microbiota contribute to the pathogenesis of schizophrenia partially through the manipulation of tryptophan-kynurenine metabolism.}, }
@article {pmid30880228, year = {2019}, author = {Davido, B and Batista, R and Dinh, A and de Truchis, P and Terveer, EM and Roberts, B and Kuijper, EJ and Caballero, S}, title = {Fifty shades of graft: How to improve the efficacy of faecal microbiota transplantation for decolonization of antibiotic-resistant bacteria.}, journal = {International journal of antimicrobial agents}, volume = {53}, number = {5}, pages = {553-556}, doi = {10.1016/j.ijantimicag.2019.03.008}, pmid = {30880228}, issn = {1872-7913}, mesh = {Bacteria/*drug effects/isolation &amp; purification ; Bacterial Infections/*microbiology/*therapy ; *Drug Resistance, Bacterial ; Fecal Microbiota Transplantation/*methods ; Humans ; Treatment Outcome ; }, abstract = {BACKGROUND: Spontaneous decolonization of antibiotic-resistant bacteria (ARB) takes time: approximately 25% after 30 days for carbapenem-producing Enterobacteriaceae or extended-spectrum beta-lactamase-producing Enterobacteriaceae. Faecal microbiota transplantation (FMT) has been proposed as a new strategy to promote decolonization in order to reduce the risk of superinfection due to these ARB. This paper discusses the literature on the use of FMT for this indication, and the improvement levers available to promote its efficacy.<br><br>METHODS: Literature available to date concerning the use of FMT to eradicate ARB was reviewed, and the different factors that may have influenced the efficacy of decolonization were evaluated.<br><br>RESULTS: Four axes that could have played major roles in the efficacy of FMT were identified: bowel preparation before FMT; donor; dose; and thermal conditioning of faeces. The positive or negative impact of each on the outcome of FMT is discussed.<br><br>CONCLUSION: Although FMT is very efficient for the eradication of Clostridium difficile, the same 'recipe' cannot be used for the eradication of ARB. Working together with expert centres may help to improve the efficacy of FMT for this indication, and enable the reduction of in-hospital isolation precautions.}, }
@article {pmid31389816, year = {2019}, author = {Berbers, RM and Franken, IA and Leavis, HL}, title = {Immunoglobulin A and microbiota in primary immunodeficiency diseases.}, journal = {Current opinion in allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1097/ACI.0000000000000581}, pmid = {31389816}, issn = {1473-6322}, abstract = {PURPOSE OF REVIEW: With the emergence of the microbiota as a potential driver of host inflammation, the role of iIgA is becoming increasingly important. This review discusses the current evidence regarding the effects of clinical IgA deficiency on the microbiota, and the possible role of microbial dysbiosis in driving inflammation in PID patients.<br><br>RECENT FINDINGS: The gut microbiota has been investigated in selective IgA deficiency and common variable immunodeficiency, revealing an important role for IgA in maintaining gut microbiota homeostasis, with disparate effects of IgA on symbionts and pathobionts. Although IgA deficiency is associated with microbial translocation and systemic inflammation, this may be partially compensated by adequate IgG and IgM induction in IgA deficiency but not in common variable immunodeficiency. Therapeutic strategies aimed at correction of the microbiota mostly focus on fecal microbiota transplantation. Whether this may reduce systemic inflammation in PID is currently unknown.<br><br>SUMMARY: Clinical IgA deficiency is associated with microbial dysbiosis and systemic inflammation. The evidence for microbiota-targeted therapies in PID is scarce, but indicates that IgA-based therapies may be beneficial, and that fecal microbiota transplantation is well tolerated in patients with antibody deficiency.}, }
@article {pmid30183502, year = {2019}, author = {Strouse, C and Mangalam, A and Zhang, J}, title = {Bugs in the system: bringing the human microbiome to bear in cancer immunotherapy.}, journal = {Gut microbes}, volume = {10}, number = {2}, pages = {109-112}, doi = {10.1080/19490976.2018.1511665}, pmid = {30183502}, issn = {1949-0984}, support = {P30 CA086862/CA/NCI NIH HHS/United States ; P30 ES005605/ES/NIEHS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Dysbiosis/immunology/microbiology/therapy ; Fecal Microbiota Transplantation ; Humans ; *Immunotherapy ; Microbiota/drug effects/genetics/*immunology ; Neoplasms/immunology/*microbiology/*therapy ; }, abstract = {The influence of the composition of the human microbiome on the efficacy of cancer directed immunotherapies, such as antibodies directed against the programmed cell death 1 protein (PD-1) or its ligand (PD-L1), has garnered increasing attention as the role of immunotherapies in the care of cancer has grown. Dysbiosis (altered microbiota) has recently been reported to adversely affect the efficacy of cancer directed immunotherapies, and correction of this dysbiosis has the potential to improve the efficacy of these treatments. However, the exact mechanisms underlying this relationship remains unknown. Current methods for characterizing the microbiome likely capture only a small portion of the highly complex interaction between the microbiome and the immune system. Here we discuss the recent reports of the influence of dysbiosis on cancer immunotherapy, methods to more fully characterize the interaction between the microbiome and the immune system, and methods of modulating the immune system to improve the efficacy of cancer immunotherapy.}, }
@article {pmid29554669, year = {2018}, author = {Tansarli, GS and Mylonakis, E}, title = {Fecal transplant by oral capsule was noninferior to delivery by colonoscopy for C difficile recurrence.}, journal = {Annals of internal medicine}, volume = {168}, number = {6}, pages = {JC31}, doi = {10.7326/ACPJC-2018-168-6-031}, pmid = {29554669}, issn = {1539-3704}, mesh = {*Clostridium difficile ; Colonoscopy ; Fecal Microbiota Transplantation ; Feces ; Humans ; Recurrence ; }, }
@article {pmid31384699, year = {2019}, author = {Santiago, M and Eysenbach, L and Allegretti, J and Aroniadis, O and Brandt, LJ and Fischer, M and Grinspan, A and Kelly, C and Morrow, C and Rodriguez, M and Osman, M and Kassam, Z and Smith, MB and Timberlake, S}, title = {Microbiome predictors of dysbiosis and VRE decolonization in patients with recurrent C. difficile infections in a multi-center retrospective study.}, journal = {AIMS microbiology}, volume = {5}, number = {1}, pages = {1-18}, doi = {10.3934/microbiol.2019.1.1}, pmid = {31384699}, issn = {2471-1888}, abstract = {The gastrointestinal microbiome is intrinsically linked to the spread of antibiotic resistance. Antibiotic treatment puts patients at risk for colonization by opportunistic pathogens like vancomycin resistant Enterococcus and Clostridioides difficile by destroying the colonization resistance provided by the commensal microbiota. Once colonized, the host is at a much higher risk for infection by that pathogen. Furthermore, we know that microbiome community differences are associated with disease states, but we do not have a good understanding of how we can use these changes to classify different patient populations. To that end, we have performed a multicenter retrospective analysis on patients who received fecal microbiota transplants to treat recurrent Clostridioides difficile infection. We performed 16S rRNA gene sequencing on fecal samples collected as part of this study and used these data to develop a microbiome disruption index. Our microbiome disruption index is a simple index that is predictive across cohorts, indications, and batch effects. We are able to classify pre-fecal transplant vs post-fecal transplant samples in patients with recurrent C. difficile infection, and we are able to predict, using previously-published data from a cohort of patients receiving hematopoietic stem cell transplants, which patients would go on to develop bloodstream infections. Finally, we also identified patients in this cohort that were initially colonized with vancomycin resistant Enterococcus and that 92% (11/12) were decolonized after the transplant, but the microbiome disruption index was unable to predict such decolonization. We, however, were able to compare the relative abundance of different taxa between the two groups, and we found that increased abundance of Enterobacteriaceae predicts whether patients were colonized with vancomycin resistant Enterococcus. This work is an early step towards a better understanding of how microbiome predictors can be used to help improve patient care and patient outcomes.}, }
@article {pmid31383855, year = {2019}, author = {Sun, J and Xu, J and Ling, Y and Wang, F and Gong, T and Yang, C and Ye, S and Ye, K and Wei, D and Song, Z and Chen, D and Liu, J}, title = {Fecal microbiota transplantation alleviated Alzheimer's disease-like pathogenesis in APP/PS1 transgenic mice.}, journal = {Translational psychiatry}, volume = {9}, number = {1}, pages = {189}, doi = {10.1038/s41398-019-0525-3}, pmid = {31383855}, issn = {2158-3188}, support = {81871094//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81871094//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Alzheimer's disease (AD) is the most common dementia in the elderly. Treatment for AD is still a difficult task in clinic. AD is associated with abnormal gut microbiota. However, little is known about the role of fecal microbiota transplantation (FMT) in AD. Here, we evaluated the efficacy of FMT for the treatment of AD. We used an APPswe/PS1dE9 transgenic (Tg) mouse model. Cognitive deficits, brain deposits of amyloid-β (Aβ) and phosphorylation of tau, synaptic plasticity as well as neuroinflammation were assessed. Gut microbiota and its metabolites short-chain fatty acids (SCFAs) were analyzed by 16S rRNA sequencing and 1H nuclear magnetic resonance (NMR). Our results showed that FMT treatment could improve cognitive deficits and reduce the brain deposition of amyloid-β (Aβ) in APPswe/PS1dE9 transgenic (Tg) mice. These improvements were accompanied by decreased phosphorylation of tau protein and the levels of Aβ40 and Aβ42. We observed an increases in synaptic plasticity in the Tg mice, showing that postsynaptic density protein 95 (PSD-95) and synapsin I expression were increased after FMT. We also observed the decrease of COX-2 and CD11b levels in Tg mice after FMT. We also found that FMT treatment reversed the changes of gut microbiota and SCFAs. Thus, FMT may be a potential therapeutic strategy for AD.}, }
@article {pmid31379808, year = {2019}, author = {Dhakal, S and Wang, L and Antony, L and Rank, J and Bernardo, P and Ghimire, S and Bondra, K and Siems, C and Lakshmanappa, YS and Renu, S and Hogshead, B and Krakowka, S and Kauffman, M and Scaria, J and LeJeune, JT and Yu, Z and Renukaradhya, GJ}, title = {Amish (Rural) vs. non-Amish (Urban) Infant Fecal Microbiotas Are Highly Diverse and Their Transplantation Lead to Differences in Mucosal Immune Maturation in a Humanized Germfree Piglet Model.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {1509}, doi = {10.3389/fimmu.2019.01509}, pmid = {31379808}, issn = {1664-3224}, abstract = {The gut microbiome plays an important role in the immune system development, maintenance of normal health status, and in disease progression. In this study, we comparatively examined the fecal microbiomes of Amish (rural) and non-Amish (urban) infants and investigated how they could affect the mucosal immune maturation in germ-free piglets that were inoculated with the two types of infant fecal microbiota (IFM). Differences in microbiome diversity and structure were noted between the two types of fecal microbiotas. The fecal microbiota of the non-Amish (urban) infants had a greater relative abundance of Actinobacteria and Bacteroidetes phyla, while that of the Amish (rural) counterparts was dominated by Firmicutes. Amish infants had greater species richness compared with the non-Amish infants' microbiota. The fecal microbiotas of the Amish and the non-Amish infants were successfully transplanted into germ-free piglets, and the diversity and structure of the microbiota in the transplanted piglets remained similar at phylum level but not at the genus level. Principal coordinates analysis (PCoA) based on Weighted-UniFrac distance revealed distinct microbiota structure in the intestines of the transplanted piglets. Shotgun metagenomic analysis also revealed clear differences in functional diversity of fecal microbiome between Amish and non-Amish donors as well as microbiota transplanted piglets. Specific functional features were enriched in either of the microbiota transplanted piglet groups directly corresponding to the predominance of certain bacterial populations in their gut environment. Some of the colonized bacterial genera were correlated with the frequency of important lymphoid and myeloid immune cells in the ileal submucosa and mesenteric lymph nodes (MLN), both important for mucosal immune maturation. Overall, this study demonstrated that transplantation of diverse IFM into germ-free piglets largely recapitulates the differences in gut microbiota structure between rural (Amish) and urban (non-Amish) infants. Thus, fecal microbiota transplantation to germ-free piglets could be a useful large animal model system for elucidating the impact of gut microbiota on the mucosal immune system development. Future studies can focus on determining the additional advantages of the pig model over the rodent model.}, }
@article {pmid30384948, year = {2018}, author = {Wilcox, CM}, title = {Study of the Microbiome Has Reached Prime Time.}, journal = {The American journal of the medical sciences}, volume = {356}, number = {5}, pages = {409-410}, doi = {10.1016/j.amjms.2018.08.006}, pmid = {30384948}, issn = {1538-2990}, mesh = {*Clostridium difficile ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, }
@article {pmid31370803, year = {2019}, author = {Ma, Y and Xu, X and Li, M and Cai, J and Wei, Q and Niu, H}, title = {Gut microbiota promote the inflammatory response in the pathogenesis of systemic lupus erythematosus.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {25}, number = {1}, pages = {35}, doi = {10.1186/s10020-019-0102-5}, pmid = {31370803}, issn = {1528-3658}, support = {2016-I2M-1-006//CAMS Initiative for Innovative Medicine/ ; 2017YFA0105204//National Key Research and Development Program (CN)/ ; }, abstract = {OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease whose onset and progression are affected by genetic and environmental factors. The purpose of this study is to identify the influence of gut microbiota in the pathogenesis of SLE, and to investigate the mechanism involved.<br><br>METHODS: Fecal microbiota from C57/BL6 mice and SLE prone mice were examined using next-generation sequencing (NGS). Germ free mice were given fecal microbiota transplantation (FMT), and their gut microbiome and gene expression in recipients' colons were examined by NGS. The anti-double stranded DNA (anti-dsDNA) antibodies in recipients were determined using an enzyme-linked immunosorbent assay (ELISA). The immune cell profiles of mice were analyzed by flow cytometry at the 3rd week after FMT, and the expression of genes associated with SLE after FMT was determined using quantitative real-time PCR (qRT-PCR).<br><br>RESULTS: The fecal microbiota of SLE mice had lower community richness and diversity than healthy mice. Fecal microbiota of recipient mice were similar to their donors. Fecal microbiome from SLE mice could lead to a significant increase of anti-dsDNA antibodies and promote the immune response in recipient mice. Our results also indicated that fecal microbiome from SLE mice resulted in significant changes in the distribution of immune cells and upregulated expression of certain lupus susceptibility genes.<br><br>CONCLUSIONS: SLE is associated with alterations of gut microbiota. Fecal microbiome from SLE mice can induce the production of anti-dsDNA antibodies in germ free mice and stimulate the inflammatory response, and alter the expression of SLE susceptibility genes in these mice.}, }
@article {pmid31369420, year = {2019}, author = {Shin, JH and Warren, CA}, title = {Prevention and treatment of recurrent Clostridioides difficile infection.}, journal = {Current opinion in infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1097/QCO.0000000000000587}, pmid = {31369420}, issn = {1473-6527}, abstract = {PURPOSE OF REVIEW: Clostridioides difficile infection (CDI) is a significant burden on the health system, especially due to high recurrence rates. Since the beginning of the CDI epidemic in early 2000s, many strategies for combatting recurrence have been explored, with moderate success so far. This review will focus on the most recent developments in recurrent CDI prevention and treatment.<br><br>RECENT FINDINGS: There are two main mechanisms of CDI recurrence: alteration in microbiome and poor antibody response. Development of new antibiotics aims to minimize damage to the microbiome. Fecal transplant or other microbiome replacement therapies seek to replenish the missing elements in the microbiome. Fecal microbiota transplant is the most effective treatment for prevention of CDI recurrenceso far, but is difficult to standardize and regulate, leading to efforts to develop microbiome-derived therapeutics. A deficiency in developing antibodies to C. difficile toxins is another mechanism of recurrence. Active immunization using toxoid vaccines or passive immunization using mAbs address this aspect.<br><br>SUMMARY: There are promising new treatments for recurrent CDI in development. Fecal microbiota transplant remains the most effective therapy for multiply recurrent CDI. New antibiotics, microbiome-derived therapeutics, and immunologic therapies are in development.}, }
@article {pmid31367877, year = {2019}, author = {Yang, Z and Bu, C and Yuan, W and Shen, Z and Quan, Y and Wu, S and Zhu, C and Wang, X}, title = {Fecal Microbiota Transplant via Endoscopic Delivering Through Small Intestine and Colon: No Difference for Crohn's Disease.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-019-05751-y}, pmid = {31367877}, issn = {1573-2568}, support = {81272736//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND AND AIMS: Crohn's disease (CD) is a chronic inflammatory bowel disorder associated with intestinal dysbiosis. This study aimed to determine the efficacy and safety of different methods of fecal microbiota transplantation (FMT), a potential therapy for CD.<br><br>METHODS: Patients with CD were randomized to receive FMT by gastroscopy or colonoscopy; a second transplantation was performed 1 week later. Patients were assessed by clinical evaluation and serum testing (at weeks 1, 2, 4, 6, and 8) and endoscopy (8 weeks after transplantation). Fecal DNA was extracted and analyzed using the Illuminal sequencing platform.<br><br>RESULTS: Of the 27 patients included in the study, clinical remission was achieved in 18 (66.7%); no significant difference was seen between the two methods. 76.9% of gastroscopy group patients and 64.3% of colonoscopy group patients experienced mild adverse events during or shortly after treatment. Microbiota diversity analyses showed that, in comparison with the donors, patients had lower operational taxonomic units (OTU; 117 vs. 258, p < 0.05) and Shannon diversity index (2.05 vs. 3.46, p < 0.05). The CD patients showed a significant increase in OTU and Shannon diversity index 2 weeks after FMT. In comparison with the donors, CD patients had lower levels of Bacteroides, Eubacterium, faecalibacterium, and Roseburia, and higher levels of Clostridium, Cronobacter, Fusobacterium, and Streptococcus.<br><br>CONCLUSIONS: FMT was seen to be safe and effective in this cohort of patients with CD. No significant differences in clinical remission rate and adverse events were seen between the gastroscopy and colonoscopy groups. FMT was seen to increase the species richness in CD patients.}, }
@article {pmid31367159, year = {2019}, author = {Liu, MT and Huang, YJ and Zhang, TY and Tan, LB and Lu, XF and Qin, J}, title = {Lingguizhugan decoction attenuates diet-induced obesity and hepatosteatosis via gut microbiota.}, journal = {World journal of gastroenterology}, volume = {25}, number = {27}, pages = {3590-3606}, doi = {10.3748/wjg.v25.i27.3590}, pmid = {31367159}, issn = {2219-2840}, abstract = {BACKGROUND: Obesity is a major risk factor for a variety of diseases such as diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Restricting energy intake, or caloric restriction (CR), can reduce body weight and improve metabolic parameters in overweight or obese patients. We previously found that Lingguizhugan decoction (LZD) in combination with CR can effectively lower plasma lipid levels in patients with metabolic syndrome. However, the mechanism underlying CR and LZD treatment is still unclear.<br><br>AIM: To investigate whether CR and LZD improve metabolic parameters by modulating gut microbiota.<br><br>METHODS: We extracted the water-soluble components out of raw materials and dried as LZD extracts. Eight-week old male C57BL/6 mice were treated with a 3-d treatment regime that included 24 h-fasting followed by gavage of LZD extracts for 2 consecutive days, followed by a normal diet (ND) ad libitum for 16 wk. To test the effects of gut microbiota on diet-induced obesity, 8-wk old male C57BL/6 mice received fecal microbiota transplantation (FMT) from CR and LZD-treated mice every 3 d and were fed with high-fat diet (HFD) ad libitum for 16 wk. Control mice received either saline gavage or FMT from ND-fed mice receiving saline gavage as mentioned above. Body weight was monitored bi-weekly. Food consumption of each cage hosting five mice was recorded weekly. To monitor blood glucose, total cholesterol, and total triglycerides, blood samples were collected via submandibular bleeding after 6 h fasting. Oxygen consumption rate was monitored with metabolic cages. Feces were collected, and fecal DNA was extracted. Profiles of gut microbiota were mapped by metagenomic sequencing.<br><br>RESULTS: We found that CR and LZD treatment significantly reduced the body weight of mice fed with ND (28.71 ± 0.29 vs 28.05 ± 0.15, P < 0.05), but did not affect plasma total cholesterol or total triglyceride levels. We then transplanted the fecal microbiota collected from CR and LZD-treated mice under ND feeding to HFD-fed mice. Intriguingly, transplanting the mice with fecal microbiota from CR and LZD-treated mice potently reduced body weight (44.95 ± 1.02 vs 40.53 ± 0.97, P < 0.001). FMT also reduced HFD-induced hepatosteatosis, in addition to improved glycemic control. Mechanistic studies found that FMT increased OCR of the mice and suppressed the expression and protein abundance of lipogenic genes in the liver. Metagenomic analysis revealed that HFD drastically altered the profile of gut microbiota, and FMT modified the profile of the gut microbiota.<br><br>CONCLUSION: Our study suggests that CR and LZD improve metabolic parameters by modulating gut microbiota.}, }
@article {pmid31363779, year = {2019}, author = {Woodworth, MH and Hayden, MK and Young, VB and Kwon, JH}, title = {The Role of Fecal Microbiota Transplantation in Reducing Intestinal Colonization With Antibiotic-Resistant Organisms: The Current Landscape and Future Directions.}, journal = {Open forum infectious diseases}, volume = {6}, number = {7}, pages = {}, doi = {10.1093/ofid/ofz288}, pmid = {31363779}, issn = {2328-8957}, abstract = {The intestinal tract is a recognized reservoir of antibiotic-resistant organisms (ARO), and a potential target for strategies to reduce ARO colonization. Microbiome therapies such as fecal microbiota transplantation (FMT) have been established as an effective treatment for recurrent Clostridioides difficile infection and may be an effective approach for reducing intestinal ARO colonization. In this article, we review the current published literature on the role of FMT for eradication of intestinal ARO colonization, review the potential benefit and limitations of the use of FMT in this setting, and outline a research agenda for the future study of FMT for intestinal ARO colonization.}, }
@article {pmid31362781, year = {2019}, author = {Wang, X and Tsai, T and Deng, F and Wei, X and Chai, J and Knapp, J and Apple, J and Maxwell, CV and Lee, JA and Li, Y and Zhao, J}, title = {Longitudinal investigation of the swine gut microbiome from birth to market reveals stage and growth performance associated bacteria.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {109}, doi = {10.1186/s40168-019-0721-7}, pmid = {31362781}, issn = {2049-2618}, support = {2018-67015-27479//USDA NIFA AFRI/ ; }, abstract = {BACKGROUND: Despite recent advances in the understanding of the swine gut microbiome at different growth stages, a comprehensive longitudinal study of the lifetime (birth to market) dynamics of the swine gut microbiome is lacking.<br><br>RESULTS: To fill in this gap of knowledge, we repeatedly collected a total of 273 rectal swabs from 18 pigs during lactation (day (d) 0, 11, 20), nursery (d 27, 33, 41, 50, 61), growing (d 76, 90, 104, 116), and finishing (d 130, 146, 159, 174) stages. DNA was extracted and subjected to sequencing with an Illumina Miseq sequencer targeting the V4 region of the 16S rRNA gene. Sequences were analyzed with the Deblur algorithm in the QIIME2 package. A total of 19 phyla were detected in the lifetime pig gut microbiome with Firmicutes and Bacteroidetes being the most abundant. Alpha diversity including community richness (e.g., number of observed features) and diversity (e.g., Shannon index) showed an overall increasing trend. Distinct shifts in microbiome structure along different growth stages were observed. LEfSe analysis revealed 91 bacterial features that are stage-specific. To validate these discoveries, we performed fecal microbiota transplantation (FMT) by inoculating weanling pigs with mature fecal microbiota from a growing stage pig. Similar stage-specific patterns in microbiome diversity and structures were also observed in both the FMT pigs and their littermates. Although FMT remarkably increased growth performance, it did not change the overall swine gut microbiome. Only a few taxa including those associated with Streptococcus and Clostridiaceae were enriched in the FMT pigs. These data, together with several other lines of evidence, indicate potential roles these taxa play in promoting animal growth performance. Diet, especially crude fiber from corn, was a major factor shaping the swine gut microbiome. The priority effect, i.e., the order and timing of species arrival, was more evident in the solid feed stages.<br><br>CONCLUSIONS: The distinct stage-associated swine gut microbiome may be determined by the differences in diet and/or gut physiology at different growth stages. Our study provides insight into mechanisms governing gut microbiome succession and also underscores the importance of optimizing stage-specific probiotics aimed at improving animal health and production.}, }
@article {pmid30486642, year = {2019}, author = {Mosso, E and Boano, V and Grassini, M and Battaglia, E and Pellicano, R}, title = {Microscopic colitis: a narrative review with clinical approach.}, journal = {Minerva gastroenterologica e dietologica}, volume = {65}, number = {1}, pages = {53-62}, doi = {10.23736/S1121-421X.18.02539-4}, pmid = {30486642}, issn = {1827-1642}, mesh = {Anti-Inflammatory Agents/therapeutic use ; Budesonide/therapeutic use ; Colitis, Microscopic/*diagnosis/epidemiology/*therapy ; Colonoscopy ; Comorbidity ; Diarrhea/etiology ; Fecal Microbiota Transplantation ; Humans ; Immunologic Factors/therapeutic use ; Probiotics/therapeutic use ; }, abstract = {Microscopic colitis (MC) is diagnosed in presence of microscopic alterations of colonic mucosa, in patients without macroscopic lesions who referred for chronic diarrhea. The two types of MC are lymphocytic colitis (LC) and collagenous colitis (CC), but it is unclear whether these are the different expression of one unique disease or if they are distinct conditions. Today, although MC represents a consistent health problem, being responsible for a large part of gastroenterological consultations for diarrhea, it remains often underestimated. The detailed pathogenesis of MC has not been determined yet. Probably, it is the result of an interaction between individual, environmental and genetic factors. The most relevant risk factor for the development of MC is the use of certain drugs (such as non-steroidal anti-inflammatory drugs [NSAIDs], proton pump inhibitors [PPIs], selective serotonin reuptake inhibitors, beta-blockers, statins). Smoking is another relevant factor reported as associated with the development of MC. Diagnosis needs the execution of a colonoscopy in patients complaining about chronic diarrhea and abdominal pain. The crucial role is played by histology: MC is characterized by the presence of colonic mucosal lymphocytic infiltrate, with intraepithelial lymphocytes ≥20 per 100 enteric surface cells, in CC there is a typical subepithelial collagen layer, whose thickness is ≥10 μm. We carried out a review of the current literature to rule out what is new on epidemiology, diagnosis and therapy of MC.}, }
@article {pmid31361890, year = {2019}, author = {Haber, SL and Raney, CRK and Larson, TL and Lau, JP}, title = {Fecal microbiota transplantation for recurrent Clostridioides difficile infection.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {76}, number = {13}, pages = {935-942}, doi = {10.1093/ajhp/zxz078}, pmid = {31361890}, issn = {1535-2900}, abstract = {PURPOSE: Randomized controlled trials investigating the efficacy and safety of fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) are reviewed, and practical issues for pharmacists to consider are discussed.<br><br>SUMMARY: Eight randomized controlled trials evaluating the use of FMT for recurrent CDI were analyzed. The trials varied in the type of sample (fresh, frozen, lyophilized), route of administration (nasogastric tube, colonoscopy, enema, oral), and comparator agent (different type of FMT, vancomycin). Efficacy rates ranged from 43.8% to 96.2% with FMT, and safety data were relatively similar. With these favorable data, pharmacists are likely to be involved at multiple steps in the delivery of FMT to patients with recurrent CDI, including the procurement, documentation, and administration of various products and patient education.<br><br>CONCLUSION: FMT is an option for recurrent CDI that is supported by findings of randomized controlled trials, although a preferred method for the delivery remains to be defined. Pharmacists can play an important role in the successful management of patients with recurrent CDI who may benefit from FMT.}, }
@article {pmid31359254, year = {2019}, author = {Oksi, J and Aalto, A and Säilä, P and Partanen, T and Anttila, VJ and Mattila, E}, title = {Real-world efficacy of bezlotoxumab for prevention of recurrent Clostridium difficile infection: a retrospective study of 46 patients in five university hospitals in Finland.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10096-019-03630-y}, pmid = {31359254}, issn = {1435-4373}, abstract = {Reports on real-world experience on efficacy of bezlotoxumab (BEZ) has been lacking thus far. We retrospectively studied the efficacy and safety of BEZ in preventing the recurrence of Clostridium difficile infection (CDI) in five university hospitals in Finland. Seventy-three percent of our 46 patients remained free of recurrence in the following 3 months and the performance remained as 71% effective also among immunocompromised patients. In severe CDI, BEZ prevented recurrence in 63% of cases. From our study patients, 78% had three or more known risk factors for recurrence of CDI. Eight of our patients were waiting for fecal microbiota transplantation but after stopping the antibiotics that were continued to prevent recurrence of CDI and after receiving BEZ, all remained free of recurrence and did not need the procedure. Success with BEZ as an adjunctive treatment in preventing recurrence of CDI in high-risk patients may be rated as high. Among a subgroup of our patients, those already evaluated to be in need of fecal microbiota transplantation, BEZ seems to be an alternative option.}, }
@article {pmid31354831, year = {2019}, author = {Nowak, A and Hedenstierna, M and Ursing, J and Lidman, C and Nowak, P}, title = {Efficacy of Routine Fecal Microbiota Transplantation for Treatment of Recurrent Clostridium difficile Infection: A Retrospective Cohort Study.}, journal = {International journal of microbiology}, volume = {2019}, number = {}, pages = {7395127}, doi = {10.1155/2019/7395127}, pmid = {31354831}, issn = {1687-918X}, abstract = {Background: Patients with recurrent Clostridium difficile infections (CDIs) constitute an increasing treatment problem. Fecal microbiota transplantation (FMT) has shown promising results of treating recurrent CDI, where treatment with antibiotics fails repeatedly. Our study describes retrospective cohort treated with FMT at two major hospitals in Stockholm.<br><br>Methods: Medical records of all patients with recurrent CDI treated with FMT during the period 2013-2017 were reviewed. We evaluated cure of CDI-related diarrhea without relapse 10 weeks after FMT.<br><br>Results: 47 patients were included. One treatment cured 25 patients (53%), and more than one treatment cured 32 patients (68%). Treatment outcome did not vary significantly with treatment with fresh donor feces or frozen fecal culture, days of use of antibiotics or days of hospitalization prior to CDI, and renal function or time from the first CDI to therapy. Treatment failure was associated with a significantly lower Karnofsky performance status score (70 points vs 90, p=0.02).<br><br>Conclusion: Fecal instillation, for the treatment of relapsing CDI, is a promising approach, with 68% success rate reported in this study. The success rate of FMT is high, regardless of multiple comorbidities, extended use of antibiotics, or long time hospitalization. Although generally FMT is performed with fresh donor feces, our data show that the usage of frozen fecal culture could be an effective treatment alternative in recurrent CDI.}, }
@article {pmid31354670, year = {2019}, author = {Metzler-Zebeli, BU and Siegerstetter, SC and Magowan, E and Lawlor, PG and O Connell, NE and Zebeli, Q}, title = {Fecal Microbiota Transplant From Highly Feed Efficient Donors Affects Cecal Physiology and Microbiota in Low- and High-Feed Efficient Chickens.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1576}, doi = {10.3389/fmicb.2019.01576}, pmid = {31354670}, issn = {1664-302X}, abstract = {Fecal microbiota transplants (FMT) may be used to improve chicken's feed efficiency (FE) via modulation of the intestinal microbiota and microbe-host signaling. This study investigated the effect of the administration of FMT from highly feed efficient donors early in life on the jejunal and cecal microbiota, visceral organ size, intestinal morphology, permeability, and expression of genes for nutrient transporters, barrier function and innate immune response in chickens of diverging residual feed intake (RFI; a metric for FE). Chicks (n = 110) were inoculated with the FMT or control transplant (CT) on 1, 6, and 9 days posthatch (dph), from which 56 chickens were selected on 30 dph as the extremes in RFI, resulting in 15 low and 13 high RFI chickens receiving the FMT and 14 low and 14 high RFI chickens receiving the CT. RFI rank and FMT only caused tendencies for alterations in the jejunal microbiota and only one unclassified Lachnospiraceae genus in cecal digesta was indicative of high RFI. By contrast, the FMT caused clear differences in the short-chain fatty acid (SCFA) profile in the crop and cecal microbiota composition compared to the CT, which indicated alterations in amylolytic, pullulanolytic and hemicellulolytic bacteria such as Lactobacillus, Dorea, and Ruminococcus. Moreover, the FMT caused alterations in intestinal development as indicated by the longer duodenum and shallower crypts in the ceca. From the observed RFI-associated variation, energy-saving mechanisms and moderation of the mucosal immune response were indicated by higher jejunal permeability, shorter villi in the ileum, and enhanced cecal expression of the anti-inflammatory cytokine IL10 in low RFI chickens. Relationships obtained from supervised multigroup data integration support that certain bacteria, including Ruminococcocaceae-, Lactobacillus-, and unclassified Clostridiales-phylotypes, and SCFA in jejunal and cecal digesta modulated expression levels of cytokines, tight-junction protein OCLN and nutrient transporters for glucose and SCFA uptake. In conclusion, results suggest that the intestine only played a moderate role for the RFI-associated variation of the present low and high RFI phenotypes, whereas modulating the early microbial colonization resulted in long-lasting changes in bacterial taxonomic and metabolite composition as well as in host intestinal development.}, }
@article {pmid31344423, year = {2019}, author = {Dey, P}, title = {Gut microbiota in phytopharmacology: A comprehensive overview of concepts, reciprocal interactions, biotransformations and mode of actions.}, journal = {Pharmacological research}, volume = {147}, number = {}, pages = {104367}, doi = {10.1016/j.phrs.2019.104367}, pmid = {31344423}, issn = {1096-1186}, abstract = {The dynamic and delicate interactions amongst intestinal microbiota, metabolome and metabolism dictates human health and disease. In recent years, our understanding of gut microbial regulation of intestinal immunometabolic and redox homeostasis have evolved mainly out of in vivo studies associated with high-fat feeding induced metabolic diseases. Techniques utilizing fecal transplantation and germ-free mice have been instrumental in reproducibly demonstrating how the gut microbiota affects disease pathogenesis. However, the pillars of modern drug discovery i.e. evidence-based pharmacological studies critically lack focus on intestinal microflora. This is primarily due to targeted in vitro molecular-approaches at cellular-level that largely overlook the etiology of disease pathogenesis from the physiological perspective. Thus, this review aims to provide a comprehensive understanding of the key notions of intestinal microbiota and dysbiosis, and highlight the microbiota-phytochemical bidirectional interactions that affects bioavailability and bioactivity of parent phytochemicals and their metabolites. Potentially by focusing on the three major aspects of gut microbiota i.e. microbial abundance, diversity, and functions, I will discuss phytochemical-microbiota reciprocal interactions, biotransformation of phytochemicals and plant-derived drugs, and pre-clinical and clinical efficacies of herbal medicine on dysbiosis. Additionally, in relation to phytochemical pharmacology, I will briefly discuss the role of dietary-patterns associated with changes in microbial profiles and review pharmacological study models considering possible microbial effects. This review therefore, emphasize on the timely and critically needed evidence-based phytochemical studies focusing on gut microbiota and will provide newer insights for future pre-clinical and clinical phytopharmacological interventions.}, }
@article {pmid29878420, year = {2018}, author = {Jalanka, J and Hillamaa, A and Arkkila, PE and Satokari, R}, title = {Letter: improvements in mental health after faecal microbiota transplantation-an underexplored treatment-related benefit? Authors' reply.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {47}, number = {11}, pages = {1563-1564}, doi = {10.1111/apt.14668}, pmid = {29878420}, issn = {1365-2036}, mesh = {*Clostridium Infections ; Fecal Microbiota Transplantation ; *Gastrointestinal Diseases ; Humans ; Mental Health ; }, }
@article {pmid29876945, year = {2018}, author = {Mullish, BH}, title = {Letter: improvements in mental health after faecal microbiota transplantation-an underexplored treatment-related benefit?.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {47}, number = {11}, pages = {1562-1563}, doi = {10.1111/apt.14626}, pmid = {29876945}, issn = {1365-2036}, support = {MR/R000875/1//Medical Research Council/United Kingdom ; }, mesh = {*Clostridium Infections ; *Clostridium difficile ; Fecal Microbiota Transplantation ; Humans ; Mental Health ; }, }
@article {pmid31063075, year = {2019}, author = {Assimos, DG}, title = {Re: Fecal Transplant Modifies Urine Chemistry Risk Factors for Urinary Stone Disease.}, journal = {The Journal of urology}, volume = {202}, number = {2}, pages = {205}, doi = {10.1097/01.JU.0000559609.65417.2e}, pmid = {31063075}, issn = {1527-3792}, mesh = {Calcium Oxalate ; Fecal Microbiota Transplantation ; Humans ; Risk Factors ; *Urinary Calculi ; *Urologic Diseases ; }, }
@article {pmid30852460, year = {2019}, author = {Wang, H and Mei, L and Deng, Y and Liu, Y and Wei, X and Liu, M and Zhou, J and Ma, H and Zheng, P and Yuan, J and Li, M}, title = {Lactobacillus brevis DM9218 ameliorates fructose-induced hyperuricemia through inosine degradation and manipulation of intestinal dysbiosis.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {62}, number = {}, pages = {63-73}, doi = {10.1016/j.nut.2018.11.018}, pmid = {30852460}, issn = {1873-1244}, abstract = {OBJECTIVE: High fructose consumption exacerbates purine degradation and intestinal dysbiosis, which are closely related to the development of hyperuricemia. Probiotics are powerful weapons to combat metabolic disturbance and intestinal dysbiosis. Previously we isolated a Lactobacillus strain named DM9218 that could reduce the serum uric acid (UA) level by assimilating purine nucleosides. The present study aimed to evaluate the effects of DM9218 on high-fructose-induced hyperuricemia and to elucidate the underlying mechanisms.<br><br>METHODS: Mice were fed a normal diet, a high-fructose diet, or high-fructose diet with DM9218. Metabolic parameters, fructose- and UA-related metabolites, and fecal microbiota were investigated. Whole-genome sequencing of strain DM9218 was also conducted. In addition, an inosine hydrolase from DM9218 was heterologously expressed in Escherichia coli, and its inosine-degrading activity was detected.<br><br>RESULTS: Our results indicated that DM9218 could decrease serum UA level and hepatic xanthine oxidase activity in fructose-fed mice. It could protect against high-fructose-induced liver damage and retard UA accumulation by degrading inosine. The modulation effect of DM9218 on high-fructose-induced intestinal dysbiosis resulted in enhancement of intestinal barrier function and reduction of liver lipopolysaccharide, which was closely correlated with the down-regulation of inflammatory cytokine-stimulated xanthine oxidase expression and activity.<br><br>CONCLUSIONS: Lactobacillus brevis DM9218 is a probiotic strain with the potential to ameliorate fructose-induced hyperuricemia.}, }
@article {pmid29870676, year = {2018}, author = {Kim, TT and Parajuli, N and Sung, MM and Bairwa, SC and Levasseur, J and Soltys, CM and Wishart, DS and Madsen, K and Schertzer, JD and Dyck, JRB}, title = {Fecal transplant from resveratrol-fed donors improves glycaemia and cardiovascular features of the metabolic syndrome in mice.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {315}, number = {4}, pages = {E511-E519}, doi = {10.1152/ajpendo.00471.2017}, pmid = {29870676}, issn = {1522-1555}, support = {//Canadian Institutes for Health Research/International ; }, mesh = {Animals ; Antioxidants/*pharmacology ; Blood Glucose/drug effects/*metabolism ; Blood Pressure ; Colon/immunology ; Cytokines/immunology ; Diet, High-Fat ; Dietary Sucrose ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Hyperglycemia ; Hypertension ; Inflammation ; Magnetic Resonance Spectroscopy ; Metabolic Syndrome/immunology/*metabolism ; Mice ; Obesity/immunology/*metabolism ; Resveratrol/*pharmacology ; }, abstract = {Oral administration of resveratrol attenuates several symptoms associated with the metabolic syndrome, such as impaired glucose homeostasis and hypertension. Recent work has shown that resveratrol can improve glucose homeostasis in obesity via changes in the gut microbiota. Studies involving fecal microbiome transplants (FMTs) suggest that either live gut microbiota or bacterial-derived metabolites from resveratrol ingestion are responsible for producing the observed benefits in recipients. Herein, we show that obese mice receiving FMTs from healthy resveratrol-fed mice have improved glucose homeostasis within 11 days of the first transplant, and that resveratrol-FMTs is more efficacious than oral supplementation of resveratrol for the same duration. The effects of FMTs from resveratrol-fed mice are also associated with decreased inflammation in the colon of obese recipient mice. Furthermore, we show that sterile fecal filtrates from resveratrol-fed mice are sufficient to improve glucose homeostasis in obese mice, demonstrating that nonliving bacterial, metabolites, or other components within the feces of resveratrol-fed mice are sufficient to reduce intestinal inflammation. These postbiotics may be an integral mechanism by which resveratrol improves hyperglycemia in obesity. Resveratrol-FMTs also reduced the systolic blood pressure of hypertensive mice within 2 wk of the first transplant, indicating that the beneficial effects of resveratrol-FMTs may also assist with improving cardiovascular conditions associated with the metabolic syndrome.}, }
@article {pmid31343677, year = {2019}, author = {Lagier, JC and Million, M and Raoult, D}, title = {Bouillabaisse or Fish soup: The Limitations of Meta-Analysis confronted to the Inconsistency of Fecal Microbiota Transplantation Studies.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciz707}, pmid = {31343677}, issn = {1537-6591}, }
@article {pmid30911125, year = {2019}, author = {Velazquez, EM and Nguyen, H and Heasley, KT and Saechao, CH and Gil, LM and Rogers, AWL and Miller, BM and Rolston, MR and Lopez, CA and Litvak, Y and Liou, MJ and Faber, F and Bronner, DN and Tiffany, CR and Byndloss, MX and Byndloss, AJ and Bäumler, AJ}, title = {Endogenous Enterobacteriaceae underlie variation in susceptibility to Salmonella infection.}, journal = {Nature microbiology}, volume = {4}, number = {6}, pages = {1057-1064}, doi = {10.1038/s41564-019-0407-8}, pmid = {30911125}, issn = {2058-5276}, support = {R56 AI112949/AI/NIAID NIH HHS/United States ; T32 AI060555/AI/NIAID NIH HHS/United States ; R01 AI044170/AI/NIAID NIH HHS/United States ; T32 OD010931/OD/NIH HHS/United States ; R01 AI096528/AI/NIAID NIH HHS/United States ; R01 AI112949/AI/NIAID NIH HHS/United States ; T35 OD010956/OD/NIH HHS/United States ; R01 AI112445/AI/NIAID NIH HHS/United States ; }, mesh = {Animal Experimentation ; Animals ; Biomarkers ; Biosynthetic Pathways ; Disease Models, Animal ; Enterobacteriaceae/classification/*physiology ; Escherichia coli/physiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/genetics ; Germ-Free Life ; Mice ; Mice, Inbred C57BL ; Microbial Interactions/*physiology ; Phenotype ; Probiotics ; Reproducibility of Results ; Salmonella ; Salmonella Infections, Animal/*microbiology ; }, abstract = {Lack of reproducibility is a prominent problem in biomedical research. An important source of variation in animal experiments is the microbiome, but little is known about specific changes in the microbiota composition that cause phenotypic differences. Here, we show that genetically similar laboratory mice obtained from four different commercial vendors exhibited marked phenotypic variation in their susceptibility to Salmonella infection. Faecal microbiota transplant into germ-free mice replicated donor susceptibility, revealing that variability was due to changes in the gut microbiota composition. Co-housing of mice only partially transferred protection against Salmonella infection, suggesting that minority species within the gut microbiota might confer this trait. Consistent with this idea, we identified endogenous Enterobacteriaceae, a low-abundance taxon, as a keystone species responsible for variation in the susceptibility to Salmonella infection. Protection conferred by endogenous Enterobacteriaceae could be modelled by inoculating mice with probiotic Escherichia coli, which conferred resistance by using its aerobic metabolism to compete with Salmonella for resources. We conclude that a mechanistic understanding of phenotypic variation can accelerate development of strategies for enhancing the reproducibility of animal experiments.}, }
@article {pmid31338570, year = {2019}, author = {Turki, AT and Bayraktar, E and Basu, O and Benkö, T and Yi, JH and Kehrmann, J and Tzalavras, A and Liebregts, T and Beelen, DW and Steckel, NK}, title = {Ileostomy for steroid-resistant acute graft-versus-host disease of the gastrointestinal tract.}, journal = {Annals of hematology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00277-019-03754-3}, pmid = {31338570}, issn = {1432-0584}, abstract = {Steroid-resistant acute graft-versus-host disease (GVHD) of the gastrointestinal tract associates with important morbidity and mortality. While high-dose steroids are the established first-line therapy in GVHD, no second-line therapy is generally accepted. In this analysis of 65 consecutive patients with severe, steroid-resistant, intestinal GVHD (92% stage 4), additional ileostomy surgery significantly reduced overall mortality (hazard ratio 0.54; 95% confidence interval, 0.36-0.81; p = 0.003) compared to conventional GVHD therapy. Median overall survival was 16 months in the ileostomy cohort compared to 4 months in the conventional therapy cohort. In the ileostomy cohort, both infectious- and GVHD-associated mortality were reduced (40% versus 77%). Significantly declined fecal volumes (p = 0.001) after surgery provide evidence of intestinal adaptation following ileostomy. Correlative studies indicated ileostomy-induced immune-modulation with a > 50% decrease of activated T cells (p = 0.04) and an increase in regulatory T cells. The observed alterations of the patients' gut microbiota may also contribute to ileostomy's therapeutic effect. These data show that ileostomy induced significant clinical responses in patients with steroid-resistant GVHD along with a reduction of pro-inflammatory immune cells and changes of the intestinal microbiota. Ileostomy is a treatment option for steroid-resistant acute GVHD of the gastrointestinal tract that needs further validation in a prospective clinical trial.}, }
@article {pmid31337728, year = {2019}, author = {Staley, C and Kaiser, T and Vaughn, BP and Graiziger, C and Hamilton, MJ and Kabage, AJ and Khoruts, A and Sadowsky, MJ}, title = {Durable Long-Term Bacterial Engraftment following Encapsulated Fecal Microbiota Transplantation To Treat Clostridium difficile Infection.}, journal = {mBio}, volume = {10}, number = {4}, pages = {}, doi = {10.1128/mBio.01586-19}, pmid = {31337728}, issn = {2150-7511}, abstract = {Fecal microbiota transplantation (FMT) has become a common rescue therapy for recurrent Clostridium difficile infection, and encapsulated delivery (cFMT) of healthy donor microbiota shows similar clinical efficacy as more traditional routes of administration. In this study, we characterized long-term patterns of bacterial engraftment in a cohort of 18 patients, who received capsules from one of three donors, up to 409 days post-FMT. Bacterial communities were characterized using Illumina sequencing of the V5-V6 hypervariable regions of the 16S rRNA gene, and engraftment was determined by using the Bayesian algorithm SourceTracker. All patients recovered clinically and were free of C. difficile infection following cFMT. The majority of patients (61%) showed high levels of engraftment after the first week following FMT, which were sustained throughout the year. A small subset, 22%, experienced a decline in donor engraftment after approximately 1 month, and a few patients (17%), two of whom were taking metformin, showed delayed and low levels of donor engraftment. Members of the genera Bacteroides, Parabacteroides, and Faecalibacterium were significantly and positively correlated with donor similarity (ρ = 0.237 to 0.373, P ≤ 0.017). Furthermore, throughout the year, patient fecal communities showed significant separation based on the donor fecal microbiota that they received (P < 0.001). Results of this study, which characterize long-term engraftment following cFMT, suggest that numerical donor similarity is not strictly related to clinical outcome and identify a persistent donor-specific effect on patient fecal microbial communities. Furthermore, results suggest that members of the Bacteroidetes may be important targets to improve engraftment via cFMT.IMPORTANCE Recurrent Clostridium difficile infection (rCDI) is the most common cause of hospital- and community-acquired diarrheal infection associated with antibiotic use. Fecal microbiota transplantation (FMT), a treatment that involves administration of fecal bacteria from a healthy donor to a recipient patient, is a highly effective rescue therapy for rCDI that is increasingly being incorporated into standard clinical practice. Encapsulated, freeze-dried preparations of fecal microbiota, administered orally, offer the simplest and most convenient route of FMT delivery for patients (cFMT). In this study, we evaluated the extent of bacterial engraftment following cFMT and the duration of donor bacterial persistence. All patients studied recovered clinically but showed differing patterns in long-term microbial community similarity to the donor that were associated with members of the bacterial group Bacteroidetes, previously shown to be prominent contributors to rCDI resistance. Results highlight long-lasting, donor-specific effects on recipient patient microbiota and reveal potential bacterial targets to improve cFMT engraftment.}, }
@article {pmid31333622, year = {2019}, author = {Lu, HF and Ren, ZG and Li, A and Zhang, H and Xu, SY and Jiang, JW and Zhou, L and Ling, Q and Wang, BH and Cui, GY and Chen, XH and Zheng, SS and Li, LJ}, title = {Fecal Microbiome Data Distinguish Liver Recipients With Normal and Abnormal Liver Function From Healthy Controls.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1518}, doi = {10.3389/fmicb.2019.01518}, pmid = {31333622}, issn = {1664-302X}, abstract = {Emerging evidence suggests that altered intestinal microbiota plays an important role in the pathogenesis of many liver diseases, mainly by promoting inflammation via the &quot;intestinal microbiota-immunity-liver&quot; axis. We aimed to investigate the fecal microbiome of liver recipients with abnormal/normal liver function using 16S rRNA gene sequencing. Fecal samples were collected from 90 liver recipients [42 with abnormal liver function (Group LT_A) and 48 with normal liver function (Group LT_N)] and 61 age- and gender-matched healthy controls (HCs). Fecal microbiomes were analyzed for comparative composition, diversity, and richness of microbial communities. Principal coordinates analysis successfully distinguished the fecal microbiomes of recipients in Group LT_A from healthy subjects, with the significant decrease of fecal microbiome diversity in recipients in Group LT_A. Other than a higher relative abundance of opportunistic pathogens such as Klebsiella and Escherichia/Shigella in all liver recipients, the main difference in gut microbiome composition between liver recipients and HC was the lower relative abundance of beneficial butyrate-producing bacteria in the recipients. Importantly, we established a fecal microbiome index (specific alterations in Staphylococcus and Prevotella) that could be used to distinguish Group LT_A from Group LT_N, with an area under the receiver operating characteristic curve value of 0.801 and sensitivity and specificity values of 0.771 and 0.786, respectively. These findings revealed unique gut microbial characteristics of liver recipients with abnormal and normal liver functions, and identified fecal microbial risk indicators of abnormal liver function in liver recipients.}, }
@article {pmid31332392, year = {2019}, author = {Qi, X and Yun, C and Sun, L and Xia, J and Wu, Q and Wang, Y and Wang, L and Zhang, Y and Liang, X and Wang, L and Gonzalez, FJ and Patterson, AD and Liu, H and Mu, L and Zhou, Z and Zhao, Y and Li, R and Liu, P and Zhong, C and Pang, Y and Jiang, C and Qiao, J}, title = {Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41591-019-0509-0}, pmid = {31332392}, issn = {1546-170X}, abstract = {Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovulatory dysfunction and polycystic ovaries1, and is often accompanied by insulin resistance2. The mechanism of ovulatory dysfunction and insulin resistance in PCOS remains elusive, thus limiting the development of therapeutics. Improved metabolic health is associated with a relatively high microbiota gene content and increased microbial diversity3,4. This study aimed to investigate the impact of the gut microbiota and its metabolites on the regulation of PCOS-associated ovarian dysfunction and insulin resistance. Here, we report that Bacteroides vulgatus was markedly elevated in the gut microbiota of individuals with PCOS, accompanied by reduced glycodeoxycholic acid and tauroursodeoxycholic acid levels. Transplantation of fecal microbiota from women with PCOS or B. vulgatus-colonized recipient mice resulted in increased disruption of ovarian functions, insulin resistance, altered bile acid metabolism, reduced interleukin-22 secretion and infertility. Mechanistically, glycodeoxycholic acid induced intestinal group 3 innate lymphoid cell IL-22 secretion through GATA binding protein 3, and IL-22 in turn improved the PCOS phenotype. This finding is consistent with the reduced levels of IL-22 in individuals with PCOS. This study suggests that modifying the gut microbiota, altering bile acid metabolism and/or increasing IL-22 levels may be of value for the treatment of PCOS.}, }
@article {pmid31332389, year = {2019}, author = {Bárcena, C and Valdés-Mas, R and Mayoral, P and Garabaya, C and Durand, S and Rodríguez, F and Fernández-García, MT and Salazar, N and Nogacka, AM and Garatachea, N and Bossut, N and Aprahamian, F and Lucia, A and Kroemer, G and Freije, JMP and Quirós, PM and López-Otín, C}, title = {Healthspan and lifespan extension by fecal microbiota transplantation into progeroid mice.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41591-019-0504-5}, pmid = {31332389}, issn = {1546-170X}, abstract = {The gut microbiome is emerging as a key regulator of several metabolic, immune and neuroendocrine pathways1,2. Gut microbiome deregulation has been implicated in major conditions such as obesity, type 2 diabetes, cardiovascular disease, non-alcoholic fatty acid liver disease and cancer3-6, but its precise role in aging remains to be elucidated. Here, we find that two different mouse models of progeria are characterized by intestinal dysbiosis with alterations that include an increase in the abundance of Proteobacteria and Cyanobacteria, and a decrease in the abundance of Verrucomicrobia. Consistent with these findings, we found that human progeria patients also display intestinal dysbiosis and that long-lived humans (that is, centenarians) exhibit a substantial increase in Verrucomicrobia and a reduction in Proteobacteria. Fecal microbiota transplantation from wild-type mice enhanced healthspan and lifespan in both progeroid mouse models, and transplantation with the verrucomicrobia Akkermansia muciniphila was sufficient to exert beneficial effects. Moreover, metabolomic analysis of ileal content points to the restoration of secondary bile acids as a possible mechanism for the beneficial effects of reestablishing a healthy microbiome. Our results demonstrate that correction of the accelerated aging-associated intestinal dysbiosis is beneficial, suggesting the existence of a link between aging and the gut microbiota that provides a rationale for microbiome-based interventions against age-related diseases.}, }
@article {pmid31327219, year = {2019}, author = {Dutta, SK and Verma, S and Jain, V and Surapaneni, BK and Vinayek, R and Phillips, L and Nair, PP}, title = {Parkinson's Disease: The Emerging Role of Gut Dysbiosis, Antibiotics, Probiotics, and Fecal Microbiota Transplantation.}, journal = {Journal of neurogastroenterology and motility}, volume = {25}, number = {3}, pages = {363-376}, doi = {10.5056/jnm19044}, pmid = {31327219}, issn = {2093-0879}, abstract = {The role of the microbiome in health and human disease has emerged at the forefront of medicine in the 21st century. Over the last 2 decades evidence has emerged to suggest that inflammation-derived oxidative damage and cytokine induced toxicity may play a significant role in the neuronal damage associated with Parkinson's disease (PD). Presence of pro-inflammatory cytokines and T cell infiltration has been observed in the brain parenchyma of patients with PD. Furthermore, evidence for inflammatory changes has been reported in the enteric nervous system, the vagus nerve branches and glial cells. The presence of α-synuclein deposits in the post-mortem brain biopsy in patients with PD has further substantiated the role of inflammation in PD. It has been suggested that the α-synuclein misfolding might begin in the gut and spread &quot;prion like&quot; via the vagus nerve into lower brainstem and ultimately to the midbrain; this is known as the Braak hypothesis. It is noteworthy that the presence of gastrointestinal symptoms (constipation, dysphagia, and hypersalivation), altered gut microbiota and leaky gut have been observed in PD patients several years prior to the clinical onset of the disease. These clinical observations have been supported by in vitro studies in mice as well, demonstrating the role of genetic (α-synuclein overexpression) and environmental (gut dysbiosis) factors in the pathogenesis of PD. The restoration of the gut microbiome in patients with PD may alter the clinical progression of PD and this alteration can be accomplished by carefully designed studies using customized probiotics and fecal microbiota transplantation.}, }
@article {pmid31326608, year = {2019}, author = {Kelly, MS and Ward, DV and Severyn, CJ and Arshad, M and Heston, SM and Jenkins, K and Martin, PL and McGill, L and Stokhuyzen, A and Bhattarai, SK and Bucci, V and Seed, PC}, title = {Gut Colonization Preceding Mucosal Barrier Injury Bloodstream Infection in Pediatric Hematopoietic Stem Cell Transplant Recipients.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbmt.2019.07.019}, pmid = {31326608}, issn = {1523-6536}, abstract = {INTRODUCTION: The gastrointestinal tract is the predicted reservoir for most bloodstream infections (BSIs) after hematopoietic stem cell transplantation (HSCT). Whole-genome sequencing and comparative genomics have the potential to improve our understanding of the dynamics of gut colonization that precede BSI in HSCT recipients.<br><br>METHODS: Within a prospective cohort study of children (<18 years) undergoing HSCT, 9 subjects met criteria for mucosal barrier injury BSI. We performed whole-genome sequencing of the blood culture isolate and weekly fecal samples preceding the BSI to compare the genetic similarity of BSI isolates to fecal strains. We evaluated temporal associations between antibiotic exposures and the abundances of BSI strains in the gut microbiota and correlated detection of antibiotic resistance genes with the phenotypic antibiotic resistance of these strains.<br><br>RESULTS: Median age was 2.6 years, and 78% were male. BSIs were caused by Escherichia coli (n=5), Enterococcus faecium (n=2), Enterobacter cloacae (n=1), and Rothia mucilaginosa (n=1). In the 6 BSI episodes with evaluable comparative genomics, the fecal strains were identical to the blood culture isolate (>99.99% genetic similarity). Gut domination by these strains preceded only 4 of 7 E. coli or E. faecium BSIs by a median (range) of 17 (6-21) days. Increasing abundances of the resulting BSI strains in the gut microbiota were frequently associated with specific antibiotic exposures. E. cloacae and R. mucilaginosa were not highly abundant in fecal samples preceding BSIs caused by these species. The detection of antibiotic resistance genes for beta-lactam antibiotics and vancomycin predicted phenotypic resistance in BSI strains.<br><br>CONCLUSIONS: Bacterial strains causing mucosal barrier injury BSI in pediatric HSCT recipients were observed in the gut microbiota prior to BSI onset, and changes in the abundances of these strains within the gut preceded most BSI episodes. However, frequent sampling of the gut microbiota and sampling of other ecological niches is likely to be necessary to effectively predict BSI in HSCT recipients.}, }
@article {pmid31316785, year = {2019}, author = {Gutin, L and Piceno, Y and Fadrosh, D and Lynch, K and Zydek, M and Kassam, Z and LaMere, B and Terdiman, J and Ma, A and Somsouk, M and Lynch, S and El-Nachef, N}, title = {Fecal microbiota transplant for Crohn disease: A study evaluating safety, efficacy, and microbiome profile.}, journal = {United European gastroenterology journal}, volume = {7}, number = {6}, pages = {807-814}, doi = {10.1177/2050640619845986}, pmid = {31316785}, issn = {2050-6406}, abstract = {Background: Emerging trials suggest fecal microbiota transplantation (FMT) is a promising treatment for ulcerative colitis; however, there is a paucity of data in Crohn disease (CD).<br><br>Objective: The objectives of this article are to determine whether single-dose FMT improves clinical and endoscopic outcomes in CD patients and to identify meaningful changes in the microbiome in response to FMT.<br><br>Methods: We performed a prospective, open-label, single-center study. Ten CD patients underwent FMT and were evaluated for clinical response (defined as decrease in Harvey-Bradshaw Index score ≥3 at one month post-FMT) and microbiome profile (16S ribosomal RNA sequencing) at one month post-FMT.<br><br>Results: Three of 10 patients responded to FMT. Two of 10 patients had significant adverse events requiring escalation of therapy. On microbiome analysis, bacterial communities of responders had increased relative abundance of bacteria commonly found in donor gut microbiota.<br><br>Conclusions: Single-dose FMT in this cohort of CD patients showed modest effect and potential for harm. Responders tended to have lower baseline alpha diversity, suggesting baseline perturbation of microbiota may be an indicator of potential responders to FMT in this patient population. Controlled trials are needed to further assess the efficacy and safety of FMT in CD and determine whether FMT is a viable option in this patient population.Clinicaltrials.gov number: NCT02460705.}, }
@article {pmid31316751, year = {2019}, author = {Lin, DM and Lin, HC}, title = {A theoretical model of temperate phages as mediators of gut microbiome dysbiosis.}, journal = {F1000Research}, volume = {8}, number = {}, pages = {}, doi = {10.12688/f1000research.18480.1}, pmid = {31316751}, issn = {2046-1402}, abstract = {Bacteriophages are the most prominent members of the gut microbiome, outnumbering their bacterial hosts by a factor of 10. Phages are bacteria-specific viruses that are gaining attention as highly influential regulators of the gut bacterial community. Dysregulation of the gut bacterial community contributes to dysbiosis, a microbiome disorder characterized by compositional and functional changes that contribute to disease. A role for phages in gut microbiome dysbiosis is emerging with evidence that the gut phage community is altered in dysbiosis-associated disorders such as colorectal cancer and inflammatory bowel disease. Several recent studies have linked successful fecal microbiota transplantation to uptake of the donor's gut phage community, offering some insight into why some recipients respond to treatment whereas others do not. Here, we review the literature supporting a role for phages in mediating the gut bacterial community, giving special attention to Western diet dysbiosis as a case study to demonstrate a theoretical phage-based mechanism for the establishment and maintenance of dysbiosis.}, }
@article {pmid31315214, year = {2019}, author = {Shin, JH and Chaplin, AS and Hays, RA and Kolling, GL and Vance, S and Guerrant, RL and Archbald-Pannone, L and Warren, CA}, title = {Outcomes of a Multidisciplinary Clinic in Evaluating Recurrent Clostridioides difficile Infection Patients for Fecal Microbiota Transplant: A Retrospective Cohort Analysis.}, journal = {Journal of clinical medicine}, volume = {8}, number = {7}, pages = {}, doi = {10.3390/jcm8071036}, pmid = {31315214}, issn = {2077-0383}, support = {5T32AI007046-39//National Institute of Allergy and Infectious Diseases/ ; Buchanan Award//University of Virginia/ ; }, abstract = {Fecal microbiota transplantation (FMT) has been shown to be an effective treatment for recurrent Clostridioides difficile infections (rCDIs). We assessed the benefits of a multidisciplinary C. difficile clinic for screening FMT eligibility in patients with rCDI. Patients seen at the University of Virginia Complicated C. difficile Clinic (CCDC) underwent comprehensive evaluation for possible FMT. Patients were eligible for FMT if there was history of greater than two episodes of rCDI. Patients were evaluated for the outcome after evaluation in the clinic. A total of 113 patients were evaluated: 77 were eligible for FMT, of which 25 patients did not undergo FMT. The rate of recurrence at three months and all-cause mortality were 4.5% and 7% for patients who received FMT and 16.7% and 12.5% for eligible patients who did not receive FMT. There were 36 patients who were not eligible for FMT, with two or fewer recurrences and a recurrence rate of 8.8% and all-cause mortality of 6%. One in three patients screened for FMT had a nutritional deficiency diagnosed, with zinc deficiency being most common (20%). Additional diagnoses, including inflammatory bowel disease, were made during the evaluation. FMT is a highly effective treatment for rCDI, most notably in patients with multiple recurrences. A systematic approach for evaluating patients with rCDI helps identify patients who benefit most from FMT and those who have other conditions.}, }
@article {pmid31313610, year = {2019}, author = {Catho, G and Huttner, BD}, title = {Strategies for the eradication of extended-spectrum beta-lactamase or carbapenemase-producing Enterobacteriaceae intestinal carriage.}, journal = {Expert review of anti-infective therapy}, volume = {}, number = {}, pages = {}, doi = {10.1080/14787210.2019.1645007}, pmid = {31313610}, issn = {1744-8336}, abstract = {Introduction: Among the multidrug resistant pathogens, extended-spectrum beta-lactamase (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE) are currently considered the main threat due to the scarcity of therapeutic options and their rapid spread around the globe. In addition to developing new antibiotics and stopping transmission, recent research has focused on &quot;decolonization&quot; strategies to eradicate the carriage of ESBL-E/CPE before infection occurs. Areas covered: In this narrative review, we aim to describe the current evidence of decolonization strategies for ESBL-E or CPE intestinal carriage. We first define decolonization and highlight the issues related to the lack of standardized definition, then we summarize the available data on the natural history of colonization. Finally, we review the strategies assessed over the past 10 years for ESBL and CPE decolonization: oral antibiotics, probiotics and more recently fecal microbiota transplantation. We conclude by presenting the risks and uncertainties associated with these strategies. Expert opinion: The evidence available today is too low to recommend decolonization strategies for ESBL-E or CPE in routine clinical practice. The potential increase of resistance and the impact of microbiome manipulation should not be underestimated. Some of these decolonization strategies may nevertheless be effective, at least in temporarily suppressing colonization, which could be useful for specific populations such as high-risk patients. Effectiveness and long-term effects must be properly assessed through well-designed randomized controlled trials.}, }
@article {pmid31306634, year = {2019}, author = {Lo, GH}, title = {The transplantation of fecal microbiota for cirrhotic patients.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2019.06.040}, pmid = {31306634}, issn = {1528-0012}, }
@article {pmid31306229, year = {2019}, author = {Chen, X and Li, HY and Hu, XM and Zhang, Y and Zhang, SY}, title = {Current understanding of gut microbiota alterations and related therapeutic intervention strategies in heart failure.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, doi = {10.1097/CM9.0000000000000330}, pmid = {31306229}, issn = {2542-5641}, abstract = {OBJECTIVE: The purpose of this review is to stress the complicated interactions between the microbiota and the development of heart failure. Moreover, the feasibility of modulating intestinal microbes and metabolites as novel therapeutic strategies is discussed.<br><br>DATA SOURCES: This study was based on data obtained from PubMed up to March 31, 2019. Articles were selected using the following search terms: &quot;gut microbiota,&quot; &quot;heart failure,&quot; &quot;trimethylamine N-oxide (TMAO),&quot; &quot;short-chain fatty acid (SCFA),&quot; &quot;bile acid,&quot; &quot;uremic toxin,&quot; &quot;treatment,&quot; &quot;diet,&quot; &quot;probiotic,&quot; &quot;prebiotic,&quot; &quot;antibiotic,&quot; and &quot;fecal microbiota transplantation.&quot;<br><br>RESULTS: Accumulated evidence has revealed that the composition of the gut microbiota varies obviously in people with heart failure compared to those with healthy status. Altered gut microbial communities contribute to heart failure through bacterial translocation or affecting multiple metabolic pathways, including the trimethylamine/TMAO, SCFA, bile acid, and uremic toxin pathways. Meanwhile, modulation of the gut microbiota through diet, pre/probiotics, fecal transplantation, and microbial enzyme inhibitors has become a potential therapeutic approach for many metabolic disorders. Specifically, a few studies have focused on the cardioprotective effects of probiotics on heart failure.<br><br>CONCLUSIONS: The composition of the gut microbiota in people with heart failure is different from those with healthy status. A reduction in SCFA-producing bacteria in patients with heart failure might be a notable characteristic for patients with heart failure. Moreover, an increase in the microbial potential to produce TMAO and lipopolysaccharides is prominent. More researches focused on the mechanisms of microbial metabolites and the clinical application of multiple therapeutic interventions is necessarily required.}, }
@article {pmid31306151, year = {2019}, author = {Allegretti, JR and Kassam, Z}, title = {Fecal Microbiota Transplantation in Patients With Primary Sclerosing Cholangitis: The Next Steps in This Promising Story.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000000317}, pmid = {31306151}, issn = {1572-0241}, }
@article {pmid31305466, year = {2019}, author = {Sun, L and Li, J and Lan, LL and Li, XA}, title = {The effect of fecal microbiota transplantation on Hepatic myelopathy: A case report.}, journal = {Medicine}, volume = {98}, number = {28}, pages = {e16430}, doi = {10.1097/MD.0000000000016430}, pmid = {31305466}, issn = {1536-5964}, abstract = {RATIONALE: Hepatic myelopathy (HM), also known as portal-systemic myelopathy, is a rare neurological complication that occurs in patients with chronic liver disease. There is no easy and feasible treatment, liver transplantation is the only accepted therapy that may be effective for patients at early stage at present. The pathogenesis of the disease is not clear yet, and the prognosis is poor. Here we describe a reversible HM after fecal microbiota transplantation.<br><br>PATIENT CONCERNS: In this report, a middle-aged female patient with hepatitis B cirrhosis, occurred HM after transjugular intrahepatic portosystemic shunt, a progressive spastic paraparesis in both legs were the main symptoms.<br><br>DIAGNOSIS: The patient was diagnosed with HM.<br><br>INTERVENTIONS: The patient received 3 times of fecal microbiota transplantations (FMT).<br><br>OUTCOMES: The patient's muscle strength of both legs were increased at various degrees, the patient's condition improved from HM2 to HM1.<br><br>LESSONS: FMT may be another effective way to treat HM. It is cheaper, more operable, and simpler than the approved treatment and worthy of further research.}, }
@article {pmid31304425, year = {2019}, author = {Borody, TJ and Clancy, A}, title = {Fecal microbiota transplantation for ulcerative colitis-where to from here?.}, journal = {Translational gastroenterology and hepatology}, volume = {4}, number = {}, pages = {48}, doi = {10.21037/tgh.2019.06.04}, pmid = {31304425}, issn = {2415-1289}, }
@article {pmid31302808, year = {2019}, author = {Selvig, D and Piceno, Y and Terdiman, J and Zydek, M and Umetsu, SE and Balitzer, D and Fadrosh, D and Lynch, K and Lamere, B and Leith, T and Kassam, Z and Beck, K and Lewin, S and Ma, A and Somsouk, M and Lynch, SV and El-Nachef, N}, title = {Fecal Microbiota Transplantation in Pouchitis: Clinical, Endoscopic, Histologic, and Microbiota Results from a Pilot Study.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-019-05715-2}, pmid = {31302808}, issn = {1573-2568}, abstract = {AIMS: This pilot study assessed the efficacy, safety, and microbiome dynamics of fecal microbiota transplantation (FMT) for patients with chronic pouchitis.<br><br>METHODS: A prospective open-label pilot study was performed at an academic center among pouchitis patients undergoing FMT. Patients received a minimum of a single FMT by pouchoscopy from healthy, screened donors. The primary outcome was clinical improvement in pouchitis assessed by patient survey at week 4. Secondary outcomes included decrease in total Pouchitis Disease Activity Index (PDAI) Score ≥ 3 at week 4, bowel movement frequency, ESR, CRP, fecal calprotectin, abdominal pain, and PDAI subscores including endoscopic and histologic changes. Stool samples were collected at baseline and 4 weeks post-FMT to assess bacterial microbiota using V4 16S rRNA sequencing.<br><br>RESULTS: Nineteen patients were enrolled; however, 1 patient was lost to follow-up. No patients had a major adverse event or escalation of therapy related to FMT. Total PDAI scores, endoscopic scores, and histologic scores did not decrease significantly post-FMT. However, there was a statistically significant improvement in bowel movement (BM) frequency (9.25-7.25 BM/day, p = 0.03) and trend for improvement in abdominal pain to improve post-FMT (p = 0.05). Bacterial microbiota profiling revealed no distinct community-level changes post-FMT, though a small number of specific bacterial taxa significantly differed in relative abundance.<br><br>CONCLUSIONS: A single FMT has a tolerable short-term safety profile and may be associated with a decrease in bowel movements in patients with chronic pouchitis; however, no robust endoscopic or histologic changes were observed.}, }
@article {pmid31301451, year = {2019}, author = {Allegretti, JR and Kassam, Z and Mullish, BH and Chiang, A and Carrellas, M and Hurtado, J and Marchesi, JR and McDonald, JAK and Pechlivanis, A and Barker, GF and Blanco, JM and Garcia-Perez, I and Wong, WF and Gerardin, Y and Silverstein, M and Kennedy, K and Thompson, C}, title = {Effects of Fecal Microbiota Transplantation With Oral Capsules in Obese Patients.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2019.07.006}, pmid = {31301451}, issn = {1542-7714}, abstract = {BACKGROUND &amp; AIMS: Studies in mice have shown that the intestinal microbiota can contribute to obesity via the anorexigenic gut hormone glucagon-like peptide 1 (GLP1) and bile acids, which affect lipid metabolism. We performed a randomized, placebo-controlled pilot study of the effects of fecal microbiota transplantation (FMT) in obese, metabolically uncompromised patients.<br><br>METHODS: We performed a double-blind study of 22 obese patients (body mass index [BMI] ≥ 35kg/m2) without a diagnosis of diabetes, non-alcoholic steatohepatitis, or metabolic syndrome. Participants were randomly assigned (1:1) to groups that received FMT by capsules (induction dose of 30 capsules at week 4 and maintenance dose of 12 capsules at week 8) or placebo capsules. FMT capsules were derived from a single, lean donor (BMI, 17.5 kg/m2). Patients were followed through week 26; the primary outcome was safety. Stool and serum samples were collected from patients at baseline and at weeks 1, 4, 6, 8 and 12 after administration of the first dose of FMT or placebo and analyzed by 16S RNA gene sequencing. Stool and serum samples were analyzed for metabolomics by liquid chromatography-mass spectrometry. Additional outcomes were change in area under the curve for GLP1 at week 12.<br><br>RESULTS: We observed no significant differences in adverse events between patients who received FMT vs placebo. There was no increase in the area under the curve of GLP1 in either group. Patients who received FMT had sustained shifts in microbiomes associated with obesity toward those of the donor (P<.001). Patients who received FMT had a sustained decrease in stool levels of taurocholic acid (P<.05), compared with baseline; bile acid profiles began to more closely resemble those of the donor. We did not observe significant changes in mean BMI at week 12 in either group.<br><br>CONCLUSIONS: In a placebo-controlled pilot study, we found that FMT capsules (derived from a lean donor) were safe but did not reduce BMI in obese metabolically uncompromised patients. The FMT capsules were well tolerated and led to sustained changes in the intestinal microbiome and bile acid profiles that were similar to those of the lean donor.}, }
@article {pmid31293718, year = {2019}, author = {Campion, D and Giovo, I and Ponzo, P and Saracco, GM and Balzola, F and Alessandria, C}, title = {Dietary approach and gut microbiota modulation for chronic hepatic encephalopathy in cirrhosis.}, journal = {World journal of hepatology}, volume = {11}, number = {6}, pages = {489-512}, doi = {10.4254/wjh.v11.i6.489}, pmid = {31293718}, issn = {1948-5182}, abstract = {Hepatic encephalopathy (HE) is a common and serious neuropsychiatric complication of cirrhosis, acute liver failure, and porto-systemic shunting. HE largely contributes to the morbidity of patients with liver disease, severely affecting the quality of life of both patients and their relatives and being associated with poor prognosis. Its presentation is largely variable, manifesting with a broad spectrum of cognitive abnormalities ranging from subtle cognitive impairment to coma. The pathogenesis of HE is complex and has historically been linked with hyperammonemia. However, in the last years, it has become evident that the interplay of multiple actors, such as intestinal dysbiosis, gut hyperpermeability, and neuroinflammation, is of crucial importance in its genesis. Therefore, HE can be considered a result of a dysregulated gut-liver-brain axis function, where cognitive impairment can be reversed or prevented by the beneficial effects induced by &quot;gut-centric&quot; therapies, such as non-absorbable disaccharides, non-absorbable antibiotics, probiotics, prebiotics, and fecal microbiota transplantation. In this context dietary modifications, by modulating the intestinal milieu, can also provide significant benefit to cirrhotic patients with HE. This review will provide a comprehensive insight into the mechanisms responsible for gut-liver-brain axis dysregulation leading to HE in cirrhosis. Furthermore, it will explore the currently available therapies and the most promising future treatments for the management of patients with HE, with a special focus on the dietary approach.}, }
@article {pmid31293562, year = {2019}, author = {Ni, J and Huang, R and Zhou, H and Xu, X and Li, Y and Cao, P and Zhong, K and Ge, M and Chen, X and Hou, B and Yu, M and Peng, B and Li, Q and Zhang, P and Gao, Y}, title = {Analysis of the Relationship Between the Degree of Dysbiosis in Gut Microbiota and Prognosis at Different Stages of Primary Hepatocellular Carcinoma.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1458}, doi = {10.3389/fmicb.2019.01458}, pmid = {31293562}, issn = {1664-302X}, abstract = {Gut microbiota dysbiosis is closely associated with primary hepatocellular carcinoma (HCC). Recent studies have evaluated the early diagnosis of primary HCC through analysis of gut microbiota dysbiosis. However, the relationship between the degree of dysbiosis and the prognosis of primary HCC remains unclear. Because primary HCC is accompanied by dysbiosis and dysbiosis usually increases the circulatory concentrations of endotoxin and other harmful bacterial substances, which further increases liver damage, we hypothesized that level of dysbiosis associated with primary HCC increases with the stage of cancer progression. To test this hypothesis, we introduced a more integrated index referred to as the degree of dysbiosis (Ddys); and we investigated Ddys of the gut microbiota with the development of primary HCC through high-throughput sequencing of 16S rRNA gene amplicons. Our results showed that compared with healthy individuals, patients with primary HCC showed increased pro-inflammatory bacteria in their fecal microbiota. The Ddys increased significantly in patients with primary HCC compared with that in healthy controls. Moreover, there was a tendency for the Ddys to increase with the development of primary HCC, although no significant difference was detected between different stages of primary HCC. Our findings provide important insights into the use of gut microbiota analysis during the treatment of primary HCC.}, }
@article {pmid31291465, year = {2019}, author = {Liu, T and Song, X and Khan, S and Li, Y and Guo, Z and Li, C and Wang, S and Dong, W and Liu, W and Wang, B and Cao, H}, title = {The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: an old story, yet mesmerizing.}, journal = {International journal of cancer}, volume = {}, number = {}, pages = {}, doi = {10.1002/ijc.32563}, pmid = {31291465}, issn = {1097-0215}, abstract = {The prevalence of colorectal cancer (CRC) dramatically increased worldwide in the last decade. Alterations of bile acid metabolism and gut microbiota have been reported to play vital roles in intestinal carcinogenesis. About trillions of bacteria inhabited in the human gut and maintained the balance of host metabolism. Bile acids are one of numerous metabolites that are synthesized in the liver and further metabolized by the gut microbiota, and are essential in maintaining the normal gut microbiota and lipid digestion. Multiple receptors such as FXR, GPBAR1, PXR, CAR and VDR act as sensors of bile acids have been reported. In this review, we mainly discussed interplay between bile acid metabolism and gut microbiota in intestinal carcinogenesis. We then summarized the critical role of bile acids receptors involving in CRC, and also addressed the rationale of multiple interventions for CRC management by regulating bile acids-microbiota axis such as probiotics, Metformin, ursodeoxycholic acid (UDCA) and fecal microbiota transplantation (FMT). Thus, by targeting the bile acids-microbiota axis may provide novel therapeutic modalities in CRC prevention and treatment. This article is protected by copyright. All rights reserved.}, }
@article {pmid31289031, year = {2019}, author = {Pianko, MJ and Devlin, SM and Littmann, ER and Chansakul, A and Mastey, D and Salcedo, M and Fontana, E and Ling, L and Tavitian, E and Slingerland, JB and Slingerland, AE and Clurman, A and Gomes, ALC and Taur, Y and Pamer, EG and Peled, JU and van den Brink, MRM and Landgren, O and Lesokhin, AM}, title = {Minimal residual disease negativity in multiple myeloma is associated with intestinal microbiota composition.}, journal = {Blood advances}, volume = {3}, number = {13}, pages = {2040-2044}, doi = {10.1182/bloodadvances.2019032276}, pmid = {31289031}, issn = {2473-9537}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P01 AG052359/AG/NIA NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; L30 CA220724/CA/NCI NIH HHS/United States ; UL1 TR000457/TR/NCATS NIH HHS/United States ; }, abstract = {Patients with multiple myeloma (MM) who achieve minimal residual disease (MRD) negativity after upfront treatment have superior outcomes compared with those who remain MRD+ Recently, associations have been shown between specific commensal microbes and development of plasma cell disorders. Here, we report the association between intestinal microbiota composition and treatment outcome in MM. Microbiota composition of fecal samples collected from 34 MM patients after induction therapy and at the time of flow cytometry-based bone marrow MRD testing was determined by 16S ribosomal RNA sequencing. We observed a higher relative abundance of Eubacterium hallii in the 16 MRD- patients relative to the 18 MRD+ patients. No association was observed between microbial relative abundance and autologous stem cell transplantation history or MM paraprotein isotype. No differences in microbiota α diversity were observed between MRD- and MRD+ patients. The potential association of microbiota composition with treatment response in MM patients is an important parameter for additional correlative and clinical investigation.}, }
@article {pmid31272391, year = {2019}, author = {Tian, Y and Zhou, Y and Huang, S and Li, J and Zhao, K and Li, X and Wen, X and Li, XA}, title = {Fecal microbiota transplantation for ulcerative colitis: a prospective clinical study.}, journal = {BMC gastroenterology}, volume = {19}, number = {1}, pages = {116}, doi = {10.1186/s12876-019-1010-4}, pmid = {31272391}, issn = {1471-230X}, support = {2016JY0090//Natural Science Foundation of Science and Technology Department of Sichuan Province/ ; 17ZD012//Science and Technology Project of The Health Planning Committee of Sichuan/ ; 16ZA0280//Natural Science Foundation of Education Department of Sichuan Province/ ; 16TD0028//Innovative Group Foundation of Education Department of Sichuan Province/ ; S16019//Foundation of the Medical Association of Sichuan Province/ ; ZYFY2017XH04//Foundation of the First Affiliated Hospital of Chengdu Medical College/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation may contribute to disease remission in ulcerative colitis; however, the factors that determine the effects of treatment remain unknown. The aim of the present study was to prospectively investigate the clinical efficacy of fecal microbiota transplantation in patients with ulcerative colitis and identify the bacterial signatures associated with clinical remission.<br><br>METHODS: A total of 20 patients with ulcerative colitis were included in this prospective and uncontrolled study. All patients underwent gastroscopy five times, once every 3 weeks. Clinical indices were used to assess the efficacy of fecal microbiota transplantation, as well as the Mayo score, a score used to evaluate the extent of intestinal mucosal lesions in patients with ulcerative colitis. The changes in intestinal flora were detected by 16S ribosomal RNA-sequencing, and the relationship between ulcerative colitis and intestinal flora was analyzed.<br><br>RESULTS: After treatment, clinical index scores for diarrhea, abdominal pain, and blood stool decreased significantly (p < 0.05). Erythrocyte sedimentation rate and C-reactive protein levels had not changed significantly; however, the clinical index score for intestinal mucosal lesions and the Mayo score decreased significantly. In addition, 16S ribosomal RNA-sequencing revealed that the intestinal flora in patients diagnosed with ulcerative colitis was different from that of donors.<br><br>CONCLUSION: Fecal microbiota transplantation has a potential therapeutic value for the treatment of ulcerative colitis as it changes the abundance of bacterial flora and improves the scores for diarrhea, abdominal pain, and mucous membrane lesions in patients with this disease.<br><br>TRIAL REGISTRATION: The clinical trial was retrospectively registered with ClinicalTrials.gov (NCT03016780) on January 11th, 2017.}, }
@article {pmid31269444, year = {2019}, author = {Bradley, KC and Finsterbusch, K and Schnepf, D and Crotta, S and Llorian, M and Davidson, S and Fuchs, SY and Staeheli, P and Wack, A}, title = {Microbiota-Driven Tonic Interferon Signals in Lung Stromal Cells Protect from Influenza Virus Infection.}, journal = {Cell reports}, volume = {28}, number = {1}, pages = {245-256.e4}, doi = {10.1016/j.celrep.2019.05.105}, pmid = {31269444}, issn = {2211-1247}, abstract = {Type I interferon (IFNα/β) pathways are fine-tuned to elicit antiviral protection while minimizing immunopathology; however, the initiating stimuli, target tissues, and underlying mechanisms are unclear. Using models of physiological and dysregulated IFNα/β receptor (IFNAR1) surface expression, we show here that IFNAR1-dependent signals set the steady-state IFN signature in both hematopoietic and stromal cells. Increased IFNAR1 levels promote a lung environment refractory to early influenza virus replication by elevating the baseline interferon signature. Commensal microbiota drive the IFN signature specifically in lung stroma, as shown by antibiotic treatment and fecal transplantation. Bone marrow chimera experiments identify lung stromal cells as crucially important for early antiviral immunity and stroma-immune cell interaction for late antiviral resistance. We propose that the microbiota-driven interferon signature in lung epithelia impedes early virus replication and that IFNAR1 surface levels fine-tune this signature. Our findings highlight the interplay between bacterial and viral exposure, with important implications for antibiotic use.}, }
@article {pmid31266629, year = {2019}, author = {Martel, B and Saint-Lorant, G}, title = {[Pharmaceutical system of fecal microbiota transplantation: Heterogeneous practices].}, journal = {Annales pharmaceutiques francaises}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pharma.2019.06.001}, pmid = {31266629}, issn = {0003-4509}, abstract = {OBJECTIVE: To describe current pharmaceutical practice in French hospitals regarding fecal microbiota transplantation in terms of prescription, preparation and compounding, as well as local legislation.<br><br>MATERIAL AND METHODS: A national survey was conducted at 28 French university hospital centers followed by the sending of a GoogleForm® questionnaire from June to August 2018 in the 16 respondent centers either performing or subcontracting fecal microbiota transplant.<br><br>RESULTS: All hospitals performing or subcontracting fecal transplant (n=16,%57) report prescription indication of recurrent Clostridium difficile infection treatment, and 6 of them also as part of a clinical trial protocol. In hospitals performing fecal transplant themselves (n=11), the number of pre-donation consultations with donors varies from one (n=6) to two (n=5). Fecal sample is collected at the donor's home in 45% of cases. Route of administration for transplant is either naso-gastric administration (n=4), rectal (n=4) or both (n=5). Fecal samples for transplant are compounded either in the hospital pharmacy (n=73%) or in the laboratory (27%). Thawing methods include refrigeration between 2-8°C (50%), room temperature (25%) and water bath (25%). Billing system and reporting to health authorities are highly heterogeneous from one hospital to another.<br><br>CONCLUSION: This survey shows significant pharmaceutical practice heterogeneity within French hospitals regarding fecal microbiota transplantation despite the existence of national and European recommendations.}, }
@article {pmid31262981, year = {2019}, author = {Morjaria, S and Schluter, J and Taylor, BP and Littmann, ER and Carter, RA and Fontana, E and Peled, JU and van den Brink, MRM and Xavier, JB and Taur, Y}, title = {Antibiotic-induced shifts in fecal microbiota density and composition during hematopoietic stem cell transplantation.}, journal = {Infection and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1128/IAI.00206-19}, pmid = {31262981}, issn = {1098-5522}, abstract = {Background: Dramatic microbiota changes and loss of commensal anaerobic bacteria are associated with adverse outcomes in hematopoietic cell transplantation (HCT) recipients. In this study, we demonstrate these dynamic changes at high-resolution through daily stool sampling and assess the impact of individual antibiotics on those changes.Methods: We collected 272 longitudinal stool samples (with mostly daily frequency) from 18 patients undergoing HCT and determined their composition by multi-parallel 16S rRNA gene sequencing, as well as density of bacteria in stool by qPCR. We calculated microbiota volatility to quantify rapid shifts and developed a new dynamic systems inference method to assess the specific impact of antibiotics.Results: The greatest shifts in microbiota composition occurred between stem cell infusion and reconstitution of healthy immune cells. Piperacillin-tazobactam caused the most severe declines among obligate anaerobes.Conclusions: Our approach of daily sampling, bacterial density determination and dynamic systems modeling allowed us to infer the independent effects of specific antibiotics on the microbiota of HCT patients.}, }
@article {pmid31261545, year = {2019}, author = {Huang, H and Xu, H and Luo, Q and He, J and Li, M and Chen, H and Tang, W and Nie, Y and Zhou, Y}, title = {Fecal microbiota transplantation to treat Parkinson's disease with constipation: A case report.}, journal = {Medicine}, volume = {98}, number = {26}, pages = {e16163}, doi = {10.1097/MD.0000000000016163}, pmid = {31261545}, issn = {1536-5964}, abstract = {RATIONALE: Fecal microbiota transplantation (FMT) is recognized as an emerging treatment through reconstruction of gut microbiota. Parkinson's disease is a neurodegenerative disorder, which is accompanied by constipation. Here we first reported a patient with Parkinson's disease and constipation that were obviously relieved after FMT.<br><br>PATIENT CONCERNS: A 71-year-old male patient presented with 7 years of resting tremor, bradykinesia (first inflicted the upper limbs and subsequently spread to lower limbs), and intractable constipation (defecation needing more than 30 minutes).<br><br>DIAGNOSES: Parkinson's disease for 7 years; constipation >3 years.<br><br>INTERVENTIONS: The patient had used madopar, pramipexole, and amantadine for anti-Parkinson and showed partially mitigation while laxative therapy for constipation failed. Finally FMT was performed.<br><br>OUTCOMES: The patient successfully defecated within 5 minutes and maintained daily unobstructed defecation until the end of follow-up. The patient's tremor in legs almost disappeared at 1 week after FMT but recurred in the right lower extremity at 2 months after FMT.<br><br>LESSONS: Gut microbiota reconstruction may have therapeutic effects for Parkinson's disease patients, especially those who have gastrointestinal symptoms and limited treatment choices.}, }
@article {pmid31258528, year = {2019}, author = {Leshem, A and Horesh, N and Elinav, E}, title = {Fecal Microbial Transplantation and Its Potential Application in Cardiometabolic Syndrome.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {1341}, doi = {10.3389/fimmu.2019.01341}, pmid = {31258528}, issn = {1664-3224}, abstract = {Newly revealed links between inflammation, obesity, and cardiometabolic syndrome have created opportunities to try previously unexplored therapeutic modalities in these common and life-risking disorders. One potential modulator of these complex disorders is the gut microbiome, which was described in recent years to be altered in patients suffering from features of cardiometabolic syndrome and to transmit cardiometabolic phenotypes upon transfer into germ-free mice. As a result, there is great interest in developing new modalities targeting the altered commensal bacteria as a means of treatment for cardiometabolic syndrome. Fecal microbiota transplantation (FMT) is one such modality in which a disease-associated microbiome is replaced by a healthy microbiome configuration. So far clinical use of FMT has been overwhelmingly successful in recurrent Clostridium difficile infection and is being extensively studied in other microbiome-associated pathologies such as cardiometabolic syndrome. This review will focus on the rationale, promises and challenges in FMT utilization in human disease. In particular, it will overview the role of the gut microbiota in cardiometabolic syndrome and the rationale, experience, and prospects of utilizing FMT treatment as a potential preventive and curative treatment of metabolic human disease.}, }
@article {pmid31258315, year = {2019}, author = {Otrompke, J}, title = {Digestive Disease Week 2019.}, journal = {P &amp; T : a peer-reviewed journal for formulary management}, volume = {44}, number = {7}, pages = {428-429}, pmid = {31258315}, issn = {1052-1372}, abstract = {We review selected sessions on the questionable benefits of fecal microbiota transplant; intrahepatic cholestasis of pregnancy; weight-loss drugs in combination with intragastric balloon endoscopy; and beta blockers in pancreatic cancer.}, }
@article {pmid31254675, year = {2019}, author = {Kelly, CR and Fischer, M and Grinspan, A and Allegretti, JR}, title = {Patients Eligible for Trials of Microbe-based Therapeutics do not Represent the Population With Recurrent Clostridioides difficile Infection.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2019.06.034}, pmid = {31254675}, issn = {1542-7714}, abstract = {BACKGROUND &amp; AIMS: Although there are many industry-funded trials of microbe-based therapeutics for Clostridioides (formerly Clostridium) difficile infection (CDI), not all patients are eligible for these trials, due to their strict enrollment criteria. Furthermore, given the widespread availability of fecal microbiota transplantation (FMT) and overwhelming evidence to support its efficacy, patients might refuse enrollment in trials with a placebo group. We analyzed willingness and eligibility of patients with recurrent CDI to participate in randomized controlled trials of microbe-based therapeutic agents.<br><br>METHODS: We performed a retrospective study of 199 patients referred to 4 tertiary referral centers for treatment of CDI from August 1, 2018 through January 31, 2019. We collected data on eligibility for FMT and enrollment in randomized controlled trials.<br><br>RESULTS: Of 130 patients deemed appropriate for FMT, 98 patients (75%) were ineligible for participation in a randomized controlled trial and 16 patients (17%) were eligible but refused to enroll. Immune compromise and inflammatory bowel diseases were the most common reasons for exclusion from trials CONCLUSIONS: Most patients with CDI who meet the guideline criteria for FMT are ineligible or unwilling to participate in randomized controlled trials of microbe-based therapeutics. Trial populations therefore do not represent the population of patients with CDI.}, }
@article {pmid31250122, year = {2019}, author = {Aron-Wisnewsky, J and Clément, K and Nieuwdorp, M}, title = {Fecal Microbiota Transplantation: a Future Therapeutic Option for Obesity/Diabetes?.}, journal = {Current diabetes reports}, volume = {19}, number = {8}, pages = {51}, doi = {10.1007/s11892-019-1180-z}, pmid = {31250122}, issn = {1539-0829}, support = {PHRC-N Drifter//Assistance Publique - Hôpitaux de Paris/ ; PHRC Micronaria//Assistance Publique - Hôpitaux de Paris/ ; HEALTH-F4-2012-305312//Metacardis/ ; JPI MICRODIET Grant (5290510105)//Metacardis/ ; JPI MICRODIET Grant (5290510105)//Metacardis/ ; LITMUS 777377//EU Horizon 2020 grant/ ; LITMUS 777377//EU Horizon 2020 grant/ ; 17CVD01//LeDucq Foundation consortium grant/ ; 17CVD01//LeDucq Foundation consortium grant/ ; 016.146.327//ZONMW-VIDI grant 2013/ ; }, abstract = {PURPOSE OF REVIEW: The aim of this review is to summarize the current data available on the metabolic effects of fecal microbiota transplantation (FMT) including obesity and glucose metabolism in humans.<br><br>RECENT FINDINGS: Gut microbiota dysbiosis is a frequent characteristic observed in obesity and related metabolic diseases. Pieces of evidence mostly generated in mouse models suggest that rescuing this dysbiosis associates with improved metabolism. In humans, dietary or bariatric surgery interventions are often accompanied by complete or partial restoration of this dysbiosis together with weight reduction and metabolic amelioration. FMT is an interesting option to modify gut microbiota and has been associated with improved clinical outcomes, albeit only used in routine care for Clostridium difficile infection. However, there are only limited data on using FMT in the metabolic context. FMT from lean donors significantly improves insulin sensitivity in obese subjects with metabolic syndrome. However, there is a wide range of clinical responses. Interestingly in subjects with high microbial gene richness at baseline and when FMT donors that are metabolically compromised are used, no metabolic improvement is seen. Moreover, more studies evaluating the effect of FMT in patients with overt type 2 diabetes are warranted. Furthermore, interventions (in the receiver prior to FMT) aiming to enhance FMT response also need evaluation.}, }
@article {pmid31250035, year = {2019}, author = {Wang, G and Huang, S and Wang, Y and Cai, S and Yu, H and Liu, H and Zeng, X and Zhang, G and Qiao, S}, title = {Bridging intestinal immunity and gut microbiota by metabolites.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00018-019-03190-6}, pmid = {31250035}, issn = {1420-9071}, support = {31420103908//National Natural Science Foundation of China/ ; 2017YFD0500506//Key Technologies Research and Development Program/ ; }, abstract = {The gastrointestinal tract is the site of nutrient digestion and absorption and is also colonized by diverse, highly mutualistic microbes. The intestinal microbiota has diverse effects on the development and function of the gut-specific immune system, and provides some protection from infectious pathogens. However, interactions between intestinal immunity and microorganisms are very complex, and recent studies have revealed that this intimate crosstalk may depend on the production and sensing abilities of multiple bioactive small molecule metabolites originating from direct produced by the gut microbiota or by the metabolism of dietary components. Here, we review the interplay between the host immune system and the microbiota, how commensal bacteria regulate the production of metabolites, and how these microbiota-derived products influence the function of several major innate and adaptive immune cells involved in modulating host immune homeostasis.}, }
@article {pmid31244784, year = {2019}, author = {Chong, PP and Chin, VK and Looi, CY and Wong, WF and Madhavan, P and Yong, VC}, title = {The Microbiome and Irritable Bowel Syndrome - A Review on the Pathophysiology, Current Research and Future Therapy.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1136}, doi = {10.3389/fmicb.2019.01136}, pmid = {31244784}, issn = {1664-302X}, abstract = {Irritable bowel syndrome (IBS) is a functional disorder which affects a large proportion of the population globally. The precise etiology of IBS is still unknown, although consensus understanding proposes IBS to be of multifactorial origin with yet undefined subtypes. Genetic and epigenetic factors, stress-related nervous and endocrine systems, immune dysregulation and the brain-gut axis seem to be contributing factors that predispose individuals to IBS. In addition to food hypersensitivity, toxins and adverse life events, chronic infections and dysbiotic gut microbiota have been suggested to trigger IBS symptoms in tandem with the predisposing factors. This review will summarize the pathophysiology of IBS and the role of gut microbiota in relation to IBS. Current methodologies for microbiome studies in IBS such as genome sequencing, metagenomics, culturomics and animal models will be discussed. The myriad of therapy options such as immunoglobulins (immune-based therapy), probiotics and prebiotics, dietary modifications including FODMAP restriction diet and gluten-free diet, as well as fecal transplantation will be reviewed. Finally this review will highlight future directions in IBS therapy research, including identification of new molecular targets, application of 3-D gut model, gut-on-a-chip and personalized therapy.}, }
@article {pmid31241182, year = {2019}, author = {Jørgensen, SMD and Hvas, CL and Dahlerup, JF and Mikkelsen, S and Ehlers, L and Hammeken, LH and Licht, TR and Bahl, MI and Erikstrup, C}, title = {Banking feces: a new frontier for public blood banks?.}, journal = {Transfusion}, volume = {}, number = {}, pages = {}, doi = {10.1111/trf.15422}, pmid = {31241182}, issn = {1537-2995}, abstract = {Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection and is potentially beneficial in other microbiota-related disorders. The provision of FMT in routine clinical practice requires an extensive infrastructure that is reliant on voluntary donors. Alongside an increasing demand for FMT, the logistic barriers of a large-scale donor-dependent operation and the difficulties among health authorities to regulate FMT limit the dissemination of sustainable FMT services. Blood centers are large organizations that handle a multitude of donor-dependent operations on a daily basis. Blood and feces share many of the same dependencies, and feces may present a new opportunity for the blood services to handle. In this paper, we describe how an FMT service may be established and embedded within the blood service infrastructure, and we explain the benefits of using blood donors as feces donors. We further explore the current indications of FMT, the challenges related to the lack of legislation, and the future perspectives for blood banks to meet a new and increasing demand.}, }
@article {pmid31239866, year = {2019}, author = {Xu, Z and Liu, T and Zhou, Q and Chen, J and Yuan, J and Yang, Z}, title = {Roles of Chinese Medicine and Gut Microbiota in Chronic Constipation.}, journal = {Evidence-based complementary and alternative medicine : eCAM}, volume = {2019}, number = {}, pages = {9372563}, doi = {10.1155/2019/9372563}, pmid = {31239866}, issn = {1741-427X}, abstract = {Chronic constipation is a common gastrointestinal dysfunction, but its aetiology and pathogenesis are still unclear. Interestingly, the compositions of the gut microbiota in constipation patients and healthy controls are different. Various studies reported the different gut microbiota alterations in constipation patients, but most studies indicated that constipation patients showed the decreased beneficial bacteria and the reduced species richness of gut bacteria. Besides, the alterations in the gut microbiota may lead to constipation and constipation-related symptoms and the regulation of gut microbiota has a positive effect on gut functional diseases such as constipation. Microbial treatment methods, such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, can be used to regulate gut microbiota. Increasing evidences have suggested that Chinese medicine (CM) has a good therapeutic effect on chronic constipation. Chinese medicine is well known for its multitarget and multimode effects on diseases as well as less side effects. In previous studies, after the treatment of constipation with CM, the gut microbiota was restored, indicating that the gut microbiota might be the target or important way for CM to exert its efficacy. In this review, we summarized the effects of microbial treatment and CM on the gut microbiota of constipation patients and discussed the relationship between CM and gut microbiota.}, }
@article {pmid31236163, year = {2019}, author = {Singh, T and Bedi, P and Bumrah, K and Singh, J and Rai, M and Seelam, S}, title = {Updates in Treatment of Recurrent Clostridium difficile Infection.}, journal = {Journal of clinical medicine research}, volume = {11}, number = {7}, pages = {465-471}, doi = {10.14740/jocmr3854}, pmid = {31236163}, issn = {1918-3003}, abstract = {Recurrent Clostridium difficile infection (CDI) is a perpetual problem that leads to increased economic burden, higher healthcare cost, and significant morbidity and mortality. Its treatment remains a challenge. While various treatment approaches have been attempted with different levels of success, robust data establishing the superiority of one approach over the others is lacking. In this article, we review the current evidence pertaining to conventional pharmacological treatment as well as fecal microbiota transplantation (FMT) as a novel, rapidly emerging treatment modality for recurrent CDI.}, }
@article {pmid31232087, year = {2019}, author = {Qi, X and Zhang, Y and Guo, H and Hai, Y and Luo, Y and Yue, T}, title = {Mechanism and intervention measures of iron side effects on the intestine.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/10408398.2019.1630599}, pmid = {31232087}, issn = {1549-7852}, abstract = {Excess oral iron in the intestinal tract usually produces reactive oxygen species via Fenton and Haber-Weiss reaction, so oxidative stress is triggered. Lipid peroxidation procedurally appears, ferroptosis, apoptosis and necrosis are often induced, subsequently, mitochondrial damage, endoplasmic reticulum dysfunction and even cell death occur. As a result, the intestinal epithelial cells are destroyed, leading to the incompleteness of intestinal mechanical barrier. Simultaneously, iron supplement can change the compositions and metabolic processes of intestinal microbes, and the intestinal inflammatory may be worsened. In principle, the easier dissociation of Fe2+ from oral iron supplements is, the more serious intestinal inflammation will occur. Fortunately, some interventions have been developed to alleviate these side effects. For instance, some antioxidants e.g. VE and ferulic acid have been used to prevent the formation of free radicals or to neutralize the formed free radicals. Furthermore, some new iron supplements with the ability of slow-releasing Fe2+, e.g. ferrous citrate liposome and EDTA iron sodium, have been successfully prepared. In order to recover the intestinal micro-ecological balance, probiotics and prebiotics, bacterial consortium transplantation, and fecal microbiota transplantation have been developed. This study is meaningful for us to develop safer oral iron supplements and to maintain intestinal micro-ecological health.}, }
@article {pmid31231707, year = {2019}, author = {Kellermayer, R}, title = {Fecal microbiota transplantation: great potential with many challenges.}, journal = {Translational gastroenterology and hepatology}, volume = {4}, number = {}, pages = {40}, doi = {10.21037/tgh.2019.05.10}, pmid = {31231707}, issn = {2415-1289}, abstract = {In January of 2019, Samuel P. Costello and colleagues published a wonderfully executed, double blind placebo-controlled trial on fecal microbiota transplantation (FMT) versus autologous stool as placebo in mild to moderately active adult ulcerative colitis [UC: one type of inflammatory bowel disease (IBD)] patients. This review-commentary examines the current state of knowledge on human gut microbiome (live microbiota + their products and surrounding environment, i.e., fecal matter) and microbial therapeutics from a gastrointestinal (GI) clinician's standpoint. The varied forms of dysbiosis as the target of FMT, recipient donor and placebo considerations are also discussed in respect to randomized control trials in IBD [and the lack thereof in Crohn's disease (CD)] with this unconventional treatment modality.}, }
@article {pmid31222022, year = {2019}, author = {Burz, SD and Abraham, AL and Fonseca, F and David, O and Chapron, A and Béguet-Crespel, F and Cénard, S and Le Roux, K and Patrascu, O and Levenez, F and Schwintner, C and Blottière, HM and Béra-Maillet, C and Lepage, P and Doré, J and Juste, C}, title = {A Guide for Ex Vivo Handling and Storage of Stool Samples Intended for Fecal Microbiota Transplantation.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {8897}, doi = {10.1038/s41598-019-45173-4}, pmid = {31222022}, issn = {2045-2322}, abstract = {Owing to the growing recognition of the gut microbiota as a main partner of human health, we are expecting that the number of indications for fecal microbiota transplantation (FMT) will increase. Thus, there is an urgent need for standardization of the entire process of fecal transplant production. This study provides a complete standardized procedure to prepare and store live and ready-to-use transplants that meet the standard requirements of good practices to applied use in pharmaceutical industry. We show that, if time before transformation to transplants would exceed 24 hours, fresh samples should not be exposed to temperatures above 20 °C, and refrigeration at 4 °C can be a safe solution. Oxygen-free atmosphere was not necessary and simply removing air above collected samples was sufficient to preserve viability. Transplants prepared in maltodextrin-trehalose solutions, stored in a -80 °C standard freezer and then rapidly thawed at 37 °C, retained the best revivification potential as proven by 16S rRNA profiles, metabolomic fingerprints, and flow cytometry assays over a 3-month observation period. Maltodextrin-trehalose containing cryoprotectants were also efficient in preserving viability of lyophilized transplants, either in their crude or purified form, an option that can be attractive for fecal transplant biobanking and oral formulation.}, }
@article {pmid31221971, year = {2019}, author = {Frisbee, AL and Saleh, MM and Young, MK and Leslie, JL and Simpson, ME and Abhyankar, MM and Cowardin, CA and Ma, JZ and Pramoonjago, P and Turner, SD and Liou, AP and Buonomo, EL and Petri, WA}, title = {IL-33 drives group 2 innate lymphoid cell-mediated protection during Clostridium difficile infection.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {2712}, doi = {10.1038/s41467-019-10733-9}, pmid = {31221971}, issn = {2041-1723}, support = {R21 AI114734/AI/NIAID NIH HHS/United States ; T32 AI007496/AI/NIAID NIH HHS/United States ; 1R21AI114734//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/International ; 5R01AI124214-02//Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/International ; F31 AI136421/AI/NIAID NIH HHS/United States ; R01 AI124214/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Anti-Bacterial Agents/adverse effects ; Bacterial Toxins/immunology/metabolism ; Clostridium difficile/*immunology/pathogenicity ; Colon/cytology/immunology/microbiology/pathology ; Disease Models, Animal ; Enterocolitis, Pseudomembranous/*immunology/microbiology/mortality/therapy ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/drug effects/immunology ; Gene Expression Profiling ; Humans ; *Immunity, Innate ; Interleukin-33/immunology/*metabolism ; Lymphocytes/*immunology/metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Up-Regulation/drug effects/immunology ; Virulence/immunology ; Young Adult ; }, abstract = {Clostridium difficile (C. difficile) incidence has tripled over the past 15 years and is attributed to the emergence of hypervirulent strains. While it is clear that C. difficile toxins cause damaging colonic inflammation, the immune mechanisms protecting from tissue damage require further investigation. Through a transcriptome analysis, we identify IL-33 as an immune target upregulated in response to hypervirulent C. difficile. We demonstrate that IL-33 prevents C. difficile-associated mortality and epithelial disruption independently of bacterial burden or toxin expression. IL-33 drives colonic group 2 innate lymphoid cell (ILC2) activation during infection and IL-33 activated ILC2s are sufficient to prevent disease. Furthermore, intestinal IL-33 expression is regulated by the microbiota as fecal microbiota transplantation (FMT) rescues antibiotic-associated depletion of IL-33. Lastly, dysregulated IL-33 signaling via the decoy receptor, sST2, predicts C. difficile-associated mortality in human patients. Thus, IL-33 signaling to ILC2s is an important mechanism of defense from C. difficile colitis.}, }
@article {pmid31220424, year = {2019}, author = {D'Haens, GR and Jobin, C}, title = {Fecal Microbial Transplantation For Diseases Beyond Recurrent Clostridium Difficile Infection.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2019.04.053}, pmid = {31220424}, issn = {1528-0012}, abstract = {As microbiome research has moved from associative to mechanistic studies, the activities of specific microbes and their products have been investigated in development of inflammatory bowel diseases, cancer, metabolic syndrome, and neuropsychiatric disorders. Findings from microbiome research have already been applied to the clinic, such as in fecal microbiota transplantation (FMT) for treatment of recurrent Clostridium difficile infection. We review the evidence for associations between alterations in the intestinal microbiome and gastrointestinal diseases and findings from clinical trials of FMT. We discuss opportunities for treatment of other diseases with FMT, based on findings from small clinical and preclinical studies.}, }
@article {pmid31218940, year = {2019}, author = {Jagessar, SAR and Long, C and Cui, B and Zhang, F}, title = {Improvement of Good's syndrome by fecal microbiota transplantation: the first case report.}, journal = {The Journal of international medical research}, volume = {}, number = {}, pages = {300060519854913}, doi = {10.1177/0300060519854913}, pmid = {31218940}, issn = {1473-2300}, }
@article {pmid31212833, year = {2019}, author = {Foligné, B and Plé, C and Titécat, M and Dendooven, A and Pagny, A and Daniel, C and Singer, E and Pottier, M and Bertin, B and Neut, C and Deplanque, D and Dubuquoy, L and Desreumaux, P and Capron, M and Standaert, A}, title = {Contribution of the Gut Microbiota in P28GST-Mediated Anti-Inflammatory Effects: Experimental and Clinical Insights.}, journal = {Cells}, volume = {8}, number = {6}, pages = {}, doi = {10.3390/cells8060577}, pmid = {31212833}, issn = {2073-4409}, support = {ANR-11-RPIB-0021//Agence Nationale de la Recherche/ ; IMITATION//SFR3I/ ; }, abstract = {An original immuno-regulatory strategy against inflammatory bowel diseases based on the use of 28 kDa glutathione S-transferase (P28GST), a unique schistosome protein, was recently proposed. Improvement of intestinal inflammation occurs through restoration of the immunological balance between pro-inflammatory T-helper 1 (Th1) responses and both T-helper 2 (Th2) and regulatory responses. However, detailed mechanisms explaining how P28GST prevents colitis and promotes gut homeostasis remain unknown. Considering the complex interplay between the adaptive and innate immune system and the intestinal microbiota, we raised the question of the possible role of the microbial ecosystem in the anti-inflammatory effects mediated by the helminth-derived P28GST protein. We first analyzed, by 16S rRNA sequencing, the bacterial profiles of mice fecal microbiota at several time points of the P28GST-immunomodulation period prior to trinitrobenzene sulfonic acid (TNBS)-colitis. The influence of gut microbiota in the P28GST-mediated anti-inflammatory effects was then assessed by fecal microbiota transplantation experiments from P28GST-immunized mice to either conventional or microbiota depleted naïve recipient mice. Finally, the experimental data were supplemented by the temporal fecal microbiota compositions of P28GST-treated Crohn's disease patients from a pilot clinical study (NCT02281916). The P28GST administration slightly modulated the diversity and composition of mouse fecal microbiota while it significantly reduced experimental colitis in mice. Fecal microbiota transplantation experiments failed to restore the P28GST-induced anti-inflammatory effects. In Crohn's disease patients, P28GST also induced slight changes in their overall fecal bacterial composition. Collectively, these results provide key elements in both the anti-inflammatory mechanisms and the safe therapeutic use of immunomodulation with such promising helminth-derived molecules.}, }
@article {pmid31212328, year = {2019}, author = {Reisinger, EC and Ebbers, M and Löbermann, M}, title = {[Clostridium Difficile: Monoclonal Antibody Therapy and Vaccines].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {144}, number = {12}, pages = {842-849}, doi = {10.1055/a-0882-7530}, pmid = {31212328}, issn = {1439-4413}, abstract = {Hospital-acquired Clostridium difficile infections have become much more frequent in recent years. Besides treatment with antibiotics and fecal microbiota transplant, new preventive strategies are available now. Bezlotoxumab is an antibody against toxin B and may reduce the risk of relapse by roughly 10 %. Several vaccine candidates against toxins A and B and surface-associated antigens were immunogenic and are tested in clinical trials to investigate the efficacy and safety.}, }
@article {pmid31208713, year = {2019}, author = {Kalinkovich, A and Livshits, G}, title = {A cross talk between dysbiosis and gut-associated immune system governs the development of inflammatory arthropathies.}, journal = {Seminars in arthritis and rheumatism}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semarthrit.2019.05.007}, pmid = {31208713}, issn = {1532-866X}, abstract = {BACKGROUND: Emerging evidence suggests that dysbiosis, imbalanced gut microbial community, might be a key player in the development of various diseases, including inflammatory arthropathies, such as rheumatoid arthritis, spondyloarthritis (mainly, ankylosing spondylitis and psoriatic arthritis), and osteoarthritis. Yet, the underlying mechanisms and corresponding interactions remain poorly understood.<br><br>METHODS: We conducted a critical and extensive literature review to explore the association between dysbiosis and the development of inflammatory arthropathies. We also reviewed the literature to assess the perspectives that ameliorate inflammatory arthropathies by manipulating the microbiota with probiotics, prebiotics or fecal microbiota transplantation.<br><br>RESULTS: Some bacterial species (e.g. Prevotella, Citrobacter rodentium, Collinsella aerofaciens, Segmented filamentous bacteria) participate in the creation of the pro-inflammatory immune status, presumably via epitope mimicry, modification of self-antigens, enhanced cell apoptosis mechanisms, and destruction of tight junction proteins and intestinal barrier integrity, all leading to the development and maintainance of inflammatory arthropathies. Whether dysbiosis is an epiphenomenon or is an active driver of these disorders remains unclear, yet, recent observations clearly suggest that dysbiosis precedes and triggers their development implying a causative relationship between dysbiosis and inflammatory arthropathies. The underlying mechanisms include dysbiosis-mediated changes in the functional activity of the intestinal immune cell subsets, such as innate lymphoid cells, mucosa-associated invariant T cells, invariant natural killer T cells, T-follicular helper and T-regulatory cells. In turn, disturbed functionality of the gut-associated immune system is shown to promote the overgrowth of many bacteria, thus establishing a detrimental vicious circle of actively maintaining arthritis.<br><br>CONCLUSIONS: Analysis of the data described in the review supports the notion that a close, dynamic and tightly regulated cross talk between dysbiosis and the gut-associated immune system governs the development of inflammatory arthropathies.}, }
@article {pmid31205136, year = {2019}, author = {Ahamed, R and Philips, CA and Augustine, P}, title = {Fecal Microbiota Transplantation for Primary Sclerosing Cholangitis-A Beautiful but Incomplete Story.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000000294}, pmid = {31205136}, issn = {1572-0241}, }
@article {pmid31205129, year = {2019}, author = {Khoruts, A and Brandt, LJ}, title = {Fecal Microbiota Transplant: A Rose by Any Other Name.}, journal = {The American journal of gastroenterology}, volume = {114}, number = {7}, pages = {1176}, doi = {10.14309/ajg.0000000000000286}, pmid = {31205129}, issn = {1572-0241}, }
@article {pmid31204469, year = {2019}, author = {Wang, B and Zhang, L and Zhu, SW and Zhang, JD and Duan, LP}, title = {Short chain fatty acids contribute to gut microbiota-induced promotion of colonic melatonin receptor expression.}, journal = {Journal of biological regulators and homeostatic agents}, volume = {33}, number = {3}, pages = {763-771}, pmid = {31204469}, issn = {0393-974X}, }
@article {pmid31204202, year = {2019}, author = {Smirnova, DV and Zalomova, LV and Zagainova, AV and Makarov, VV and Mezhevikina, LM and Fesenko, EE and Yudin, SM}, title = {Cryopreservation of the human gut microbiota: Current state and perspectives.}, journal = {International journal of medical microbiology : IJMM}, volume = {309}, number = {5}, pages = {259-269}, doi = {10.1016/j.ijmm.2019.06.001}, pmid = {31204202}, issn = {1618-0607}, abstract = {The human intestinal microbiota is a complex ecosystem that consists of thousands of bacterial species that are responsible for human health and disease. The intestinal microbiota is a natural resource for production of therapeutic and preventive medicals, such as probiotics and fecal transplants. Modern lifestyles have resulted in the extinction of evolutionally selected microbial populations upon exposure to environmental factors. Therefore, it is very important to preserve the human gut microbiota to have the opportunity for timely restoration with minimal safety risks. Cryopreservation techniques that are suitable for the preservation of viable, mixed microbial communities and a biobanking approach are currently under development in different countries. However, the number of studies in this area is very limited. The variety of morphological and physiological characteristics of microbes in the microbiota, the different cryopreservation goals, and the criteria for the evaluation of cryopreservation effectiveness are the main challenges in the creation of a universal and standardized cryopreservation protocol. In this review, we summarized the current progress of the main cryopreservation techniques for gut microbiota communities and the methods for the assessment of the effectiveness of these techniques in the context of practical application.}, }
@article {pmid31201994, year = {2019}, author = {Baron, SA and Cassir, N and Mékidèche, T and Mlaga, KD and Brouqui, P and Rolain, JM}, title = {Successful treatment and digestive decolonization of a patient with osteitis caused by a Carbapenemase-producing Klebsiella pneumoniae isolate harboring both NDM-1 and OXA-48 enzymes.}, journal = {Journal of global antimicrobial resistance}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jgar.2019.06.001}, pmid = {31201994}, issn = {2213-7173}, abstract = {OBJECTIVES: Carbapenem resistance in Klebsiella pneumoniae (CRKP) is an increasing problem worldwide and infections caused by this bacterium can be difficult to treat. Here we reported the case of a patient from Romania hospitalized in Bulgaria after an accident trauma that came in France for the treatment of an osteitis caused by a K. pneumoniae carrying both blaNDM-1 and blaOXA-48.<br><br>METHOD: The resistome of this extremely-drug-resistant bacterium was analyzed both with phenotypic (large antibiotic susceptibility testing) and genomic method (genome sequencing). The genetic environment of the two carbapenemases was studied.<br><br>RESULTS: K. pneumoniae ST307 carrying both a blaNDM-1 gene and a blaOXA-48 gene located on two different plasmids, an Inc L/M and an IncFII. Patient was successfully treated by a combination of intravenous colistin (9 MUI, then 4.5 MUI 2 times/day), intravenous fosfomycin (4 g 3 times/day) and oral doxycycline (100 mg 2 times/day) for 3 months. Fecal microbiota transplantation was successfully conducted for a stool carriage.<br><br>CONCLUSION: The ST307 type is becoming endemic in hospital environment and is frequently associated with carbapenem resistance. Treatment of infection caused by multi-drug resistant bacteria are a clinical challenge and the use of old antibiotics associated with a screening and decolonization of the reservoirs can be an efficient therapeutic alternative.}, }
@article {pmid31201141, year = {2019}, author = {Wortelboer, K and Nieuwdorp, M and Herrema, H}, title = {Fecal microbiota transplantation beyond Clostridioides difficile infections.}, journal = {EBioMedicine}, volume = {44}, number = {}, pages = {716-729}, doi = {10.1016/j.ebiom.2019.05.066}, pmid = {31201141}, issn = {2352-3964}, abstract = {The importance of the commensal microbiota to human health and well-being has become increasingly evident over the past decades. From a therapeutic perspective, the popularity of fecal microbiota transplantation (FMT) to restore a disrupted microbiota and amend imbalances has increased. To date, most clinical experience with FMT originates from the treatment of recurrent or refractory Clostridioides difficile infections (rCDI), with resolution rates up to 90%. In addition to CDI, a role for the intestinal microbiome has been implicated in several disorders. FMT has been tested in several randomized controlled trials for the treatment of inflammatory bowel disease, irritable bowel disease and constipation with mixed results. FMT has also been explored for extra-gastrointestinal disorders such as metabolic syndrome, hepatic encephalopathy and graft-versus-host disease. With the exception of recurrent CDI, FMT is currently used in experimental settings only and should not yet be offered as standard care. In addition, it is critical to further standardize and optimize procedures for FMT preparation. This includes determination of active components of FMT to develop (personalized) approaches to treat disease.}, }
@article {pmid31197926, year = {2019}, author = {Wang, JW and Wang, YK and Zhang, F and Su, YC and Wang, JY and Wu, DC and Hsu, WH}, title = {Initial experience of fecal microbiota transplantation in gastrointestinal disease: A case series.}, journal = {The Kaohsiung journal of medical sciences}, volume = {}, number = {}, pages = {}, doi = {10.1002/kjm2.12094}, pmid = {31197926}, issn = {2410-8650}, support = {MOHW107-TDU-B-212-113006//Ministry of Health and Welfare, Taiwan/ ; KMU105-5M01//Kaohsiung Medical University Hospital/ ; MOST108-2321-B-037-001//Ministry of Science and Technology/ ; }, abstract = {Current studies have proven the strong association between gut microbiota dysbiosis and the pathogenesis of gastrointestinal diseases. Fecal microbiota transplantation (FMT) from a healthy donor is a promising therapeutic strategy to change and restore composition of the recipient's gut microbiota. Rapidly increasing clinical literatures confirmed the truth of the benefits of FMT on recurrent Clostridium difficile infection (rCDI) and inflammatory bowel disease. This article retrospectively reviewed nine cases (four cases had ulcerative colitis [UC], five cases had rCDI) who received FMT in Kaohsiung Medical University Hospital from April 2016 to November 2018. We summarized the procedure including donor selection, fecal materials preparation, transplantation delivery methods, and clinical outcomes. All of the four UC cases got clinical improvement and four rCDI cases achieved clinical remission after FMT. The other one rCDI case remained positive stool Toxin A+B result after FMT, and got remission after salvage treatment with fidaxomicin. FMT is considered to be a well-tolerated adjuvant treatment for UC and effective salvage treatment for rCDI in our initial experience. Multiple infusions of FMT in UC and rCDI might have exceptional clinical efficiency, and enteral tube insertion could be a useful method to reach this goal and make multiple sessions of FMT easier.}, }
@article {pmid31195433, year = {2019}, author = {Na, SY and Moon, W}, title = {Perspectives on Current and Novel Treatments for Inflammatory Bowel Disease.}, journal = {Gut and liver}, volume = {}, number = {}, pages = {}, doi = {10.5009/gnl19019}, pmid = {31195433}, issn = {2005-1212}, abstract = {New therapeutic strategies in inflammatory bowel disease (IBD) have shifted from symptom control towards treat-totarget algorithms in order to optimize treatment results. The treatment of IBD has evolved with the development of tumor necrosis factor-α inhibitors beyond the conventional therapies. In spite of their long-term effectiveness, many patients do not respond to or cannot sustain treatment with these drugs, which have various side effects. Therefore, the development of new drugs targeting specific pathways in the pathogenesis of IBD has become necessary. Some novel biologics and small molecule drugs have shown potential in IBD clinical trials, providing safe and effective results. In addition, clinicians are now trying to target the dysbiotic microbiome of patients with IBD using fecal microbiota transplantation. New tools such as stem cells have also been developed. The available therapeutic options for IBD are expanding rapidly. In the next few years, physicians will face an unprecedented number of options when choosing the best treatments for patients with IBD. This review provides an overview of recent advances in IBD treatment options.}, }
@article {pmid31190948, year = {2019}, author = {Ilan, Y}, title = {Why targeting the microbiome is not so successful: can randomness overcome the adaptation that occurs following gut manipulation?.}, journal = {Clinical and experimental gastroenterology}, volume = {12}, number = {}, pages = {209-217}, doi = {10.2147/CEG.S203823}, pmid = {31190948}, issn = {1178-7023}, abstract = {The microbiome is explored as a potential target for therapy of bowel and systemic diseases. Fecal microbiota transplantation (FMT) has demonstrated efficacy in Clostridium difficile infection. However, clinical results regarding other diseases are modest, despite the abundant research on the microbiome over the last decade. Both high rate variability of the microbiome and adaptation to gut manipulations may underlie the lack of ultimate effects of FMT, probiotics, prebiotics, synbiotics, and antibiotics, which are aimed at restoring a healthier microbiome. The present review discusses the inherent variability of the microbiome and multiple factors that affect its diversity, as possible causes of the adaptation of the gut microbiome to chronic manipulation. The potential use of randomness is proposed, as a means of overcoming the adaptation and of restoring some of the inherent variability, with the goal of improving the long-term efficacy of these therapies.}, }
@article {pmid31190584, year = {2019}, author = {Mazzawi, T and Hausken, T and Hov, JR and Valeur, J and Sangnes, DA and El-Salhy, M and Gilja, OH and Hatlebakk, JG and Lied, GA}, title = {Clinical response to fecal microbiota transplantation in patients with diarrhea-predominant irritable bowel syndrome is associated with normalization of fecal microbiota composition and short-chain fatty acid levels.}, journal = {Scandinavian journal of gastroenterology}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/00365521.2019.1624815}, pmid = {31190584}, issn = {1502-7708}, abstract = {Objectives: Irritable bowel syndrome (IBS) may be associated with disturbances in gut microbiota composition and functions. We recently performed a study of fecal microbiota transplantation (FMT) in diarrhea-predominant IBS (IBS-D) and found that IBS symptoms improved and the gut microbiota profile changed following FMT. We now aimed to explore the effects of FMT on the gut microenvironment in further detail by using 16S rRNA sequencing for more extended microbiota profiling and analyzing bacterial fermentation products (SCFAs: short chain fatty acids). Materials and methods: The study included 13 patients (four females and nine males) with IBS-D according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered into duodenum via gastroscopy. The patients completed symptom and quality of life (QoL) questionnaires and delivered feces before and 1, 3, 12 and 20/28 weeks after FMT. Microbiota analysis was performed by sequencing 16S rRNA gene with Illumina Miseq technology. Fecal concentrations of SCFAs were analyzed by vacuum distillation followed by gas chromatography. Results: Several gut microbiota taxa and SCFAs were significantly different in the patients at baseline compared to their donors. These differences normalized by the third week following FMT in parallel with significant improvement in symptoms and QoL. Responders had different gut microbiota profile and SCFAs than nonresponders. Significant correlations were found between the gut microenvironment and IBS symptoms. No adverse effects were reported. Conclusions: FMT restores alterations of the gut microenvironment in IBS-D patients during the first 3 weeks and improves their symptoms for up to 28 weeks. ClinicalTrials.gov ID: NCT03333291.}, }
@article {pmid31184735, year = {2019}, author = {Costello, SP and Conlon, MA and Andrews, JM}, title = {Fecal Microbiota Transplantation for Ulcerative Colitis-Reply.}, journal = {JAMA}, volume = {321}, number = {22}, pages = {2240-2241}, doi = {10.1001/jama.2019.3950}, pmid = {31184735}, issn = {1538-3598}, mesh = {*Colitis, Ulcerative ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; }, }
@article {pmid31184729, year = {2019}, author = {Benech, N and Kapel, N and Sokol, H}, title = {Fecal Microbiota Transplantation for Ulcerative Colitis.}, journal = {JAMA}, volume = {321}, number = {22}, pages = {2240}, doi = {10.1001/jama.2019.3946}, pmid = {31184729}, issn = {1538-3598}, mesh = {*Colitis, Ulcerative ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; }, }
@article {pmid31183574, year = {2019}, author = {Smibert, O and Satlin, MJ and Nellore, A and Peleg, AY}, title = {Carbapenem-Resistant Enterobacteriaceae in Solid Organ Transplantation: Management Principles.}, journal = {Current infectious disease reports}, volume = {21}, number = {7}, pages = {26}, doi = {10.1007/s11908-019-0679-4}, pmid = {31183574}, issn = {1523-3847}, abstract = {PURPOSE OF REVIEW: Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as a worldwide problem. Given their degree of immunosuppression and the level of contact with the healthcare system, solid organ transplant (SOT) recipients are at a disproportionately higher risk of acquisition, colonization, and infection with CRE, and outcomes from infection tend to be worse compared to non-transplant patients. Therapeutic options are limited for CRE infections although several newer agents have recently been approved for use. How well these agents perform in the setting of immunosuppression and SOT is unclear. We sought to review the epidemiology of CRE in SOT and the management principles.<br><br>RECENT FINDINGS: CRE infections are becoming an increasing problem in SOT, and donor-derived infections present a challenge in the peri-transplant period. Newer treatments for CRE are emerging that are less toxic and potentially more effective than prior CRE-active agents, but supportive clinical data are limited. Newer beta-lactamase inhibitors have good activity against KPC carbapenemases, but they lack activity against metallo-beta-lactamases (e.g., NDM). Promising data is emerging with newer agents that have activity against most carbapenemases, but, again, clinical data is needed. Combination therapy in addition to optimal pharmacokinetic and pharmacodynamics may go some way to improve outcomes against these difficult-to-treat organisms. Other novel therapies that prevent the emergence of resistance (oral beta-lactamase inhibitors) and eradication of resistant Gram-negative colonization (fecal microbiota transplant) may eventually become part of a bundle approach to reduce CRE infections in the future. As in non-transplant patients, CRE infections in the transplant setting are challenging to treat and prevent. Infection prevention and control remains crucial to prevent widespread dissemination, and unique challenges exist with donor-derived CRE and how best to manage recipients in the peri-transplant period. Newer treatments are now in early-phase clinical studies, and in vitro activity data are supportive for several agents providing hope for improved outcomes with these typically difficult-to-treat and highly morbid infections in transplant recipients.}, }
@article {pmid31178906, year = {2019}, author = {Lam, WC and Zhao, C and Ma, WJ and Yao, L}, title = {The Clinical and Steroid-Free Remission of Fecal Microbiota Transplantation to Patients with Ulcerative Colitis: A Meta-Analysis.}, journal = {Gastroenterology research and practice}, volume = {2019}, number = {}, pages = {1287493}, doi = {10.1155/2019/1287493}, pmid = {31178906}, issn = {1687-6121}, abstract = {Background and Purpose: Since the first case of fecal microbiota transplantation for the treatment of ulcerative colitis was described in the year 1989, there have been an increment of case reports, case series, cohort studies, and randomized controlled trials (RCTs). In this study, we were going to investigate general clinical remission, clinical response, and steroid-free remission of fecal microbiota transplantation.<br><br>Methods: We searched Ovid Medline, Ovid EMBASE, and Cochrane Library, focusing prospective studies including randomized controlled trials and cohort studies. The outcomes were clinical remission, clinical response, steroid-free remission, and serious adverse events. We used RevMan 5.3 software for meta-analyses.<br><br>Key Results: A total of 4 RCTs and 2 cohort studies (340 cases from 5 countries) were included. We found that FMT might be more effective than placebo on clinical remission (OR, 3.85 [2.21, 6.7]; P < 0.001; I2 = 0%) and clinical response (OR, 2.75 [1.33, 5.67]; P = 0.006; I2 = 49%), but no statistical difference on steroid-free remission (OR, 2.08 [0.41, 10.5]; P = 0.37; I2 = 69%) and serious adverse events (OR, 2.0 [0.17, 22.97]; P = 0.44; I2 = 0%).<br><br>Conclusions and Inferences: Fecal microbiota transplantations were associated with significant clinical remission and response in ulcerative colitis patients while there was no significant difference found between FMT and placebo in steroid-free remission. Moreover, a common consensus on the route, volume, timing, preferred donor characteristics, and frequency of fecal administration is necessary to achieve remission.}, }
@article {pmid31178437, year = {2019}, author = {Lui, RN and Wong, SH and Lau, LHS and Chan, TT and Cheung, KCY and Li, A and Chin, ML and Tang, W and Ching, JYL and Lam, KLY and Chan, PKS and Wu, JCY and Sung, JJY and Chan, FKL and Ng, SC}, title = {Faecal microbiota transplantation for treatment of recurrent or refractory Clostridioides difficile infection in Hong Kong.}, journal = {Hong Kong medical journal = Xianggang yi xue za zhi}, volume = {25}, number = {3}, pages = {178-182}, doi = {10.12809/hkmj197855}, pmid = {31178437}, issn = {1024-2708}, abstract = {INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infection globally, causing significant morbidity and mortality. Faecal microbiota transplantation (FMT) has emerged as a promising option for recurrent and refractory CDI. This study aimed to assess the safety, efficacy, and feasibility of FMT for CDI in Hong Kong.<br><br>METHODS: We conducted a single-centre, retrospective study for all consecutive cases of recurrent or refractory CDI who underwent FMT from 2013 to 2018. Clinical demographics, outcome, and safety parameters were collected.<br><br>RESULTS: A total of 24 patients with recurrent or refractory CDI (median age 70 years, interquartile range=45.0-78.3 years; 67% male) were included. Over 80% had been recently hospitalised or were long-term care facility residents. Faecal microbiota transplantation was delivered by feeding tube in 11 (45.8%), oesophagogastroduodenoscopy in eight (33.3%), and colonoscopy in six (25%) of the patients. Resolution of diarrhoea without relapse within 8 weeks was achieved in 21 out of 24 patients (87.5%) after FMT. No deaths occurred within 30 days. The FMT was well tolerated and no serious adverse events attributable to FMT were reported.<br><br>CONCLUSION: Our results confirm that FMT is a safe, efficacious, and feasible intervention for patients with refractory or recurrent CDI in Hong Kong. Given the increasing disease burden and the lack of effective alternatives in Hong Kong for difficult-to-treat cases of CDI, we recommend that a territory-wide FMT service be established to address increasing demand for this treatment.}, }
@article {pmid31173991, year = {2019}, author = {Borody, TJ and Eslick, GD and Clancy, RL}, title = {Fecal microbiota transplantation as a new therapy: from Clostridioides difficile infection to inflammatory bowel disease, irritable bowel syndrome, and colon cancer.}, journal = {Current opinion in pharmacology}, volume = {49}, number = {}, pages = {43-51}, doi = {10.1016/j.coph.2019.04.017}, pmid = {31173991}, issn = {1471-4973}, abstract = {Fecal microbiota transplantation (FMT) represents the most effective means of therapeutically manipulating the gastrointestinal microbiome. Originally employed as a treatment of last-resort in patients with life-threatening Clostridioides difficile infection (CDI), FMT gained widespread acceptance during the CDI epidemic, where it achieved resolution rates approaching 100%. Following our newfound appreciation for the role of the gut microbiome in both health and disease and owing to FMT's unique mechanism/s of action, FMT is rapidly advancing as an effective treatment for a number of conditions in which the gastrointestinal microbiome is thought to play a role. We review the role of FMT from its beginnings in CDI to its expansion into inflammatory bowel disease, irritable bowel syndrome, and colon cancer.}, }
@article {pmid31172007, year = {2019}, author = {Herfarth, H and Barnes, EL and Long, MD and Isaacs, KL and Leith, T and Silverstein, M and Gerardin, Y and Kassam, Z}, title = {Combined Endoscopic and Oral Fecal Microbiota Transplantation in Patients with Antibiotic-Dependent Pouchitis: Low Clinical Efficacy due to Low Donor Microbial Engraftment.}, journal = {Inflammatory intestinal diseases}, volume = {4}, number = {1}, pages = {1-6}, doi = {10.1159/000497042}, pmid = {31172007}, issn = {2296-9365}, abstract = {Background and Objective: A significant number of pouch patients develop antibiotic-dependent pouchitis (ADP). Microbial dysbiosis is thought to be a major driver of clinical symptoms in ADP. The objective of this proof of concept study was to evaluate safety, efficacy, and donor microbial engraftment of an intensified fecal microbiota transplant (FMT) consisting of a single endoscopic FMT followed by daily oral FMT for 2 weeks in patients with ADP.<br><br>Methods: We performed a prospective placebo-controlled double-blind FMT trial in patents with established ADP and planned to enroll 20 patients in this proof of concept study. In case of non-response, patients were offered an optional open label active FMT treatment. The endpoints were safety, clinical remission without need for antibiotics during 16 weeks of follow-up, quantitative changes of fecal calprotectin (FCP), and engraftment of donor FMT as determined by metagenomic sequencing of the V4 region of the 16S rRNA gene.<br><br>Results: Due to a lower than expected clinical remission rate and low FMT engraftment, enrollment in the study was stopped prematurely after 6 patients were included. All 6 patients enrolled in the placebo-controlled portion failed to respond and needed antibiotic rescue therapy shortly after FMT. FCP increased in the majority of patients in the setting of relapse after FMT. In the active open label FMT extension study 1 out of 5 patients achieved antibiotic-free clinical remission. FMT engraftment after active FMT was observed only in this single patient, whereas engraftment of donor FMT occurred in none of the other patients receiving active FMT, paralleling the lack of clinical response.<br><br>Conclusions: Low donor FMT engraftment resulted in low clinical efficacy of FMT in patients with ADP. Before embarking on larger clinical trials with FMT in patients with ADP or other forms of pouchitis, it is mandatory to explore approaches for superior FMT engraftment.}, }
@article {pmid31171823, year = {2019}, author = {Martínez, N and Hidalgo-Cantabrana, C and Delgado, S and Margolles, A and Sánchez, B}, title = {Filling the gap between collection, transport and storage of the human gut microbiota.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {8327}, doi = {10.1038/s41598-019-44888-8}, pmid = {31171823}, issn = {2045-2322}, abstract = {Stool collection devices minimizing the exposure of gut bacteria to oxygen are critical for the standardization of further microbiota-based studies, analysis and developments. The aim of this work was to evidence that keeping anaerobiosis has a deep impact on the viability and diversity of the fecal microbiota that is recovered in the laboratory. Recovering certain microbial populations, such as obligate anaerobic bacteria, is particularly critical if the purpose of the study is to envisage personalized therapeutic purposes, such as autologous Fecal Microbiota Transplant. In this study the same fecal specimens were sampled in conventional stool containers and GutAlive, a disposable device that minimizes exposure of the gut microbiota to oxygen. Samples from five healthy donors were analysed and 150 differential colonies were recovered and identified by 16S rRNA gene sequencing. Globally, GutAlive maintained extremely oxygen sensitive (EOS) populations that were lost in conventional stool containers, and thus viability of species such as as Akkermansia muciniphila, Faecalibacterium prausnitzii and a novel member of the Clostridiales order was kept. These obligate anaerobes were not recovered using the conventional stool collection device. In conclusion, the use of GutAlive for stool collection and transport optimized the viability and recovery of EOS bacteria in the lab by diminishing oxygen toxicity.}, }
@article {pmid31169545, year = {2019}, author = {Gurram, B and Sue, PK}, title = {Fecal microbiota transplantation in children: current concepts.}, journal = {Current opinion in pediatrics}, volume = {}, number = {}, pages = {}, doi = {10.1097/MOP.0000000000000787}, pmid = {31169545}, issn = {1531-698X}, abstract = {PURPOSE OF REVIEW: Administration of fecal material into the gastrointestinal tract, termed fecal microbiota transplantation (FMT), is increasingly recognized as an effective treatment option for recurrent Clostridium difficile infection (RCDI). The impact of FMT on host microbial communities and subsequent disease states has also been explored in recent years for conditions as varied as inflammatory bowel disease especially ulcerative colitis, metabolic diseases, such as diabetes, graft-versus-host disease in hematopoietic stem cell transplant recipients, and autism and autism spectrum disorders. The purpose of this article is to review the evidence for FMT as a treatment option in various pediatric illnesses.<br><br>RECENT FINDINGS: The rate of C. difficile infection is rising among children, and is associated with significant morbidity and disease, with recurrence in up to 20% of pediatric patients. Several randomized controlled trials evaluating the utility of FMT in RCDI in comparison to vancomycin have been published and demonstrate high rates of efficacy between 70 and 100%. In addition, the safety of FMT in the treatment of RCDI has been well described in the adult population, with several pediatric case series demonstrating similar rates of tolerability and adverse events. FMT in ulcerative colitis appears promising, especially with multiple infusions administered via the lower gastrointestinal tract. However, there are several limitations, including the lack of uniformity of protocols used, source of FMT, route of administration and the lack of standardization of concomitant therapies. The data on usage of FMT for other indications are preliminary and limited.<br><br>SUMMARY: FMT is recognized as an effective treatment option for RCDI and is increasing sought by parents. Although limited, pediatric studies to date on the use of FMT for RCDI demonstrate similar efficacy rates as in the adult population. FMT has been proposed as a treatment option for an increasing number of pediatric conditions, and additional studies are needed to delineate the efficacy of FMT outside of RCDI, as well as its short and long-term impacts on human health.}, }
@article {pmid31165961, year = {2019}, author = {Lee, CH and Chai, J and Hammond, K and Jeon, SR and Patel, Y and Goldeh, C and Kim, P}, title = {Long-term durability and safety of fecal microbiota transplantation for recurrent or refractory Clostridioides difficile infection with or without antibiotic exposure.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10096-019-03602-2}, pmid = {31165961}, issn = {1435-4373}, abstract = {Fecal microbiota transplant (FMT) is a safe and effective treatment for recurrent or refractory Clostridioides (Clostridium) difficile infection (RCDI) in the short term. However, there are a paucity of data on long-term durability and safety of FMT. The aim of this study is to determine the long-term efficacy and safety of FMT for RCDI. Ninety-four patients underwent FMT via retention enema for RCDI between 2008 and 2012 and completed a follow-up questionnaire 4 to 8 years following the last FMT. Of these, 32 were unreachable and 37 were deceased; 23 of the remaining 25 participants completed the survey. No CDI recurrences were reported in patients treated with FMT; 12 of the 23 participants (52.2%) received at least one course of non-CDI antibiotic(s). Nine participants (40.9%) received probiotics and 4 (17.4%) received both non-CDI antibiotics and probiotics. All 23 participants rated their overall health compared with pre-FMT. Current health was considered &quot;much better&quot; in 17 patients (73.9%); &quot;somewhat better&quot; in 3 patients (13.0%); and &quot;about the same&quot; in 3 patients (13.0%). A total of 11 participants (47.8%) reported an increase in weight of more than 5 kg (kg) post-FMT and 9 participants (39.1%) reported no change in weight (± 5 kg). Four of the 23 participants (17.4%) reported improvement or resolution (undifferentiated colitis, n = 1; Crohn's disease, n = 2; ulcerative colitis, n = 1) of pre-existing gastrointestinal condition following FMT. Eight of 23 participants (34.8%) experienced new medical condition(s) post-FMT. The long-term efficacy (48-96 months) of FMT for RCDI appears to be durable even after non-CDI antibiotic use. Thirty percent had improvement of their pre-existing medical conditions following FMT; 73.9% reported &quot;much better&quot; overall health following FMT.}, }
@article {pmid31164642, year = {2019}, author = {Stebegg, M and Silva-Cayetano, A and Innocentin, S and Jenkins, TP and Cantacessi, C and Gilbert, C and Linterman, MA}, title = {Heterochronic faecal transplantation boosts gut germinal centres in aged mice.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {2443}, doi = {10.1038/s41467-019-10430-7}, pmid = {31164642}, issn = {2041-1723}, support = {675395//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/International ; BBS/E/B/000C0407//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/International ; 637801//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/International ; BBS/E/B/000C0407//Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/B/000C0427//RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)/International ; }, mesh = {Aging/*immunology ; Animals ; Cholera Toxin/immunology ; Dysbiosis/*immunology ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*immunology ; Germinal Center/*immunology ; Immunization ; Immunoglobulin A/immunology ; Mice ; Nitrophenols/immunology ; Peyer's Patches/*immunology ; Phenylacetates/immunology ; }, abstract = {Ageing is a complex multifactorial process associated with a plethora of disorders, which contribute significantly to morbidity worldwide. One of the organs significantly affected by age is the gut. Age-dependent changes of the gut-associated microbiome have been linked to increased frailty and systemic inflammation. This change in microbial composition with age occurs in parallel with a decline in function of the gut immune system; however, it is not clear whether there is a causal link between the two. Here we report that the defective germinal centre reaction in Peyer's patches of aged mice can be rescued by faecal transfers from younger adults into aged mice and by immunisations with cholera toxin, without affecting germinal centre reactions in peripheral lymph nodes. This demonstrates that the poor germinal centre reaction in aged animals is not irreversible, and that it is possible to improve this response in older individuals by providing appropriate stimuli.}, }
@article {pmid31154727, year = {2019}, author = {Yin, GF and Li, B and Fan, XM}, title = {[Effects and mechanism of fecal transplantation on acute lung injury induced by lipopolysaccharide in rats].}, journal = {Zhonghua yi xue za zhi}, volume = {99}, number = {20}, pages = {1582-1587}, doi = {10.3760/cma.j.issn.0376-2491.2019.20.013}, pmid = {31154727}, issn = {0376-2491}, mesh = {*Acute Lung Injury ; Animals ; *Fecal Microbiota Transplantation ; Lipopolysaccharides ; Lung ; NF-kappa B ; Phosphatidylinositol 3-Kinases ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; }, abstract = {Objective: To investigate the effect of fecal microbiota transplantation (FMT) on acute lung injury (ALI) induced by lipopolysaccharide (LPS) and its regulatory mechanism. Methods: Fifteen rats were divided into control group, LPS group and LPS+FMT group by random number table method. LPS group and LPS+FMT group were intraperitoneally injected with LPS to generate rat ALI model. After 24 h of modeling, feces (10 ml/kg) were given to the LPS+FMT group twice a day, and the control group and LPS group were given the same amount of normal saline. The intervention lasted for 2 days. After 24 h of the last fecal microbiota transplantation, arterial blood gas analysis was performed in each group. Then rats were sacrificed and enzyme-linked immunosorbent (ELISA) method was used to detect intercellular adhesion molecule 1 (ICAM-1) content in the serum and bronchoalveolar lavage fluid (BALF). The lung wet-dry weight ratio (W/D) was evaluated; HE staining and lung tissue pathology scoring, immunohistochemical detection of nuclear factor-kappa B (NF-κB) predominate nuclear expression and expression of ICAM-1 of alveolar epithelial cells were conducted; Western blot was used to detect the expression of proteins related to the intracellular phosphatidylinositol kinase (PI3K)/protein kinase (AKT) signaling pathway. Samples of rat feces were collected and DNA was extracted. Polymerase chain reaction (PCR) products of the V3 and V4 regions of the 16S ribosomal RNA gene (16SrDNA) were sequenced at high throughput, and bioinformatics analysis was conducted on the microbial community based on the operational classification unit. Results: The lung W/D and lung histopathological score of the LPS group were significantly higher than those of the control group, while the arterial partial oxygen pressure (PaO(2)) of the LPS group was significantly lower than that of the control group [(79.2±5.89 vs 95.2±2.77) mmHg, 1 mmHg=0.133 kPa](all P<0.05). The results of intestinal flora sequencing revealed that the diversity index of LPS group was significantly higher than that of the control group, while the lactobacillus of LPS group rats was significantly lower than that of the control group. The content of ICAM-1 in serum, BALF and its relative expression on the cell membrane in the LPS group was significantly higher than that in the control group [(8.64±0.87) vs (7.40±0.32) ng/L; (0.941±0.035) vs (0.739±0.079) ng/L; (0.250±0.010) vs (0.076±0.010)] (all P<0.05). Moreover, the relative expression levels of phosphorylated P65 (p-P65), p-PI3K and p-AKT nucleoprotein in the LPS group were significantly higher than those in the control group (4.89±0.27 vs 3.28±0.13, 0.265±0.030 vs 0.036±0.013 and 0.444±0.040 vs 0.109±0.016) (all P<0.05). The above injury effect was reduced after fecal fungus transplantation. The lung W/D and lung pathological score of LPS+FMT group were significantly lower than those of LPS group, and PaO(2) of LPS+FMT group was significantly higher than that of LPS group [(88.0±3.53) mmHg]. The results of intestinal flora sequencing revealed that the diversity index of LPS+FMT group was significantly lower than that of LPS group, and the lactobacillus genus of LPS+FMT group was significantly higher than that of LPS group. ICAM-1 in the blood serum ((7.44±0.46) ng/L), BALF (0.834±0.040) ng/L) and its relative expression on alveolar epithelial cell membrane (0.173±0.030), the relative expression of p-P65, p-PI3K and p-AKT protein of NF-κB in alveolar epithelial cells was down-regulated ((2.99±0.28, 0.090±0.013 and 0.206±0.018) in LPS+FMT group than those of LPS group, the differences were statistically significant (all P<0.05). Conclusion: Fecal transplantation can alleviate lipopolysaccharide-induced acute lung injury in rats, and its regulatory effect may be related to inhibiting the activation of PI3K/AKT/NF-κB signaling pathway and reducing the expression of inflammatory factor ICAM-1.}, }
@article {pmid31154629, year = {2019}, author = {Kim, KO and Schwartz, MA and Lin, OST and Chiorean, MV and Gluck, M}, title = {Reducing Cost and Complexity of Fecal Microbiota Transplantation Using Universal Donors for Recurrent Clostridium difficile Infection.}, journal = {Advances in therapy}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12325-019-00974-x}, pmid = {31154629}, issn = {1865-8652}, abstract = {INTRODUCTION: Fecal microbiota transplantation resolves recurrent Clostridium difficile infections in greater than 82% of patients. Highly screened, processed universal donor fecal material is available. We compared cost and scheduling efficiency of fecal microbiota transplantation by universal donors to patient-directed donors.<br><br>METHODS: Medical records from a prospectively maintained database of recurrent C. difficile patients who underwent fecal microbiota transplantation between 2012 and 2017 were reviewed retrospectively. Patient-directed donor stool was prepared in our microbiology laboratory using protocol-based screening. We transitioned to purchasing and using universal donor fecal material in 2015. Clinical outcomes, adverse events, time between consult to infusion, consultation fees, and material costs were compared. This was a retrospective comparison of two historical cohorts.<br><br>RESULTS: A total of 111 fecal microbiota transplantations were performed on 105 patients (56 from patient-directed donors and 55 from universal donors). Median recipient age was 66 years (18-96) with male to female ratio of 1:2.7, equivalent in both cohorts. Total consultation fees were significantly lower in the universal donor group owing to fewer infectious disease consultations. Costs for donor screening and stool preparation were lower in the universal donor cohort ($485.0 vs. $1189.90 ± 541.4, p < 0.001, 95% CI 559.9-849.9). Time from consultations to infusion was shorter in the universal donor cohort (18.9 ± 19.1 vs. 36.4 ± 23.3 days, p < 0.001, 95% CI 9.521-25.591). Recurrences within 8 weeks after fecal microbiota transplantation were equivalent (p = 0.354). Adverse events were equivalent.<br><br>CONCLUSIONS: Fecal microbiota transplantation using universal donors versus patient-directed donors for recurrent C. difficile showed comparable efficacy and short-term complications. The use of universal donors resulted in significant cost savings and scheduling efficiency.}, }
@article {pmid31145641, year = {2019}, author = {Ji, J and Ge, X and Chen, Y and Zhu, B and Wu, Q and Zhang, J and Shan, J and Cheng, H and Shi, L}, title = {Daphnetin ameliorates experimental colitis by modulating microbiota composition and Treg/Th17 balance.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {}, number = {}, pages = {fj201802659RR}, doi = {10.1096/fj.201802659RR}, pmid = {31145641}, issn = {1530-6860}, abstract = {Inflammatory bowel diseases (IBDs) are characterized by chronic pathologies associated with extensive gut dysbiosis and intestinal inflammation. Hence, endeavors to improve the inflammatory pathology by manipulating gut microbiota are ongoing. Daphnetin (DAPH) is a coumarin derivative extracted from Daphne odora var with anti-inflammatory and immune-regulatory properties that has been widely used in treating inflammatory disorders. Herein, we showed that DAPH remarkably alleviated experimental colitis by reducing colonic inflammation, improving colonic integrity, and reestablishing immune and metabolic homeostasis in the inflicted intestines. Our analysis showed that DAPH modified the composition of gut microbiota and altered the metabolic profiles in dextran sulfate sodium-treated mice. In particular, this agent significantly elevated the abundance of short-chain fatty acid (SCFA)-producing gut microbiota, causatively related with the enhanced development of Treg cells and the reduced proinflammatory Th17 cell differentiation. More critically, the protective effect of DAPH was shown to be transmissible among colitic mice through cohousing or fecal microbiota transplantation, further substantiating the importance of SCFA-producing gut microbiota in DAPH action. We thus for the first time reveal the potential of DAPH in resetting the gut microbiome and reestablishing immune homeostasis in colitic mice, which may have clinical implications for treating IBD.-Ji, J., Ge, X., Chen, Y., Zhu, B., Wu, Q., Zhang, J., Shan, J., Cheng, H., Shi, L. Daphnetin ameliorates experimental colitis by modulating microbiota composition and Treg/Th17 balance.}, }
@article {pmid31143780, year = {2019}, author = {Zeng, W and Shen, J and Bo, T and Peng, L and Xu, H and Nasser, MI and Zhuang, Q and Zhao, M}, title = {Cutting Edge: Probiotics and Fecal Microbiota Transplantation in Immunomodulation.}, journal = {Journal of immunology research}, volume = {2019}, number = {}, pages = {1603758}, doi = {10.1155/2019/1603758}, pmid = {31143780}, issn = {2314-7156}, abstract = {Probiotics are commensal or nonpathogenic microbes that confer beneficial effects on the host through several mechanisms such as competitive exclusion, antibacterial effects, and modulation of immune responses. Some probiotics have been found to regulate immune responses via immune regulatory mechanisms. T regulatory (Treg) cells, T helper cell balances, dendritic cells, macrophages, B cells, and natural killer (NK) cells can be considered as the most determinant dysregulated mediators in immunomodulatory status. Recently, fecal microbiota transplantation (FMT) has been defined as the transfer of distal gut microbial communities from a healthy individual to a patient's intestinal tract to cure some immune disorders (mainly inflammatory bowel diseases). The aim of this review was followed through the recent literature survey on immunomodulatory effects and mechanisms of probiotics and FMT and also efficacy and safety of probiotics and FMT in clinical trials and applications.}, }
@article {pmid31142049, year = {2019}, author = {Burrello, C and Giuffrè, MR and Macandog, AD and Diaz-Basabe, A and Cribiù, FM and Lopez, G and Borgo, F and Nezi, L and Caprioli, F and Vecchi, M and Facciotti, F}, title = {Fecal Microbiota Transplantation Controls Murine Chronic Intestinal Inflammation by Modulating Immune Cell Functions and Gut Microbiota Composition.}, journal = {Cells}, volume = {8}, number = {6}, pages = {}, doi = {10.3390/cells8060517}, pmid = {31142049}, issn = {2073-4409}, support = {14378//Associazione Italiana per la Ricerca sul Cancro/ ; GR-2016-02361741//Ministero della Salute/ ; 5X1000//Fondazione IRCCS Policlinico Maggiore Milano/ ; }, abstract = {Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.}, }
@article {pmid31133692, year = {2019}, author = {Aagaard, K and Hohmann, E}, title = {Regulating microbiome manipulation.}, journal = {Nature medicine}, volume = {25}, number = {6}, pages = {874-876}, doi = {10.1038/s41591-019-0451-1}, pmid = {31133692}, issn = {1546-170X}, mesh = {Drug Approval/legislation &amp; jurisprudence ; Fecal Microbiota Transplantation/adverse effects ; Humans ; Legislation, Medical ; *Microbiota ; Risk Factors ; Safety/legislation &amp; jurisprudence ; United States ; United States Food and Drug Administration/legislation &amp; jurisprudence ; }, }
@article {pmid31127327, year = {2019}, author = {Alagna, L and Haak, BW and Gori, A}, title = {Fecal microbiota transplantation in the ICU: perspectives on future implementations.}, journal = {Intensive care medicine}, volume = {45}, number = {7}, pages = {998-1001}, doi = {10.1007/s00134-019-05645-7}, pmid = {31127327}, issn = {1432-1238}, }
@article {pmid31125783, year = {2019}, author = {Cavuoto, KM and Banerjee, S and Galor, A}, title = {Relationship between the microbiome and ocular health.}, journal = {The ocular surface}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtos.2019.05.006}, pmid = {31125783}, issn = {1937-5913}, support = {I01 CX001089/CX/CSRD VA/United States ; L30 EY019842/EY/NEI NIH HHS/United States ; R01 EY026174/EY/NEI NIH HHS/United States ; }, abstract = {The microbiome is important to the host as a whole, both in maintenance of health and in the pathophysiology of disease. The purpose of this review is to explore the relationship between the gut, ocular microbiome, and ocular disease states. We will also discuss how the microbiome can serve as a potential target for treatment, by methods such as modulation of diet, probiotics and fecal microbiota transplantation. The information discussed in the review has been gathered using literature published from 2004 to November 2018, as indexed in PubMed.}, }
@article {pmid31124558, year = {2019}, author = {Sharpton, SR and Maraj, B and Harding-Theobald, E and Vittinghoff, E and Terrault, NA}, title = {Gut microbiome-targeted therapies in nonalcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression.}, journal = {The American journal of clinical nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1093/ajcn/nqz042}, pmid = {31124558}, issn = {1938-3207}, abstract = {BACKGROUND: Preclinical evidence suggests that modulation of the gut microbiome could represent a new therapeutic target in nonalcoholic fatty liver disease (NAFLD).<br><br>OBJECTIVES: The aim of this study was to evaluate the most current evidence for liver-specific and metabolic effects of microbiome-targeted therapies (MTTs) in persons with NAFLD.<br><br>METHODS: We searched multiple electronic databases for randomized controlled trials (RCTs) published from January 1, 2005 to December 1, 2018 that enrolled persons with NAFLD who received MTT rather than placebo or usual care. MTT was defined as antibiotics, probiotics, synbiotics, or fecal microbiota transplantation (FMT). Clinical outcomes were pooled with the use of random-effects models and heterogeneity was assessed with the I2 statistic. A random-effects meta-regression was performed to determine sources of heterogeneity in prevalence estimates between studies.<br><br>RESULTS: Twenty-one RCTs (1252 participants) were included; 9 evaluated probiotics and 12 evaluated synbiotics, with treatment duration ranging from 8 to 28 wk. No RCTs examined the efficacy of antibiotics or FMT. Probiotics/synbiotics were associated with a significant reduction in alanine aminotransferase activity [ALT, weighted mean difference (WMD): -11.23 IU/L; 95% CI: -15.02, -7.44 IU/L] and liver stiffness measurement (LSM) by elastography (reflecting inflammation and fibrosis) (WMD: -0.70 kPa; 95% CI: -1.00, -0.40 kPa), although analyses showed heterogeneity (I2 = 90.6% and I2 = 93.4%, respectively). Probiotics/synbiotics were also associated with increased odds of improvement in hepatic steatosis, as graded by ultrasound (OR: 2.40; 95% CI: 1.50, 3.84; I2 = 22.4%). No RCTs examined sequential liver biopsy findings. Probiotics (WMD: -1.84; 95% CI: -3.30, -0.38; I2 = 23.6%), but not synbiotics (WMD: -0.85; 95% CI: -2.17, 0.47; I2 = 96.6%), were associated with a significant reduction in body mass index.<br><br>CONCLUSIONS: The use of probiotics/synbiotics was associated with improvement in liver-specific markers of hepatic inflammation, LSM, and steatosis in persons with NAFLD. Although promising, given the heterogeneity in pooled analyses, additional well-designed RCTs are needed to define the efficacy of probiotics/synbiotics for treatment of NAFLD. This study was registered with PROSPERO as CRD42018091455.}, }
@article {pmid31124390, year = {2019}, author = {Li, N and Wang, Q and Wang, Y and Sun, A and Lin, Y and Jin, Y and Li, X}, title = {Fecal microbiota transplantation from chronic unpredictable mild stress mice donors affects anxiety-like and depression-like behavior in recipient mice via the gut microbiota-inflammation-brain axis.}, journal = {Stress (Amsterdam, Netherlands)}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/10253890.2019.1617267}, pmid = {31124390}, issn = {1607-8888}, abstract = {Recent studies have demonstrated that there are significant changes in the gut microbiota (GM) of humans with depression and animal models of depression and chronic stress. In our present study, we determined whether an alteration in GM is a decisive factor in anxiety-like and depression-like behavior and its impact on brain neurochemistry. An antibiotic cocktail was used to deplete the GM of mice before they were colonized, via fecal microbiota transplantation (FMT), by the GM of control mice or mice that had been exposed to chronic unpredictable mild stress (CUMS donors). The CUMS-donor group of mice and the mice that were colonized by their microbiota (the CUMS-recipient group) both showed higher levels of anxiety- and depression-like behavior compared to the controls. The GM community of the CUMS-donor and CUMS-recipient was distinctively different from the controls, with the CUMS group characterized by a lower relative abundance of Lactobacillus and a higher relative abundance of Akkermansia. Interestingly, FMT affected both behavior and neuroinflammation. Mice given the CUMS microbiota had significant elevations of interferon-γ (IFN-γ) and the tumor necrosis factor-alpha (TNF-α) in the hippocampus, which were accompanied by upregulated indoleamine 2,3-dioxygenase 1 (IDO1) in the hippocampus. These results suggest that GM modulates pro-inflammatory cytokines in the hippocampus through dysfunctional microbiota-gut-brain axis, exacerbating anxiety- and depression-like phenotypes. Key Points Chronic unpredictable mild stress increased anxiety- and depression-like behavior in mice. Mice colonized with gut microbiota (GM) from stressed mice showed similar behaviors. The GM composition of the donor and recipient mice was also comparable. Their relative pattern of two bacteria has been tied to neuroinflammatory activity. The results suggest a link between GM, brain function, and anxiety and depression.}, }
@article {pmid31123874, year = {2019}, author = {Yousi, F and Kainan, C and Junnan, Z and Chuanxing, X and Lina, F and Bangzhou, Z and Jianlin, R and Baishan, F}, title = {Evaluation of the effects of four media on human intestinal microbiota culture in vitro.}, journal = {AMB Express}, volume = {9}, number = {1}, pages = {69}, doi = {10.1186/s13568-019-0790-9}, pmid = {31123874}, issn = {2191-0855}, support = {81770558//National Natural Science Foundation of China/ ; }, abstract = {The human intestinal microbiota has an important role in the maintenance of human health and disease pathogenesis. The aim of this research was to investigate the impact of four media on human intestinal microbiota metabolite and composition changes, we performed in vitro batch culture using intestinal microbiota samples from three fecal microbiota transplantation (FMT) donors. After 48 h culture, gut microbiota medium (GMM) had the highest production of acetic acid (73.00 ± 7.56 mM) and propionic acid (16.79 ± 1.59 mM), bacterial growth media (BGM) had the highest production of butyric acid (13.39 ± 0.56 mM). In addition, brain heart infusion (BHI) promoted (p < 0.05) the growth of Bacteroidetes, especially Bacteroides after 48 h, GMM resulted in a significant increase (p < 0.05) in Actinobacteria and increased the beneficial genus Bifidobacterium, fastidious anaerobe broth (FAB) increased Firmicutes population, and BGM promoted the growth of Escherichia-Shigella and Akkermansia. The results suggest that four media had different effects on the human intestinal microbiota metabolism and composition in vitro. These results may facilitate the culture of bacteria from the human intestinal microbiota.}, }
@article {pmid31123221, year = {2019}, author = {Yu, F and Han, W and Zhan, G and Li, S and Xiang, S and Zhu, B and Jiang, X and Yang, L and Luo, A and Hua, F and Yang, C}, title = {Abnormal gut microbiota composition contributes to cognitive dysfunction in streptozotocin-induced diabetic mice.}, journal = {Aging}, volume = {11}, number = {10}, pages = {3262-3279}, doi = {10.18632/aging.101978}, pmid = {31123221}, issn = {1945-4589}, abstract = {Both diabetes and Alzheimer's disease are age-related disorders, and numerous studies have demonstrated that patients with diabetes are at an increased risk of cognitive dysfunction (CD) and Alzheimer's disease, suggesting shared or interacting pathomechanisms. The present study investigated the role of abnormal gut microbiota in diabetes-induced CD and the potential underlying mechanisms. An intraperitoneal injection of streptozotocin administered for 5 consecutive days was used for establishing a diabetic animal model. Hierarchical cluster analysis of Morris water maze (MWM) performance indices (escape latency and target quadrant crossing) was adopted to classify the diabetic model mice into CD and Non-CD phenotypes. Both β-diversity and relative abundance of several gut bacteria significantly differed between the CD and Non-CD groups. Further, fecal bacteria transplantation from Non-CD mice, but not from CD mice, into the gut of pseudo-germ-free mice significantly improved host MWM performance, an effect associated with alterations in β-diversity and relative abundance of host gut bacteria. Collectively, these findings suggest that abnormal gut microbiota composition contributes to the onset of diabetes-induced CD and that improving gut microbiota composition is a potential therapeutic strategy for diabetes and related comorbidities.}, }
@article {pmid31122134, year = {2019}, author = {McSweeney, B and Allegretti, JR and Fischer, M and Xu, H and Goodman, KJ and Monaghan, T and McLeod, C and Mullish, BH and Petrof, EO and Phelps, EL and Chis, R and Edmison, A and Juby, A and Ennis-Davis, R and Roach, B and Wong, K and Kao, D}, title = {In search of stool donors: a multicenter study of prior knowledge, perceptions, motivators, and deterrents among potential donors for fecal microbiota transplantation.}, journal = {Gut microbes}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/19490976.2019.1611153}, pmid = {31122134}, issn = {1949-0984}, abstract = {Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection. Stool donors are essential, but difficult to recruit and retain. We aimed to identify factors influencing willingness to donate stool. This multi-center study with a 32-item questionnaire targeted young adults and health care workers via social media and university email lists in Edmonton and Kingston, Canada; London and Nottingham, England; and Indianapolis and Boston, USA. Items included baseline demographics and FMT knowledge and perception. Investigated motivators and deterrents included economic compensation, screening process, time commitment, and stool donation logistics. Logistic regression and linear regression models estimated associations of study variables with self-assessed willingness to donate stool. 802 respondents completed our questionnaire: 387 (48.3%) age 21-30 years, 573 (71.4%) female, 323 (40%) health care workers. Country of residence, age and occupation were not associated with willingness to donate stool. Factors increasing willingness to donate were: already a blood donor (OR 1.64), male, altruism, economic benefit, knowledge of how FMT can help patients (OR 1.32), and positive attitudes towards FMT (OR 1.39). Factors decreasing willingness to donate were: stool collection unpleasant (OR 0.92), screening process invasive (OR 0.92), higher stool donation frequency, negative social perception of stool, and logistics of collection/transporting feces. We conclude that 1) blood donors and males are more willing to consider stool donation; 2) altruism, economic compensation, and positive feedback are motivators; and 3) screening process, high donation frequency, logistics of collection/transporting feces, lack of public awareness, and negative social perception are deterrents. Considering these variables could maximize donor recruitment and retention.}, }
@article {pmid31119397, year = {2019}, author = {Contreras, GA and Munita, JM and Arias, CA}, title = {Novel Strategies for the Management of Vancomycin-Resistant Enterococcal Infections.}, journal = {Current infectious disease reports}, volume = {21}, number = {7}, pages = {22}, doi = {10.1007/s11908-019-0680-y}, pmid = {31119397}, issn = {1523-3847}, abstract = {PURPOSE OF REVIEW: Vancomycin-resistant enterococci (VRE) are important nosocomial pathogens that commonly affect critically ill patients. VRE have a remarkable genetic plasticity allowing them to acquire genes associated with antimicrobial resistance. Therefore, the treatment of deep-seated infections due to VRE has become a challenge for the clinician. The purpose of this review is to assess the current and future strategies for the management of recalcitrant deep-seated VRE infections and efforts for infection control in the hospital setting.<br><br>RECENT FINDINGS: Preventing colonization and decolonization of multidrug-resistant bacteria are becoming the most promising novel strategies to control and eradicate VRE from the hospital environment. Fecal microbiota transplantation (FMT) has shown remarkable results on treating colonization and infection due to Clostridiodes difficille and VRE, as well as to recover the integrity of the gut microbiota under antibiotic pressure. Initial reports have shown the efficacy of FMT on reestablishing patient microbiota diversity in the gut and reducing the dominance of VRE in the gastrointestinal tract. In addition, the use of bacteriophages may be a promising strategy in eradicating VRE from the gut of patients. Until these strategies become widely available in the hospital setting, the implementation of infection control measures and stewardship programs are paramount for the control of this pathogen and each program should provide recommendations for the proper use of antibiotics and develop strategies that help to detect populations at risk of VRE colonization, prevent and control nosocomial transmission of VRE, and develop educational programs for all healthcare workers addressing the epidemiology of VRE and the potential impact of these pathogens on the cost and outcomes of patients. In terms of antibiotic strategies, daptomycin has become the standard of care for the management of deep-seated infections due to VRE. However, recent evidence indicates that the efficacy of this antibiotic is limited, and higher (10-12 mg/kg) doses and/or combination with β-lactams is needed for therapeutic success. Clinical data to support the best use of daptomycin against VRE are urgently needed. This review provides an overview of recent developments regarding the prevention, treatment, control, and eradication of VRE in the hospital setting. We aim to provide an update of the most recent therapeutic strategies to treat deep-seated infections due to VRE.}, }
@article {pmid31117340, year = {2019}, author = {Cho, JM and Pestana, L and Pardi, R and Pardi, DS and Khanna, S}, title = {Fecal microbiota transplant via colonoscopy may be preferred due to intraprocedure findings.}, journal = {Intestinal research}, volume = {}, number = {}, pages = {}, doi = {10.5217/ir.2019.00056}, pmid = {31117340}, issn = {1598-9100}, }
@article {pmid31116134, year = {2019}, author = {Revolinski, SL and Munoz-Price, LS}, title = {Clostridioides difficile in transplant patients: early diagnosis, treatment, and prevention.}, journal = {Current opinion in infectious diseases}, volume = {32}, number = {4}, pages = {307-313}, doi = {10.1097/QCO.0000000000000560}, pmid = {31116134}, issn = {1473-6527}, abstract = {PURPOSE OF REVIEW: Clostridioides difficile infection is common in solid organ transplant and hematopoietic stem-cell transplant recipients and is associated with significant morbidity and mortality. These populations are also underrepresented in clinical trials, making optimal management difficult. Because of this, management of these populations follows national guideline recommendations. This review aims to summarize the recent relevant literature pertaining to the clinical management of C. difficile infection in transplant patients, with a particular focus on diagnosis, treatment, and prevention.<br><br>RECENT FINDINGS: Early diagnosis of C. difficile colonization may mitigate both horizontal and vertical transmission (progression from colonization to colitis) of infection. Once diagnosed, recent literature suggests antibiotic treatment should align with that recommended by national guidelines. Fecal microbiota transplant is an emerging therapy for recurrent C. difficile infection, and recent data have demonstrated safety and efficacy. Prevention strategies including antimicrobial stewardship, probiotic administration, antibiotic administration, and bezlotoxumab may be beneficial in transplant populations, but more data are needed to confirm recent findings.<br><br>SUMMARY: Studies evaluating C. difficile infection in transplant patients are only recently starting to emerge. Further research is needed to identify optimal treatment and prevention strategies, and to examine novel strategies such as microbiome manipulation.}, }
@article {pmid31113785, year = {2019}, author = {Krensky, C and Poutanen, SM and Hota, SS}, title = {Diarrhea after fecal microbiota transplantation for recurrent Clostridioides difficile infection.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {191}, number = {20}, pages = {E559-E561}, doi = {10.1503/cmaj.181193}, pmid = {31113785}, issn = {1488-2329}, }
@article {pmid31105766, year = {2019}, author = {Saha, S and Khanna, S}, title = {Management of Clostridioides difficile colitis: insights for the gastroenterologist.}, journal = {Therapeutic advances in gastroenterology}, volume = {12}, number = {}, pages = {1756284819847651}, doi = {10.1177/1756284819847651}, pmid = {31105766}, issn = {1756-283X}, abstract = {Clostridioides difficile infection (CDI) is a common cause of diarrhea in both inpatient and outpatient settings. The last few years have seen major changes in the treatment spectrum of CDI, most notably, recommendations against using metronidazole for initial CDI, the addition of fidaxomicin and bezlotoxumab, and emergence of microbial replacement therapies. Several other therapies are undergoing clinical trials. This narrative review focuses on the treatment of CDI with a summary of literature on the newer modalities and the treatment guidelines issued by Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases.}, }
@article {pmid31105675, year = {2019}, author = {Wang, J and Lang, T and Shen, J and Dai, J and Tian, L and Wang, X}, title = {Core Gut Bacteria Analysis of Healthy Mice.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {887}, doi = {10.3389/fmicb.2019.00887}, pmid = {31105675}, issn = {1664-302X}, abstract = {Previous studies revealed that there existed great individual variations of gut microbiota in mice, and the gut bacteria of mice were changed with the occurrence and development of diseases. To identify the core gut bacteria in healthy mice and explore their relationships with the host phenotypes would help to understand the underlying mechanisms. In this study, we identified 37 genus-level core bacteria from feces of 101 healthy mice with different ages, sexes, and mouse strains in three previous studies. They collectively represented nearly half of the total sequences, and predominantly included carbohydrate- and amino acids-metabolizing bacteria and immunomodulatory bacteria. Among them, Anaerostipes indwelt the gut of all healthy mice. Co-abundance analysis showed that these core genera were clustered into five groups (Group C1-C5), which were ecologically related. For example, the abundances of Group C2 including probiotics Bifidobacterium and Lactobacillus slightly positively correlated with those of Group C1. Principal component analysis (PCA) and multivariate analysis of variance test revealed that these core gut genera were distinguished with age and sex, and also associated with their health/disease state. Linear discriminant analysis effect size (LEfSe) method showed that bacteria in Group C1 and C2/C3 increased with the age in infancy and early adulthood, and were more abundant in female mice than in male ones. The metabolic syndrome (MS) induced by high fat diet (HFD) and accelerated postnatal growth would decrease Group C2 genera, whereas probiotics intervention would reverse HFD-induced reduction of Group C2. Spearman correlation analysis indicated that the principal components based on the abundance of the 37 core genera were significantly correlated with host characteristic parameters of MS. These results demonstrated that the 37 core genera in five co-abundance groups from healthy mice were related to host phenotypes. It was indicated that these prevalent gut bacterial genera could be representative of the healthy gut microbiome in gnotobiotic animal models, and might also be candidates of probiotics and fecal microbiota transplantation.}, }
@article {pmid31103793, year = {2019}, author = {Dailey, FE and Turse, EP and Daglilar, E and Tahan, V}, title = {The dirty aspects of fecal microbiota transplantation: a review of its adverse effects and complications.}, journal = {Current opinion in pharmacology}, volume = {49}, number = {}, pages = {29-33}, doi = {10.1016/j.coph.2019.04.008}, pmid = {31103793}, issn = {1471-4973}, abstract = {Fecal microbiota transplantation is becoming a growing therapy for a variety of indications, including recurrent or refractory Clostridium difficile infection (CDI), as well as many other gastrointestinal and extra-intestinal diseases. In fact, fecal microbiota transplantation is now strongly recommended as the treatment of choice for multiple recurrences of CDI, given its strong efficacy and a favorable short-term side effect profile. As the application of this therapy expands, awareness of its adverse events has also developed. The purpose of this review is to bring to light the side effects and complications associated with fecal microbiota transplantation, with an emphasis on findings from recently published studies.}, }
@article {pmid31095511, year = {2019}, author = {Sasmita, AO}, title = {Modification of the gut microbiome to combat neurodegeneration.}, journal = {Reviews in the neurosciences}, volume = {}, number = {}, pages = {}, doi = {10.1515/revneuro-2019-0005}, pmid = {31095511}, issn = {0334-1763}, abstract = {The gut microbiome was extensively researched for its biological variety and its potential role in propagating diseases outside of the gastrointestinal (GI) tract. Recently, a lot of effort was focused on comprehending the gut-brain axis and the bizarre communication between the GI system and the nervous system. Ample amount of studies being carried out also revealed the involvement of the gut microbiome in enhancing the degree of many neurological disorders, including neurodegenerative diseases. It was widely observed that there were distinct microbiome profiles and dysbiosis within patients suffering from Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Various approaches to re-establish the balance of the gut microbiome, from antibiotic therapy, fecal microbiota transplant, or ingestion of psychobiotics, are discussed within this review within the specific context of combating neurodegenerative diseases. Present studies and clinical trials indicate that although there is an immense potential of gut microbiome modification to be preventive or therapeutic, there are still many intercalated components of the gut-brain axis at play and thus, more research needs to be carried out to delineate microbiome factors that may potentially alleviate symptoms of neurodegeneration.}, }
@article {pmid31091761, year = {2019}, author = {Noce, A and Marrone, G and Di Daniele, F and Ottaviani, E and Wilson Jones, G and Bernini, R and Romani, A and Rovella, V}, title = {Impact of Gut Microbiota Composition on Onset and Progression of Chronic Non-Communicable Diseases.}, journal = {Nutrients}, volume = {11}, number = {5}, pages = {}, doi = {10.3390/nu11051073}, pmid = {31091761}, issn = {2072-6643}, abstract = {In recent years, mounting scientific evidence has emerged regarding the evaluation of the putative correlation between the gut microbiota composition and the presence of chronic non-communicable diseases (NCDs), such as diabetes mellitus, chronic kidney disease, and arterial hypertension. The aim of this narrative review is to examine the current literature with respect to the relationship between intestinal dysbiosis and the insurgence/progression of chronic NCDs, analyzing the physiopathological mechanisms that can induce microbiota modification in the course of these pathologies, and the possible effect induced by microbiota alteration upon disease onset. Therapy based on probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplant can represent a useful therapeutic tool, as has been highlighted on animal studies. To this moment, clinical studies that intended to demonstrate the beneficial effect induced by this kind of oral supplementation on the gut microbiota composition, and subsequent amelioration of signs and symptoms of chronic NCDs have been conducted on limited sample populations for a limited follow-up period. Therefore, to fully evaluate the therapeutic value of this kind of intervention, it would be ideal to design ample population; randomized clinical trials with a lengthy follow up period.}, }
@article {pmid31088542, year = {2019}, author = {Prevel, R and Boyer, A and M'Zali, F and Lasheras, A and Zahar, JR and Rogues, AM and Gruson, D}, title = {Is systematic fecal carriage screening of extended-spectrum beta-lactamase-producing Enterobacteriaceae still useful in intensive care unit: a systematic review.}, journal = {Critical care (London, England)}, volume = {23}, number = {1}, pages = {170}, doi = {10.1186/s13054-019-2460-3}, pmid = {31088542}, issn = {1466-609X}, abstract = {BACKGROUND: Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are disseminating worldwide leading to increased hospital length of stay and mortality in intensive care units (ICU). ESBL-E dissemination was first due to outbreaks in hospital settings which led to the implementation of systematic fecal carriage screening to improve hygiene procedures by contact precautions. ESBLs have since spread in the community, and the relevance of contact precautions is questioned. ESBL-E dissemination led to an overuse of carbapenems triggering the emergence of carbapenem-resistant Enterobacteriaceae. Empirical antimicrobial therapy based on ESBL-E fecal carriage has been proposed but is debated as it could increase the consumption of carbapenems among ESBL-E carriers without any clinical benefit. Finally, selective decontamination among ESBL-E fecal carriers is evoked to decrease the risk for subsequent ESBL-E infection, but its efficacy remains debated. We propose to systematically review the evidence to recommend or not such systematic ESBL-E fecal carriage screening in adult ICU.<br><br>METHODS: Every article focusing on ESBL-E and ICU available on the MEDLINE database was assessed. Articles were included if focusing on cross-transmission, efficacy of hygiene procedures, link between ESBL-E colonization and infection or guidance of empirical therapy or selective decontamination efficacy.<br><br>RESULTS: Among 330 articles referenced on PubMed, 39 abstracts were selected for full-text assessment and 25 studies were included. Systematic screening of ESBL-E fecal carriage to guide contact precautions do not seem to decrease the rate of ESBL-E cross-transmission. It has a very good negative predictive value for subsequent ESBL-E infections but a positive predictive value between 40 and 50% and so does not help to spare carbapenems. Cessation of ESBL-E carriage systematic screening could decrease the use of carbapenems in ICU without any clinical harm. Nevertheless, further studies are needed to validate these results from monocentric before-after study. Selective decontamination strategy applied to ESBL-E fecal carriers could be helpful, but available data are conflicting.<br><br>CONCLUSION: Current knowledge lacks of high-quality evidence to strongly recommend in favor of or against a systematic ESBL-E fecal carriage screening policy for ICU patients in a non-outbreak situation. Further evaluation of selective decontamination or fecal microbiota transplantation among ESBL-E fecal carriers is needed.}, }
@article {pmid31085417, year = {2019}, author = {Turse, EP and Dailey, FE and Ghouri, YA and Tahan, V}, title = {Fecal microbiota transplantation donation: the gift that keeps on giving.}, journal = {Current opinion in pharmacology}, volume = {49}, number = {}, pages = {24-28}, doi = {10.1016/j.coph.2019.04.009}, pmid = {31085417}, issn = {1471-4973}, abstract = {Fecal microbiota transplantation (FMT) is being studied and utilized for various medical conditions including Clostridium difficile colitis, inflammatory bowel diseases (IBD), obesity, myasthenia gravis, and so on. Yet, FMT donation, whether from an individual or a stool bank, can be challenging given the numerous requirements and donor costs. Furthermore, data outcomes on recipients of FMT regarding donor's health co-morbidities, age, and weight are limited but emerging. The purpose of this review is to evaluate cost, safety, and accessibility in FMT donation.}, }
@article {pmid31082878, year = {2019}, author = {Shaukat, A and Brenner, DM}, title = {Fecal Microbiota Transplant for Irritable Bowel Syndrome: Panacea or Placebo?.}, journal = {The American journal of gastroenterology}, volume = {114}, number = {7}, pages = {1032-1033}, doi = {10.14309/ajg.0000000000000259}, pmid = {31082878}, issn = {1572-0241}, abstract = {Irritable bowel syndrome (IBS) is a common disorder of heterogeneous pathogenesis, and alterations in the gut microbiome/dysbiosis play a role in the development of symptoms in a subset of individuals with IBS. Consequently, it stands to reason that modulation of the microbiome via fecal microbial transplant (FMT) may serve as an effective treatment strategy because this has proven effective for treating other illnesses such as Clostridium difficile colitis. Small studies completed to date have offered conflicting results and the strains used, route of administration, and IBS subtypes may all play a role in treatment outcomes. A better understanding of the altered microbiome of patients with IBS and more rigorous trials are warranted before the utility of fecal microbial transplant for IBS symptoms can be determined.}, }
@article {pmid31076926, year = {2019}, author = {Lin, C and Wan, J and Lu, Y and Zhang, H and Chen, X and Su, Y and Zhu, W}, title = {Active bacterial communities of pig fecal microbiota transplantation suspension prepared and preserved under different conditions.}, journal = {AMB Express}, volume = {9}, number = {1}, pages = {63}, doi = {10.1186/s13568-019-0787-4}, pmid = {31076926}, issn = {2191-0855}, support = {31572414//National Natural Science Foundation of China/ ; 3187130113//National Natural Science Foundation of China/ ; 2018YFD0500404//National Key R &amp; D Program of China/ ; }, abstract = {Although fecal microbiota transplantation (FMT) has become a research hotspot, studies on comparison of the active fecal bacteria suspension under different preparation conditions are limited. This study investigated the abundances of active bacterial community in pig FMT suspension that produced under different oxygen concentrations or cryopreservation conditions. Fecal samples from a Landrace × Yorkshire sow were used to prepare fecal bacteria suspension under the anaerobic (AN group) and aerobic conditions (AE group), respectively. And then half of the anaerobic fecal bacteria suspension was cryopreservation in - 80 °C (AN-CR group) for 1 week. The microbial RNA in the fecal bacteria suspension was extracted before and after cryopreservation, and reverse transcribed into cDNA. MiSeq sequencing 16S rRNA gene of bacterial cDNA showed that the bacterial diversity in the AN group was significantly higher than that in the AE group. Comparing with the sows' fecal sample, the relative abundances of Lactobacillus johnsonii, Lactobacillus coleohominis and Parabacteroides merdae in AN, AE and AN-CR groups were reduced. The short-term cryopreservation had low impact on the structure of the active bacterial community in the fecal bacterial suspension. These results suggest that fecal bacteria suspension can be better prepared under strict anaerobic condition, and that fecal bacteria suspension can be cryopreserved in - 80 °C for a short time.}, }
@article {pmid31073525, year = {2019}, author = {Jia, Q and Zhang, L and Zhang, J and Pei, F and Zhu, S and Sun, Q and Duan, L}, title = {Fecal Microbiota of Diarrhea-Predominant Irritable Bowel Syndrome Patients Causes Hepatic Inflammation of Germ-Free Rats and Berberine Reverses It Partially.}, journal = {BioMed research international}, volume = {2019}, number = {}, pages = {4530203}, doi = {10.1155/2019/4530203}, pmid = {31073525}, issn = {2314-6141}, abstract = {Effects of the microbiome associated with diarrhea-predominant irritable bowel syndrome (IBS-D) on the gut have been reported, but no study has reported the effects of the IBS-D gut microbiome on the liver. We transplanted the fecal microbiota from an IBS-D patient and from a healthy volunteer to GF rats. The hepatic inflammation, serum biochemical parameters and metabolome, fecal microbiota profile, fecal short-chain fatty acids (SCFAs), and correlations among them before and after berberine intervention were assessed. Compared with the healthy control fecal microbiome transplantation (FMT) rats, the fecal microbiota of IBS-D patients induces significant Kupffer cell hyperplasia, hepatic sinusoid hypertrophy, and elevated levels of hepatic tumor necrosis factor-α and interferon-γ and decreases the synthesis of ALB in GF rats. This is possibly related to Faecalibacterium and Bifidobacterium attributable to fecal formate, acetate, and propionate levels, which are associated with the host linoleic acid pathway. Berberine can partially reverse the Kupffer cell hyperplasia, Faecalibacterium, fecal formate, acetate, and propionate by modulating the gut microbiome composition. These results may imply that IBS-D not only is an intestinal functional disorder but can cause liver inflammation, thus providing some implications regarding the clinical cognition and treatment of IBS-D.}, }
@article {pmid31070838, year = {2019}, author = {Huang, HL and Chen, HT and Luo, QL and Xu, HM and He, J and Li, YQ and Zhou, YL and Yao, F and Nie, YQ and Zhou, YJ}, title = {Relief of irritable bowel syndrome by fecal microbiota transplantation is associated with changes in diversity and composition of the gut microbiota.}, journal = {Journal of digestive diseases}, volume = {}, number = {}, pages = {}, doi = {10.1111/1751-2980.12756}, pmid = {31070838}, issn = {1751-2980}, support = {20181A011007//Guangzhou General Science and Technology Project of Health and Family Planning/ ; 201707010275//Guangzhou Planned Project of Science and Technology/ ; 201904010132//Guangzhou Planned Project of Science and Technology/ ; 2018A030313676//Natural Science Foundation of Guangdong Province/ ; }, abstract = {OBJECTIVE: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for refractory irritable bowel syndrome (IBS).<br><br>METHODS: Microbiota suspensions from feces of the donors were injected into the intestines of 30 Chinese patients with refractory IBS. Microbiota composition analysis and genomic DNA extraction of fecal samples obtained from these patients at baseline and 1 month after FMT were performed. Clinical efficacy and safety of FMT were assessed using questionnaires covering four aspects of IBS therapeutic efficacy and assessment of adverse effects during a 6-month follow-up.<br><br>RESULTS: FMT improved IBS gastrointestinal symptoms and alleviated depression and anxiety, as shown by the improved IBS-QOL, IBS-SSS, GSRS, HAMA and HAMD scores at 1 month and 3 months after FMT. A total adverse event rate of FMT was 6.7% (2/30). Gut microbiota analysis revealed that FMT responders had a significantly higher Shannon diversity index before FMT than non-responders. In addition, analysis of differences in bacterial composition before and after FMT in responders showed specific abundance of the phyla Verrucomincrobia and Euryarchaeota at 1 month after FMT. At the genus level, Methanobrevibacter and Akkermansia were the most abundant fecal microbiota 1 month after FMT compared with those before FMT.<br><br>CONCLUSIONS: FMT may be an effective and safe therapeutic strategy for treating IBS that achieves a sustained clinical response 3-6 months after the first procedure. Changes in the diversity and dominant flora may contribute to its therapeutic effect.}, }
@article {pmid31068891, year = {2019}, author = {Xia, GH and You, C and Gao, XX and Zeng, XL and Zhu, JJ and Xu, KY and Tan, CH and Xu, RT and Wu, QH and Zhou, HW and He, Y and Yin, J}, title = {Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of Stroke.}, journal = {Frontiers in neurology}, volume = {10}, number = {}, pages = {397}, doi = {10.3389/fneur.2019.00397}, pmid = {31068891}, issn = {1664-2295}, abstract = {Background: Significant dysbiosis occurs in the gut microbiome of stroke patients. Condensing these broad, complex changes into one index would greatly facilitate the clinical usage of gut microbiome data. Here, we formulated a gut microbiota index in patients with acute ischemic stroke based on their gut microbiota dysbiosis patterns and tested whether the index was correlated with brain injury and early outcome. Methods: A total of 104 patients with acute ischemic stroke and 90 healthy individuals were recruited, and their gut microbiotas were compared and to model a Stroke Dysbiosis Index (SDI), which representing stroke-associated dysbiosis patterns overall. Another 83 patients and 70 controls were recruited for validation. The association of SDI with stroke severity (National Institutes of Health Stroke Scale [NIHSS] score) and outcome (modified Rankin scale [mRS] score: favorable, 0-2; unfavorable, >2) at discharge was also assessed. A middle cerebral artery occlusion (MCAO) model was used in human flora-associated (HFA) animals to explore the causal relationship between gut dysbiosis and stroke outcome. Results: Eighteen genera were significantly different between stroke patients and healthy individuals. The SDI formula was devised based on these microbiome differences; SDI was significantly higher in stroke patients than in healthy controls. SDI alone discriminated stroke patients from controls with AUCs of 74.9% in the training cohort and 84.3% in the validation cohort. SDI was significantly and positively correlated with NIHSS score on admission and mRS score at discharge. Logistic regression analysis showed that SDI was an independent predictor of severe stroke (NIHSS ≥8) and early unfavorable outcome (mRS >2). Mice receiving fecal transplants from high-SDI patients developed severe brain injury with elevated IL-17+ γδ T cells in gut compared to mice receiving transplants from low-SDI patients (all P < 0.05). Conclusions: We developed an index to measure gut microbiota dysbiosis in stroke patients; this index was significantly correlated with patients' outcome and was causally related to outcome in a mouse model of stroke. Our model facilitates the potential clinical application of gut microbiota data in stroke and adds quantitative evidence linking the gut microbiota to stroke.}, }
@article {pmid31066530, year = {2019}, author = {Gilbert, B and Schrenzel, J}, title = {[Fecal microbiota transplantation : current status and prospects].}, journal = {Revue medicale suisse}, volume = {15}, number = {650}, pages = {976-983}, pmid = {31066530}, issn = {1660-9379}, mesh = {*Clostridium Infections/therapy ; *Colitis, Ulcerative ; *Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Metabolic Diseases/therapy ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is approved as a safe and effective treatment of recurrent Clostridium difficile infections. The technique is now being studied for other indications, usually involving chronic inflammation, metabolic disorders, or autoimmunity, for which the gut microbiota appears to play a key role. We detail thereafter, according to their degree of evidence, the potential future indications, in which FMT has already been tried on Humans. Except for ulcerative colitis and metabolic syndrome, the methodology of the published trials is often insufficiently described and inhomogeneous. Further randomized placebo-controlled trials and standardization of practice will be needed to confirm these preliminary but encouraging results.}, }
@article {pmid31065565, year = {2019}, author = {Galloway-Peña, JR and Peterson, CB and Malik, F and Sahasrabhojane, PV and Shah, DP and Brumlow, CE and Carlin, LG and Chemaly, RF and Im, JS and Rondon, G and Felix, E and Veillon, L and Lorenzi, PL and Alousi, AM and Jenq, RR and Kontoyiannis, DP and Shpall, EJ and Shelburne, SA and Okhuysen, PC}, title = {Fecal Microbiome, Metabolites, and Stem Cell Transplant Outcomes: A Single-Center Pilot Study.}, journal = {Open forum infectious diseases}, volume = {6}, number = {5}, pages = {ofz173}, doi = {10.1093/ofid/ofz173}, pmid = {31065565}, issn = {2328-8957}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; S10 OD012304/OD/NIH HHS/United States ; }, abstract = {Background: Accumulating evidence suggests that the intestinal microbiome may dramatically affect the outcomes of hematopoietic stem cell transplant (HSCT) recipients. Providing 16S ribosomal RNA based microbiome characterization in a clinically actionable time frame is currently problematic. Thus, determination of microbial metabolites as surrogates for microbiome composition could offer practical biomarkers.<br><br>Methods: Longitudinal fecal specimens (n = 451) were collected from 44 patients before HSCT through 100 days after transplantation, as well as 1-time samples from healthy volunteers (n = 18) as controls. Microbiota composition was determined using 16S ribosomal RNA V4 sequencing. Fecal indole and butyrate levels were determined using liquid chromatography tandem mass spectrometry.<br><br>Results: Among HSCT recipients, both fecal indole and butyrate levels correlated with the Shannon diversity index at baseline (P = .02 and P = .002, respectively) and directly after transplantation (P = .006 and P < .001, respectively). Samples with high butyrate levels were enriched for Clostridiales, whereas samples containing high indole were also enriched for Bacteroidales. A lower Shannon diversity index at the time of engraftment was associated with increased incidence of acute intestinal graft-vs-host disease (iGVHD) (P = .02) and transplant-related deaths (P = .03). Although fecal metabolites were not associated with acute iGVHD or overall survival, patients contracting bloodstream infections within 30 days after transplantation had significantly lower levels of fecal butyrate (P = .03).<br><br>Conclusions: Longitudinal analysis of fecal microbiome and metabolites after HSCT identified butyrate and indole as potential surrogate markers for microbial diversity and specific taxa. Further studies are needed to ascertain whether fecal metabolites can be used as biomarkers of acute iGVHD or bacteremia after HSCT.}, }
@article {pmid31064848, year = {2019}, author = {Buchta Rosean, C and Bostic, RR and Ferey, JCM and Feng, TY and Azar, FN and Tung, KS and Dozmorov, MG and Smirnova, E and Bos, PD and Rutkowski, MR}, title = {Preexisting Commensal Dysbiosis Is a Host-Intrinsic Regulator of Tissue Inflammation and Tumor Cell Dissemination in Hormone Receptor-Positive Breast Cancer.}, journal = {Cancer research}, volume = {79}, number = {14}, pages = {3662-3675}, doi = {10.1158/0008-5472.CAN-18-3464}, pmid = {31064848}, issn = {1538-7445}, abstract = {It is unknown why some patients with hormone receptor-positive (HR+) breast cancer present with more aggressive and invasive disease. Metastatic dissemination occurs early in disease and is facilitated by cross-talk between the tumor and tissue environment, suggesting that undefined host-intrinsic factors enhance early dissemination and the probability of developing metastatic disease. Here, we have identified commensal dysbiosis as a host-intrinsic factor associated with metastatic dissemination. Using a mouse model of HR+ mammary cancer, we demonstrate that a preestablished disruption of commensal homeostasis results in enhanced circulating tumor cells and subsequent dissemination to the tumor-draining lymph nodes and lungs. Commensal dysbiosis promoted early inflammation within the mammary gland that was sustained during HR+ mammary tumor progression. Furthermore, dysbiosis enhanced fibrosis and collagen deposition both systemically and locally within the tumor microenvironment and induced significant myeloid infiltration into the mammary gland and breast tumor. These effects were recapitulated both by directly targeting gut microbes using nonabsorbable antibiotics and by fecal microbiota transplantation of dysbiotic cecal contents, demonstrating the direct impact of gut dysbiosis on mammary tumor dissemination. This study identifies dysbiosis as a preexisting, host-intrinsic regulator of tissue inflammation, myeloid recruitment, fibrosis, and dissemination of tumor cells in HR+ breast cancer. SIGNIFICANCE: Identification of commensal dysbiosis as a host-intrinsic factor mediating evolution of metastatic breast cancer allows for development of interventions or diagnostic tools for patients at highest risk for developing metastatic disease.See related commentary by Ingman, p. 3539.}, }
@article {pmid31059962, year = {2019}, author = {Zhang, F and Zhang, T and Zhu, H and Borody, TJ}, title = {Evolution of fecal microbiota transplantation in methodology and ethical issues.}, journal = {Current opinion in pharmacology}, volume = {49}, number = {}, pages = {11-16}, doi = {10.1016/j.coph.2019.04.004}, pmid = {31059962}, issn = {1471-4973}, abstract = {Fecal microbiota transplantation (FMT), the core therapy for remodeling the gut microbiota with a long medical history, has gained great attention worldwide in recent years. Increasing studies have explored its indications, methodology, efficacy, safety, and ethics. Purified forms of FMT, using an automated method for the purification of fecal microbiota from stool, has become a reality. Colonic transendoscopic enteral tubing makes frequent FMT delivery into the whole colon feasible. This review focuses on the recent progress in laboratory preparation, updated clinical strategies, novel delivery methods, and ethical issues surrounding FMT in clinical studies.}, }
@article {pmid31057522, year = {2019}, author = {Fiedorová, K and Radvanský, M and Němcová, E and Grombiříková, H and Bosák, J and Černochová, M and Lexa, M and Šmajs, D and Freiberger, T}, title = {The Impact of DNA Extraction Methods on Stool Bacterial and Fungal Microbiota Community Recovery.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {821}, doi = {10.3389/fmicb.2019.00821}, pmid = {31057522}, issn = {1664-302X}, abstract = {Our understanding of human gut microbiota in health and disease depends on accurate and reproducible microbial data acquisition. The critical step in this process is to apply an appropriate methodology to extract microbial DNA, since biases introduced during the DNA extraction process may result in inaccurate microbial representation. In this study, we attempted to find a DNA extraction protocol which could be effectively used to analyze both the bacterial and fungal community. We evaluated the effect of five DNA extraction methods (QIAamp DNA Stool Mini Kit, PureLinkTM Microbiome DNA Purification Kit, ZR Fecal DNA MiniPrepTM Kit, NucleoSpin® DNA Stool Kit, and IHMS protocol Q) on bacterial and fungal gut microbiome recovery using (i) a defined system of germ-free mice feces spiked with bacterial or fungal strains, and (ii) non-spiked human feces. In our experimental setup, we confirmed that the examined methods significantly differed in efficiency and quality, which affected the identified stool microbiome composition. In addition, our results indicated that fungal DNA extraction might be prone to be affected by reagent/kit contamination, and thus an appropriate blank control should be included in mycobiome research. Overall, standardized IHMS protocol Q, recommended by the International Human Microbiome Consortium, performed the best when considering all the parameters analyzed, and thus could be applied not only in bacterial, but also in fungal microbiome research.}, }
@article {pmid31055584, year = {2019}, author = {Lynch, SM and Mu, J and Grady, JJ and Stevens, RG and Devers, TJ}, title = {Fecal Microbiota Transplantation for Clostridium difficile Infection: A One-Center Experience.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {}, number = {}, pages = {1-6}, doi = {10.1159/000499873}, pmid = {31055584}, issn = {1421-9875}, abstract = {BACKGROUND: Clostridium difficile is a gram-positive, anaerobic, and spore-forming bacillus, which is responsible for the majority of antibiotic-associated diarrhea and colitis.<br><br>OBJECTIVE: Determine if fecal microbiota transplantation (FMT) is effective in a population sample from Connecticut.<br><br>METHODS: We report the clinical experience of 92 consecutive patients from one gastroenterology practice in central Connecticut treated by colonoscopy with FMT for infection with Clostridium difficile from 2012 to 2017. The analyses are based on clinical follow-up up to 3 months after the FMT procedure and on medical chart review.<br><br>RESULTS: Overall, complete recovery occurred in 86% of patients. As previously reported in a limited number of previous studies, community-acquired cases were more common than hospital-acquired cases, and community-acquired cases were more likely to be female.<br><br>CONCLUSIONS: Consistent with some previous reports, we found the following: the source of the donor for FMT did not make a difference in recovery: material from nonrelatives was as effective as from close relatives; and the presence of multiple comorbidities did not make a difference in recovery: patients with 2 or more comorbidities did as well as those with one or none.}, }
@article {pmid31054313, year = {2019}, author = {Khanna, S and Gerding, DN}, title = {Current and future trends in clostridioides (clostridium) difficile infection management.}, journal = {Anaerobe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.anaerobe.2019.04.010}, pmid = {31054313}, issn = {1095-8274}, abstract = {Current and future management of Clostridioides difficile infection (CDI) including antibiotic treatment is increasingly focused on preventive strategies, either prevention of recurrent CDI (rCDI) or primary prevention of CDI. In addition to newer narrow spectrum antibiotics and pulse dosing of antibiotic treatment, multiple widely differing approaches to prevention of CDI and rCDI are under clinical development or recently approved for clinical use. They include immunologics, both passive monoclonal antibodies and active vaccines targeted at C. difficile toxins, approaches to reduce antibiotic dysbiosis in the gut, microbiome restoration using fecal microbiome transplants (FMT) or biotherapeutic bacterial derivatives, and substitution of non-toxigenic C. difficile (NTCD) for toxigenic C. difficile. Newer antibiotics, monoclonal antibodies, and FMT are targeted at reducing rCDI whereas vaccines and reduction of antibiotic dysbiosis in the gut are targeted at prevention of primary CDI. Biotherapeutics may be used for prevention of either primary CDI or rCDI. Approaches such as monoclonal antibodies, FMT, and biotherapeutics provide rapid but transient preventive benefits, whereas vaccines require weeks to months to be effective, but will presumably provide long term prevention. More rapid but transient prevention strategies such as FMT and biotherapeutics could be used in combination with vaccines to provide both rapid and durable CDI prevention.}, }
@article {pmid31049232, year = {2019}, author = {Zhang, J and Ren, G and Li, M and Lu, P and Yi, S}, title = {The Effects of Fecal Donors with Different Feeding Patterns on Diarrhea in a Patient Undergoing Hematopoietic Stem Cell Transplantation.}, journal = {Case reports in hematology}, volume = {2019}, number = {}, pages = {4505238}, doi = {10.1155/2019/4505238}, pmid = {31049232}, issn = {2090-6560}, abstract = {Almost 90% of patients undergoing hematopoietic stem cell transplantation (HSCT) experience diarrheal episodes, which represent a severe, often life-threatening complication for these patients. Although fecal microbiota transplantation (FMT) represents an alternative treatment option for infection-related diarrhea, the application of FMT in HSCT patients is greatly restricted for safety reasons. Furthermore, the therapeutic outcomes of FMT as a diarrhea treatment are somewhat related to the choice of the FMT donor. Here, we comprehensively profiled the dynamic changes in the intestinal microbiota after FMT from two donors with different feeding patterns and the same severely diarrheal recipient undergoing HSCT via a 45-day clinical observation. Importantly, no adverse events attributed to FMT were observed. The stool volume and frequency of the patient were reduced when we used feces from donor #1 (mixed feeding), but these changes were not observed after FMT from donor #2 (exclusive breastfeeding). Interestingly, no obvious differences in overall diversity (Shannon) or richness (Chao1) between the two donors were observed. Additionally, Bifidobacterium accounted for 29.9% and 18.1% of OTUs in the stools of donors #1 and #2, respectively. Lactobacillus accounted for 16.3% and 2.9% of the stools of donors #1 and #2, respectively. Furthermore, through longitudinal monitoring of the patient, we identified 6 OTUs that were particularly sensitive to the different FMT complements. Together, we present a case report suggesting that the overall diversity of the intestinal microbiota may not be the only important element in the selection of an effective FMT donor.}, }
@article {pmid31046972, year = {2019}, author = {Lavelle, A and Hill, C}, title = {Gut Microbiome in Health and Disease: Emerging Diagnostic Opportunities.}, journal = {Gastroenterology clinics of North America}, volume = {48}, number = {2}, pages = {221-235}, doi = {10.1016/j.gtc.2019.02.003}, pmid = {31046972}, issn = {1558-1942}, abstract = {The gut microbiome is fundamental to human health and development. Altered microbiomes have been associated with many diseases. However, variation between individuals, environmental effects, and a lack of standardization across studies makes differentiation between health and disease challenging. Large-scale population cohorts in different countries will be required to match disease subjects with healthy controls, whereas standardized, reproducible pipelines for analysis are required to compare findings between studies. Despite this, several conditions have already demonstrated great promise for developing microbiome-based biomarkers as well as providing a gateway into integrated personalized medicine.}, }
@article {pmid31037552, year = {2019}, author = {Vujkovic-Cvijin, I and Somsouk, M}, title = {HIV and the Gut Microbiota: Composition, Consequences, and Avenues for Amelioration.}, journal = {Current HIV/AIDS reports}, volume = {16}, number = {3}, pages = {204-213}, doi = {10.1007/s11904-019-00441-w}, pmid = {31037552}, issn = {1548-3576}, support = {Z99 AI999999/NULL/Intramural NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: We discuss recent advances in understanding of gut bacterial microbiota composition in HIV-infected subjects and comment on controversies. We discuss the putative effects of microbiota shifts on systemic inflammation and HIV disease progression and potential mechanisms, as well as ongoing strategies being developed to modulate the gut microbiota in humans for amelioration of infectious and inflammatory diseases.<br><br>RECENT FINDINGS: Lifestyle and behavioral factors relevant to HIV infection studies have independent effects on the microbiota. Microbial metabolism of immunomodulatory compounds and direct immune stimulation by translocation of microbes are putative mechanisms contributing to HIV disease. Fecal microbiota transplantation, microbial enzyme inhibition, phage therapy, and rationally selected probiotic cocktails have emerged as promising strategies for microbiota modulation. Numerous surveys of the HIV gut microbiota matched for lifestyle factors suggest consistent shifts in gut microbiota composition among HIV-infected subjects. Evidence exists for a complex pathogenic role of the gut microbiota in HIV disease progression, warranting further study.}, }
@article {pmid31019401, year = {2019}, author = {Campbell, CT and Poisson, MO and Hand, EO}, title = {An Updated Review of Clostridium difficile Treatment in Pediatrics.}, journal = {The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG}, volume = {24}, number = {2}, pages = {90-98}, doi = {10.5863/1551-6776-24.2.90}, pmid = {31019401}, issn = {1551-6776}, abstract = {Clostridium difficile infection (CDI) continues to have clinical and economic impact across all health care settings. Pediatrics accounts for a small percentage of worldwide infection; however, screening and diagnosis are confounded by asymptomatic colonization in young infants. Metronidazole and oral vancomycin have historically been the agents used to manage CDI in both pediatrics and adults. Newer agents and alternative therapies, such as fecal microbiota transplantation, may offer additional benefit. Recent guidelines updates from the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America separate pediatric and adult recommendations for epidemiology, diagnosis, and treatment. This review will discuss the risk factors, management, prevention, and updated guideline recommendations for CDI in the pediatric population.}, }
@article {pmid31017741, year = {2019}, author = {Hsu, WH and Wang, JY and Kuo, CH}, title = {Current applications of fecal microbiota transplantation in intestinal disorders.}, journal = {The Kaohsiung journal of medical sciences}, volume = {35}, number = {6}, pages = {327-331}, doi = {10.1002/kjm2.12069}, pmid = {31017741}, issn = {2410-8650}, support = {KMUH103-3M02//Kaohsiung Medical University Hospital, Taiwan/ ; MOHW107-TDU-B-212-113006//Ministry of Health and Welfare/ ; MOST108-2321-B-037-001//Ministry of Science and Technology/ ; }, abstract = {Fecal microbiota transplantation (FMT) had been an ancient remedy for severe illness several centuries ago. Under modern medical analysis and evidence-based research, it has been proved as an alternative treatment for recurrent Clostridium difficile infection and recent randomized control study also showed that FMT could be an adjuvant treatment for inflammatory bowel disease. As we get a better understanding of the relationship between gut microbiota and systemic disease, FMT became a potential treatment to explore. This article summarized procedures such as donor selection, fecal material preparation, transplantation delivery methods, and adverse events. We also review the present evidence about FMT in clinical practice.}, }
@article {pmid31009795, year = {2019}, author = {Nicholson, MR and Mitchell, PD and Alexander, E and Ballal, S and Bartlett, M and Becker, P and Davidovics, Z and Docktor, M and Dole, M and Felix, G and Gisser, J and Hourigan, SK and Jensen, MK and Kaplan, JL and Kelsen, J and Kennedy, M and Khanna, S and Knackstedt, E and Leier, M and Lewis, J and Lodarek, A and Michail, S and Oliva-Hemker, M and Patton, T and Queliza, K and Russell, GH and Singh, N and Solomon, A and Suskind, DL and Werlin, S and Kellermayer, R and Kahn, SA}, title = {Efficacy of Fecal Microbiota Transplantation for Clostridium difficile Infection in Children.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2019.04.037}, pmid = {31009795}, issn = {1542-7714}, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI.<br><br>METHODS: We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMTs at 18 pediatric centers, from February 1, 2004, to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT.<br><br>RESULTS: Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39-5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26-4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05-4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04-1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations.<br><br>CONCLUSIONS: Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients-factors associated with success differ from those of adult patients.}, }
@article {pmid31005136, year = {2019}, author = {Misch, EA and Safdar, N}, title = {Clostridioides difficile Infection in the Stem Cell Transplant and Hematologic Malignancy Population.}, journal = {Infectious disease clinics of North America}, volume = {33}, number = {2}, pages = {447-466}, doi = {10.1016/j.idc.2019.02.010}, pmid = {31005136}, issn = {1557-9824}, abstract = {Clostridioides difficile infection (CDI) is common in the stem cell transplant (SCT) and hematologic malignancy (HM) population and mostly occurs in the early posttransplant period. Treatment of CDI in SCT/HM is the same as for the general population, with the exception that fecal microbiota transplant (FMT) has not been widely adopted because of safety concerns. Several case reports, small series, and retrospective studies have shown that FMT is effective and safe. A randomized controlled trial of FMT for prophylaxis of CDI in SCT patients is underway. In addition, an abundance of novel therapeutics for CDI is currently in development.}, }
@article {pmid31004524, year = {2019}, author = {Xie, Y and Matsumoto, H and Kennedy, S and Newberry, EP and Moritz, W and DeBosch, BJ and Moley, KH and Rubin, DC and Warner, BW and Kau, AL and Tarr, PI and Wylie, TN and Wylie, KM and Davidson, NO}, title = {Impaired Chylomicron Assembly Modifies Hepatic Metabolism Through Bile Acid-Dependent and Transmissible Microbial Adaptations.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/hep.30669}, pmid = {31004524}, issn = {1527-3350}, support = {P30 DK-56341//National Institute of Diabetes and Digestive and Kidney Diseases/ ; P30 DK-020579//National Institute of Diabetes and Digestive and Kidney Diseases/ ; DK-56260//National Institute of Diabetes and Digestive and Kidney Diseases/ ; //Robert Wood Johnson Foundation/ ; DK-112378//National Institute of Diabetes and Digestive and Kidney Diseases/ ; HD-083895//National Institute of Child Health and Human Development/ ; KO8-AI 113184//National Institute of Allergy and Infectious Diseases/ ; DK-106382//National Institute of Diabetes and Digestive and Kidney Diseases/ ; P30 DK-52574//National Institute of Diabetes and Digestive and Kidney Diseases/ ; Gilead AGA Research Scholar Award//American Gastroenterological Association/ ; HL-38180//National Heart, Lung, and Blood Institute/ ; //Manpei Suzuki Diabetes Foundation/ ; K08 AI113184/AI/NIAID NIH HHS/United States ; HD-065435//National Institute of Child Health and Human Development/ ; }, abstract = {The mechanisms by which alterations in intestinal bile acid (BA) metabolism improve systemic glucose tolerance and hepatic metabolic homeostasis are incompletely understood. We examined metabolic adaptations in mice with conditional intestinal deletion of the abetalipoproteinemia (ABL) gene microsomal triglyceride transfer protein (Mttp-IKO), which blocks chylomicron assembly and impairs intestinal lipid transport. Mttp-IKO mice exhibit improved hepatic glucose metabolism and augmented insulin signaling, without weight loss. These adaptations included decreased BA excretion, increased pool size, altered BA composition, and increased fibroblast growth factor 15 production. Mttp-IKO mice absorb fructose normally but are protected against dietary fructose-induced hepatic steatosis, without weight loss or changes in energy expenditure. In addition, Mttp-IKO mice exhibit altered cecal microbial communities, both at baseline and following fructose feeding, including increased abundance of Bacteroides and Lactobacillus genera. Transplantation of cecal microbiota from chow-fed Mttp-IKO mice into antibiotic-treated wild-type recipients conferred transmissible protection against fructose-induced hepatic steatosis in association with a bloom in Akkermansia and increased Clostridium XIVa genera, whose abundance was positively correlated with fecal coprostanol and total neutral sterol excretion in recipient mice. However, antibiotic-treated Mttp-IKO mice were still protected against fructose-induced hepatic steatosis, suggesting that changes in microbiota are not required for this phenotype. Nevertheless, we found increased abundance of fecal Akkermansia from two adult ABL subjects with MTTP mutations compared to their heterozygous parents and within the range noted in six healthy control subjects. Furthermore, Akkermansia abundance across all subjects was positively correlated with fecal coprostanol excretion. Conclusion: The findings collectively suggest multiple adaptive pathways of metabolic regulation following blocked chylomicron assembly, including shifts in BA signaling and altered microbial composition that confer a transmissible phenotype.}, }
@article {pmid30999462, year = {2019}, author = {Jones, EW and Carlson, JM}, title = {Steady-state reduction of generalized Lotka-Volterra systems in the microbiome.}, journal = {Physical review. E}, volume = {99}, number = {3-1}, pages = {032403}, doi = {10.1103/PhysRevE.99.032403}, pmid = {30999462}, issn = {2470-0053}, mesh = {Algorithms ; Animals ; Anti-Bacterial Agents/adverse effects ; Clostridium Infections/etiology/microbiology/therapy ; Clostridium difficile ; Computer Simulation ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Humans ; Mice ; *Models, Biological ; Population Dynamics ; }, abstract = {The generalized Lotka-Volterra (gLV) equations, a classic model from theoretical ecology, describe the population dynamics of a set of interacting species. As the number of species in these systems grow in number, their dynamics become increasingly complex and intractable. We introduce steady-state reduction (SSR), a method that reduces a gLV system of many ecological species into two-dimensional subsystems that each obey gLV dynamics and whose basis vectors are steady states of the high-dimensional model. We apply this method to an experimentally-derived model of the gut microbiome in order to observe the transition between &quot;healthy&quot; and &quot;diseased&quot; microbial states. Specifically, we use SSR to investigate how fecal microbiota transplantation, a promising clinical treatment for dysbiosis, can revert a diseased microbial state to health.}, }
@article {pmid30997086, year = {2019}, author = {Nishida, A and Imaeda, H and Inatomi, O and Bamba, S and Sugimoto, M and Andoh, A}, title = {The efficacy of fecal microbiota transplantation for patients with chronic pouchitis: A case series.}, journal = {Clinical case reports}, volume = {7}, number = {4}, pages = {782-788}, doi = {10.1002/ccr3.2096}, pmid = {30997086}, issn = {2050-0904}, abstract = {Pouchitis is one of the most common complications that develop after restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. Single fecal microbiota transplantation (FMT) by colonoscopy was performed safely on three patients with pouchitis. However, the efficacy of FMT on pouchitis was limited.}, }
@article {pmid30987771, year = {2019}, author = {Abreu Y Abreu, AT and Velarde-Ruiz Velasco, JA and Zavala-Solares, MR and Remes-Troche, JM and Carmona-Sánchez, RI and Aldana-Ledesma, JM and Camacho-Ortiz, A and Contreras-Omaña, R and Díaz-Seoane, R and Elizondo-Vázquez, CT and Garza-González, E and Grajales-Figueroa, G and Gómez-Escudero, O and Jacobo-Karam, JS and Morales-Arámbula, M and Olivares-Guzmán, LO and Sifuentes-Osornio, J and Siu-Moguel, AG and Soto-Solís, R and Valdovinos-García, LR and Valdovinos-Díaz, MA and Vázquez-Elizondo, G and Lazo-de la Vega Jasso, SA}, title = {Consensus on the prevention, diagnosis, and treatment of Clostridium difficile infection.}, journal = {Revista de gastroenterologia de Mexico}, volume = {84}, number = {2}, pages = {204-219}, doi = {10.1016/j.rgmx.2018.12.001}, pmid = {30987771}, issn = {0375-0906}, abstract = {In recent decades, Clostridium difficile infection (CDI) has become a worldwide health problem. Mexico is no exception, and therefore the Asociación Mexicana de Gastroenterología brought together a multidisciplinary group (gastroenterologists, endoscopists, internists, infectious disease specialists, and microbiologists) to carry out the &quot;Consensus on the prevention, diagnosis, and treatment of Clostridium difficile infection&quot;, establishing useful recommendations (in relation to the adult population) for the medical community. Said recommendations are presented herein. Among them, it was recognized that CDI should be suspected in subjects with diarrhea that have a history of antibiotic and/or immunosuppressant use, but that it can also be a community-acquired infection. A 2-step diagnostic algorithm was proposed, in which a highly sensitive test, such as glutamate dehydrogenase (GDH), is first utilized, and if positive, confirmed by the detection of toxins through immunoassay or nucleic acid detection tests. Another recommendation was that CDI based on clinical evaluation be categorized as mild-moderate, severe, and complicated severe, given that such a classification enables better therapeutic decisions to be made. In mild-moderate CDI, oral vancomycin is the medication of choice, and metronidazole is recommended as an alternative treatment. In addition, fecal microbiota transplantation was recognized as an efficacious option in patients with recurrence or in the more severe cases of infection, and surgery should be reserved for patients with severe colitis (toxic megacolon), in whom all medical treatment has failed.}, }
@article {pmid30986885, year = {2019}, author = {Stallmach, A and Grunert, P and Pieper, D and Steube, A}, title = {[Ulcerative colitis: Does the modulation of gut microbiota induce long-lasting remission?].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {57}, number = {7}, pages = {834-842}, doi = {10.1055/a-0874-6603}, pmid = {30986885}, issn = {1439-7803}, abstract = {Although the pathogenesis of ulcerative colitis (UC) remains elusive, substantial progress in understanding its development and progression has been achieved in the past decades, and novel effective treatment strategies have been developed. Changes in gut microbiota, environmental triggers, deregulation of immunological responses, and genetic predisposition have been identified as pathogenic key factors. There are several lines of clinical observations, which support a close connection of altered gut microbiota with the development and course of UC. Despite a plethora of microbiota alterations in UC, it is currently unclear whether the observed changes in inflammation are cause or effect of the altered microbiota state.Fecal microbiota transplantation (FMT) provides a novel, perhaps complementary, strategy to restore gut microbial diversity, bacterial richness, and microbial homeostasis in UC. FMT is an already established treatment option for recurrent Clostridioides difficile infection, and several case series and randomized controlled trials have described its use in UC. In this review, we evaluate recent efficacy and safety data on FMT for UC, discuss possible pitfalls and show possible areas of future development. Although FMT could become a promising treatment modality for UC, based on currently available data, FMT should be only performed in clinical trials as controlled studies focusing on long-term outcomes and safety are warranted.}, }
@article {pmid30977692, year = {2019}, author = {Belga, S and Chiang, D and Kabbani, D and Abraldes, JG and Cervera, C}, title = {The direct and indirect effects of vancomycin-resistant enterococci colonization in liver transplant candidates and recipients.}, journal = {Expert review of anti-infective therapy}, volume = {17}, number = {5}, pages = {363-373}, doi = {10.1080/14787210.2019.1607297}, pmid = {30977692}, issn = {1744-8336}, abstract = {Introduction: Vancomycin-resistant enterococci (VRE) colonization and subsequent infection results in increased morbidity, mortality and use of health-care resources. The burden of VRE colonization in liver transplant candidates and recipients is significant. VRE colonization is a marker of gut dysbiosis and its impact on the microbiota-liver axis, may negatively affect graft function and result in negative outcomes pre- and post-transplantation. Areas covered: In this article we describe the epidemiology of VRE colonization, risk factors for VRE infection, health-care costs associated with VRE, with a focus on the impact of VRE colonization on liver transplant recipients' fecal microbiota, the therapeutic strategies for VRE decolonization and proposed pathophysiologic mechanisms of VRE colonization in liver transplant recipients. Expert opinion: VRE colonization results in a significant loss of bacterial microbiome diversity. This may have metabolic consequences, with low production of short-chain fatty acids which may, in turn, result in immune dysregulation. As antibiotics have failed to decolonize the gut, alternative strategies such as fecal microbiota transplantation (FMT), stimulation of intestinal antimicrobial peptides and phage therapy warrants future studies.}, }
@article {pmid30972640, year = {2019}, author = {Ding, X and Li, Q and Li, P and Zhang, T and Cui, B and Ji, G and Lu, X and Zhang, F}, title = {Long-Term Safety and Efficacy of Fecal Microbiota Transplant in Active Ulcerative Colitis.}, journal = {Drug safety}, volume = {42}, number = {7}, pages = {869-880}, doi = {10.1007/s40264-019-00809-2}, pmid = {30972640}, issn = {1179-1942}, support = {81600417//National Natural Science Foundation of China/ ; 81670495//National Natural Science Foundation of China/ ; LGY2017080//Top-notch Talent Research Projects/ ; 201502026//Project of National Health and Family Planning Commission/ ; 2015BAI13B07//National Clinical Research Center for Digestive Diseases, Xi'an, China/ ; }, abstract = {INTRODUCTION AND OBJECTIVE: The therapeutic role of fecal microbiota transplantation in ulcerative colitis varies across different reports. This study aims to evaluate the long-term safety and efficacy of a strategy called step-up fecal microbiota transplantation for ulcerative colitis.<br><br>METHODS: Two clinical trials (NCT01790061, NCT02560727) for moderate-to-severe ulcerative colitis (Mayo score range 6-12) were performed from November 2012 to July 2017. Both studies were pooled for analysis on the safety and efficacy of fecal microbiota transplantation in patients with ulcerative colitis over a 1-year follow-up. The step-up fecal microbiota transplantation strategy included step 1: single fecal microbiota transplantation; step 2: two or more fecal microbiota transplantations; and step 3: fecal microbiota transplantations followed by immunosuppressants. Long-term clinical efficacy and adverse events were assessed, and multiple factors related to fecal microbiota transplantation were evaluated.<br><br>RESULTS: Of 134 eligible patients in this real-word study, 81.3% (109/134) were included for analysis. The follow-up ranged from 1 to 5 years. Fecal microbiota transplantation-related adverse events were observed in 17.4% (43/247) of fecal microbiota transplantation procedures including one serious adverse event (myasthenia gravis) and 56 non-serious adverse events. Multivariable logistic regression analysis showed that both the method of preparation of microbiota from stool using the automatic system and the delivery method of colonic transendoscopic enteral tubing were associated with a lower rate of fecal microbiota transplantation-related adverse events (p = 0.023, p = 0.017, respectively). In total, 74.3% (81/109) and 51.4% (56/109) of patients achieved clinical response at 1 month and 3 months after step-up fecal microbiota transplantation, respectively.<br><br>CONCLUSIONS: Fecal microbiota transplantation should be a safe and promising therapy for ulcerative colitis. The improved fecal microbiota preparation and colonic transendoscopic enteral tubing might reduce the rate of adverse events in ulcerative colitis.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT01790061, NCT02560727.}, }
@article {pmid30969490, year = {2019}, author = {Galperine, TK and Guery, B}, title = {[Customised infectiology - Fecal microbiota transplantation : following the Clostridioides difficile pathway].}, journal = {Revue medicale suisse}, volume = {15}, number = {646}, pages = {776-779}, pmid = {30969490}, issn = {1660-9379}, mesh = {*Clostridium Infections/therapy ; *Clostridium difficile ; *Fecal Microbiota Transplantation ; Humans ; Switzerland ; }, abstract = {Fecal microbiota transplantation (FMT) raised, in the recent years, a growing interest, mostly in Clostridioides difficile infections (CDI). The concept of FMT is quite simple based on the administration of fecal matter from a healthy donor to a patient with a disease related to the gut microbiota imbalance (dysbiosis). Although the theory seems straightforward, the fine mechanisms are multiple and not yet completely understood. In Switzerland, FMT is considered as a drug under the pharmacist responsibility. The only official indication for FMT is multi-recurrent CDI. For practical reasons, most of the FMT are performed with fresh stools, but development of frozen forms and capsules should considerably enhance treatment delivery. Other indications are currently investigated but not yet in the clinical routine.}, }
@article {pmid30969003, year = {2019}, author = {Alukal, J and Dutta, SK and Surapaneni, BK and Le, M and Tabbaa, O and Phillips, L and Mattar, MC}, title = {Safety and efficacy of fecal microbiota transplant in 9 critically ill patients with severe and complicated Clostridium difficile infection with impending colectomy.}, journal = {Journal of digestive diseases}, volume = {20}, number = {6}, pages = {301-307}, doi = {10.1111/1751-2980.12750}, pmid = {30969003}, issn = {1751-2980}, abstract = {OBJECTIVE: Significant data support the efficacy and safety of fecal microbiota transplant (FMT) in recurrent Clostridium difficile infection (CDI). The objective of our study was to determine the success rate of FMT in patients diagnosed with severe and complicated CDI with impending colectomy in the intensive care setting.<br><br>METHODS: This was a 2-center study of 9 patients who met the criteria for severe and complicated CDI and had an impending colectomy. All 9 patients had failed conventional antibiotic therapy and were deemed too unstable to undergo a colectomy. Hence, FMT was considered to be the next step in managing their condition.<br><br>RESULTS: Following FMT there was marked improvement in the patients' clinical status, with the resolution of diarrhea, reduced requirement for vasopressor, and the reduction in abdominal distention and pain. The primary cure rate of our study after a single round of FMT was 78% (7/9). Of the 9 patients 8 (88.88%) avoided a colectomy during the same hospital admission. the CDI-related death rate was 12.5% (1/9) and that of non-CDI was 12.5% (1/9).<br><br>CONCLUSION: Our success with FMT in fulminant CDI shows that this therapeutic modality is a promising alternative to a colectomy and could be a potential bowel-saving intervention.}, }
@article {pmid30967971, year = {2019}, author = {Mrazek, K and Bereswill, S and Heimesaat, MM}, title = {Fecal Microbiota Transplantation Decreases Intestinal Loads of Multi-Drug Resistant Pseudomonas aeruginosa in Murine Carriers.}, journal = {European journal of microbiology &amp; immunology}, volume = {9}, number = {1}, pages = {14-22}, doi = {10.1556/1886.2019.00002}, pmid = {30967971}, issn = {2062-509X}, abstract = {Intestinal carriage of multi-drug resistant (MDR) Gram-negative bacteria including Pseudomonas aeruginosa (Psae) constitutes a pivotal prerequisite for subsequent fatal endogenous infections in patients at risk. We here addressed whether fecal microbiota transplantation (FMT) could effectively combat MDR-Psae carriage. Therefore, secondary abiotic mice were challenged with MDR-Psae by gavage. One week later, mice were subjected to peroral FMT from either murine or human donors on 3 consecutive days. Irrespective of murine or human origin of fecal transplant, intestinal MDR-Psae loads decreased as early as 24 h after the initial FMT. Remarkably, the murine FMT could lower intestinal MDR-Psae burdens by approximately 4 log orders of magnitude within 1 week. In another intervention study, mice harboring a human gut microbiota were perorally challenged with MDR-Psae and subjected to murine FMT on 3 consecutive days, 1 week later. Strikingly, within 5 days, murine FMT resulted in lower loads and carrier rates of MDR-Psae in mice with a human gut microbiota. In conclusion, FMT might be a promising antibiotics-independent option to combat intestinal MDR-Psae carriage and thus prevent from future endogenous infections of patients at risk.}, }
@article {pmid30967875, year = {2019}, author = {Bereswill, S and Escher, U and Grunau, A and Kühl, AA and Dunay, IR and Tamas, A and Reglodi, D and Heimesaat, MM}, title = {Pituitary Adenylate Cyclase-Activating Polypeptide-A Neuropeptide as Novel Treatment Option for Subacute Ileitis in Mice Harboring a Human Gut Microbiota.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {554}, doi = {10.3389/fimmu.2019.00554}, pmid = {30967875}, issn = {1664-3224}, abstract = {The neuropeptide Pituitary adenylate cyclase-activating polypeptide (PACAP) is well-known for its important functions in immunity and inflammation. Data regarding anti-inflammatory properties of PACAP in the intestinal tract are limited, however. In our present preclinical intervention study we addressed whether PACAP treatment could alleviate experimental subacute ileitis mimicking human gut microbiota conditions. Therefore, secondary abioitic mice were subjected to human fecal microbiota transplantation (FMT) and perorally infected with low-dose Toxoplasma gondii to induce subacute ileitis on day 0. From day 3 until day 8 post-infection, mice were either treated with synthetic PACAP38 or placebo. At day 9 post-infection, placebo, but not PACAP treated mice exhibited overt macroscopic sequelae of intestinal immunopathology. PACAP treatment further resulted in less distinct apoptotic responses in ileal and colonic epithelia that were accompanied by lower T cell numbers in the mucosa and lamina propria and less secretion of pro-inflammatory cytokines in intestinal ex vivo biopsies. Notably, ileitis-associated gut microbiota shifts were less distinct in PACAP as compared to placebo treated mice. Inflammation-ameliorating effects of PACAP were not restricted to the intestines, but could also be observed in extra-intestinal including systemic compartments as indicated by lower apoptotic cell counts and less pro-inflammatory cytokine secretion in liver and lungs taken from PACAP treated as compared to placebo control mice, which also held true for markedly lower serum TNF and IL-6 concentrations in the former as compared to the latter. Our preclinical intervention study provides strong evidence that synthetic PACAP alleviates subacute ileitis and extra-intestinal including systemic sequelae of T cell-driven immunopathology. These findings further support PACAP as a novel treatment option for intestinal inflammation including inflammatory bowel diseases (IBD).}, }
@article {pmid30967657, year = {2019}, author = {Kang, DW and Adams, JB and Coleman, DM and Pollard, EL and Maldonado, J and McDonough-Means, S and Caporaso, JG and Krajmalnik-Brown, R}, title = {Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {5821}, doi = {10.1038/s41598-019-42183-0}, pmid = {30967657}, issn = {2045-2322}, abstract = {Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between gut microbiome and autism-like behaviors. Modifying the gut microbiome is a potential route to improve gastrointestinal (GI) and behavioral symptoms in children with ASD, and fecal microbiota transplant could transform the dysbiotic gut microbiome toward a healthy one by delivering a large number of commensal microbes from a healthy donor. We previously performed an open-label trial of Microbiota Transfer Therapy (MTT) that combined antibiotics, a bowel cleanse, a stomach-acid suppressant, and fecal microbiota transplant, and observed significant improvements in GI symptoms, autism-related symptoms, and gut microbiota. Here, we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. Important changes in gut microbiota at the end of treatment remained at follow-up, including significant increases in bacterial diversity and relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the long-term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo-controlled trial in the future.}, }
@article {pmid30967260, year = {2019}, author = {He, Y and Yu, H and Ge, Y and Li, X and Jiang, M and Liu, Y and Li, X and Wang, Y and Guo, M and Qin, X and Wang, X}, title = {Bacterial β-glucuronidase alleviates dextran sulfate sodium-induced colitis in mice: A possible crucial new diagnostic and therapeutic target for inflammatory bowel disease.}, journal = {Biochemical and biophysical research communications}, volume = {513}, number = {2}, pages = {426-433}, doi = {10.1016/j.bbrc.2019.03.196}, pmid = {30967260}, issn = {1090-2104}, abstract = {OBJECTIVE: Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are devastating diseases of the gut. At present, all the treatments are mainly targeting symptoms like inflammation. The disease remains regarded as incurable, largely due to lacking of knowledge on its etiology. Our previous studies suggested that impaired inactivation of digestive proteases by deconjugated bilirubin in experimental colitis, thus bacterial β-glucuronidase for catalyzing the reaction, may have played critical role in the pathogenesis of IBD.<br><br>METHODS: We first analyzed β-glucuronidase activity in gut tissue and feces of mice by a colitis model. Then the effect of β-glucuronidase on experimental colitis was investigated in detail by administration of β-glucuronidase (from E. coli) and fecal material transplantation to mice with 3% DSS in drinking water for 7 days.<br><br>RESULTS: Mice with colitis showed unchanged activity of β-glucuronidase in colon tissue but decreased activity in feces. Treatment with bacterial β-glucuronidase at 100 U or above alleviated DSS-induced colitis as demonstrated by the less body weight loss, less disease activity score, increased expression of tight junction proteins and decreased gut permeability, decreases in MPO, TNF-α, IL-1β, TLR-4 and MyD88, and increase in IL-10 and IκBα in gut, restored fecal β-glucuronidase and gut microbiota along with decreases in fecal digestive proteases. Transplantation of fecal material from control to colitis mice showed similar effects as treatment with β-glucuronidase.<br><br>CONCLUSIONS: Bacterial β-glucuronidase showed strong inhibition on colitis along with the reduction in fecal digestive proteases, which may be a crucial diagnostic and therapeutic target for IBD.}, }
@article {pmid30965098, year = {2019}, author = {Kuijper, EJ and Vendrik, KEW and Vehreschild, MJGT}, title = {Manipulation of the microbiota to eradicate multidrug-resistant Enterobacteriaceae from the human intestinal tract.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {25}, number = {7}, pages = {786-789}, doi = {10.1016/j.cmi.2019.03.025}, pmid = {30965098}, issn = {1469-0691}, mesh = {Anti-Bacterial Agents ; Enterobacteriaceae ; Enterobacteriaceae Infections/*microbiology ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid30957161, year = {2019}, author = {Tariq, R and Pardi, DS and Bartlett, MG and Khanna, S}, title = {Low Cure Rates in Controlled Trials of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection: A Systematic Review and Meta-analysis.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {68}, number = {8}, pages = {1351-1358}, doi = {10.1093/cid/ciy721}, pmid = {30957161}, issn = {1537-6591}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridium difficile infection (CDI) in observational studies (>90%), but cure rates in clinical trials are lower. We performed a systematic review and meta-analysis to assess the efficacy of FMT for recurrent CDI in open-label studies and clinical trials .<br><br>METHODS: A systematic search from January 1978 to March 2017 was performed to include clinical trials of FMT for CDI. We analyzed CDI resolution by calculating weighted pooled rates (WPRs).<br><br>RESULTS: Thirteen trials were included, comprising 610 patients with CDI treated with single FMT. Overall, 439 patients had clinical cure (WPR, 76.1%; 95% confidence interval (CI), 66.4%-85.7%). There was significant heterogeneity among studies (I2 = 91.35%). Cure rates were lower in randomized trials (139/216 patients; WPR, 67.7%; 95% CI, 54.2%-81.3%) than in open-label studies (300/394 patients; WPR, 82.7%; 71.1%-94.3%) (P < .001). Subgroup analysis by FMT delivery modality showed lower cure rates with enema than colonoscopy (WPR, 66.3% vs 87.4%; P < .001) but no difference between colonoscopy and oral delivery (WPR, 87.4% vs 81.4%; P = .17). Lower rates were seen for studies including both recurrent and refractory CDI than for those including only recurrent CDI (WPR, 63.9% vs 79%; P < .001).<br><br>CONCLUSIONS: FMT was associated with lower cure rates in randomized trials than in open-label and in observational studies. Colonoscopy and oral route are more effective than enema for stool delivery. The efficacy also seems to be higher for recurrent than for refractory CDI.}, }
@article {pmid30946615, year = {2019}, author = {Cold, F and Browne, PD and Günther, S and Halkjaer, SI and Petersen, AM and Al-Gibouri, Z and Hansen, LH and Christensen, AH}, title = {Multidonor FMT capsules improve symptoms and decrease fecal calprotectin in ulcerative colitis patients while treated - an open-label pilot study.}, journal = {Scandinavian journal of gastroenterology}, volume = {54}, number = {3}, pages = {289-296}, doi = {10.1080/00365521.2019.1585939}, pmid = {30946615}, issn = {1502-7708}, abstract = {Background: Growing evidence indicates that gut dysbiosis is a factor in the pathogenesis of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) appears to be promising in inducing UC remission, but there are no reports regarding administration using capsules. Methods: Seven patients with active UC, aged 27-50 years, were treated with 25 multidonor FMT capsules daily for 50 days as a supplement to their standard treatment in an open-label pilot study. The primary objective was to follow symptoms through the Simple Clinical Colitis Activity Index (SCCAI). Secondary objectives were to follow changes in fecal calprotectin and microbial diversity through fecal samples and quality of life through the Inflammatory Bowel Disease Questionnaire (IBDQ). Participants were followed through regular visits for six months. Results: From a median of 6 at baseline, the SCCAI of all participants decreased, with median decreases of 5 (p = .001) and 6 (p = .001) after 4 and 8 weeks, respectively. Three of the seven patients had flare-up/relapse of symptoms after the active treatment period. The median F-calprotectin of ≥1800 mg/kg at baseline decreased significantly during the treatment period, but increased again in the follow-up period. The median IBDQ improved at all visits compared to baseline. The fecal microbiota α-diversity did not increase in the study period compared to baseline. All participants completed the treatment and no serious adverse events were reported. Conclusion: Fifty days of daily multidonor FMT capsules temporarily improved symptoms and health-related life quality and decreased F-calprotectin in patients with active UC.}, }
@article {pmid30945014, year = {2019}, author = {Czepiel, J and Dróżdż, M and Pituch, H and Kuijper, EJ and Perucki, W and Mielimonka, A and Goldman, S and Wultańska, D and Garlicki, A and Biesiada, G}, title = {Clostridium difficile infection: review.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {38}, number = {7}, pages = {1211-1221}, doi = {10.1007/s10096-019-03539-6}, pmid = {30945014}, issn = {1435-4373}, abstract = {Clostridium difficile (C. difficile) is a Gram-positive, spore-forming, anaerobic bacillus, which is widely distributed in the intestinal tract of humans and animals and in the environment. In the last decade, the frequency and severity of C. difficile infection has been increasing worldwide to become one of the most common hospital-acquired infections. Transmission of this pathogen occurs by the fecal-oral route and the most important risk factors include antibiotic therapy, old age, and hospital or nursing home stay. The clinical picture is diverse and ranges from asymptomatic carrier status, through various degrees of diarrhea, to the most severe, life threatening colitis resulting with death. Diagnosis is based on direct detection of C. difficile toxins in feces, most commonly with the use of EIA assay, but no single test is suitable as a stand-alone test confirming CDI. Antibiotics of choice are vancomycin, fidaxomicin, and metronidazole, though metronidazole is considered as inferior. The goal of this review is to update physicians on current scientific knowledge of C. difficile infection, focusing also on fecal microbiota transplantation which is a promising therapy.}, }
@article {pmid30943129, year = {2019}, author = {Selvanderan, SP and Goldblatt, F and Nguyen, NQ and Costello, SP}, title = {Faecal microbiota transplantation for Clostridium difficile infection resulting in a decrease in psoriatic arthritis disease activity.}, journal = {Clinical and experimental rheumatology}, volume = {37}, number = {3}, pages = {514-515}, pmid = {30943129}, issn = {0392-856X}, mesh = {Arthritis, Psoriatic/microbiology/therapy ; *Clostridium Infections/microbiology/therapy ; *Fecal Microbiota Transplantation ; Feces ; Humans ; }, }
@article {pmid30940601, year = {2019}, author = {Wardill, HR and Secombe, KR and Bryant, RV and Hazenberg, MD and Costello, SP}, title = {Adjunctive fecal microbiota transplantation in supportive oncology: Emerging indications and considerations in immunocompromised patients.}, journal = {EBioMedicine}, volume = {44}, number = {}, pages = {730-740}, doi = {10.1016/j.ebiom.2019.03.070}, pmid = {30940601}, issn = {2352-3964}, abstract = {FMT has gained enormous momentum in the treatment of acute inflammatory and infectious diseases. Despite an encouraging safety profile, FMT has been met with caution in the oncological setting due to perceived infectious risks in immunocompromised patients. Theoretical risks aside, the application of FMT in oncology may stand to benefit patients, via modulation of treatment efficacy and the mitigation of treatment complications. Here, we summarize most recent safety data of FMT in immunocompromised cohorts, including people with cancer, highlighting that FMT may actually provide protection against bacterial translocation via introduction of a diverse microbiome and restoration of epithelial defenses. We also discuss the emerging translational applications of FMT within supportive oncology, including the prevention and treatment of graft vs. host disease and sepsis, treatment of immunotherapy-induced colitis and restoration of the gut microbiome in survivors of childhood cancer.}, }
@article {pmid30936486, year = {2019}, author = {Ingle, H and Lee, S and Ai, T and Orvedahl, A and Rodgers, R and Zhao, G and Sullender, M and Peterson, ST and Locke, M and Liu, TC and Yokoyama, CC and Sharp, B and Schultz-Cherry, S and Miner, JJ and Baldridge, MT}, title = {Viral complementation of immunodeficiency confers protection against enteric pathogens via interferon-λ.}, journal = {Nature microbiology}, volume = {4}, number = {7}, pages = {1120-1128}, doi = {10.1038/s41564-019-0416-7}, pmid = {30936486}, issn = {2058-5276}, support = {R01 AI141478/AI/NIAID NIH HHS/United States ; R01 AI139314/AI/NIAID NIH HHS/United States ; R01 AI127552/AI/NIAID NIH HHS/United States ; K22 AI127846/AI/NIAID NIH HHS/United States ; R03 AI126101/AI/NIAID NIH HHS/United States ; T32 AI106688/AI/NIAID NIH HHS/United States ; T32 AI007163/AI/NIAID NIH HHS/United States ; P30 DK052574/DK/NIDDK NIH HHS/United States ; K08 AR070918/AR/NIAMS NIH HHS/United States ; }, abstract = {Commensal microbes profoundly impact host immunity to enteric viral infections1. We have shown that the bacterial microbiota and host antiviral cytokine interferon-λ (IFN-λ) determine the persistence of murine norovirus in the gut2,3. However, the effects of the virome in modulating enteric infections remain unexplored. Here, we report that murine astrovirus can complement primary immunodeficiency to protect against murine norovirus and rotavirus infections. Protection against infection was horizontally transferable between immunocompromised mouse strains by co-housing and fecal transplantation. Furthermore, protection against enteric pathogens corresponded with the presence of a specific strain of murine astrovirus in the gut, and this complementation of immunodeficiency required IFN-λ signalling in gut epithelial cells. Our study demonstrates that elements of the virome can protect against enteric pathogens in an immunodeficient host.}, }
@article {pmid30930793, year = {2019}, author = {Toral, M and Robles-Vera, I and de la Visitación, N and Romero, M and Yang, T and Sánchez, M and Gómez-Guzmán, M and Jiménez, R and Raizada, MK and Duarte, J}, title = {Critical Role of the Interaction Gut Microbiota - Sympathetic Nervous System in the Regulation of Blood Pressure.}, journal = {Frontiers in physiology}, volume = {10}, number = {}, pages = {231}, doi = {10.3389/fphys.2019.00231}, pmid = {30930793}, issn = {1664-042X}, abstract = {Association between gut dysbiosis and neurogenic diseases, such as hypertension, has been described. The aim of this study was to investigate whether changes in the gut microbiota alter gut-brain interactions inducing changes in blood pressure (BP). Recipient normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were orally gavaged with donor fecal contents from SHR and WKY. We divided the animals into four groups: WKY transplanted with WKY microbiota (W-W), SHR with SHR (S-S), WKY with SHR (W-S) and SHR with WKY (S-W). Basal systolic BP (SBP) and diastolic BP (DBP) were reduced with no change in heart rate as a result of fecal microbiota transplantation (FMT) from WKY rats to SHR. Similarly, FMT from SHR to WKY increased basal SBP and DBP. Increases in both NADPH oxidase-driven reactive oxygen species production and proinflammatory cytokines in brain paraventricular nucleus linked to higher BP drop with pentolinium and plasmatic noradrenaline (NA) levels were found in the S-S group as compared to the W-W group. These parameters were reduced by FMT from WKY to SHR. Increased levels of pro-inflammatory cytokines, tyrosine hydroxylase mRNA levels and NA content in the proximal colon, whereas reduced mRNA levels of gap junction proteins, were found in the S-S group as compared to the W-W group. These changes were inhibited by FMT from WKY to SHR. According to our correlation analyses, the abundance of Blautia and Odoribacter showed a negative correlation with high SBP. In conclusion, in SHR gut microbiota is an important factor involved in BP control, at least in part, as consequence of its effect on neuroinflammation and the sympathetic nervous system activity.}, }
@article {pmid30929665, year = {2019}, author = {Caesar, R}, title = {Pharmacologic and Nonpharmacologic Therapies for the Gut Microbiota in Type 2 Diabetes.}, journal = {Canadian journal of diabetes}, volume = {43}, number = {3}, pages = {224-231}, doi = {10.1016/j.jcjd.2019.01.007}, pmid = {30929665}, issn = {2352-3840}, abstract = {The gut microbiota is an important regulator of host metabolism. Metagenome analyses have demonstrated that the gut microbiota differs between patients with type 2 diabetes and healthy subjects, and several studies have shown that impaired glucose metabolism is associated with decreased levels of butyrate-producing bacteria. Gut microbiota-produced metabolites, such as short-chain fatty acids, amino acid derivatives and secondary bile acids, participate in metabolic and immunologic processes and, hence, pose putative links between the gut microbiota and glucose homeostasis. Strategies to prevent and treat type 2 diabetes through manipulation of the gut microbiota are being developed. These include replacement of the gut microbiota by fecal transplantation, consumption of fibres to promote the function and growth of beneficial bacteria and treatment with probiotic bacterial strains. Furthermore, it has been shown that many drugs, including drugs used for treatment of diabetes, have major impacts on gut microbiota and, thereby, potentially on glucose metabolism. In particular, the commonly used drug metformin has been shown to influence the functional capacity of the gut microbiota, and recent evidence indicates that this may contribute to the antidiabetes effect of metformin.}, }
@article {pmid30924853, year = {2019}, author = {Suzumura, EA and Bersch-Ferreira, ÂC and Torreglosa, CR and da Silva, JT and Coqueiro, AY and Kuntz, MGF and Chrispim, PP and Weber, B and Cavalcanti, AB}, title = {Effects of oral supplementation with probiotics or synbiotics in overweight and obese adults: a systematic review and meta-analyses of randomized trials.}, journal = {Nutrition reviews}, volume = {77}, number = {6}, pages = {430-450}, doi = {10.1093/nutrit/nuz001}, pmid = {30924853}, issn = {1753-4887}, abstract = {CONTEXT: Recent evidence suggests that modulation of the gut microbiota may contribute to body weight control.<br><br>OBJECTIVE: This systematic review aimed to assess the effects of oral supplementation with probiotics or synbiotics on body weight, body mass index (BMI), and waist circumference in overweight and obese adults (BMI ≥ 25 kg/m2).<br><br>DATA SOURCES: Five electronic databases-PubMed, Embase, Cochrane Library/CENTRAL, LILACS, and Web of Science-were searched from inception to August 2017. No language restrictions were applied.<br><br>STUDY SELECTION: Randomized and quasi-randomized parallel trials that assessed the effects of oral supplementation with probiotics or synbiotics vs any other intervention but bariatric surgery or fecal transplantation in overweight or obese adults were selected.<br><br>DATA EXTRACTION: Three teams of 2 authors independently assessed risk of bias and extracted data from the included trials. Data were pooled using inverse-variance random-effects meta-analyses. The quality of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.<br><br>RESULTS: Nineteen randomized trials (28 publications, 1412 participants) were included. There were no differences in mean body weight change [mean difference (MD), -0.54 kg; 95%CI, -1.09 to 0.01; I2 = 0%; moderate quality of evidence) or mean BMI change (MD, -0.19 kg/m2; 95%CI, -0.43 to 0.04; I2 = 51%; low quality of evidence) between groups who received probiotics or synbiotics and control groups. Oral supplementation with probiotics or synbiotics reduced mean waist circumference compared with control (MD, -0.82 cm; 95%CI, -1.43 to -0.21; I2 = 46%; low quality of evidence).<br><br>CONCLUSIONS: The findings suggest that oral supplementation with probiotics or synbiotics has a small effect to reduce waist circumference but no effect on body weight or BMI, although the quality of evidence is low to moderate. Therefore, the current evidence is not definitive. Large-scale trials are needed and may help to better inform clinical practice.<br><br>PROSPERO registration number CRD42018075126.}, }
@article {pmid30922964, year = {2019}, author = {Liao, X and Song, L and Zeng, B and Liu, B and Qiu, Y and Qu, H and Zheng, Y and Long, M and Zhou, H and Wang, Y and Du, Y and Xu, J and Shen, R and Tong, Q and Cai, L and Li, X and Guo, S and Yang, G and Zhu, Z and Pu, X and Wei, H and Zheng, H}, title = {Alteration of gut microbiota induced by DPP-4i treatment improves glucose homeostasis.}, journal = {EBioMedicine}, volume = {44}, number = {}, pages = {665-674}, doi = {10.1016/j.ebiom.2019.03.057}, pmid = {30922964}, issn = {2352-3964}, abstract = {BACKGROUND: Increasing evidence indicates that the gut microbiota contributes to the occurrence and development of metabolic diseases. However, little is known about the effects of commonly used antidiabetic agents on the gut microbiota. In this study, we investigated the roles of dipeptidyl peptidase-4 inhibitors (DPP-4i) and α-glucosidase inhibitor in modulating the gut microbiota.<br><br>METHODS: 16S-rDNA sequencing was performed to analyse the effects of DPP-4i and acarbose on the gut microbiota in mice fed a high-fat diet (HFD). Fecal microbiota transplantation (FMT) from type 2 diabetes patients to germ-free mice was performed to investigate the contribution of the altered microbiome to antidiabetic effects of the drugs. Fecal metabolomics was also analysed by untargeted and targeted GC-MS systems.<br><br>FINDINGS: Although DPP-4i and α-glucosidase inhibitor both altered the gut microbial composition, only the microbiome modulation of DPP-4i contributed to its hypoglycemic effect. Specifically, the changes of 68.6% genera induced by HFD were rescued by DPP-4i. FMT showed that the DPP-4i-altered microbiome improved glucose tolerance in colonized mice, while acarbose did not. Moreover, DPP-4i increased the abundance of Bacteroidetes, and also promoted a functional shift in the gut microbiome, especially increasing the production of succinate.<br><br>INTERPRETATION: Our findings demonstrate an important effect of DPP-4i on the gut microbiota, revealing a new hypoglycemic mechanism and an additional benefit of it. Furthermore, modulating the microbial composition, and the functional shift arising from changes in the microbiome, might be a potential strategy for improving glucose homeostasis. FUND: This work was supported by grants from the National Natural Science Foundation of China (No. 81700757, No. 81471039, No. 81700714 and No. 81770434), the National Key R&amp;D Program of China (No. 2017YFC1309602, No. 2016YFC1101100, No. 2017YFD0500503 and No. 2017YFD0501001), and the Natural Science Foundation of Chongqing (No. cstc2014jcyjjq10006, No. cstc2016jcyjA0093 and No. cstc2016jcyjA0518).}, }
@article {pmid30920413, year = {2019}, author = {Bajaj, JS and Hays, RA}, title = {Manipulation of the Gut-Liver Axis Using Microbiome Restoration Therapy in Primary Sclerosing Cholangitis.}, journal = {The American journal of gastroenterology}, volume = {114}, number = {7}, pages = {1027-1029}, doi = {10.14309/ajg.0000000000000191}, pmid = {30920413}, issn = {1572-0241}, abstract = {Alteration of the normal gut-liver axis is important in primary sclerosing cholangitis (PSC). Lack of effective medical therapy for PSC makes microbiome restoration an alluring therapeutic target. Allegretti et al. performed an open-label safety trial of fecal microbiota transplant (FMT) in noncirrhotic PSC patients with inflammatory bowel disease in remission on minimal therapy. FMT was safe in this population, and after FMT, there was a stable, early increase in microbial diversity and donor engraftment with mixed effects on alkaline phosphatase but no significant change in fecal bile acid profile. Further trials are needed to find whether FMT has a role to play in PSC therapy.}, }
@article {pmid30919462, year = {2019}, author = {Matsuo, K and Haku, A and Bi, B and Takahashi, H and Kamada, N and Yaguchi, T and Saijo, S and Yoneyama, M and Goto, Y}, title = {Fecal microbiota transplantation prevents Candida albicans from colonizing the gastrointestinal tract.}, journal = {Microbiology and immunology}, volume = {63}, number = {5}, pages = {155-163}, doi = {10.1111/1348-0421.12680}, pmid = {30919462}, issn = {1348-0421}, mesh = {Animals ; Anti-Bacterial Agents/administration &amp; dosage/pharmacology ; *Bacteria/drug effects ; Candida albicans/*pathogenicity ; Candidiasis/*prevention &amp; control ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Gastrointestinal Tract/*microbiology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Symbiosis ; }, abstract = {Gut microbes symbiotically colonize the gastrointestinal (GI) tract, interacting with each other and their host to maintain GI tract homeostasis. Recent reports have shown that gut microbes help protect the gut from colonization by pathogenic microbes. Here, we report that commensal microbes prevent colonization of the GI tract by the pathogenic fungus, Candida albicans. Wild-type specific pathogen-free (SPF) mice are resistant to C. albicans colonization of the GI tract. However, administering certain antibiotics to SPF mice enables C. albicans colonization. Quantitative kinetics of commensal bacteria are inversely correlated with the number of C. albicans in the gut. Here, we provide further evidence that transplantation of fecal microbiota is effective in preventing Candida colonization of the GI tract. These data demonstrate the importance of commensal bacteria as a barrier for the GI tract surface and highlight the potential clinical applications of commensal bacteria in preventing pathogenic fungal infections.}, }
@article {pmid30919208, year = {2019}, author = {Adler, E and Tabaa, A and Kassam, Z and Zydek, M and Terdiman, J and El-Nachef, N}, title = {Capsule-Delivered Fecal Microbiota Transplant Is Safe and Well Tolerated in Patients with Ulcerative Colitis.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-019-05596-5}, pmid = {30919208}, issn = {1573-2568}, }
@article {pmid30909689, year = {2019}, author = {Kim, KO and Gluck, M}, title = {Fecal Microbiota Transplantation: An Update on Clinical Practice.}, journal = {Clinical endoscopy}, volume = {52}, number = {2}, pages = {137-143}, doi = {10.5946/ce.2019.009}, pmid = {30909689}, issn = {2234-2400}, abstract = {Fecal microbiota transplantation (FMT) is an infusion in the colon, or the delivery through the upper gastrointestinal tract, of stool from a healthy donor to a recipient with a disease believed to be related to an unhealthy gut microbiome. FMT has been successfully used to treat recurrent Clostridium difficile infection (rCDI). The short-term success of FMT in rCDI has led to investigations of its application to other gastrointestinal disorders and extra-intestinal diseases with presumed gut dysbiosis. Despite the promising results of FMT in these conditions, several barriers remain, including determining the characteristics of a healthy microbiome, ensuring the safety of the recipient with respect to long-term outcomes, adequate monitoring of the recipient of fecal material, achieving high-quality control, and maintaining reasonable costs. For these reasons, establishing uniform protocols for stool preparation, finding the best modes of FMT administration, maintaining large databases of donors and recipients, and assuring that oral ingestion is equivalent to the more widely accepted colonoscopic infusion are issues that need to be addressed.}, }
@article {pmid30908299, year = {2019}, author = {Xu, D and Chen, VL and Steiner, CA and Berinstein, JA and Eswaran, S and Waljee, AK and Higgins, PDR and Owyang, C}, title = {Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis.}, journal = {The American journal of gastroenterology}, volume = {114}, number = {7}, pages = {1043-1050}, doi = {10.14309/ajg.0000000000000198}, pmid = {30908299}, issn = {1572-0241}, abstract = {OBJECTIVES: Irritable bowel syndrome (IBS) is a common gastrointestinal condition with a heterogeneous pathophysiology. An altered gut microbiome has been identified in some IBS patients, and fecal microbiota transplantation (FMT) has been suggested to treat IBS. We performed meta-analyses and systematic review of available randomized controlled trials (RCTs) to evaluate the efficacy of FMT in IBS.<br><br>METHODS: We performed a systematic literature search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science. Selection criteria included RCTs of FMT vs placebo using FMT excipients or autologous FMT in IBS. Meta-analyses were conducted to evaluate the summary relative risk (RR) and 95% confidence intervals (CIs) of combined studies for primary outcome of improvement in global IBS symptoms as measured by accepted integrative symptom questionnaires or dichotomous responses to questions of overall symptom improvement.<br><br>RESULTS: Among 742 citations identified, 7 were deemed to be potentially relevant, of which 4 studies involving 254 participants met eligibility. No significant difference in global improvement of IBS symptoms was observed at 12 weeks in FMT vs placebo (RR = 0.93; 95% CI 0.48-1.79). Heterogeneity among studies was significant (I = 79%). Subgroup analyses revealed benefits of single-dose FMT using colonoscopy and nasojejunal tubes in comparison with autologous FMT for placebo treatment (number needed to treat = 5, RR = 1.59; 95% CI 1.06-2.39; I = 0%) and a reduction in likelihood of improvement of multiple-dose capsule FMT RCTs (number needed to harm = 3, RR = 0.54; 95% CI 0.34-0.85; I = 13%). Placebo response was 33.7% in nonoral FMT RCTs and 67.8% in capsule FMT RCTs. The Grading of Recommendations Assessment, Development and Evaluation quality of the body of evidence was very low.<br><br>DISCUSSION: Current evidence from RCTs does not suggest a benefit of FMT for global IBS symptoms. There remain questions regarding the efficacy of FMT in IBS as well as the lack of a clean explanation on the discrepant results among RCTs in subgroup analyses.}, }
@article {pmid30906449, year = {2019}, author = {Zhou, J and Zhou, Z and Ji, P and Ma, M and Guo, J and Jiang, S}, title = {Effect of fecal microbiota transplantation on experimental colitis in mice.}, journal = {Experimental and therapeutic medicine}, volume = {17}, number = {4}, pages = {2581-2586}, doi = {10.3892/etm.2019.7263}, pmid = {30906449}, issn = {1792-0981}, abstract = {The aim of the present study was to investigate the effect of fecal microbiota transplantation (FMT) on the acute inflammatory response in a murine model of dextran sulfate sodium (DSS)-induced colitis, and to delineate the putative underlying mechanism(s). Mice were divided into four groups, namely the normal control, DSS, 5-aminosalicylic acid (5-ASA) and FMT group. Mice in the DSS, 5-ASA and FMT groups were orally administered 3% DSS (w/v) solution for 7 days to induce colitis. On days 1, 3, 5 and 7, mice in the DSS, 5-ASA and FMT groups were respectively administered 0.5% carboxymethylcellulose sodium, 5-ASA suspension and fecal suspension by enema. The disease activity index of each mouse was calculated on a daily basis. All mice were sacrificed on day 8, and the length of their colons was measured. Myeloperoxidase (MPO) activity, and the levels of tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-10 in the colon tissues of each group were also measured. Compared with that in the DSS group, FMT ameliorated the severity of inflammation due to ulcerative colitis in mice, which was accompanied by a significantly decreased MPO activity, reduced levels of TNF-α and IL-1β, and an increased level of IL-10 in colon tissue (all P<0.05). Taken together, these results demonstrated that FMT exerted a therapeutic effect on experimental colitis in mice, and the associated mechanism is likely to involve the remodeling of the intestinal flora and regulation of intestinal T-cell immunity homeostasis.}, }
@article {pmid30906424, year = {2019}, author = {Levy, AN and Allegretti, JR}, title = {Insights into the role of fecal microbiota transplantation for the treatment of inflammatory bowel disease.}, journal = {Therapeutic advances in gastroenterology}, volume = {12}, number = {}, pages = {1756284819836893}, doi = {10.1177/1756284819836893}, pmid = {30906424}, issn = {1756-283X}, abstract = {Fecal microbiota transplantation (FMT) has changed the treatment landscape of Clostridium difficile infection (CDI). Emerging evidence has shown that FMT can also be an effective and safe treatment strategy in CDI with underlying inflammatory bowel disease (IBD). Recently, randomized controlled trials of FMT in ulcerative colitis support its expanding role in restoring gut homeostasis in this disease. However, heterogeneous study designs leave several questions yet to be answered, including how to best position this novel therapy in the treatment approach of Crohn's disease and pouchitis. Additional studies are needed to validate whether FMT can assume a complementary role in the standard treatment of IBD.}, }
@article {pmid30905818, year = {2019}, author = {Wu, X and Zhang, T and Chen, X and Ji, G and Zhang, F}, title = {Microbiota transplantation: Targeting cancer treatment.}, journal = {Cancer letters}, volume = {452}, number = {}, pages = {144-151}, doi = {10.1016/j.canlet.2019.03.010}, pmid = {30905818}, issn = {1872-7980}, abstract = {Mounting evidence have demonstrated that gut microbiota plays a critical role in cancer patients' therapeutic responses to chemotherapy, radiotherapy and immunotherapy, including clinical efficacy and sensitivity to toxicity. These fascinating findings evoke a possibility of manipulating gut microbiota to optimize anti-cancer treatment from bench to beside. Microbiota transplantation (MT), including fecal microbiota transplantation (FMT) and selective microbiota transplantation (SMT), may improve the effect of anti-cancer treatment and/or reduce the related side effects. The safety and efficacy of MT in cancer treatment are the core of translational research in this promising field, which inspire us to focus on the MT technology and mechanism of MT targeting anti-cancer treatment. To perform clean FMT based on automatic methods by machine in exclusive laboratory has become true. Colonic transendoscopic enteral tubing as a novel delivering way for MT should bring convenience for frequent delivering in practice and feasible tool for confirming the therapeutic effect in research. The present review focuses on the recent findings on role of microbiota on chemotherapy, radiotherapy and immunotherapy, and the methodology, feasibility and challenges of MT in anti-cancer treatment.}, }
@article {pmid30899209, year = {2019}, author = {Fischer, M}, title = {Recent Research on Fecal Microbiota Transplantation in Inflammatory Bowel Disease Patients.}, journal = {Gastroenterology &amp; hepatology}, volume = {15}, number = {1}, pages = {44-47}, pmid = {30899209}, issn = {1554-7914}, }
@article {pmid30899006, year = {2019}, author = {Wang, W and Lin, L and Du, Y and Song, Y and Peng, X and Chen, X and Yang, CJ}, title = {Assessing the viability of transplanted gut microbiota by sequential tagging with D-amino acid-based metabolic probes.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {1317}, doi = {10.1038/s41467-019-09267-x}, pmid = {30899006}, issn = {2041-1723}, mesh = {Amino Acids/*administration &amp; dosage/chemistry ; Animals ; Anti-Bacterial Agents/pharmacology ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Fluorescent Dyes/chemistry ; Gastrointestinal Microbiome/*drug effects/genetics ; Gastrointestinal Tract/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Microbial Viability/drug effects ; RNA, Ribosomal, 16S/*genetics ; Staining and Labeling/*methods ; Stereoisomerism ; }, abstract = {Currently, there are more than 200 fecal microbiota transplantation (FMT) clinical trials worldwide. However, our knowledge of this microbial therapy is still limited. Here we develop a strategy using sequential tagging with D-amino acid-based metabolic probes (STAMP) for assessing the viabilities of transplanted microbiotas. A fluorescent D-amino acid (FDAA) is first administered to donor mice to metabolically label the gut microbiotas in vivo. The labeled microbiotas are transplanted to recipient mice, which receive a second FDAA with a different color. The surviving transplants should incorporate both FDAAs and can be readily distinguished by presenting two colors simultaneously. Isolation of surviving bacteria and 16S rDNA sequencing identify several enriched genera, suggesting the importance of specific bacteria in FMT. In addition, using STAMP, we evaluate the effects on transplant survival of pre-treating recipients using different antibiotics. We propose STAMP as a versatile tool for deciphering the complex biology of FMT, and potentially improving its treatment efficacy.}, }
@article {pmid30898649, year = {2019}, author = {Papanicolas, LE and Wesselingh, SL and Rogers, GB}, title = {Do we really understand how faecal microbiota transplantation works? Authors' reply.}, journal = {EBioMedicine}, volume = {42}, number = {}, pages = {40}, doi = {10.1016/j.ebiom.2019.03.030}, pmid = {30898649}, issn = {2352-3964}, mesh = {*Clostridium Infections ; *Fecal Microbiota Transplantation ; Feces ; Humans ; }, }
@article {pmid30893082, year = {2019}, author = {Alsahhar, JS and Rahimi, RS}, title = {Updates on the pathophysiology and therapeutic targets for hepatic encephalopathy.}, journal = {Current opinion in gastroenterology}, volume = {35}, number = {3}, pages = {145-154}, doi = {10.1097/MOG.0000000000000527}, pmid = {30893082}, issn = {1531-7056}, abstract = {PURPOSE OF REVIEW: Hepatic encephalopathy is one of the most debilitating clinical manifestations of cirrhosis and associated with increased morbidity and mortality. Treatment modalities available include the nonabsorbable disaccharides (lactulose) and the nonabsorbable antibiotics (rifaximin).<br><br>RECENT FINDINGS: Newer therapeutic targets under evaluation include ammonia scavengers (ornithine phenylacetate) and modulation of gut microbiota (fecal microbiota transplantation).<br><br>SUMMARY: This review will focus on the pathophysiology of hepatic encephalopathy along with an update on therapeutic targets under investigation.}, }
@article {pmid30890952, year = {2019}, author = {Wan, JJ and Lin, CH and Ren, ED and Su, Y and Zhu, WY}, title = {Effects of Early Intervention With Maternal Fecal Bacteria and Antibiotics on Liver Metabolome and Transcription in Neonatal Pigs.}, journal = {Frontiers in physiology}, volume = {10}, number = {}, pages = {171}, doi = {10.3389/fphys.2019.00171}, pmid = {30890952}, issn = {1664-042X}, abstract = {The establishment of a stable bacterial flora in early life is associated with host metabolism. Studies of fecal microbiota transplantation (FMT) and antibiotics on neonatal pig mainly focused on intestinal development and mucosal immunity, but the information on metabolism is lacking. The objective of this study was to investigate the responses of metabolome and transcriptome in the livers of neonatal piglets that were orally inoculated with maternal fecal bacteria suspension and amoxicillin (AM) solution. Five litters of Duroc × Landrace × Yorkshire neonatal piglets were used as five replicates and nine piglets in each litter were randomly assigned to the control (CO), AM or FMT groups. Neonatal piglets in three groups were fed with 3 mL saline (0.9%), AM solution (6.94 mg/mL) or fecal bacteria suspension (>109/mL), respectively, on days 1-6. At the age of 7 and 21 days, one piglet from each group in each litter was sacrificed, and the serum and liver were collected for analysis. The RNA sequencing analysis showed that the mRNA expressions of arachidonate 12-lipoxygenase (ALOX12), acetyl-CoA acyltransferase 2 (ACAA2), cytochrome P450 family 1 subfamily A member 2 (CYP1A2), glutamic-pyruvic transaminase 2 (GPT2) and argininosuccinate synthase 1 (ASS1) were downregulated (P < 0.05) by AM on day 7, and that the mRNA expressions of arachidonate 15-lipoxygenase (ALOX15), CYP1A2 and GPT2 were downregulated (P < 0.05) by FMT on day 7. GC-MS analysis showed that AM and FMT treatments mainly affected fatty acid metabolism and amino acid metabolism on days 7 and 21. AM and FMT both reduced (P < 0.05) the blood levels of triglycerides and low density lipoprotein cholesterol (LDL-C) on day 7. AM reduced (P < 0.05) the blood level of cholesterol on day 21, and FMT reduced the blood levels of cholesterol, triglycerides and LDL-C on day 21. These results indicate that early intervention with FMT or AM can reduce fatty acid oxidative catabolism and amino acid biosynthesis of neonatal piglets, which provides a reference for regulation host metabolism through early intervention in animal production and even human health.}, }
@article {pmid30889205, year = {2019}, author = {Ohara, T}, title = {Identification of the microbial diversity after fecal microbiota transplantation therapy for chronic intractable constipation using 16s rRNA amplicon sequencing.}, journal = {PloS one}, volume = {14}, number = {3}, pages = {e0214085}, doi = {10.1371/journal.pone.0214085}, pmid = {30889205}, issn = {1932-6203}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective therapeutic approach for the treatment of functional gastrointestinal disease by restoring gut microbiota; however, there is a lack of sufficient understanding regarding which microbial populations successfully colonize the recipient gut. This study characterized microbial composition and diversity in patients diagnosed with chronic constipation at 1 month and 1 year after FMT.<br><br>METHODS: We explored the microbial diversity of pre- and posttransplant stool specimens from patients using 16S rRNA gene sequencing, followed by functional analysis.<br><br>RESULTS: The results identified 22 species of microorganisms colonized in the recipients from the donors at 1 month after FMT. One-year follow-up of the patient identified the colonization of 18 species of microorganisms, resulting in identification of species in significant abundance, including Bacteroides fragilis and Hungatella hathewayi in the recipient at 1 month after FMT and Dialister succinatiphilus, Coprococcus catus, and Sutterella stercoricanis at 1 year after FMT. The majority of the colonized species belong to the phylum Firmicutes and carry genes related to polysaccharide metabolism and that enhance the energy-harvesting efficiency of the host.<br><br>CONCLUSION: These results suggest that FMT is effective for the treatment of chronic constipation through the restoration and colonization of donor microbiota in the recipient gut up to 1 year after FMT.}, }
@article {pmid30886607, year = {2019}, author = {Liu, Z and Wang, N and Ma, Y and Wen, D}, title = {Hydroxytyrosol Improves Obesity and Insulin Resistance by Modulating Gut Microbiota in High-Fat Diet-Induced Obese Mice.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {390}, doi = {10.3389/fmicb.2019.00390}, pmid = {30886607}, issn = {1664-302X}, abstract = {Obesity is a common chronic metabolic disease that is harmful to human health and predisposes the affected individuals to a cluster of pathologies. Insulin resistance (IR) is one of the most frequent complications of obesity. Hydroxytyrosol (HT) may reduce obesity and IR in high-fat diet (HFD)-fed mice; however, the mechanism underlying is still unknown. Systemic low-grade inflammation and intestinal dysfunction are thought to be associated with obesity and IR. In this study, we found that HFD feeding for 8 weeks altered the intestinal microbiota, injured intestinal barrier function, increased endotoxin release into the blood, enhanced the expression of inflammatory factors (TNF-α, IL-1β, IL-6) and lipid accumulation in liver, caused obesity, and aggravated IR via the JNK/IRS (Ser 307) pathway in HFD mice. We also found that HT gavage could reverse those effects and the beneficial effects of HT were transferable through fecal microbiota transplantation. Our data indicate that HT can improve obesity and IR by altering the composition of the intestinal microbiota and improving integrity of the intestinal wall. We propose that HT replenishment may be used as a dietary intervention strategy to prevent obesity and IR.}, }
@article {pmid30882536, year = {2019}, author = {Allegretti, JR and Kassam, Z and Fischer, M and Kelly, C and Chan, WW}, title = {Risk Factors for Gastrointestinal Symptoms Following Successful Eradication of Clostridium difficile by Fecal Microbiota Transplantation (FMT).}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000001194}, pmid = {30882536}, issn = {1539-2031}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a promising therapy for recurrent Clostridioides difficile infection (CDI). Many patients report altered bowel habits including constipation, bloating, gas and loose stool post-FMT despite resolution of CDI, and the etiology remains unclear.<br><br>METHODS: This was a prospective cohort study of adult patients with recurrent CDI who underwent FMT (1) via colonoscopy with patient-selected donor stool, (2) via colonoscopy from a universal stool bank donor, or (3) via capsules from a universal stool bank. Reassessment occurred 8 weeks post-FMT. Those cured were assessed for gastrointestinal symptoms (bloating, loose stools, constipation). Multivariate logistic regression was performed to assess predictors of post-FMT gastrointestinal symptoms.<br><br>RESULTS: A total of 150 subjects underwent FMT for recurrent CDI, of which 68.7% (103) were female, mean age was 61.5 years±18.1 and 31 patients (20.7%) had preexisting irritable bowel syndrome. Thirty-six had FMT via colonoscopy with a patient-selected donor, 67 via colonoscopy with stool bank donors, and 47 via FMT capsules from stool bank donors. Among those cured, 41 (31.2%) had gastrointestinal symptoms post-FMT. The factors associated with symptoms included younger age (57.2 vs. 64.1 y, P=0.03), a baseline history of irritable bowel syndrome (36.6% vs. 13.3%, P=0.002) and preexisting inflammatory bowel disease (31.7% vs. 10%, P=0.002). Small bowel exposure to donor stool was not related to symptoms (63.4% vs. 62.2%, P=0.89).<br><br>CONCLUSIONS: Altered bowel habits are a consequence of CDI and are common after FMT. This study suggests that donor type and FMT delivery modality are not related to the presence of irregular gastrointestinal symptoms after FMT.}, }
@article {pmid30877020, year = {2019}, author = {Uchiyama, K and Naito, Y and Takagi, T}, title = {Intestinal microbiome as a novel therapeutic target for local and systemic inflammation.}, journal = {Pharmacology &amp; therapeutics}, volume = {199}, number = {}, pages = {164-172}, doi = {10.1016/j.pharmthera.2019.03.006}, pmid = {30877020}, issn = {1879-016X}, abstract = {Recently, the pathogenesis of systemic inflammatory disease such as inflammatory bowel disease (IBD), multiple sclerosis (MS), systemic inflammatory arthritis, asthma, and non-alcoholic fatty liver disease has been reported to be related to the dysbiosis of gut microbiota. The contribution of special bacteria for the development of those diseases has been elucidated by disease animal models such as germ-free mice. Besides, the contribution by several bacteria for the pathogenesis of those diseases has been suggested by detailed analysis of the 16 small ribosomal subunit RNA (16S rRNA) from stool samples of the patients. Gut microbiota-targeted treatment for systemic inflammatory diseases such as fecal microbiota transplant (FMT), and probiotics has been now reported. Though there are several issues to be understood, these treatments have been highlighted as an innovative approach to intractable systemic inflammatory disease. In the present review, recent reports regarding the relation between gut microbiota and systemic inflammatory diseases are discussed with treatments to target gut microbiota.}, }
@article {pmid30876614, year = {2019}, author = {Ramesh, MS and Yee, J}, title = {Clostridioides difficile Infection in Chronic Kidney Disease/End-Stage Renal Disease.}, journal = {Advances in chronic kidney disease}, volume = {26}, number = {1}, pages = {30-34}, doi = {10.1053/j.ackd.2019.01.001}, pmid = {30876614}, issn = {1548-5609}, abstract = {Clostridioides difficile infection (CDI) is a major health-care burden and increasingly seen in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Increased antibiotic use, alteration in host defenses, and gastric acid suppression are some of the etiologies for increased risk of CDI in these populations. Patients with CKD/ESRD have a higher risk of initial episode, recurrence, and development of severe CDI than those without CKD or ESRD. Diagnosis and management of CDI in patients with CKD/ESRD are similar to that in the general population. The mortality, length of stay, and health-care costs are higher in patients with CDI and CKD/ESRD. Antimicrobial stewardship with reduction in antibiotic use along with infection-control measures such as contact isolation and hand hygiene with soap and water is essential in the control and prevention of CDI in patients with CKD/ESRD.}, }
@article {pmid30873549, year = {2019}, author = {Sood, A and Mahajan, R and Singh, A and Midha, V and Mehta, V and Narang, V and Singh, T and Pannu, AS}, title = {Role of Fecal Microbiota Transplantation for Maintenance of Remission in Patients with Ulcerative Colitis: A Pilot Study.}, journal = {Journal of Crohn's &amp; colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjz060}, pmid = {30873549}, issn = {1876-4479}, abstract = {OBJECTIVES: To study the role of fecal microbiota transplantation (FMT) in maintenance of remission in ulcerative colitis (UC).<br><br>METHODS: In this pilot study, patients with UC in clinical remission after multi-session FMT were randomly allocated to either maintenance FMT or placebo colonoscopic infusion every 8 weeks, for 48 weeks. The standard of care (SOC) therapy was continued in all patients. The primary end point was maintenance of steroid-free clinical remission (Mayo score ≤2, all sub scores ≤ 1) at week 48. Secondary end points were achievement of endoscopic remission (endoscopic Mayo score 0) and histological remission (Nancy grade 0, 1) at week 48.<br><br>RESULTS: Sixty one patients in clinical remission were randomized to receive either FMT n=31) or placebo (n=30). The primary outcome was achieved in 27/31 (87.1%) patients allocated FMT versus 20/30 (66.7%) patients assigned placebo (p=0.111). Secondary end points of endoscopic remission [FMT: 18/31 (58.1%) versus placebo: 8/30 (26.7%), p=0.026] and histological remission [FMT: 14/31 (45.2%) versus placebo: 5/30 (16.7%), p=0. 033] were achieved in significantly higher number of patients with FMT. Three patients receiving FMT (9.7%) and 8 patients on placebo (26.7%) relapsed. There were no serious adverse events necessitating discontinuation in patients on FMT, 1 patient who relapsed on placebo required colectomy.<br><br>CONCLUSIONS: Maintenance FMT in patients who are in clinical remission may help sustain clinical, endoscopic and histological remission in patients with UC. Keywords: Inflammatory Bowel Disease; Clinical remission; Endoscopic remission; Histological remission.}, }
@article {pmid30867532, year = {2019}, author = {Xu, X and Fukui, H and Ran, Y and Tomita, T and Oshima, T and Watari, J and Miwa, H}, title = {Alteration of GLP-1/GPR43 expression and gastrointestinal motility in dysbiotic mice treated with vancomycin.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {4381}, doi = {10.1038/s41598-019-40978-9}, pmid = {30867532}, issn = {2045-2322}, support = {17K09363//Ministry of Education, Culture, Sports, Science and Technology (MEXT)/ ; }, abstract = {Gut microbiota plays a pivotal role in various aspects of host physiology, including metabolism, gastrointestinal (GI) motility and hormonal secretion. In the present study, we investigated the effect of antibiotic-associated dysbiosis on metabolism and GI motility in relation to colonic expression of glucagon-like peptide-1 (GLP-1) and G protein coupled receptor (GPR)43. Specific pathogen-free (SPF) mice (ICR, 6 weeks old, female) were orally administered vancomycin (0.2 mg/ml) in drinking water for 7 days. In another experiment, germ-free (GF) mice (ICR, 6 weeks old, female) were subjected to oral fecal transplantation (FT) using a fecal bacterial suspension prepared from SPF mice that had received vancomycin treatment (FT-V) or one from untreated control SPF mice (FT-C). The gastrointestinal transit time (GITT) was measured by administration of carmine red (6% w/v) solution. The expression of GLP-1 and GPR43 was examined by immunohistochemistry and realtime RT-PCR, and the plasma GLP-1 level was measured by ELISA. In vancomycin-treated SPF mice, the diversity of the gut microbiota was significantly reduced and the abundance of Lactobacillus was markedly increased. Significant increases in body weight, cecum weight, plasma GLP-1 level and colonic GLP-1/GPR43 expression were also noted relative to the controls. These alterations were reproducible in GF mice with FT-V. Moreover, FT-V GF mice showed a significantly increased food intake and a significantly prolonged GITT in comparison with FT-C GF mice. Vancomycin-induced dysbiosis promotes body weight gain and prolongs GITT, accompanied by an increase of colonic GLP-1/GPR43 expression.}, }
@article {pmid30861553, year = {2019}, author = {Roggenbrod, S and Schuler, C and Haller, B and Sohn, M and Storr, M and Schepp, W and Gundling, F}, title = {[Patient perception and approval of fecal microbiota transplantation (FMT) as an alternative treatment option for ulcerative colitis].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {57}, number = {3}, pages = {296-303}, doi = {10.1055/a-0821-7166}, pmid = {30861553}, issn = {1439-7803}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) represents a treatment option for recurring Clostridium difficile-associated colitis. However, there is also evidence that FMT can be effective in treating ulcerative colitis. This study examined the approval and willingness of affected patients who underwent FMT.<br><br>METHODS: A standardized questionnaire containing 27 polar and open questions was dispatched to a cohort of 262 patients suffering from UC. It included questions regarding the FMT process, donors, and possible concerns. Additionally, aspects of social background and disease activity were addressed.<br><br>RESULTS: The response rate was 31.3 % (n = 82). Forty-eight (58.5 %) patients were already aware of FMT. Forty-six (56.1 %) were willing to undergo FMT if given a respective indication. The effectiveness of the procedure (40.2 %), followed by failure of all other therapies (17.1 %), formed the principal motivation. The transmission of possible infectious agents (26.8 %), and the potential contamination of the stool graft leading to a deterioration of clinical symptoms, raised the most concerns. (20.7 %).The preferred delivery system of FMT was capsules (67.1 %), followed by colonoscopic application (47.6 %). The patients were in favour of a donor proposed by the physician (52,4 %). Willingness to undergo FMT did not differ significantly between genders (56.4 % women vs. 57.1 % men). Smokers (88.9 %), patients who did not watch television at all (77.8 %) and those with private health insurance, showed an increased willingness to undergo FMT.<br><br>CONCLUSION: For the majority of the UC patients surveyed, FMT represents a feasible treatment option. Approximately half of the respondents would consider FMT as an alternative treatment option, even inspite of a satisfactory disease response to current standard therapies. Unsurprisingly, there are concerns regarding the transmission of possible infectious agents and the hygienic implementation of FMT itself.}, }
@article {pmid30861317, year = {2019}, author = {Joseph, J and Saha, S and Greenberg-Worisek, AJ}, title = {Fecal Microbiota Transplantation: An Ambiguous Translational Pathway for a Promising Treatment.}, journal = {Clinical and translational science}, volume = {12}, number = {3}, pages = {206-208}, doi = {10.1111/cts.12621}, pmid = {30861317}, issn = {1752-8062}, }
@article {pmid30859364, year = {2019}, author = {Wang, J and Wang, P and Li, D and Hu, X and Chen, F}, title = {Beneficial effects of ginger on prevention of obesity through modulation of gut microbiota in mice.}, journal = {European journal of nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00394-019-01938-1}, pmid = {30859364}, issn = {1436-6215}, support = {D16110500540001//Beijing Municipal Science and Technology Project/ ; }, abstract = {PURPOSE: Recent evidence has demonstrated that the gut microbiota plays a critical role in the treatment of obesity and other metabolic dysfunctions. Ginger (Zingiber officinale Roscoe), one of the most commonly used spices and dietary supplements, has been shown to exert beneficial effects against obesity and related disorders. However, to date, the mechanisms linking these effects to the gut microbiota remain unclear. This study aims to investigate the relationship between the gut microbiota and the metabolic adaptations resulting from ginger supplementation in mice.<br><br>METHODS: Four groups of mice were fed a normal chow diet (NCD) or a high-fat diet (HFD) with or without ginger supplementation for 16 weeks. Lipid profiles, proinflammatory cytokines, glucose tolerance, microbiota composition and short-chain fatty acid (SCFA) concentrations were analyzed at the end of the experiment. In addition, microbiota-depleted mice were transplanted with the fecal microbiota of mice fed a HFD or mice fed a HFD along with ginger supplementation. Glucose tolerance and microbiota composition were assessed after a 8-week fecal microbiota transplantation (FMT).<br><br>RESULTS: We observed marked decreases in body weight, liver steatosis, and low-grade inflammation as well as amelioration of insulin resistance in the HFD-fed mice treated with ginger. Furthermore, ginger supplementation modulated the gut microbiota composition and increased species belonging to the Bifidobacterium genus and SCFA-producing bacteria (Alloprevotella and Allobaculum), along with increases in fecal SCFA concentrations. The FMT experiment showed anti-obesity and microbiota-modulating effects similar to those observed in the oral ginger-feeding experiment.<br><br>CONCLUSIONS: This study suggests that modulation of the gut microbiota as a result of ginger supplementation has a therapeutic effect on obesity in mice.}, }
@article {pmid30858872, year = {2019}, author = {Sartelli, M and Di Bella, S and McFarland, LV and Khanna, S and Furuya-Kanamori, L and Abuzeid, N and Abu-Zidan, FM and Ansaloni, L and Augustin, G and Bala, M and Ben-Ishay, O and Biffl, WL and Brecher, SM and Camacho-Ortiz, A and Caínzos, MA and Chan, S and Cherry-Bukowiec, JR and Clanton, J and Coccolini, F and Cocuz, ME and Coimbra, R and Cortese, F and Cui, Y and Czepiel, J and Demetrashvili, Z and Di Carlo, I and Di Saverio, S and Dumitru, IM and Eckmann, C and Eiland, EH and Forrester, JD and Fraga, GP and Frossard, JL and Fry, DE and Galeiras, R and Ghnnam, W and Gomes, CA and Griffiths, EA and Guirao, X and Ahmed, MH and Herzog, T and Kim, JI and Iqbal, T and Isik, A and Itani, KMF and Labricciosa, FM and Lee, YY and Juang, P and Karamarkovic, A and Kim, PK and Kluger, Y and Leppaniemi, A and Lohsiriwat, V and Machain, GM and Marwah, S and Mazuski, JE and Metan, G and Moore, EE and Moore, FA and Ordoñez, CA and Pagani, L and Petrosillo, N and Portela, F and Rasa, K and Rems, M and Sakakushev, BE and Segovia-Lohse, H and Sganga, G and Shelat, VG and Spigaglia, P and Tattevin, P and Tranà, C and Urbánek, L and Ulrych, J and Viale, P and Baiocchi, GL and Catena, F}, title = {2019 update of the WSES guidelines for management of Clostridioides (Clostridium) difficile infection in surgical patients.}, journal = {World journal of emergency surgery : WJES}, volume = {14}, number = {}, pages = {8}, doi = {10.1186/s13017-019-0228-3}, pmid = {30858872}, issn = {1749-7922}, mesh = {Anti-Bacterial Agents/therapeutic use ; Antimicrobial Stewardship ; Clostridium Infections/diagnosis/*therapy ; Clostridium difficile/*pathogenicity ; Enterocolitis, Pseudomembranous/etiology/prevention &amp; control ; Fecal Microbiota Transplantation/methods/trends ; Guidelines as Topic ; Humans ; Incidence ; Infection Control/methods/trends ; Postoperative Complications/*therapy ; Risk Factors ; }, abstract = {In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.}, }
@article {pmid30852592, year = {2019}, author = {Hirten, RP and Grinspan, A and Fu, SC and Luo, Y and Suarez-Farinas, M and Rowland, J and Contijoch, EJ and Mogno, I and Yang, N and Luong, T and Labrias, PR and Peter, I and Cho, JH and Sands, BE and Colombel, JF and Faith, JJ and Clemente, JC}, title = {Microbial Engraftment and Efficacy of Fecal Microbiota Transplant for Clostridium Difficile in Patients With and Without Inflammatory Bowel Disease.}, journal = {Inflammatory bowel diseases}, volume = {25}, number = {6}, pages = {969-979}, doi = {10.1093/ibd/izy398}, pmid = {30852592}, issn = {1536-4844}, support = {F31 DK112679/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: Recurrent and severe Clostridium difficile infections (CDI) are treated with fecal microbiota transplant (FMT). Uncertainty exists regarding FMT effectiveness for CDI with underlying inflammatory bowel disease (IBD) and regarding its effects on disease activity and effectiveness in transferring the donor microbiota to patients with and without IBD.<br><br>METHODS: Subjects with and without IBD who underwent FMT for recurrent or severe CDI between 2013 and 2016 at The Mount Sinai Hospital were followed for up to 6 months. The primary outcome was CDI recurrence 6 months after FMT. Secondary outcomes were (1) CDI recurrence 2 months after FMT; (2) frequency of IBD flare after FMT; (3) microbiota engraftment after FMT; (and 4) predictors of CDI recurrence.<br><br>RESULTS: One hundred thirty-four patients, 46 with IBD, were treated with FMT. Follow-up was available in 83 and 118 patients at 6 and 2 months, respectively. There was no difference in recurrence in patients with and without IBD at 6 months (38.7% vs 36.5%; P > 0.99) and 2 months (22.5% vs 17.9%; P = 0.63). Proton pump inhibitor use, severe CDI, and comorbid conditions were predictors of recurrence. Pre-FMT microbiota was not predictive of CDI recurrence. Subjects with active disease requiring medication escalation had reduced engraftment, with no difference in engraftment based on CDI recurrence or IBD endoscopic severity at FMT.<br><br>CONCLUSIONS: Inflammatory bowel disease did not affect CDI recurrence rates 6 months after FMT. Pre-FMT microbiota was not predictive of recurrence, and microbial engraftment was impacted in those requiring IBD treatment escalation, though not by CDI recurrence or IBD disease severity.}, }
@article {pmid30851429, year = {2019}, author = {Hibbard, J and Jiang, ZD and DuPont, HL}, title = {Fecal calprotectin and fecal indole predict outcome of fecal microbiota transplantation in subjects with recurrent Clostridium difficile infection.}, journal = {Anaerobe}, volume = {56}, number = {}, pages = {102-105}, doi = {10.1016/j.anaerobe.2019.03.006}, pmid = {30851429}, issn = {1095-8274}, abstract = {Fecal calprotectin and indole were studied in 134 subjects with recurrent CDI before and after FMT. Reduced fecal calprotectin (p = 0.0353, 95% CI 0.1305-0.1439) and rising levels of indole (p < 0.0001, 95% CI < 0.0001-0.0003) predicted successful treatment. A ratio of recal calprotectin/indole may provide prognostic value for FMT (p = 0.0004, 95% CI 0.22-0.87).}, }
@article {pmid30850823, year = {2019}, author = {Cammarota, G and Ianiro, G}, title = {FMT for ulcerative colitis: closer to the turning point.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {16}, number = {5}, pages = {266-268}, doi = {10.1038/s41575-019-0131-0}, pmid = {30850823}, issn = {1759-5053}, mesh = {*Colitis, Ulcerative ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Microbiota ; }, }
@article {pmid30848026, year = {2019}, author = {Chen, CC and Chen, YN and Liou, JM and Wu, MS and , }, title = {From germ theory to germ therapy.}, journal = {The Kaohsiung journal of medical sciences}, volume = {35}, number = {2}, pages = {73-82}, doi = {10.1002/kjm2.12011}, pmid = {30848026}, issn = {2410-8650}, support = {NTUH 106-P06//National Taiwan University Hospital/ ; NTUH 104-P05//National Taiwan University Hospital/ ; 107-0210-01-19-04//Translational Innovation of Biopharmaceutical Development-Technology Supporting Platform Axis/ ; MOHW107-TDU-B-211-123 002//Ministry of Health and Welfare of Taiwan/ ; MOHW106-TDU-B-211-113 002//Ministry of Health and Welfare of Taiwan/ ; MOST 107-3017-F-002-002//Ministry of Science and Technology, Executive Yuan, ROC, Taiwan/ ; TCTC-TR2 106-2321-B-002-025//Ministry of Science and Technology, Executive Yuan, ROC, Taiwan/ ; NTU-107 L9014-1//Ministry of Education (MOE) in Taiwan/ ; }, abstract = {Germ theory of disease and Koch's postulates has been governing our understanding of the role of microbes in human health since 19th century. The discovery of Helicobacter pylori (H. pylori) and H. pylori associated diseases has typically represented the concept and framework of Koch's postulates. Eradication of H. pylori to prevent peptic ulcers recurrence and gastric cancer is the triumph of this microbiology paradigm. Advances of next generation sequencing provide great insight into the unculturable microbes and show trillions of microbes have evolved with human beings. Research into the microbiome-the microbial communities (microbiota) and the host environment that they inhabit-has changed our understanding about microbes in human health and disease. The gut microbiota, the largest reservoir of the microbiome in human, plays a critical role in our catabolic-metabolism and immunity. This review will show the changes of the view of microbes on human health. We will briefly discuss dysbiosis, the disruption of symbiotic relationship between the host and microbiota, and the associated diseases. This leads to an idea to manipulate the microbiota, either by restoring missing functions or by eliminating harmful functions, to prevent or treat a variety of diseases. Current evidences of two common germ therapies, fecal microbiota transplantation and probiotics, in treating diseases will be reviewed.}, }
@article {pmid30847461, year = {2019}, author = {Olmedo, M and Reigadas, E and Valerio, M and Vázquez-Cuesta, S and Pajares, JA and Matilla, A and Muñoz, P and Bouza, E}, title = {Is it reasonable to perform Fecal Microbiota Transplantation for recurrent Clostridium difficile Infection in patients with liver cirrhosis?.}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {32}, number = {2}, pages = {205-207}, pmid = {30847461}, issn = {1988-9518}, }
@article {pmid30845942, year = {2019}, author = {Biagi, E and Zama, D and Rampelli, S and Turroni, S and Brigidi, P and Consolandi, C and Severgnini, M and Picotti, E and Gasperini, P and Merli, P and Decembrino, N and Zecca, M and Cesaro, S and Faraci, M and Prete, A and Locatelli, F and Pession, A and Candela, M and Masetti, R}, title = {Early gut microbiota signature of aGvHD in children given allogeneic hematopoietic cell transplantation for hematological disorders.}, journal = {BMC medical genomics}, volume = {12}, number = {1}, pages = {49}, doi = {10.1186/s12920-019-0494-7}, pmid = {30845942}, issn = {1755-8794}, support = {GR-2013-02357136//Ministero della Salute/ ; IG- 17200 and &quot;5xmille&quot;-9962//Associazione Italiana per la Ricerca sul Cancro/ ; }, abstract = {BACKGROUND: The onset of acute Graft-versus-Host Disease (aGvHD) has been correlated with the gut microbiota (GM) composition, but experimental observations are still few, mainly involving cohorts of adult patients. In the current scenario where fecal microbiota transplantation has been used as a pioneer therapeutic approach to treat steroid-refractory aGvHD, there is an urgent need to expand existing observational studies of the GM dynamics in Hematopoietic Stem Cell Transplantation (HSCT). Aim of the present study is to explore the GM trajectory in 36 pediatric HSCT recipients in relation to aGvHD onset.<br><br>METHODS: Thirty-six pediatric patients, from four transplantation centers, undergoing HSCT were enrolled in the study. Stools were collected at three time points: before HSCT, at time of engraftment and > 30 days following HSCT. Changes in the GM phylogenetic structure were studied by 16S rRNA gene Illumina sequencing and phylogenetic assignation.<br><br>RESULTS: Children developing gut aGvHD had a dysbiotic GM layout before HSCT occurred. This putative aGvHD-predisposing ecosystem state was characterized by (i) reduced diversity, (ii) lower Blautia content, (iii) increase in Fusobacterium abundance. At time of engraftment, the GM structure underwent a deep rearrangement in all patients but, regardless of the occurrence of aGvHD and its treatment, it reacquired a eubiotic configuration from day 30.<br><br>CONCLUSIONS: We found a specific GM signature before HSCT predictive of subsequent gut aGvHD occurrence. Our data may open the way to a GM-based stratification of the risk of developing aGvHD in children undergoing HSCT, potentially useful also to identify patients benefiting from prophylactic fecal transplantation.}, }
@article {pmid30844549, year = {2019}, author = {Meng, X and Zhou, HY and Shen, HH and Lufumpa, E and Li, XM and Guo, B and Li, BZ}, title = {Microbe-metabolite-host axis, two-way action in the pathogenesis and treatment of human autoimmunity.}, journal = {Autoimmunity reviews}, volume = {18}, number = {5}, pages = {455-475}, doi = {10.1016/j.autrev.2019.03.006}, pmid = {30844549}, issn = {1873-0183}, mesh = {Autoimmune Diseases/immunology/*metabolism/*microbiology/*therapy ; Autoimmunity/physiology ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/immunology/physiology ; Host Microbial Interactions/*physiology ; Humans ; Metabolic Networks and Pathways/immunology ; Prebiotics/microbiology ; Probiotics/metabolism/therapeutic use ; }, abstract = {The role of microorganism in human diseases cannot be ignored. These microorganisms have evolved together with humans and worked together with body's mechanism to maintain immune and metabolic function. Emerging evidence shows that gut microbe and their metabolites open up new doors for the study of human response mechanism. The complexity and interdependence of these microbe-metabolite-host interactions are rapidly being elucidated. There are various changes of microbial levels in models or in patients of various autoimmune diseases (AIDs). In addition, the relevant metabolites involved in mechanism mainly include short-chain fatty acids (SCFAs), bile acids (BAs), and polysaccharide A (PSA). Meanwhile, the interaction between microbes and host genes is also a factor that must be considered. It has been demonstrated that human microbes are involved in the development of a variety of AIDs, including organ-specific AIDs and systemic AIDs. At the same time, microbes or related products can be used to remodel body's response to alleviate or cure diseases. This review summarizes the latest research of microbes and their related metabolites in AIDs. More importantly, it highlights novel and potential therapeutics, including fecal microbial transplantation, probiotics, prebiotics, and synbiotics. Nonetheless, exact mechanisms still remain elusive, and future research will focus on finding a specific strain that can act as a biomarker of an autoimmune disease.}, }
@article {pmid30844145, year = {2019}, author = {Chang, CS and Ruan, JW and Kao, CY}, title = {An overview of microbiome based strategies on anti-obesity.}, journal = {The Kaohsiung journal of medical sciences}, volume = {35}, number = {1}, pages = {7-16}, doi = {10.1002/kjm2.12010}, pmid = {30844145}, issn = {2410-8650}, support = {106-2628-B-400-001-MY3//Ministry of Science and Technology, Taiwan (MOST)/ ; 104-2320-B-400-019-MY3//Ministry of Science and Technology, Taiwan (MOST)/ ; IM-107-PP-04//National Health Research Institutes (NHRI)/ ; }, abstract = {With the significant global obesity epidemic and emerging strong scientific evidence that connected gut microbiota to obesity, intervening obesity by targeting gut microbiota has become a trendy strategy. Particularly the application of probiotics has become remarkably popular because of their expected association with gut microbiota modulation. Although there are many literatures on the effects of probiotics in obese animal models, most of them reported the effects of probiotic bacteria on metabolic indications with limited information on anti-obesity itself. Besides, some probiotics have been shown to reduce certain metabolic symptoms but they failed to achieve weight loss. This report reviewed the current literatures on the anti-obesity effects of next-generation probiotics in various animal obesity models and discussed the beneficial potential of fecal microbiota transplantation in treating obesity in humans. The purpose of this article is to help guide further research improve the probiotic bacteria experiments in more precise animal obesity models by standardizing the anti-obesogenesis, obesity control, and treatment assays and hopefully the evidence-based investigations on harnessing gut microbiota through next-generation probiotics or fecal microbiota transplantation will develop new interventions to promote and achieve anti-obesity.}, }
@article {pmid30841760, year = {2019}, author = {Cammarota, G and Gallo, A and Ianiro, G and Montalto, M}, title = {Emerging drugs for the treatment of clostridium difficile.}, journal = {Expert opinion on emerging drugs}, volume = {24}, number = {1}, pages = {17-28}, doi = {10.1080/14728214.2019.1591371}, pmid = {30841760}, issn = {1744-7623}, mesh = {Anti-Bacterial Agents/*administration &amp; dosage ; Clostridium Infections/*drug therapy/epidemiology/microbiology ; Clostridium difficile/isolation &amp; purification ; Cross Infection/*drug therapy/epidemiology/microbiology ; Drug Development/methods ; Fecal Microbiota Transplantation/methods ; Humans ; Practice Guidelines as Topic ; }, abstract = {INTRODUCTION: Clostridium difficile or Clostridioides difficile (C. difficile) infection represents the most common cause of healthcare-associated infection. Over the last decades, the incidence and severity of C. difficile infection is rapidly increasing, with a significant impact on morbidity and mortality, and burden on health care system. Orally administered vancomycin and fidaxomicin are the therapeutic options of choice for initial C. difficile infection and fecal microbiota transplant for the recurrence infection. Furthermore, in recent years several new antibiotics with narrow-spectrum activity and low intestinal resorption have been developed, including surotomycin, cadazolid, and ridinilazol, and novel toxoid vaccines are expected to be efficacious in the prevention of C. difficile infection. Areas covered: Literature review was performed to select publications about current guidelines and phase-II/III trials on emerging drugs. These include novel antibiotics, monoclonal antibodies, vaccines, and fecal microbiota transplantation. Expert opinion: We have today a wide spectrum of promising therapeutic possibilities against infection. Pivotal future clinical trials may be crucial in developing effective strategies to optimize outcomes, mainly in high-risk population.}, }
@article {pmid30840758, year = {2019}, author = {Petito, V and Fiore, L and Lopetuso, LR and Scaldaferri, F}, title = {Commentary to &quot;Safety, Clinical Response, and Microbiome Findings Following Fecal Microbiota Transplant in Children With Inflammatory Bowel Disease&quot;.}, journal = {Inflammatory bowel diseases}, volume = {25}, number = {8}, pages = {e101}, doi = {10.1093/ibd/izz031}, pmid = {30840758}, issn = {1536-4844}, }
@article {pmid30837698, year = {2019}, author = {Thoma, C}, title = {Bile salt hydrolases involved in the effectiveness of FMT for Clostridium difficile infection.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {16}, number = {4}, pages = {198}, doi = {10.1038/s41575-019-0128-8}, pmid = {30837698}, issn = {1759-5053}, mesh = {Amidohydrolases ; *Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid30834334, year = {2019}, author = {Kim, P and Gadani, A and Abdul-Baki, H and Mitre, R and Mitre, M}, title = {Fecal microbiota transplantation in recurrent Clostridium difficile infection: A retrospective single-center chart review.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {3}, number = {1}, pages = {4-9}, doi = {10.1002/jgh3.12093}, pmid = {30834334}, issn = {2397-9070}, abstract = {Background and Aim: Fecal microbiota transplantation (FMT) has been proposed as a treatment option for patients with recurrent Clostridium difficile (C. difficile) infection but remains a novel option. We examined if FMT is an effective means of treating recurrent C. difficile infection.<br><br>Methods: A retrospective review of 35 patients who underwent FMT was completed. Demographics and other variables, including the use of proton pump inhibitor therapy and history of inflammatory bowel disease, were collected.<br><br>Results: Twenty-five patients (71.4%) belonged to a high-risk population (working in a hospital setting, rehabilitation center, or nursing facility) and a total of 74.3% of patients (n = 26 patients) had no history of proton pump inhibitor use. Twenty-five patients (71.4%) had used metronidazole prior to transplantation, 35 patients (100%) had used vancomycin, and 7 patients (20%) had used fidaxomicin for prior infection. Four patients (11.4%) had used all three antibiotics during prior treatment. Of the eight patients who had a history of inflammatory bowel disease, six (75%) experienced resolution of symptoms after transplantation. A total of 30 patients (85.7%) had resolution of their symptoms 6-8 weeks' posttransplant, while 5 patients (14.3%) continued to have symptoms.<br><br>Conclusions: Our retrospective chart review supports that patients benefit from FMT in the setting of recurrent C. difficile infection.}, }
@article {pmid30832423, year = {2019}, author = {Álvarez-Mercado, AI and Navarro-Oliveros, M and Robles-Sánchez, C and Plaza-Díaz, J and Sáez-Lara, MJ and Muñoz-Quezada, S and Fontana, L and Abadía-Molina, F}, title = {Microbial Population Changes and Their Relationship with Human Health and Disease.}, journal = {Microorganisms}, volume = {7}, number = {3}, pages = {}, doi = {10.3390/microorganisms7030068}, pmid = {30832423}, issn = {2076-2607}, support = {PI-0538-2017//Junta de Andalucía/ ; }, abstract = {Specific microbial profiles and changes in intestinal microbiota have been widely demonstrated to be associated with the pathogenesis of a number of extra-intestinal (obesity and metabolic syndrome) and intestinal (inflammatory bowel disease) diseases as well as other metabolic disorders, such as non-alcoholic fatty liver disease and type 2 diabetes. Thus, maintaining a healthy gut ecosystem could aid in avoiding the early onset and development of these diseases. Furthermore, it is mandatory to evaluate the alterations in the microbiota associated with pathophysiological conditions and how to counteract them to restore intestinal homeostasis. This review highlights and critically discusses recent literature focused on identifying changes in and developing gut microbiota-targeted interventions (probiotics, prebiotics, diet, and fecal microbiota transplantation, among others) for the above-mentioned pathologies. We also discuss future directions and promising approaches to counteract unhealthy alterations in the gut microbiota. Altogether, we conclude that research in this field is currently in its infancy, which may be due to the large number of factors that can elicit such alterations, the variety of related pathologies, and the heterogeneity of the population involved. Further research on the effects of probiotics, prebiotics, or fecal transplantations on the composition of the human gut microbiome is necessary.}, }
@article {pmid30827274, year = {2019}, author = {Albarrak, AA and Romana, BS and Uraz, S and Yousef, MH and Al Juboori, A and Tahan, V}, title = {Clostridium difficile infection in Inflammatory Bowel Disease Patients.}, journal = {Endocrine, metabolic &amp; immune disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/1871530319666190301120558}, pmid = {30827274}, issn = {2212-3873}, abstract = {BACKGROUND: The rising incidence of Clostridium difficile infection (CDI) in the general population has been recognized by health care organizations worldwide. The emergence of hypervirulent strains has made CDI more challenging to understand and treat. Inflammatory bowel disease (IBD) patients are at higher risk of infection, including CDI.<br><br>OBJECTIVE: A diagnostic approach for recurrent CDI has yet to be validated, particularly for IBD patients. Enzyme immunoassay (EIA) for toxins A and B, as well as glutamate dehydrogenase EIA, are both rapid testing options for the identification of CDI. Without a high index of suspicion, it is challenging to initially differentiate CDI from an IBD flare based on clinical evaluation alone.<br><br>METHOD/RESULTS: Here, we provide and up-to-date review on CDI in IBD patients. When caring for an IBD patient with suspected CDI, it is appropriate to empirically treat the presumed infection while awaiting further test results. Treatment with vancomycin or fidaxomicin, but not oral metronidazole, has been advocated by an expert review from the clinical practice update committee of the American Gastroenterology Association. Recurrent CDI is more common in IBD patients compared to non-IBD patients (32% versus 24%), thus more aggressive treatment is recommended for IBD patients along with early consideration of fecal microbiota transplant.<br><br>CONCLUSION: Although the use of infliximab during CDI has been debated, clinical experience exists supporting its use in an IBD flare, even with active CDI when needed.}, }
@article {pmid30821676, year = {2019}, author = {Grace, E and Chahine, EB}, title = {Updates on Clostridioides (Clostridium) difficile Infection With Emphasis on Long-Term Care.}, journal = {The Senior care pharmacist}, volume = {34}, number = {1}, pages = {29-42}, doi = {10.4140/TCP.n.2019.29}, pmid = {30821676}, issn = {2639-9636}, abstract = {OBJECTIVE: To provide a review of the classification, epidemiology, risk factors, diagnosis, treatment, and prevention of Clostridioides (Clostridium) difficile (C. difficile) infection (CDI) with an emphasis on longterm care.<br><br>DATA SOURCES: PubMed and Google Scholar were searched for relevant literature using a combination of the following terms: C. difficile, classification, epidemilogy, risk factors, diagnosis, treatment, prevention, and long-term care. Sources were limited to human data.<br><br>The main article reviewed was the 2017 CDI guidelines of the Infectious Diseases Society of American and the Society for Healthcare Epidemiology of America. Other articles were reviewed for relevance to CDI in long-term care settings.<br><br>DATA SYNTHESIS: CDI is associated with significant morbidity and mortality, particularly in older adults. The primary risk factors are advanced age and receipt of antibiotics. Diagnosis is suspected based on signs and symptoms and confirmed by laboratory tests. Vancomycin and fidaxomicin have replaced metronidazole as the drugs of choice for CDI. Fidaxomicin is associated with a lower risk of recurrence than vancomycin. Fecal microbiota transplantation is reserved for patients with multiple recurrences. Bezlotoxumab can be used in addition to standard therapy to prevent CDIs in patients at high risk for recurrence. Infection control strategies and antibiotic stewardship programs are known to reduce the rates of CDIs in institutional settings.<br><br>CONCLUSION: CDI is largely iatrogenic, and diagnosis is based on clinical presentation and laboratory tests. Treatment options include vancomycin, fidaxomicin, and fecal microbiota transplantation. Prevention centers around infection control and antibiotic stewardship. More research is needed in long-term care settings.}, }
@article {pmid30820491, year = {2019}, author = {Lam, TJ and Ye, Y}, title = {CRISPRs for Strain Tracking and Their Application to Microbiota Transplantation Data Analysis.}, journal = {The CRISPR journal}, volume = {2}, number = {1}, pages = {41-50}, doi = {10.1089/crispr.2018.0046}, pmid = {30820491}, issn = {2573-1599}, support = {R01 AI108888/AI/NIAID NIH HHS/United States ; R01 AI143254/AI/NIAID NIH HHS/United States ; }, abstract = {CRISPR-Cas systems are adaptive immune systems naturally found in bacteria and archaea. Prokaryotes use these immune systems to defend against invaders, which include phages, plasmids, and other mobile genetic elements. Relying on the integration of spacers derived from invader sequences (protospacers) into CRISPR loci (forming spacers flanked by repeats), CRISPR-Cas systems are able to store the memory of past immunological encounters. While CRISPR-Cas systems have evolved in response to invading mobile genetic elements, invaders have also developed mechanisms to avoid detection. As a result of an arms race between CRISPR-Cas systems and their targets, CRISPR arrays typically undergo rapid turnover of spacers through the acquisition and loss events. Additionally, microbiomes of different individuals rarely share spacers. Here, we present a computational pipeline, CRISPRtrack, for strain tracking based on CRISPR spacer content, and we applied it to fecal transplantation microbiome data to study the retention of donor strains in recipients. Our results demonstrate the potential use of CRISPRs as a simple yet effective tool for donor-strain tracking in fecal transplantation and as a general purpose tool for quantifying microbiome similarity.}, }
@article {pmid30820331, year = {2019}, author = {Gundling, F and Roggenbrod, S and Schleifer, S and Sohn, M and Schepp, W}, title = {Patient perception and approval of faecal microbiota transplantation (FMT) as an alternative treatment option for obesity.}, journal = {Obesity science &amp; practice}, volume = {5}, number = {1}, pages = {68-74}, doi = {10.1002/osp4.302}, pmid = {30820331}, issn = {2055-2238}, abstract = {Introduction: Fecal microbiota transplantation (FMT) represents a treatment option for some diseases, e.g. recurring Clostridium difficile-associated colitis. However, there is also evidence that FMT can be effective in treating obesity. This pilot study established the approval and willingness of obese patients to undergo FMT.<br><br>Methods: We conducted a survey of adults with obesity using a questionnaire containing 21 both multiple choice and open questions was dispatched to a cohort of 101 persons with obesity. It included questions aiming at the process of FMT itself, donors as well as possible concerns. Additionally aspects of social background and disease activity were dealt with.<br><br>Results: The response rate amounted to 30.1% (n = 31). In our population, mean BMI was 40.5 kg/m2 while the vast majority already tried out treatment modalities to lose weight before. 25.8% of persons with obesity were aware of FMT. 62.1% were willing to undergo FMT if the donor was healthy and anonymous while only 6.9% clearly refused this option. Sixty preferred an anonymous donor or a person proposed by their doctor while colonoscopy was the preferred application by 76.7%. The absence of risks of the procedure (47.8%) formed the principal motivation while reduction of medication was considered as least important reason (in 26.1). Insufficient testing of the faeces concerning infections raised the most concerns (in 61.6%).<br><br>Conclusion: For the majority of the persons with obesity surveyed FMT represents a treatment option. Approximately two thirds of the questionees would consider FMT as an alternative treatment option, even in spite of a satisfactory disease response to current standard therapies. Unsurprisingly there are concerns in regard to the transmission of possible infectious agents as well as to the hygieneic implementation of FMT itself.}, }
@article {pmid30817479, year = {2019}, author = {Kay, E and Hawramee, S and Pollani, S and Mandel, ED}, title = {Nonpharmacologic options for treating irritable bowel syndrome.}, journal = {JAAPA : official journal of the American Academy of Physician Assistants}, volume = {32}, number = {3}, pages = {38-42}, doi = {10.1097/01.JAA.0000553384.82884.b8}, pmid = {30817479}, issn = {1547-1896}, abstract = {Irritable bowel syndrome (IBS) is a chronic functional disorder with no organic cause. Risk factors are multifactorial and treatment typically consists of antimotility or stimulant laxatives and antidepressants. This article reviews several newer areas of interest: probiotics, fecal microbiota transplant, a low FODMAP diet, and cognitive behavioral therapy.}, }
@article {pmid30815845, year = {2019}, author = {Zhou, ZL and Jia, XB and Sun, MF and Zhu, YL and Qiao, CM and Zhang, BP and Zhao, LP and Yang, Q and Cui, C and Chen, X and Shen, YQ}, title = {Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson's Disease Mice via Gut Microbiota and Metabolites.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1007/s13311-019-00719-2}, pmid = {30815845}, issn = {1878-7479}, support = {81771384//National Natural Science Foundation of China/ ; 81801276//National Natural Science Foundation of China/ ; KYCX18_1870//Postgraduate Research &amp; Practice Innovation/ ; 2014-27//Jiangsu Double Innovation Plan/ ; JUFSTR20180101//National first-class discipline program of Food Science and Technology/ ; }, abstract = {Parkinson's disease (PD) is strongly associated with life style, especially dietary habits, which have gained attention as disease modifiers. Here, we report a fasting mimicking diet (FMD), fasting 3 days followed by 4 days of refeeding for three 1-week cycles, which accelerated the retention of motor function and attenuated the loss of dopaminergic neurons in the substantia nigra in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mice. Levels of brain-derived neurotrophic factor (BDNF), known to promote the survival of dopaminergic neurons, were increased in PD mice after FMD, suggesting an involvement of BDNF in FMD-mediated neuroprotection. Furthermore, FMD decreased the number of glial cells as well as the release of TNF-α and IL-1β in PD mice, showing that FMD also inhibited neuro-inflammation. 16S and 18S rRNA sequencing of fecal microbiota showed that FMD treatment modulated the shifts in gut microbiota composition, including higher abundance of Firmicutes, Tenericutes, and Opisthokonta and lower abundance of Proteobacteria at the phylum level in PD mice. Gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry revealed that FMD modulated the MPTP-induced lower propionic acid and isobutyric acid, and higher butyric acid and valeric acid and other metabolites. Transplantation of fecal microbiota, from normal mice with FMD treatment to antibiotic-pretreated PD mice increased dopamine levels in the recipient PD mice, suggesting that gut microbiota contributed to the neuroprotection of FMD for PD. These findings demonstrate that FMD can be a new means of preventing and treating PD through promoting a favorable gut microbiota composition and metabolites.}, }
@article {pmid30815766, year = {2019}, author = {Abu-Sbeih, H and Ali, FS and Wang, Y}, title = {Clinical Review on the Utility of Fecal Microbiota Transplantation in Immunocompromised Patients.}, journal = {Current gastroenterology reports}, volume = {21}, number = {4}, pages = {8}, doi = {10.1007/s11894-019-0677-6}, pmid = {30815766}, issn = {1534-312X}, abstract = {Fecal microbiota transplantation (FMT) represents a promising management modality for Clostridium difficile infection (CDI). In immunocompromised patients, FMT is utilized for CDI as well as emerging non-CDI indications such as inflammatory bowel disease and graft versus host disease. PURPOSE OF REVIEW: This review aims to shed light on the safety and efficacy of FMT in immunocompromised patients, including patients suffering for human immunodeficiency virus infection, solid organ and hematopoietic stem cell transplant recipients, cancer patients, and patients on immunosuppressive therapies. RECENT FINDINGS: Though the body of evidence concerning the use of FMT in immunocompromised is growing, no clinical trials exist to date. Present literature weighs in favor of FMT in immunocompromised patients, with an acceptable adverse effect profile and minimal risk of infectious adverse events. Further large scale studies and randomized controlled trials to validate the utility of FMT in immunocompromised individuals will be a welcomed endeavor.}, }
@article {pmid30810508, year = {2019}, author = {Falony, G and Vandeputte, D and Caenepeel, C and Vieira-Silva, S and Daryoush, T and Vermeire, S and Raes, J}, title = {The human microbiome in health and disease: hype or hope.}, journal = {Acta clinica Belgica}, volume = {74}, number = {2}, pages = {53-64}, doi = {10.1080/17843286.2019.1583782}, pmid = {30810508}, issn = {2295-3337}, mesh = {Colon/microbiology ; Disease ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {OBJECTIVES: The prognostic, diagnostic, and therapeutic potential of the human gut microbiota is widely recognised. However, translation of microbiome findings to clinical practice is challenging. Here, we discuss current knowledge and applications in the field.<br><br>METHODS: We revisit some recent advances in the field of faecal microbiome analyses with a focus on covariate analyses and ecological interpretation.<br><br>RESULTS: Population-level characterization of gut microbiota variation among healthy volunteers has allowed identifying microbiome covariates required for clinical studies. Currently, microbiome research is moving from relative to quantitative approaches that will shed a new light on microbiota-host interactions in health and disease.<br><br>CONCLUSIONS: Covariate characterization and technical advances increase reproducibility of microbiome research. Targeted in vitro/in vivo intervention studies will accelerate clinical implementation of microbiota findings.}, }
@article {pmid30809523, year = {2019}, author = {Ohkusa, T and Koido, S and Nishikawa, Y and Sato, N}, title = {Gut Microbiota and Chronic Constipation: A Review and Update.}, journal = {Frontiers in medicine}, volume = {6}, number = {}, pages = {19}, doi = {10.3389/fmed.2019.00019}, pmid = {30809523}, issn = {2296-858X}, abstract = {Background: Chronic constipation, including functional constipation and constipation-type irritable bowel syndrome, is a prevalent, multifactorial gastrointestinal disorder, and its etiology and pathophysiology remain poorly understood. Recently studies using 16S rRNA-based microbiota profiling have demonstrated dysbiosis of gut microbiota in chronic constipation. Aims: To provide an overview of recent studies for microbiota in chronic constipation and treatments for chronic constipation using probiotics, prebiotics, synbiotics, antibiotics and fecal microbiota transplantation (FMT). Methods: PubMed searches were performed up to 1 August 2018 using keywords: &quot;IBS,&quot; &quot;IBS-C,&quot; &quot;irritable bowel syndrome,&quot; &quot;irritable bowel syndrome with constipation,&quot; &quot;functional constipation,&quot; &quot;chronic constipation&quot; in combination with &quot;gut microbiota,&quot; &quot;dysbiosis,&quot; &quot;gut microflora&quot; for microbiota in chronic constipation, and in combination with &quot;probiotics,&quot; &quot;prebiotics,&quot; &quot;synbiotics,&quot; &quot;antibiotics,&quot; and &quot;fecal microbiota transplantation.&quot; Results: The findings of gut microbiota in functional constipation are inconsistent, and currently no consensus exists. Although no clear consensus exists, compared with healthy subjects, IBS-C patients have a lower level of Actinobacteria, including Bifidobacteria, in their fecal samples and a higher level of Bacteroidetes in their mucosa. In most randomized controlled and parallel-group trials, probiotics, prebiotics, synbiotics, antibiotics, and FMT therapy for chronic constipation were effective with few side effects. However, there are many studies in a small number and the types of probiotics are different, it is difficult to evaluate the effect. Conclusions: Evidence indicates that dysbiosis of gut microbiota may contribute to functional constipation and constipation-type irritable bowel syndrome. Targeting treatments for the dysbiosis of constipation by probiotics, prebiotics, synbiotics, antibiotics, and FMT may be a new option, especially for refractory constipation to conventional therapies.}, }
@article {pmid30809438, year = {2019}, author = {Li, Y and Zou, Z and Bian, X and Huang, Y and Wang, Y and Yang, C and Zhao, J and Xie, L}, title = {Fecal microbiota transplantation research output from 2004 to 2017: a bibliometric analysis.}, journal = {PeerJ}, volume = {7}, number = {}, pages = {e6411}, doi = {10.7717/peerj.6411}, pmid = {30809438}, issn = {2167-8359}, abstract = {Background: Fecal microbiota transplantation (FMT) is an emerging therapy against Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). Although the therapy has gained prominence, there has been no bibliometric analysis of FMT.<br><br>Methods: Studies published from 2004 to 2017 were extracted from the Science Citation Index Expanded. Bibliometric analysis was used to evaluate the number or cooperation network of publications, countries, citations, references, journals, authors, institutions and keywords.<br><br>Results: A total of 796 items were included, showing an increasing trend annually. Publications mainly came from 10 countries, led by the US (n = 363). In the top 100 articles ranked by the number of citations (range 47-1,158), American Journal of Gastroenterology (2017 IF = 10.231) took the top spot. The co-citation network had 7 co-citation clusters headed by 'recurrent Clostridium difficile infection'. The top 7 keywords with the strongest citation bursts had three parts, 'microbiota', ' diarrhea ', and 'case series'. All keywords were divided into four domains, 'disease', 'nosogenesis', 'trial', and 'therapy'.<br><br>Conclusions: This study shows the research performance of FMT from 2004 to 2017 and helps investigators master the trend of FMT, which is also an ongoing hotspot of research.}, }
@article {pmid30807838, year = {2019}, author = {Sougiannis, AT and VanderVeen, BN and Enos, RT and Velazquez, KT and Bader, JE and Carson, M and Chatzistamou, I and Walla, M and Pena, MM and Kubinak, JL and Nagarkatti, M and Carson, JA and Murphy, EA}, title = {Impact of 5 fluorouracil chemotherapy on gut inflammation, functional parameters, and gut microbiota.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2019.02.020}, pmid = {30807838}, issn = {1090-2139}, support = {F99 CA234920/CA/NCI NIH HHS/United States ; P20 GM103641/GM/NIGMS NIH HHS/United States ; P30 GM103336/GM/NIGMS NIH HHS/United States ; }, abstract = {Emerging evidence suggests that gut microbiota may influence the response to chemotherapy. We sought to characterize the effects of 5 fluorouracil (5FU) chemotherapy on colon inflammation and functional measures in colorectal cancer (CRC) and to further determine whether gut microbiota can influence this response. 50 C57BL/6 were randomized into four groups; Control + Vehicle (n = 10), Control + 5FU (n = 10), AOM/DSS + Vehicle (n = 15), and AOM/DSS + 5FU (n = 15). CRC was induced chemically by a single 10 mg/kg injection of azoxymethane (AOM) followed by two cycles (2% and 1%) of dextran sodium sulfate (DSS). Mice were then treated with 3 cycles of vehicle or 5FU (cycle 1: 40 mg/kg, cycle 2 + 3: 20 mg/kg). Functional tests (grip strength and run-to-fatigue) were performed prior to 5FU treatment (baseline) and at the completion of the second cycle of 5FU. Following the third 5FU cycle, mice were euthanized and the colon was evaluated for expression of inflammatory genes using RT-qPCR and stool samples were profiled using 16S rRNA sequencing. A second experiment used fecal microbiota transplantation from 5FU treated mice to control mice (n = 10-15/group) to determine whether 5FU associated changes in the microbiota could influence functional measures and colon inflammation. 5FU reduced grip strength (p < 0.05) and caused a trending decrease in run-to-fatigue performance in cancer mice (p = 0.06). Select intestinal inflammatory genes were significantly elevated with 5FU treatment and this was further exacerbated with cancer (p < 0.05). Microbiota analysis revealed increased dissimilarity and alterations in bacterial taxonomy in 5FU and AOM/DSS-treated mice (p < 0.05). Fecal transplant from 5FU treated mice reduced functional performance (p < 0.05) and altered select colon inflammatory markers (p < 0.05). This study provides evidence of an effect of 5FU on inflammatory responses and functional measures in a mouse model of CRC and suggests that gut microbes may play a role in some, but not all, 5FU related perturbations.}, }
@article {pmid30804820, year = {2019}, author = {Cheung, SG and Goldenthal, AR and Uhlemann, AC and Mann, JJ and Miller, JM and Sublette, ME}, title = {Systematic Review of Gut Microbiota and Major Depression.}, journal = {Frontiers in psychiatry}, volume = {10}, number = {}, pages = {34}, doi = {10.3389/fpsyt.2019.00034}, pmid = {30804820}, issn = {1664-0640}, support = {P50 MH090964/MH/NIMH NIH HHS/United States ; R01 AI116939/AI/NIAID NIH HHS/United States ; }, abstract = {Background: Recently discovered relationships between the gastrointestinal microbiome and the brain have implications for psychiatric disorders, including major depressive disorder (MDD). Bacterial transplantation from MDD patients to rodents produces depression-like behaviors. In humans, case-control studies have examined the gut microbiome in healthy and affected individuals. We systematically reviewed existing studies comparing gut microbial composition in MDD and healthy volunteers. Methods: A PubMed literature search combined the terms &quot;depression,&quot; &quot;depressive disorder,&quot; &quot;stool,&quot; &quot;fecal,&quot; &quot;gut,&quot; and &quot;microbiome&quot; to identify human case-control studies that investigated relationships between MDD and microbiota quantified from stool. We evaluated the resulting studies, focusing on bacterial taxa that were different between MDD and healthy controls. Results: Six eligible studies were found in which 50 taxa exhibited differences (p < 0.05) between patients with MDD and controls. Patient characteristics and methodologies varied widely between studies. Five phyla-Bacteroidetes, Firmicutes, Actinobacteria, Fusobacteria, and Protobacteria-were represented; however, divergent results occurred across studies for all phyla. The largest number of differentiating taxa were within phylum Firmicutes, in which nine families and 12 genera differentiated the diagnostic groups. The majority of these families and genera were found to be statistically different between the two groups in two identified studies. Family Lachnospiraceae differentiated the diagnostic groups in four studies (with an even split in directionality). Across all five phyla, nine genera were higher in MDD (Anaerostipes, Blautia, Clostridium, Klebsiella, Lachnospiraceae incertae sedis, Parabacteroides, Parasutterella, Phascolarctobacterium, and Streptococcus), six were lower (Bifidobacterium, Dialister, Escherichia/Shigella, Faecalibacterium, and Ruminococcus), and six were divergent (Alistipes, Bacteroides, Megamonas, Oscillibacter, Prevotella, and Roseburia). We highlight mechanisms and products of bacterial metabolism as they may relate to the etiology of depression. Conclusions: No consensus has emerged from existing human studies of depression and gut microbiome concerning which bacterial taxa are most relevant to depression. This may in part be due to differences in study design. Given that bacterial functions are conserved across taxonomic groups, we propose that studying microbial functioning may be more productive than a purely taxonomic approach to understanding the gut microbiome in depression.}, }
@article {pmid30803179, year = {2019}, author = {Mo, R and Ren, RR and Zhang, XW and Yang, YS}, title = {[Fecal microbiota transplantation for the treatment of ulcerative colitis: a Meta-analysis].}, journal = {Zhonghua nei ke za zhi}, volume = {58}, number = {3}, pages = {202-208}, doi = {10.3760/cma.j.issn.0578-1426.2019.03.010}, pmid = {30803179}, issn = {0578-1426}, support = {2015AA020701//National High Technology Research and Development Program of China/ ; }, mesh = {Colitis, Ulcerative/*microbiology/*therapy ; *Drug-Related Side Effects and Adverse Reactions ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Gastrointestinal Microbiome ; Humans ; Inclusion Bodies ; Microbiota ; Randomized Controlled Trials as Topic ; Remission Induction ; Treatment Outcome ; }, abstract = {Objective: We aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for the treatment of ulcerative colitis (UC) in this Meta-analysis. Methods: Literature related to FMT for the treatment of UC from PubMed, Embase, Cochrane databases, CNKI, VIP and Wanfang Data were searched and screened with update study in May 2018. Two independent investigators extracted information according to inclusion and exclusion criteria. The Meta-analysis was conducted by Stata 12.0 software. Results: A total of 4 randomized controlled trials (RCTs) and 19 non-randomized controlled trials (non-RCTs) including 536 participants met the inclusion criteria. Meta-analysis of RCTs showed that FMT significantly increased the clinical remission rate (OR=2.47, 95%CI 1.40-4.33, P=0.02) and clinical response rate (OR=1.86, 95%CI 1.15-3.02, P=0.01) in UC patients without increasing the incidence of severe adverse effects (OR=1.40, 95%CI 0.51-3.79, P=0.51). The results from 19 non-RCTs showed that clinical remission rate in UC patients with FMT treatment was 20%(95%CI 13%-28%) and the clinical response rate was 50%(95%CI 36%-65%). All adverse events were graded as mild and self-resolving. No FMT-related severe adverse effects were reported. Conclusions: Our analysis suggests that FMT is a safe and effective method for the treatment of UC. Considering several limitations of this Meta-analysis and previous clinical trials, further large-scale multicenter RCTs are still required to further verify the conclusion.}, }
@article {pmid30796005, year = {2019}, author = {Papanicolas, LE and Choo, JM and Wang, Y and Leong, LEX and Costello, SP and Gordon, DL and Wesselingh, SL and Rogers, GB}, title = {Bacterial viability in faecal transplants: Which bacteria survive?.}, journal = {EBioMedicine}, volume = {41}, number = {}, pages = {509-516}, doi = {10.1016/j.ebiom.2019.02.023}, pmid = {30796005}, issn = {2352-3964}, mesh = {Acetates/metabolism ; Bacteria/genetics/isolation &amp; purification/*metabolism ; Bacterial Proteins/genetics ; Butyrates/metabolism ; Coenzyme A-Transferases/genetics ; Fatty Acids, Volatile/biosynthesis ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Freezing ; Gastrointestinal Microbiome ; Humans ; Microbial Viability ; RNA, Ribosomal, 16S/chemistry/genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: The therapeutic potential of faecal microbiota transplantation (FMT) is under investigation for a range of inflammatory conditions. While mechanisms of benefit are poorly understood, most models rely on the viability of transplanted microbes. We hypothesised that protocols commonly used in the preparation of faecal transplants will substantially reduce the number, diversity and functional potential of viable microbes.<br><br>METHODS: Stools from eight screened donors were processed under strict anaerobic conditions, in ambient air, and freeze-thawed. Propidium monoazide (PMA) sample treatment was combined with quantitative PCR, 16S rRNA gene amplicon sequencing and short-chain fatty acid (SCFA) analysis to define the viable microbiota composition and functional potential.<br><br>FINDINGS: Approximately 50% of bacterial content of stool processed immediately under strict anaerobic conditions was non-viable. Homogenisation in ambient air or freeze-thaw reduced viability to 19% and 23% respectively. Processing of samples in ambient air resulted in up to 12-fold reductions in the abundance of important commensal taxa, including the highly butyrogenic species Faecalibacterium prausnitzii, Subdoligranulum variable, and Eubacterium hallii. The adverse impact of atmospheric oxygen exposure on the capacity of the transplanted microbiota to support SCFA biosynthesis was demonstrated by significantly reduced butyrate and acetate production by faecal slurries processed in ambient air. In contrast, while reducing overall levels of viable bacteria, freeze-thaw did not significantly alter viable microbiota composition.<br><br>INTERPRETATION: The practice of preparing material for faecal transplantation in ambient air profoundly affects viable microbial content, disproportionately reducing the abundance of anaerobic commensals and the capacity for biosynthesis of important anti-inflammatory metabolites. FUND: This work was supported by the South Australian Health and Medical Research Institute. LP is supported by a scholarship from the Flinders Foundation. GR is supported by a Matthew Flinders Research Fellowship.}, }
@article {pmid30792981, year = {2019}, author = {Shin, W and Wu, A and Massidda, MW and Foster, C and Thomas, N and Lee, DW and Koh, H and Ju, Y and Kim, J and Kim, HJ}, title = {A Robust Longitudinal Co-culture of Obligate Anaerobic Gut Microbiome With Human Intestinal Epithelium in an Anoxic-Oxic Interface-on-a-Chip.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {7}, number = {}, pages = {13}, doi = {10.3389/fbioe.2019.00013}, pmid = {30792981}, issn = {2296-4185}, abstract = {The majority of human gut microbiome is comprised of obligate anaerobic bacteria that exert essential metabolic functions in the human colon. These anaerobic gut bacteria constantly crosstalk with the colonic epithelium in a mucosal anoxic-oxic interface (AOI). However, in vitro recreation of the metabolically mismatched colonic AOI has been technically challenging. Furthermore, stable co-culture of the obligate anaerobic commensal microbiome and epithelial cells in a mechanically dynamic condition is essential for demonstrating the host-gut microbiome crosstalk. Here, we developed an anoxic-oxic interface-on-a-chip (AOI Chip) by leveraging a modified human gut-on-a-chip to demonstrate a controlled oxygen gradient in the lumen-capillary transepithelial interface by flowing anoxic and oxic culture medium at various physiological milieus. Computational simulation and experimental results revealed that the presence of the epithelial cell layer and the flow-dependent conditioning in the lumen microchannel is necessary and sufficient to create the steady-state vertical oxygen gradient in the AOI Chip. We confirmed that the created AOI does not compromise the viability, barrier function, mucin production, and the expression and localization of tight junction proteins in the 3D intestinal epithelial layer. Two obligate anaerobic commensal gut microbiome, Bifidobacterium adolescentis and Eubacterium hallii, that exert metabolic cross-feeding in vivo, were independently co-cultured with epithelial cells in the AOI Chip for up to a week without compromising any cell viability. Our new protocol for creating an AOI in a microfluidic gut-on-a-chip may enable to demonstrate the key physiological interactions of obligate anaerobic gut microbiome with the host cells associated with intestinal metabolism, homeostasis, and immune regulation.}, }
@article {pmid30791840, year = {2019}, author = {Lauro, A and Lacaille, F}, title = {Short bowel syndrome in children and adults: from rehabilitation to transplantation.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {13}, number = {1}, pages = {55-70}, doi = {10.1080/17474124.2019.1541736}, pmid = {30791840}, issn = {1747-4132}, mesh = {Adult ; Age Factors ; Child ; Child, Preschool ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Infant ; Infant, Newborn ; Intestinal Absorption ; Intestines/microbiology/physiopathology/*transplantation ; Nutritional Status ; *Parenteral Nutrition/adverse effects ; Recovery of Function ; Risk Factors ; Short Bowel Syndrome/epidemiology/physiopathology/*rehabilitation/*surgery ; Treatment Outcome ; }, abstract = {INTRODUCTION: Short bowel syndrome (SBS) is a dramatic clinical condition in both children and adults; the residual bowel length is not sufficient to avoid intestinal failure, with subsequent malnutrition and growth retardation, and intravenous support is required to provide the nutrients normally coming from the intestine. Apart from the primary disease, the medical status can be worsened by complications of intestinal failure: if there are irreversible, the prognosis is poor unless a successful intestinal rehabilitation is achieved. Areas covered: The rescue of the remnant small bowel requires a multidisciplinary expertise to achieve digestive autonomy. The use of intestinal trophic factors has shown encouraging results in improving the intestinal adaptation process. Whenever the residual bowel length is inadequate, in a well-selected population weaning parenteral nutrition (PN) off could be attempted by surgery through lengthening procedures. A further subset of patients, with total and irreversible intestinal failure and severe complications on PN, may have an indication to intestinal transplantation. This procedure is still affected by poor long-term results. Expert commentary: Novel approaches developed through a multidisciplinary team work, such as manipulation of microbiota or tissue bioengineering, should be added to current therapies to treat successfully SBS.}, }
@article {pmid30791837, year = {2019}, author = {Hatton, G and Shawcross, DL}, title = {Is treating the gut microbiome the key to achieving better outcomes in cirrhosis?.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {13}, number = {1}, pages = {1-2}, doi = {10.1080/17474124.2019.1543587}, pmid = {30791837}, issn = {1747-4132}, mesh = {Animals ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Bacteria/*drug effects/growth &amp; development/immunology ; Dysbiosis ; *Fecal Microbiota Transplantation/adverse effects ; Gastrointestinal Microbiome/*drug effects ; Host-Pathogen Interactions ; Humans ; Immunity, Innate ; Intestines/*drug effects/immunology/microbiology ; Liver Cirrhosis/diagnosis/immunology/microbiology/*therapy ; Probiotics/adverse effects/*therapeutic use ; Treatment Outcome ; }, }
@article {pmid30791767, year = {2019}, author = {Suk, KT and Kim, DJ}, title = {Gut microbiota: novel therapeutic target for nonalcoholic fatty liver disease.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {13}, number = {3}, pages = {193-204}, doi = {10.1080/17474124.2019.1569513}, pmid = {30791767}, issn = {1747-4132}, mesh = {Animals ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Bacteria/*drug effects/growth &amp; development ; *Dietary Supplements/adverse effects ; Dysbiosis ; *Fecal Microbiota Transplantation/adverse effects ; Gastrointestinal Microbiome/*drug effects ; Host Microbial Interactions ; Humans ; Intestines/*drug effects/microbiology ; Non-alcoholic Fatty Liver Disease/diagnosis/epidemiology/microbiology/*therapy ; Prebiotics ; Prevalence ; Probiotics/therapeutic use ; Risk Factors ; Synbiotics ; Treatment Outcome ; }, abstract = {INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is one of the most common and increasing liver diseases worldwide with a prevalence of 20-33%. NAFLD may progress to fibrosis, compensated cirrhosis, advanced cirrhosis, or hepatocellular carcinoma. Despite the increasing prevalence of NAFLD, definitive medical treatment has not been established, with the exception of lifestyle modification with exercise. Because of the direct connection via portal vein between the intestines and the liver (gut-gut microbiota-liver axis), gut microbiota and associated dysbiosis have been known as regulators in the pathophysiology of NAFLD. Area covered: New therapeutic approaches for modulation of gut microbiota have been proposed and the effectiveness of new therapies including probiotics, prebiotics, synbiotics, bile acid regulation, absorbent, and fecal microbiota transplantation have been demonstrated in recent several studies. This review focuses on the available evidences for new therapies modulating gut microbiota in the management and the prevention of NAFLD. Expert commentary: Gut-gut microbiota-liver axis may play an important role in the etiology of many liver diseases, including NAFLD. It is logical to seek the manipulation of this axis, and further studies are required to understand the underlying precise mechanisms of microbiota-modulation on NAFLD.}, }
@article {pmid30783183, year = {2019}, author = {Khan, N and Mendonca, L and Dhariwal, A and Fontes, G and Menzies, D and Xia, J and Divangahi, M and King, IL}, title = {Intestinal dysbiosis compromises alveolar macrophage immunity to Mycobacterium tuberculosis.}, journal = {Mucosal immunology}, volume = {12}, number = {3}, pages = {772-783}, doi = {10.1038/s41385-019-0147-3}, pmid = {30783183}, issn = {1935-3456}, support = {MOP-130579//CIHR/Canada ; FDN-143273//CIHR/Canada ; }, mesh = {Animals ; Antibiotics, Antitubercular/*therapeutic use ; Disease Models, Animal ; Drug-Related Side Effects and Adverse Reactions/*immunology ; Dysbiosis/etiology/*immunology ; Gastrointestinal Microbiome/drug effects/*physiology ; Host-Pathogen Interactions ; Humans ; Immunity, Innate/drug effects ; Immunomodulation ; Isoniazid/therapeutic use ; Macrophages, Alveolar/drug effects/*metabolism ; Mice ; Mice, Inbred C57BL ; Mycobacterium tuberculosis/*physiology ; Pyrazinamide/therapeutic use ; Rifampin/therapeutic use ; Tuberculosis, Pulmonary/*drug therapy ; }, abstract = {Current treatments for tuberculosis (TB) are effective in controlling Mycobacterium tuberculosis (Mtb) growth, yet have significant side effects and do not prevent reinfection. Therefore, it is critical to understand why our host defense system is unable to generate permanent immunity to Mtb despite prolonged anti-tuberculosis therapy (ATT). Here, we demonstrate that treatment of mice with the most widely used anti-TB drugs, rifampicin (RIF) or isoniazid (INH) and pyrazinamide (PYZ), significantly altered the composition of the gut microbiota. Unexpectedly, treatment of mice with the pro-Mtb drugs INH and PYZ, but not RIF, prior to Mtb infection resulted in an increased bacterial burden, an effect that was reversible by fecal transplantation from untreated animals. Mechanistically, susceptibility of INH/PYZ-treated mice was associated with impaired metabolism of alveolar macrophages and defective bactericidal activity. Collectively, these data indicate that dysbiosis induced by ATT administered to millions of individuals worldwide may have adverse effects on the anti-Mtb response of alveolar macrophages.}, }
@article {pmid30782238, year = {2019}, author = {Cai, T and Shi, X and Yuan, LZ and Tang, D and Wang, F}, title = {Fecal microbiota transplantation in an elderly patient with mental depression.}, journal = {International psychogeriatrics}, volume = {}, number = {}, pages = {1-2}, doi = {10.1017/S1041610219000115}, pmid = {30782238}, issn = {1741-203X}, }
@article {pmid30778870, year = {2019}, author = {Allegretti, JR and Fischer, M and Sagi, SV and Bohm, ME and Fadda, HM and Ranmal, SR and Budree, S and Basit, AW and Glettig, DL and de la Serna, EL and Gentile, A and Gerardin, Y and Timberlake, S and Sadovsky, R and Smith, M and Kassam, Z}, title = {Correction to: Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Low Dose.}, journal = {Digestive diseases and sciences}, volume = {64}, number = {7}, pages = {2059}, doi = {10.1007/s10620-019-05527-4}, pmid = {30778870}, issn = {1573-2568}, abstract = {The original version of the article unfortunately contained an error in article title. The corrected title is 'Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Low Dose'.}, }
@article {pmid30771528, year = {2019}, author = {Huttner, BD and Galperine, T and Kapel, N and Harbarth, S}, title = {'A five-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae' - Author's reply.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {25}, number = {7}, pages = {914-915}, doi = {10.1016/j.cmi.2019.02.001}, pmid = {30771528}, issn = {1469-0691}, mesh = {Anti-Bacterial Agents ; *Enterobacteriaceae ; *Enterobacteriaceae Infections ; Fecal Microbiota Transplantation ; Humans ; beta-Lactamases ; }, }
@article {pmid30763538, year = {2019}, author = {Gogokhia, L and Buhrke, K and Bell, R and Hoffman, B and Brown, DG and Hanke-Gogokhia, C and Ajami, NJ and Wong, MC and Ghazaryan, A and Valentine, JF and Porter, N and Martens, E and O'Connell, R and Jacob, V and Scherl, E and Crawford, C and Stephens, WZ and Casjens, SR and Longman, RS and Round, JL}, title = {Expansion of Bacteriophages Is Linked to Aggravated Intestinal Inflammation and Colitis.}, journal = {Cell host &amp; microbe}, volume = {25}, number = {2}, pages = {285-299.e8}, doi = {10.1016/j.chom.2019.01.008}, pmid = {30763538}, issn = {1934-6069}, support = {//Wellcome Trust/United Kingdom ; DP2 GM111099/GM/NIGMS NIH HHS/United States ; R00 HL102228/HL/NHLBI NIH HHS/United States ; R01 GM114817/GM/NIGMS NIH HHS/United States ; R01 DK114252/DK/NIDDK NIH HHS/United States ; DP2 AT008746/AT/NCCIH NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*virology ; *Bacteriophages ; CD4-Positive T-Lymphocytes/metabolism ; Colitis, Ulcerative/*immunology/*microbiology/pathology ; Colorectal Neoplasms/*immunology/*microbiology/pathology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Interferon-gamma/metabolism ; Intestinal Mucosa/*immunology/*microbiology/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pilot Projects ; Prospective Studies ; Specific Pathogen-Free Organisms ; }, abstract = {Bacteriophages are the most abundant members of the microbiota and have the potential to shape gut bacterial communities. Changes to bacteriophage composition are associated with disease, but how phages impact mammalian health remains unclear. We noted an induction of host immunity when experimentally treating bacterially driven cancer, leading us to test whether bacteriophages alter immune responses. Treating germ-free mice with bacteriophages leads to immune cell expansion in the gut. Lactobacillus, Escherichia, and Bacteroides bacteriophages and phage DNA stimulated IFN-γ via the nucleotide-sensing receptor TLR9. The resultant immune responses were both phage and bacteria specific. Additionally, increasing bacteriophage levels exacerbated colitis via TLR9 and IFN-γ. Similarly, ulcerative colitis (UC) patients responsive to fecal microbiota transplantation (FMT) have reduced phages compared to non-responders, and mucosal IFN-γ positively correlates with bacteriophage levels. Bacteriophages from active UC patients induced more IFN-γ compared to healthy individuals. Collectively, these results indicate that bacteriophages can alter mucosal immunity to impact mammalian health.}, }
@article {pmid30761273, year = {2019}, author = {Li, X and Song, L and Zhu, S and Xiao, Y and Huang, Y and Hua, Y and Chu, Q and Ren, Z}, title = {Two Strains of Lactobacilli Effectively Decrease the Colonization of VRE in a Mouse Model.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {6}, doi = {10.3389/fcimb.2019.00006}, pmid = {30761273}, issn = {2235-2988}, abstract = {Vancomycin-resistant Enterococcus (VRE) infection is a serious challenge for clinical management and there is no effective treatment at present. Fecal microbiota transplantation (FMT) and probiotic intervention have been shown to be promising approaches for reducing the colonization of certain pathogenic bacteria in the gastrointestinal tract, however, no such studies have been done on VRE. In this study, we evaluated the effect of FMT and two Lactobacillus strains (Y74 and HT121) on the colonization of VRE in a VRE-infection mouse model. We found that both Lactobacilli strains reduced VRE colonization rapidly. Fecal microbiota and colon mRNA expression analyses further showed that mice in FMT and the two Lactobacilli treatment groups restored their intestinal microbiota diversity faster than those in the phosphate buffer saline (PBS) treated group. Administration of Lactobacilli restored Firmicutes more quickly to the normal level, compared to FMT or PBS treatment, but restored Bacteroides to their normal level less quickly than FMT did. Furthermore, these treatments also had an impact on the relative abundance of intestinal microbiota composition from phylum to species level. RNA-seq showed that FMT treatment induced the expression of more genes in the colon, compared to the Lactobacilli treatment. Defense-related genes such as defensin α, Apoa1, and RegIII were down-regulated in both FMT and the two Lactobacilli treatment groups. Taken together, our findings indicate that both FMT and Lactobacilli treatments were effective in decreasing the colonization of VRE in the gut.}, }
@article {pmid30761129, year = {2019}, author = {Heimesaat, MM and Escher, U and Grunau, A and Kühl, AA and Bereswill, S}, title = {Multidrug-Resistant Pseudomonas aeruginosa Accelerate Intestinal, Extra-Intestinal, and Systemic Inflammatory Responses in Human Microbiota-Associated Mice With Subacute Ileitis.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {49}, doi = {10.3389/fimmu.2019.00049}, pmid = {30761129}, issn = {1664-3224}, abstract = {The globally rising incidences of multidrug-resistant (MDR) Pseudomonas aeruginosa (Psae) in humans and live-stock animals has prompted the World Health Organization to rate MDR Psae as serious threat for human health. Only little is known, however, regarding factors facilitating gastrointestinal Psae-acquisition by the vertebrate host and subsequently induced inflammatory sequelae. In the present study, we addressed whether subacute ileitis predisposed mice harboring a human gut microbiota for intestinal MDR Psae carriage and whether inflammatory responses might be induced following peroral challenge with the opportunistic pathogen. To accomplish this, secondary abiotic mice were associated with a human gut microbiota by fecal microbiota transplantation. Ten days later (i.e., on day 0), subacute ileitis was induced in human microbiota associated (hma) mice by peroral low-dose Toxoplasma gondii infection. On day 5 post-infection, mice were perorally challenged with 109 colony forming units of a clinical MDR Psae isolate by gavage and the fecal bacterial loads surveyed thereafter. Four days post-peroral challenge, only approximately one third of mice with a human gut microbiota and subacute ileitis harbored the opportunistic pathogen in the intestinal tract. Notably, the gut microbiota composition was virtually unaffected by the Psae-carriage status during subacute ileitis of hma mice. The Psae challenge resulted, however, in more pronounced intestinal epithelial apoptotic cell and T lymphocyte responses upon ileitis induction that were not restricted to the ileum, but also affected the large intestines. Higher Psae-induced abundances of T cells could additionally be observed in extra-intestinal compartments including liver, kidney, lung, and heart of hma mice with subacute ileitis. Furthermore, higher apoptotic cell numbers, but lower anti-inflammatory IL-10 concentrations were assessed in the liver of Psae as compared to mock treated mice with ileitis. Remarkably, Psae-challenge was accompanied by even more pronounced systemic secretion of pro-inflammatory cytokines such as TNF and IL-6 at day 9 post ileitis induction. In conclusion, whereas in one third of hma mice with subacute ileitis Psae could be isolated from the intestines upon peroral challenge, the opportunistic pathogen was responsible for inflammatory sequelae in intestinal, extra-intestinal, and even systemic compartments and thus worsened subacute ileitis outcome irrespective of the Psae-carrier status.}, }
@article {pmid30747433, year = {2018}, author = {Polívková, S and Vojtilová, L and Husa, P and Beneš, J}, title = {[Guideline for fecal bacteriotherapy to treat recurrent Clostridium difficile colitis].}, journal = {Klinicka mikrobiologie a infekcni lekarstvi}, volume = {24}, number = {2}, pages = {57-64}, pmid = {30747433}, issn = {1211-264X}, mesh = {Adolescent ; Anti-N-Methyl-D-Aspartate Receptor Encephalitis/*complications ; Clostridium Infections/*therapy ; Clostridium difficile/*isolation &amp; purification ; *Fecal Microbiota Transplantation ; Female ; Humans ; Yellow Fever Vaccine/*adverse effects/*immunology ; }, abstract = {We present a case of a 17-year-old female with anti-NMDAR encephalitis probably associated with vaccination against yellow fever. Her symptoms occurred 27 days after vaccination against yellow fever. Anti-NMDAR encephalitis manifested as acute psychosis, memory loss and catatonia following fever with complex partial epileptic seizures. Interictal electroencephalogram showed slow-wave delta background activity with &quot;delta brushes&quot;. The diagnosis was confirmed by NMDAR antibody positivity in serum and cerebrospinal fluid. Since ovarian teratoma, as the most common cause of anti-NMDAR encephalitis, did not develop within five years from its onset, the association with vaccination against yellow fever seems to be highly probable.}, }
@article {pmid30738489, year = {2019}, author = {Qi, L and Li, F}, title = {[Current Advances in the Fecal Microbiota Transplantation and Its Application in the Hematologic Diseases--Review].}, journal = {Zhongguo shi yan xue ye xue za zhi}, volume = {27}, number = {1}, pages = {306-310}, doi = {10.7534/j.issn.1009-2137.2019.01.051}, pmid = {30738489}, issn = {1009-2137}, mesh = {Clostridium Infections ; Clostridium difficile ; Dysbiosis ; Fecal Microbiota Transplantation ; *Hematologic Diseases ; Humans ; Treatment Outcome ; }, abstract = {Intestinal microbiome closely relates with human health and disease, which plays a critical role in the immune response, homeostasis, drug metabolism and tumorigenesis. Imbalances in the composition and function of these intestinal microbes associate with diseases. Fecal microbiota transplantation (FMT) is an established successful treatment modality for recurrent Clostridium difficile infection (CDI). The safety profile and potential therapeutic advantages of FMT for diseases associated with dysbiosis and immune dysfunction have led to many publications, mainly case series. The literature on the use of FMT for hematologic diseases is very limited, however, immune thrombocytopenic purpura（ITP）, CDI and aGVHD after HSCT were reported to be improved by FMT. The aim of this review is to briefly summarize the research current state, procedures and clinical application of FMT.}, }
@article {pmid30733264, year = {2019}, author = {Battipaglia, G and Malard, F and Rubio, MT and Ruggeri, A and Mamez, AC and Brissot, E and Giannotti, F and Dulery, R and Joly, AC and Baylatry, MT and Kossman, MJ and Tankovic, J and Beaugerie, L and Sokol, H and Mohty, M}, title = {Fecal microbiota transplantation before or after allogeneic hematopoietic transplantation in patients with hematological malignancies carrying multidrug-resistance bacteria.}, journal = {Haematologica}, volume = {}, number = {}, pages = {}, doi = {10.3324/haematol.2018.198549}, pmid = {30733264}, issn = {1592-8721}, abstract = {Fecal microbiota transplantation is an effective treatment in recurrent Clostridium difficile infection. Promising results to eradicate multidrug-resistant bacteria have also been reported with this procedure, but there are safety concerns in immunocompromised patients. We report results in 10 adult patients colonized with multidrug-resistant bacteria, undergoing fecal microbiota transplantation before (n=4) or after (n=6) allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Stools were obtained from healthy related or unrelated donors. Fecal material was delivered either by enema or via nasogastric tube. Patients were colonized or had infections from either carbapenemase-producing bacteria (n=8) or vancomycin-resistant enterococci (n=2). The median age at fecal microbiota transplantation was 48 (range 16-64) years. Three patients needed a second transplant from the same donor, due to initial failure of the procedure. With a median follow-up of 13 (range 4-40) months, decolonization was achieved in seven out of ten patients. In all patients, fecal microbiota transplantation was safe: one patient presented with constipation during the first 5 days after FMT and 2 patients had grade I diarrhea. One case of gut grade III acute graft-versus-host disease occurred after fecal microbiota transplantation. In patients carrying or infected by multidrug-resistant bacteria, fecal microbiota transplantation is an effective and safe decolonization strategy, even in those with hematologic malignancies undergoing hematopoietic stem cell transplantation.}, }
@article {pmid30731251, year = {2019}, author = {Bekker, V and Zwittink, RD and Knetsch, CW and Sanders, IMJG and Berghuis, D and Heidt, PJ and Vossen, JMJJ and de Vos, WM and Belzer, C and Bredius, RGM and Van't Hof, PJ and Lankester, AC and Kuijper, EJ}, title = {Dynamics of the Gut Microbiota in Children Receiving Selective or Total Gut Decontamination Treatment during Hematopoietic Stem Cell Transplantation.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {25}, number = {6}, pages = {1164-1171}, doi = {10.1016/j.bbmt.2019.01.037}, pmid = {30731251}, issn = {1523-6536}, abstract = {Bloodstream infections and graft-versus-host disease are common complications after hematopoietic stem cell transplantation (HSCT) procedures, associated with the gut microbiota that acts as a reservoir for opportunistic pathogens. Selective gut decontamination (SGD) and total gut decontamination (TGD) during HSCT have been associated with a decreased risk of developing these complications after transplantation. However, because studies have shown conflicting results, the use of these treatments remains subject of debate. In addition, their impact on the gut microbiota is not well studied. The aim of this study was to elucidate the dynamics of the microbiota during and after TGD and to compare these with the dynamics of SGD. In this prospective, observational, single-center study fecal samples were longitudinally collected from 19 children eligible for allogenic HSCT (TGD, n=12; SGD, n=7), weekly during hospital admission and monthly after discharge. In addition, fecal samples were collected from 3 family stem cell donors. Fecal microbiota structure of patients and donors was determined by 16S rRNA gene amplicon sequencing. Microbiota richness and diversity markedly decreased during SGD and TGD and gradually increased after cessation of decontamination treatment. During SGD, gut microbiota composition was relatively stable and dominated by Bacteroides, whereas it showed high inter- and intraindividual variation and low Bacteroides abundance during TGD. In some children TGD allowed the genera Enterococcus and Streptococcus to thrive during treatment. A gut microbiota dominated by Bacteroides was associated with increased predicted activity of several metabolic processes. Comparing the microbiota of recipients and their donors indicated that receiving an SCT did not alter the patient's microbiota to become more similar to that of its donor. Overall, our findings indicate that SGD and TGD affect gut microbiota structure in a treatment-specific manner. Whether these treatments affect clinical outcomes via interference with the gut microbiota needs to be further elucidated.}, }
@article {pmid30730351, year = {2019}, author = {Allegretti, JR and Kassam, Z and Carrellas, M and Mullish, BH and Marchesi, JR and Pechlivanis, A and Smith, M and Gerardin, Y and Timberlake, S and Pratt, DS and Korzenik, JR}, title = {Fecal Microbiota Transplantation in Patients With Primary Sclerosing Cholangitis: A Pilot Clinical Trial.}, journal = {The American journal of gastroenterology}, volume = {114}, number = {7}, pages = {1071-1079}, doi = {10.14309/ajg.0000000000000115}, pmid = {30730351}, issn = {1572-0241}, abstract = {BACKGROUND: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with no effective medical therapies. A perturbation of the gut microbiota has been described in association with PSC, and fecal microbiota transplantation (FMT) has been reported to restore the microbiome in other disease states. Accordingly, we aimed at evaluating the safety, change in liver enzymes, microbiota, and metabolomic profiles in patients with PSC after FMT.<br><br>METHODS: An open-label pilot study of patients with PSC with concurrent inflammatory bowel disease and alkaline phosphatase (ALP) > 1.5× the upper limit of normal was conducted. The patients underwent a single FMT by colonoscopy. Liver enzyme profiles and stool microbiome and metabolomic analysis were conducted at baseline and weeks 1, 4, 8, 12, and 24 post-FMT. The primary outcome was safety, and the secondary outcome was a decrease in ALP levels ≥50% from baseline by week 24 post-FMT; stool microbiota (by 16S rRNA gene profiling) and metabonomic dynamics were assessed.<br><br>RESULTS: Ten patients underwent FMT. Nine patients had ulcerative colitis, and 1 had Crohn's colitis. The mean baseline ALP level was 489 U/L. There were no related adverse events. Overall, 30% (3/10) experienced a ≥50% decrease in ALP levels. The diversity increased in all patients post-FMT, as early as week 1 (P < 0.01). Importantly, abundance of engrafter operational taxonomic units in patients post-FMT correlated with decreased ALP levels (P = 0.02).<br><br>DISCUSSION: To our knowledge, this is the first study to demonstrate that FMT in PSC is safe. In addition, increases in bacterial diversity and engraftment may correlate with an improvement in ALP among patients with PSC.}, }
@article {pmid30728535, year = {2019}, author = {Chakradhar, S}, title = {Positive selection.}, journal = {Nature medicine}, volume = {25}, number = {2}, pages = {192-194}, doi = {10.1038/s41591-019-0351-4}, pmid = {30728535}, issn = {1546-170X}, mesh = {Bacteria/isolation &amp; purification/*metabolism ; Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Probiotics/pharmacology ; }, }
@article {pmid30725005, year = {2018}, author = {Cruz, R and Monrroy, H and Flandez, J and Pérez, CM and Álvarez-Lobos, M and Hernández-Rocha, C}, title = {[Practical clues for a fecal microbiota transplantation by colonoscopy for recurrent Clostridium difficile infection. Experience in a University center].}, journal = {Revista chilena de infectologia : organo oficial de la Sociedad Chilena de Infectologia}, volume = {35}, number = {5}, pages = {566-573}, doi = {10.4067/s0716-10182018000500566}, pmid = {30725005}, issn = {0717-6341}, abstract = {Fecal microbiota transplantation (FMT) is a highly effective therapy in recurrent Clostridium difficile. The best route to administrate the fecal matter has not been established yet. However, the lower gastrointestinal route by colonoscopy is effective and safe, presenting a higher acceptance by patients. In addition, this route allows an evaluation of colonic mucosa seeking for differential diagnostics. We present a case series of FMT performed in our institution by colonoscopy, highlighting outcomes and practical aspects for its implementation.}, }
@article {pmid30721960, year = {2019}, author = {Cuevas-Sierra, A and Ramos-Lopez, O and Riezu-Boj, JI and Milagro, FI and Martinez, JA}, title = {Diet, Gut Microbiota, and Obesity: Links with Host Genetics and Epigenetics and Potential Applications.}, journal = {Advances in nutrition (Bethesda, Md.)}, volume = {10}, number = {suppl_1}, pages = {S17-S30}, doi = {10.1093/advances/nmy078}, pmid = {30721960}, issn = {2156-5376}, abstract = {Diverse evidence suggests that the gut microbiota is involved in the development of obesity and associated comorbidities. It has been reported that the composition of the gut microbiota differs in obese and lean subjects, suggesting that microbiota dysbiosis can contribute to changes in body weight. However, the mechanisms by which the gut microbiota participates in energy homeostasis are unclear. Gut microbiota can be modulated positively or negatively by different lifestyle and dietary factors. Interestingly, complex interactions between genetic background, gut microbiota, and diet have also been reported concerning the risk of developing obesity and metabolic syndrome features. Moreover, microbial metabolites can induce epigenetic modifications (i.e., changes in DNA methylation and micro-RNA expression), with potential implications for health status and susceptibility to obesity. Also, microbial products, such as short-chain fatty acids or membrane proteins, may affect host metabolism by regulating appetite, lipogenesis, gluconeogenesis, inflammation, and other functions. Metabolomic approaches are being used to identify new postbiotics with biological activity in the host, allowing discovery of new targets and tools for incorporation into personalized therapies. This review summarizes the current understanding of the relations between the human gut microbiota and the onset and development of obesity. These scientific insights are paving the way to understanding the complex relation between obesity and microbiota. Among novel approaches, prebiotics, probiotics, postbiotics, and fecal microbiome transplantation could be useful to restore gut dysbiosis.}, }
@article {pmid30719428, year = {2019}, author = {Wilson, BC and Vatanen, T and Cutfield, WS and O'Sullivan, JM}, title = {The Super-Donor Phenomenon in Fecal Microbiota Transplantation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {2}, doi = {10.3389/fcimb.2019.00002}, pmid = {30719428}, issn = {2235-2988}, abstract = {Fecal microbiota transplantation (FMT) has become a highly effective bacteriotherapy for recurrent Clostridium difficile infection. Meanwhile the efficacy of FMT for treating chronic diseases associated with microbial dysbiosis has so far been modest with a much higher variability in patient response. Notably, a number of studies suggest that FMT success is dependent on the microbial diversity and composition of the stool donor, leading to the proposition of the existence of FMT super-donors. The identification and subsequent characterization of super-donor gut microbiomes will inevitably advance our understanding of the microbial component of chronic diseases and allow for more targeted bacteriotherapy approaches in the future. Here, we review the evidence for super-donors in FMT and explore the concept of keystone species as predictors of FMT success. Possible effects of host-genetics and diet on FMT engraftment and maintenance are also considered. Finally, we discuss the potential long-term applicability of FMT for chronic disease and highlight how super-donors could provide the basis for dysbiosis-matched FMTs.}, }
@article {pmid30719359, year = {2019}, author = {Harsch, IA and Konturek, PC}, title = {Adhesion Ileus after Fecal Microbiota Transplantation in Long-Standing Radiation Colitis.}, journal = {Case reports in gastrointestinal medicine}, volume = {2019}, number = {}, pages = {2543808}, doi = {10.1155/2019/2543808}, pmid = {30719359}, issn = {2090-6528}, abstract = {Fecal microbiota transplantation (FMT) is a novel strategy for the therapy of dysbiosis-associated disorders via modulation of the gut microbiota. Intestinal dysbiosis is associated not only with digestive disorders, but also with a variety of extra-digestive disorders. A worldwide increasing number of FMT can be expected in the future as well as an increase in adverse events. We describe the case of a patient with chronic radiation colitis that developed adhesion ileus 2 days after FMT. Since these problems never occured before and the short time interval favours a causality, we speculate about FMT-induced alterations in gut motility causing a &quot;trapping&quot; of the small intestine in an adhesion and other mechanisms beyond &quot;pure&quot; coincidence.}, }
@article {pmid30709065, year = {2019}, author = {Evrensel, A and Önen Ünsalver, B and Ceylan, ME}, title = {Therapeutic Potential of the Microbiome in the Treatment of Neuropsychiatric Disorders.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {7}, number = {2}, pages = {}, doi = {10.3390/medsci7020021}, pmid = {30709065}, issn = {2076-3271}, abstract = {The search for rational treatment of neuropsychiatric disorders began with the discovery of chlorpromazine in 1951 and continues to evolve. Day by day, new details of the intestinal microbiota⁻brain axis are coming to light. As the role of microbiota in the etiopathogenesis of neuropsychiatric disorders is more clearly understood, microbiota-based (or as we propose, &quot;fecomodulation&quot;) treatment options are increasingly discussed in the context of treatment. Although their history dates back to ancient times, the importance of psychobiotics and fecal microbiota transplantation (FMT) has only recently been recognized. Despite there being few preclinical and clinical studies, the evidence gathered to this point suggests that consideration of the microbiome in the treatment of neuropsychiatric disorders represents an area of significant therapeutic potential. It is increasingly hoped that such treatment options will be more reliable in terms of their side effects, cost, and ease of implementation. However, there remains much to be researched. Questions will be answered through germ-free animal experiments and randomized controlled trials. In this article, the therapeutic potential of microbiota-based options in the treatment of neuropsychiatric disorders is discussed in light of recent research.}, }
@article {pmid30705252, year = {2019}, author = {Yang, C and Fang, X and Zhan, G and Huang, N and Li, S and Bi, J and Jiang, R and Yang, L and Miao, L and Zhu, B and Luo, A and Hashimoto, K}, title = {Key role of gut microbiota in anhedonia-like phenotype in rodents with neuropathic pain.}, journal = {Translational psychiatry}, volume = {9}, number = {1}, pages = {57}, doi = {10.1038/s41398-019-0379-8}, pmid = {30705252}, issn = {2158-3188}, mesh = {Anhedonia/*physiology ; Animals ; Behavior, Animal ; Depression/complications/*microbiology ; Disease Models, Animal ; *Gastrointestinal Microbiome ; Male ; Mice, Inbred C57BL ; Neuralgia/complications/*microbiology/*psychology ; Phenotype ; Rats, Sprague-Dawley ; Sciatic Nerve/injuries ; }, abstract = {Patients with chronic neuropathic pain frequently suffer from symptoms of anhedonia, which is a core symptom of depression. Accumulating studies suggest that gut microbiota may play a role in depression via gut-microbiota-brain axis. However, it is unknown whether gut microbiota plays a role in neuropathic pain-associated anhedonia. Here, we used a rat model of spared nerve injury (SNI). Hierarchical cluster analysis of sucrose preference test (SPT) results was used to classify the SNI rats with or without anhedonia-like phenotype. The 16S ribosomal RNA sequencing analysis showed abnormal composition of gut microbiota in the anhedonia susceptible compared to sham-operated rats and resilient rats. Furthermore, antibiotics-treated mice showed pain as well as depression-like and anhedonia-like phenotypes, suggesting a role of gut microbiota in these abnormal behaviors. Transplantation of fecal microbiota from anhedonia susceptible rats into antibiotics-treated pseudo-germ-free mice significantly exaggerated pain and depression-like phenotypes, including anhedonia. In contrast, transplantation of fecal microbiota from resilient rats into antibiotics-treated pseudo-germ-free mice significantly improved pain and depression-like phenotypes, including anhedonia. In conclusion, this study suggests that abnormal composition of gut microbiota may contribute to anhedonia susceptibility post SNI surgery, and that gut microbiota also plays a role in the pain as well as depression-like phenotypes. Interestingly, fecal microbiota transplantation from SNI rats with or without anhedonia can alter pain, depression-like and anhedonia-like phenotypes in the pseudo-germ-free mice. Therefore, it is likely that gut microbiota plays a key role in the pain as well as depression-like phenotypes including anhedonia in rodents with neuropathic pain.}, }
@article {pmid30704621, year = {2019}, author = {Sun, SS and Wang, K and Ma, K and Bao, L and Liu, HW}, title = {An insoluble polysaccharide from the sclerotium of Poria cocos improves hyperglycemia, hyperlipidemia and hepatic steatosis in ob/ob mice via modulation of gut microbiota.}, journal = {Chinese journal of natural medicines}, volume = {17}, number = {1}, pages = {3-14}, doi = {10.1016/S1875-5364(19)30003-2}, pmid = {30704621}, issn = {1875-5364}, mesh = {Animals ; Bacteria/classification/genetics/isolation &amp; purification/metabolism ; Butyrates/metabolism ; Fatty Liver/drug therapy ; Fungal Polysaccharides/chemistry/*pharmacology/*therapeutic use ; Gastrointestinal Microbiome/*drug effects/genetics ; Hyperglycemia/drug therapy ; Hyperlipidemias/drug therapy ; Intestines/drug effects/microbiology ; Male ; Metabolic Syndrome/*drug therapy ; Mice ; Mice, Obese ; Prebiotics ; Wolfiporia/*chemistry ; }, abstract = {Metabolic syndrome characterized by obesity, hyperglycemia and liver steatosis is becoming prevalent all over the world. Herein, a water insoluble polysaccharide (WIP) was isolated and identified from the sclerotium of Poria cocos, a widely used Traditional Chinese Medicine. WIP was confirmed to be a (1-3)-β-D-glucan with an average Mw of 4.486 × 106 Da by NMR and SEC-RI-MALLS analyses. Furthermore, oral treatment with WIP from P. cocos significantly improved glucose and lipid metabolism and alleviated hepatic steatosis in ob/ob mice. 16S DNA sequencing analysis of cecum content from WIP-treated mice indicated the increase of butyrate-producing bacteria Lachnospiracea, Clostridium. It was also observed that WIP treatment elevated the level of butyrate in gut, improved the gut mucosal integrity and activated the intestinal PPAR-γ pathway. Fecal transplantation experiments definitely confirmed the causative role of gut microbiota in mediating the benefits of WIP. It is the first report that the water insoluble polysaccharide from the sclerotium of P. cocos modulates gut microbiota to improve hyperglycemia and hyperlipidemia. Thereby, WIP from P. cocos, as a prebiotic, has the potential for the prevention or cure of metabolic diseases and may elucidate new mechanism for the efficacies of this traditional herbal medicine on the regulation of lipid and glucose metabolism.}, }
@article {pmid30700240, year = {2019}, author = {Marchukov, D and Misselwitz, B}, title = {[Insights into the Pathogenesis of Inflammatory Bowel Diseases: Genetics and Microbiota].}, journal = {Therapeutische Umschau. Revue therapeutique}, volume = {75}, number = {5}, pages = {273-279}, doi = {10.1024/0040-5930/a000999}, pmid = {30700240}, issn = {0040-5930}, mesh = {Genome-Wide Association Study ; Humans ; *Inflammatory Bowel Diseases/genetics/microbiology ; *Microbiota ; }, abstract = {Insights into the Pathogenesis of Inflammatory Bowel Diseases: Genetics and Microbiota Abstract. An inadequate immune response against bacteria of the gastrointestinal tract is the basic mechanism mediating the pathophysiology of inflammatory bowel diseases (IBD). The risk of IBD is partially heritable and approximately 12 % of patients have a family history of IBD. Large genome-wide association studies (GWAS) were able to identify 240 genetic regions associated with IBD. Many of the implicated genes have a function in the immune system, are associated with primary immunodeficiencies or the defense against mycobacteria. Together these 240 genetic regions form an excellent framework for further investigations into the pathogenesis and therapy of IBD. However, GWAS so far were able to unravel only a fraction of the genetic IBD risk. New strategies like genome wide sequencing are currently used to identify additional (rare) genetic variants. In rare cases, IBD is also inherited as a monogenetic disease. Moreover, there likely is significant interaction between genes and environmental factors which can only be unraveled if both, genes and the environment are simultaneously considered. Interestingly, the information provided by genetic risk factors for IBD is unable to predict the clinical course of IBD. New GWAS therefore focus on IBD prognosis and first insights have already been made. The gastrointestinal tract harbors a huge number of microorganisms (microbiota). It remains an enormous challenge for the immune system to contain this bacterial load while enabling the host to benefit from the many essential contributions of the microbiota. In IBD, the microbiota is altered to a dysfunctional (dysbiotic) state showing reduced diversity and a higher amount of potential pathogenic Proteobacteriae, such as Escherichia coli. In IBD, the microbiota is also more dynamic in its composition over time compared to health. Further, IBD dysbiosis is more pronounced in Crohn's disease than in ulcerative colitis. In animal experiments, dysbiosis could be transferred by fecal microbiota transplantation from one mouse to another, triggering inflammation in the recipient. In contrast, a healthy microbiota can downregulate the immune response of the host, for instance by bacterial short chain fatty acids (SCFA) synthesis. In addition, some bacteria with close physical contact to the intestinal wall also have specific immunosuppressive properties. So far, the highly complex network of microbiota, genetics, immune system and environment is only partially understood. The microbiota is a potential therapeutic target which up to now can only be non-specifically influenced by antibiotics, probiotics, prebiotics or fecal microbiota transplantation. A better understanding of the microbiota will likely yield in the discovery of new therapeutic options in the future.}, }
@article {pmid30696813, year = {2019}, author = {Jianguo, L and Xueyang, J and Cui, W and Changxin, W and Xuemei, Q}, title = {Altered gut metabolome contributes to depression-like behaviors in rats exposed to chronic unpredictable mild stress.}, journal = {Translational psychiatry}, volume = {9}, number = {1}, pages = {40}, doi = {10.1038/s41398-019-0391-z}, pmid = {30696813}, issn = {2158-3188}, mesh = {Animals ; Behavior, Animal ; Depression/etiology/*metabolism/*microbiology ; *Feces/microbiology ; *Gastrointestinal Microbiome ; Male ; Metabolome ; Rats, Sprague-Dawley ; Stress, Psychological/*complications ; }, abstract = {The gut microbiota has been increasingly correlated with depressive disorder. It was recently shown that the transplantation of the gut microbiota from depressed patients to animals can produce depressive-like behaviors, suggesting that the gut microbiota plays a causal role in the development of depression. In addition, metabolic disorder, which is strongly associated with depression, is exacerbated by changes in the composition of the gut microbiota and is alleviated by treatment with antidepressants. However, the key players and pathways that link the gut microbiota to the pathogenesis of depression remain largely unknown. To evaluate the relationships between depression and metabolic disorders in feces and plasma, we monitored changes in fecal and plasma metabolomes during the development of depressive-like behaviors in rats exposed to chronic unpredictable mild stress (CUMS). In these animals, the fecal metabolome was altered first and subjected to changes in the plasma metabolome. Changes in the abundance of fecal metabolites were associated with depressive-like behaviors and with altered levels of neurotransmitters in the hippocampus. Furthermore, the analysis of the fecal metabolome and the fecal microbiota in CUMS rats demonstrated consistent changes in the levels of several amino acids, including L-threonine, isoleucine, alanine, serine, tyrosine, and oxidized proline. Finally, we observed significant correlations between these amino acids and the altered fecal microbiota. The results of this study suggest that changes in amino acid metabolism by the gut microbiota contribute to changes in circulating amino acids and are associated with the behavior indices of depression.}, }
@article {pmid30694953, year = {2019}, author = {Rancich, M and Roman, C}, title = {Updated guidelines for diagnosing and managing Clostridium difficile.}, journal = {JAAPA : official journal of the American Academy of Physician Assistants}, volume = {32}, number = {2}, pages = {48-50}, doi = {10.1097/01.JAA.0000552734.33929.01}, pmid = {30694953}, issn = {1547-1896}, mesh = {Anti-Bacterial Agents/*standards/therapeutic use ; *Clostridium difficile ; Enterocolitis, Pseudomembranous/diagnosis/microbiology/*therapy ; Fecal Microbiota Transplantation/*standards ; Humans ; Metronidazole/*standards/therapeutic use ; Practice Guidelines as Topic ; }, abstract = {The updated Infectious Disease Society of America guidelines for managing Clostridium difficile infections remove metronidazole as first-line therapy and add fecal microbiota transplants to the treatment options. This article reviews the new guidelines and strategies for diagnosis and infection control.}, }
@article {pmid30692975, year = {2018}, author = {Le Roy, T and Debédat, J and Marquet, F and Da-Cunha, C and Ichou, F and Guerre-Millo, M and Kapel, N and Aron-Wisnewsky, J and Clément, K}, title = {Comparative Evaluation of Microbiota Engraftment Following Fecal Microbiota Transfer in Mice Models: Age, Kinetic and Microbial Status Matter.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3289}, doi = {10.3389/fmicb.2018.03289}, pmid = {30692975}, issn = {1664-302X}, abstract = {The intestinal microbiota and its functions are intricately interwoven with host physiology. Colonizing rodents with donor microbiota provides insights into host-microbiota interactions characterization and the understanding of disease physiopathology. However, a better assessment of inoculation methods and recipient mouse models is needed. Here, we compare the engraftment at short and long term of genetically obese mice microbiota in germ-free (GF) mice and juvenile and adult specific pathogen free (SPF) mice. We also tested the effects of initial microbiota depletion before microbiota transfer. In the present work, donor microbiota engraftment was better in juvenile SPF mice than in adult SPF mice. In juvenile mice, initial microbiota depletion using laxatives or antibiotics improved donor microbiota engraftment 9 weeks but not 3 weeks after microbiota transfer. Microbiota-depleted juvenile mice performed better than GF mice 3 weeks after the microbiota transfer. However, 9 weeks after transfer, colonized GF mice microbiota had the lowest Unifrac distance to the donor microbiota. Colonized GF mice were also characterized by a chronic alteration in intestinal absorptive function. With these collective results, we show that the use of juvenile mice subjected to initial microbiota depletion constitutes a valid alternative to GF mice in microbiota transfer studies.}, }
@article {pmid30689174, year = {2019}, author = {Dinleyici, M and Vandenplas, Y}, title = {Clostridium difficile Colitis Prevention and Treatment.}, journal = {Advances in experimental medicine and biology}, volume = {1125}, number = {}, pages = {139-146}, doi = {10.1007/5584_2018_322}, pmid = {30689174}, issn = {0065-2598}, abstract = {Clostridium difficile (C. diff) is the most common causative agent of antibiotic-associated diarrhea and colitis. This spore-forming, obligate anaerobic, gram-positive bacillus is becoming responsible for an increasing number of infections worldwide, both in community and in hospital settings, whose severity can vary widely from an asymptomatic infection to a lethal disease. While discontinuation of antimicrobial agents and antibiotic treatment of the infection remain the cornerstone of therapy, the use of probiotics, especially Saccharomyces boulardii, and more recently of fecal microbiota transplantation have become valid forms of prevention and/or therapy and are here critically examined.}, }
@article {pmid30687107, year = {2018}, author = {Basso, PJ and Câmara, NOS and Sales-Campos, H}, title = {Microbial-Based Therapies in the Treatment of Inflammatory Bowel Disease - An Overview of Human Studies.}, journal = {Frontiers in pharmacology}, volume = {9}, number = {}, pages = {1571}, doi = {10.3389/fphar.2018.01571}, pmid = {30687107}, issn = {1663-9812}, abstract = {Inflammatory bowel disease (IBD) is a group of multifactorial and inflammatory infirmities comprised of two main entities: Ulcerative colitis (UC) and Crohn's disease (CD). Classic strategies to treat IBD are focused on decreasing inflammation besides inducing and extending disease remission. However, these approaches have several limitations such as low responsiveness, excessive immunosuppression, and refractoriness. Despite the multifactorial causality of IBD, immune disturbances and intestinal dysbiosis have been suggested as the central players in disease pathogenesis. Hence, therapies aiming at modulating intestinal microbial composition may represent a promising strategy in IBD control. Fecal microbiota transplantation (FMT) and probiotics have been explored as promising candidates to reestablish microbial balance in several immune-mediated diseases such as IBD. These microbial-based therapies have demonstrated the ability to reduce both the dysbiotic environment and production of inflammatory mediators, thus inducing remission, especially in UC. Despite these promising results, there is still no consensus on the relevance of such treatments in IBD as a potential clinical strategy. Thus, this review aims to critically review and describe the use of FMT and probiotics to treat patients with IBD.}, }
@article {pmid30678445, year = {2019}, author = {Fukuda, T and Naganuma, M and Kanai, T}, title = {Current new challenges in the management of ulcerative colitis.}, journal = {Intestinal research}, volume = {17}, number = {1}, pages = {36-44}, doi = {10.5217/ir.2018.00126}, pmid = {30678445}, issn = {1598-9100}, abstract = {Ulcerative colitis (UC) is a chronic inflammatory condition of the gastrointestinal tract. Although the cause of UC is postulated to be multifactorial in nature, including genetic predisposition, epithelial barrier defects, dysregulation of immune responses, and environmental factors, the specific pathogenesis of UC is still incompletely understood. In the treatment of UC so far, a method of suppressing immunity and treating it has been mainstream. Immunosuppressant drugs, including thiopurines (azathioprine or 6-mercaptopurine), anti-tumor necrosis factor-α (anti-TNF-α) antibody (infliximab and adalimumab), and calcineurin inhibitor, can be used in treat patients with corticosteroid-dependent and/or corticosteroid-refractory moderateto- severe UC. Recently, in addition to such a conventional therapeutic agent, golimumab, which is the first transgenic human monoclonal anti-TNF-α antibody to be fabricated, anti α-4/β-7 integrin antibody, and Janus kinase inhibitor have been reported to novel immunosuppressant therapy. Furthermore, other treatments with unique mechanisms different from immunosuppression, have also been suggested, including fecal microbiota transplantation and Indigo naturalis, which is a Chinese herbal medicine. We compared the features and efficacy of these new treatments. In this issue, the features and treatment options for these new treatments is reviewed.}, }
@article {pmid30678444, year = {2019}, author = {Cho, YS}, title = {Multi-session fecal microbiota transplantation using colonoscopy has favorable outcomes for the treatment of steroid-dependent ulcerative colitis.}, journal = {Intestinal research}, volume = {17}, number = {1}, pages = {6-8}, doi = {10.5217/ir.2018.00171}, pmid = {30678444}, issn = {1598-9100}, }
@article {pmid30673716, year = {2019}, author = {Hui, W and Li, T and Liu, W and Zhou, C and Gao, F}, title = {Fecal microbiota transplantation for treatment of recurrent C. difficile infection: An updated randomized controlled trial meta-analysis.}, journal = {PloS one}, volume = {14}, number = {1}, pages = {e0210016}, doi = {10.1371/journal.pone.0210016}, pmid = {30673716}, issn = {1932-6203}, abstract = {OBJECTIVES: Although systematic evaluation has confirmed the efficacy of fresh fecal microbiota transplantation (FMT) for treatment of recurrent and/or refractory and/or relapse C. difficile infection (RCDI), it lacks the support of well-designed randomized controlled trials (RCTs), and the latest guidelines do not optimize the management of FMT. In this paper, we focus on an in-depth study of fresh FMT and fecal infusion times to guide clinical practice.<br><br>METHODS: We reviewed studies in PubMed, Medline, Embase, the Cochrane library and Cochrane Central written in English. The retrieval period was from the establishment of the databases to September 20th, 2018. The retrieval objects were published RCTs of RCDI treated by fresh FMT. The intervention group was fresh FMT group, while the control group included antibiotic therapy or placebo or frozen FMT or capsule. The primary and secondary outcomes were the clinical remission of diarrhea without relapse after 8-17 weeks and the occurrence of severe adverse events, respectively. Subgroup analysis analyzed the effect of single and multiple fecal infusions. Two authors independently completed the information extraction and assessed risk of bias and overall quality of the evidence.<br><br>RESULTS: 8 randomized controlled trials met the inclusion criteria, involving 537 patients (273 in the fresh FMT group and 264 in the control group). The recurrence rate of clinical diarrhea in the fresh FMT group was 11.0% (30/273), which was significantly lower than the control group (24.6%, 65/264; P < 0.05); the pooled relative risk (RR) was 0.38 (95%CI:0.16-0.87; I2 = 67%; P = 0.02) in the fresh FMT group, and the clinical heterogeneity was significant and random effects model was used; However, there was no significant difference neither for the effect of antibiotic treatment/frozen feces transplanted by enema (RR = 1.07; 95%CI: 0.64-1.80; I2 = 0%; P = 0.79) or capsule/frozen feces transplanted by colonoscopy (RR = 0.42; 95%CI: 0.05-3.94; I2 = 43%; P = 0.45) compared with fresh FMT. The subgroup analysis showed that FMT by multiple infusions could effectively and significantly (RR = 0.24; 95%CI:0.10-0.58; I2 = 0%; P = 0.001) improve the clinical diarrhea remission rate. Most mild to moderate adverse events caused by FMT were self-limited and could be quickly alleviated; no severe adverse events happened because of FMT.<br><br>CONCLUSIONS: Overall, the use of fresh feces for bacterial transplantation was the best efficiency for RCDI compared to antibiotic therapy or placebo. The fecal transmission method by enema was not ideal, but capsules or frozen feces transported by colonoscopy could be an alternative treatment compared to fresh FMT. For patients with severe RCDI, multiple fecal transplants can effectively improve their diarrhea remission rate. The focus of future research should be on how to standardize the production of capsules or frozen feces to better guide the clinical management of RCDI patients by FMT.}, }
@article {pmid30667386, year = {2018}, author = {De Sire, R and Talocco, C and Petito, V and Lopetuso, LR and Graziani, C and Gasbarrini, A and Scaldaferri, F}, title = {[Microbiota and inflammatory bowel disease: an update.].}, journal = {Recenti progressi in medicina}, volume = {109}, number = {12}, pages = {570-573}, doi = {10.1701/3082.30741}, pmid = {30667386}, issn = {2038-1840}, abstract = {Over the last few years, the gut microbiota has been the focus of countless studies conducted both on mouse models and human population, aimed at analyzing its functions and interactions with the host, including nutrition, metabolic homeostasis, protection from infections and development of systemic and mucosal immunity both in inflammatory bowel disease (IBD) as well as other intestinal and extra-intestinal diseases. In IBD microbiota is impaired in overall composition and biodiversity, stability as well as functions. Microbial signature of IBD can be considered also a decrease in F. prausnitzii, increase of Proteonbacteria as well as the described increase of Candida albicans, Basidiomycota/Ascomycota ratio over Saccharomyces cerevisiae and of the Caudovirales over Microviridae. The indirect (through antibiotics, probiotics) and direct (through fecal microbiota transplantation) modulation of gut microbiota has relevant clinical implication in IBD management. In the near future role and clinical implication of gut microbiota characterization in the therapeutic personalized approach to IBD patients will eventually become clear.}, }
@article {pmid30666957, year = {2019}, author = {Contijoch, EJ and Britton, GJ and Yang, C and Mogno, I and Li, Z and Ng, R and Llewellyn, SR and Hira, S and Johnson, C and Rabinowitz, KM and Barkan, R and Dotan, I and Hirten, RP and Fu, SC and Luo, Y and Yang, N and Luong, T and Labrias, PR and Lira, S and Peter, I and Grinspan, A and Clemente, JC and Kosoy, R and Kim-Schulze, S and Qin, X and Castillo, A and Hurley, A and Atreja, A and Rogers, J and Fasihuddin, F and Saliaj, M and Nolan, A and Reyes-Mercedes, P and Rodriguez, C and Aly, S and Santa-Cruz, K and Peters, L and Suárez-Fariñas, M and Huang, R and Hao, K and Zhu, J and Zhang, B and Losic, B and Irizar, H and Song, WM and Di Narzo, A and Wang, W and Cohen, BL and DiMaio, C and Greenwald, D and Itzkowitz, S and Lucas, A and Marion, J and Maser, E and Ungaro, R and Naymagon, S and Novak, J and Shah, B and Ullman, T and Rubin, P and George, J and Legnani, P and Telesco, SE and Friedman, JR and Brodmerkel, C and Plevy, S and Cho, JH and Colombel, JF and Schadt, EE and Argmann, C and Dubinsky, M and Kasarskis, A and Sands, B and Faith, JJ}, title = {Gut microbiota density influences host physiology and is shaped by host and microbial factors.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, doi = {10.7554/eLife.40553}, pmid = {30666957}, issn = {2050-084X}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; GM108505//National Institute of General Medical Sciences/ ; DK112679//National Institute of Diabetes and Digestive and Kidney Diseases/ ; R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 GM108505/GM/NIGMS NIH HHS/United States ; F31 DK112679/DK/NIDDK NIH HHS/United States ; GM007280//National Institute of General Medical Sciences/ ; }, abstract = {To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohn's disease, ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Clostridium difficile infection had lower density and reduced fitness that were restored by fecal microbiota transplantation. Understanding the interplay between microbiota and disease in terms of microbiota density, host carrying capacity, and microbiota fitness provide new insights into microbiome structure and microbiome targeted therapeutics.<br><br>Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).}, }
@article {pmid30664879, year = {2019}, author = {Bajaj, JS and Fagan, A and Gavis, EA and Kassam, Z and Sikaroodi, M and Gillevet, PM}, title = {Long-term Outcomes of Fecal Microbiota Transplantation in Patients With Cirrhosis.}, journal = {Gastroenterology}, volume = {156}, number = {6}, pages = {1921-1923.e3}, doi = {10.1053/j.gastro.2019.01.033}, pmid = {30664879}, issn = {1528-0012}, support = {I01 CX001076/CX/CSRD VA/United States ; R21 TR002024/TR/NCATS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; *Cognition ; *Fecal Microbiota Transplantation ; Follow-Up Studies ; Gastrointestinal Agents/therapeutic use ; Gastrointestinal Microbiome ; Hepatic Encephalopathy/*etiology/*therapy ; *Hospitalization ; Humans ; Lactulose/therapeutic use ; Liver Cirrhosis/*complications ; Patient Selection ; Rifaximin/therapeutic use ; Stroop Test ; Time Factors ; }, }
@article {pmid30664020, year = {2019}, author = {van der Sluis, WB and Bouman, MB and Mullender, MG and Degen, MC and Savelkoul, PHM and Meijerink, WJHJ and de Boer, NKH and van Bodegraven, AA and Budding, AE}, title = {The effect of surgical fecal stream diversion of the healthy colon on the colonic microbiota.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {31}, number = {4}, pages = {451-457}, doi = {10.1097/MEG.0000000000001330}, pmid = {30664020}, issn = {1473-5687}, mesh = {Adolescent ; Adult ; Bacteria/classification/isolation &amp; purification ; Bacterial Typing Techniques ; Bacteroidetes/classification/isolation &amp; purification ; Colon/*microbiology ; Colon, Sigmoid/transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Postoperative Period ; Rectum/microbiology ; Sex Reassignment Surgery/methods ; Skin/microbiology ; Vagina/*surgery ; Young Adult ; }, abstract = {OBJECTIVES: The intestinal microbiota plays an important role in intestinal health. After colonic diversion from the fecal stream, luminal nutrients for bacteria are expected to be depleted, inducing changes in microbial composition. In this study, we describe microbial changes in the healthy colon following surgical fecal stream diversion, studied in the surgically constructed sigmoid-derived neovagina.<br><br>METHODS: At various postoperative times after sigmoid vaginoplasty, rectal, neovaginal, and skin microbial swabs were obtained for microbial analysis by interspacer profiling, a PCR-based bacterial profiling technique. Differences in bacterial profiles, in terms of bacterial abundance and phylum diversity, were assessed. Microbial dissimilarities between anatomical locations were analyzed with principal coordinate analysis and partial least squares discriminant analysis.<br><br>RESULTS: Bacterial samples were obtained from 28 patients who underwent sigmoid vaginoplasty. By principal coordinate analysis, microbial profiles of samples from the sigmoid-derived neovagina were distinctively different from rectal samples. Partial least squares discriminant analysis showed that the most discriminative species derived from the phylum Bacteroidetes. The abundance and diversity of Bacteroidetes species were reduced following fecal stream diversion compared with rectal samples (median Shannon diversity index of 2.76 vs. 2.18, P<0.01). Similar abundance of Phyla Firmicutes, Actinobacteria, Fusobacteria, Verrucomicrobia, and Proteobacteria was observed.<br><br>CONCLUSION: By analyzing the microbiome of sigmoid-derived neovaginas, we studied the effects of fecal diversion on the microbial composition of the healthy intestine. Most changes were observed in the phylum Bacteroidetes, indicating that these bacteria are likely part of the diet-dependent (butyrate-producing) colonic microbiome. Bacteria of other phyla are likely to be part of the diet-independent microbiome.}, }
@article {pmid30663928, year = {2019}, author = {Ihekweazu, FD and Fofanova, TY and Queliza, K and Nagy-Szakal, D and Stewart, CJ and Engevik, MA and Hulten, KG and Tatevian, N and Graham, DY and Versalovic, J and Petrosino, JF and Kellermayer, R}, title = {Bacteroides ovatus ATCC 8483 monotherapy is superior to traditional fecal transplant and multi-strain bacteriotherapy in a murine colitis model.}, journal = {Gut microbes}, volume = {10}, number = {4}, pages = {504-520}, doi = {10.1080/19490976.2018.1560753}, pmid = {30663928}, issn = {1949-0984}, abstract = {Background and aims: Bacteriotherapy aimed at addressing dysbiosis may be therapeutic for Inflammatory Bowel Diseases (IBDs). We sought to determine if defined Bacteroides-based bacteriotherapy could be an effective and consistent alternative to fecal microbiota transplantation (FMT) in a murine model of IBD. Methods: We induced experimental colitis in 8- 12-week-old C57BL/6 mice using 2-3% dextran sodium sulfate. Mice were simultaneously treated by oral gavage with a triple-Bacteroides cocktail, individual Bacteroides strains, FMT using stool from healthy donor mice, or their own stool as a control. Survival, weight loss and markers of inflammation (histology, serum amyloid A, cytokine production) were correlated to 16S rRNA gene profiling of fecal and mucosal microbiomes. Results: Triple-Bacteroides combination therapy was more protective against weight loss and mortality than traditional FMT therapy. B. ovatus ATCC8483 was more effective than any individual strain, or a combination of strains, in preventing weight loss, decreasing histological damage, dampening inflammatory response, and stimulating epithelial recovery. Irrespective of the treatment group, overall Bacteroides abundance associated with treatment success and decreased cytokine production while the presence of Akkermansia correlated with treatment failure. However, the therapeutic benefit associated with high Bacteroides abundance was negated in the presence of Streptococcus. Conclusions: Bacteroides ovatus monotherapy was more consistent and effective than traditional FMT at ameliorating colitis and stimulating epithelial recovery in a murine model of IBD. Given the tolerability of Bacteroides ovatus ATCC 8483 in an active, on-going human study, this therapy may be repurposed for the management of IBD in a clinically expedient timeline.}, }
@article {pmid30662590, year = {2018}, author = {Xiao, J and Peng, Z and Liao, Y and Sun, H and Chen, W and Chen, X and Wei, Z and Yang, C and Nüssler, AK and Liu, J and Yang, W}, title = {Organ transplantation and gut microbiota: current reviews and future challenges.}, journal = {American journal of translational research}, volume = {10}, number = {11}, pages = {3330-3344}, pmid = {30662590}, issn = {1943-8141}, abstract = {Organ transplantation is often the only effective treatment for patients with end-stage diseases, such as heart, liver, kidney and small bowel failure and is carried out frequently worldwide. Still the post-transplantation complications remain health- and life-threatening outcome that needed to be resolved. With the rapid development of molecular technologies in recent years, more and more researchers realize that the gut microbiota may play a critical role in human diseases. The intestinal microbiome has been proved to provide a lot of functions to the host, such as digesting food, modulating metabolism, promoting angiogenesis and regulating the immune system. Several studies have investigated the alteration of intestinal microbiota in post-transplantation patients and observed significant changes in the intestinal microbiome compared to the pre-transplant condition. Due to the abovementioned features that the gut microbiota may be used in the prognosis of clinical outcome of organ transplantation. In addition, the FMT (fecal microbiota transplantation), probiotics and prebiotics as the newest therapy methods, effectiveness of which has been verified in some diseases, such as Clostridium difficile infection, inflammatory bowel disease and other chronic disorders, might be used as the prognosis tool in organ transplantation as well. The purpose of this present review is to elucidate the relationship between gut microbiota and organ transplantation as well as the potential use of new therapies like fecal microbiota transplantation, probiotic and prebiotic administration after the transplantation, and provide some ideas for future researches in field of organ transplantation.}, }
@article {pmid30661163, year = {2019}, author = {Knox, NC and Forbes, JD and Van Domselaar, G and Bernstein, CN}, title = {The Gut Microbiome as a Target for IBD Treatment: Are We There Yet?.}, journal = {Current treatment options in gastroenterology}, volume = {17}, number = {1}, pages = {115-126}, doi = {10.1007/s11938-019-00221-w}, pmid = {30661163}, issn = {1092-8472}, abstract = {PURPOSE OF REVIEW: This review aims to highlight recent research on the gut microbiome in IBD and the application of microbiome-modulating therapies for the treatment of IBD including the use of the microbiome as an indicator for disease severity and treatment response.<br><br>RECENT FINDINGS: Despite the high number of gut microbiome studies and emerging evidence supporting the gut microbiome's involvement in disease pathogenesis, no single microorganism has been identified as a pathogenic agent in IBD. Retrospective studies and meta-analyses on antibiotic use in ulcerative colitis and Crohn's disease and long-term outcomes are conflicting. Similarly, the use of probiotics for the treatment of IBD remains inconclusive; however, some encouraging results are emerging as microbial concoctions are optimized to include beneficial bacterial strains. Fecal microbial transplantation (FMT) is currently emerging as one of the more promising microbiome-modulating IBD therapies. FMT studies in ulcerative colitis have shown improved remission rates compared to placebo; however, relatively small study sample sizes and varied treatment methods, limit definitive conclusions. With clear evidence of an IBD gut dysbiosis, novel therapies to treat and prevent disease relapse will undoubtedly require a microbiome-modulating approach. The complexity and variability of IBD disease pathogenesis (disease phenotype, gut microbiome, host genetic susceptibility, and environmental factors) will likely require a personalized and multidimensional treatment approach where microbiome-modulating therapy is coupled with other therapies to target other IBD disease components.}, }
@article {pmid30658519, year = {2019}, author = {Milosevic, I and Vujovic, A and Barac, A and Djelic, M and Korac, M and Radovanovic Spurnic, A and Gmizic, I and Stevanovic, O and Djordjevic, V and Lekic, N and Russo, E and Amedei, A}, title = {Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature.}, journal = {International journal of molecular sciences}, volume = {20}, number = {2}, pages = {}, doi = {10.3390/ijms20020395}, pmid = {30658519}, issn = {1422-0067}, mesh = {Animals ; *Disease Susceptibility ; Dysbiosis ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/immunology/*metabolism/*microbiology ; Humans ; Liver/immunology/*metabolism/pathology ; Liver Diseases/*etiology/*metabolism/pathology/therapy ; Prebiotics ; Probiotics ; Symbiosis ; }, abstract = {The rapid scientific interest in gut microbiota (GM) has coincided with a global increase in the prevalence of infectious and non-infectivous liver diseases. GM, which is also called &quot;the new virtual metabolic organ&quot;, makes axis with a number of extraintestinal organs, such as kidneys, brain, cardiovascular, and the bone system. The gut-liver axis has attracted greater attention in recent years. GM communication is bi-directional and involves endocrine and immunological mechanisms. In this way, gut-dysbiosis and composition of &quot;ancient&quot; microbiota could be linked to pathogenesis of numerous chronic liver diseases such as chronic hepatitis B (CHB), chronic hepatitis C (CHC), alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), development of liver cirrhosis, and hepatocellular carcinoma (HCC). In this paper, we discuss the current evidence supporting a GM role in the management of different chronic liver diseases and potential new therapeutic GM targets, like fecal transplantation, antibiotics, probiotics, prebiotics, and symbiotics. We conclude that population-level shifts in GM could play a regulatory role in the gut-liver axis and, consequently, etiopathogenesis of chronic liver diseases. This could have a positive impact on future therapeutic strategies.}, }
@article {pmid30655087, year = {2019}, author = {Markowski, MC and Boorjian, SA and Burton, JP and Hahn, NM and Ingersoll, MA and Maleki Vareki, S and Pal, SK and Sfanos, KS}, title = {The Microbiome and Genitourinary Cancer: A Collaborative Review.}, journal = {European urology}, volume = {75}, number = {4}, pages = {637-646}, doi = {10.1016/j.eururo.2018.12.043}, pmid = {30655087}, issn = {1873-7560}, abstract = {CONTEXT: The recent discovery of the existence of a human genitourinary microbiome has led to the investigation of its role in mediating the pathogenesis of genitourinary malignancies, including bladder, kidney, and prostate cancers. Furthermore, although it is largely recognized that members of the gastrointestinal microbiota are actively involved in drug metabolism, new studies demonstrate additional roles and the potential necessity of the gastrointestinal microbiota in dictating cancer treatment response.<br><br>OBJECTIVE: To summarize the current evidence of a mechanistic role for the genitourinary and gastrointestinal microbiome in genitourinary cancer initiation and treatment response.<br><br>EVIDENCE ACQUISITION: We conducted a literature search up to October 2018. Search terms included microbiome, microbiota, urinary microbiome, bladder cancer, urothelial carcinoma, renal cell carcinoma, kidney cancer, testicular cancer, and prostate cancer.<br><br>EVIDENCE SYNTHESIS: There is preliminary evidence to implicate the members of the genitourinary microbiota as causative factors or cofactors in genitourinary malignancy. Likewise, the current evidence for gastrointestinal microbes in dictating cancer treatment response is mainly correlative; however, we provide examples where therapeutic agents used for the treatment of genitourinary cancers are affected by the human-associated microbiota, or vice versa. Clinical trials, such as fecal microbiota transplant to increase the efficacy of immunotherapy, are currently underway.<br><br>CONCLUSIONS: The role of the microbiome in genitourinary cancer is an emerging field that merits further studies. Translating microbiome research into clinical action will require incorporation of microbiome surveillance into ongoing and future clinical trials as well as expansion of studies to include metagenomic sequencing and metabolomics.<br><br>PATIENT SUMMARY: This review covers recent evidence that microbial populations that reside in the genitourinary tract-and were previously not known to exist-may influence the development of genitourinary malignancies including bladder, kidney, and prostate cancers. Furthermore, microbial populations that exist at sites outside of the genitourinary tract, such as those that reside in our gut, may influence cancer development and/or treatment response.}, }
@article {pmid30655033, year = {2019}, author = {Weng, MT and Chiu, YT and Wei, PY and Chiang, CW and Fang, HL and Wei, SC}, title = {Microbiota and gastrointestinal cancer.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {118 Suppl 1}, number = {}, pages = {S32-S41}, doi = {10.1016/j.jfma.2019.01.002}, pmid = {30655033}, issn = {0929-6646}, mesh = {Carcinogenesis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gastrointestinal Neoplasms/*microbiology/*prevention &amp; control ; Gastrointestinal Tract/*microbiology ; Humans ; Risk Factors ; Synbiotics/administration &amp; dosage ; }, abstract = {Gut microbiota plays important roles in many diseases, including cancer. It may promote carcinogenesis by inducing oxidative stress, genotoxicity, host immune response disturbance, and chronic inflammation. Colorectal cancer, hepatocellular carcinoma, and gastric cancer are the major gastrointestinal tract cancers in Taiwan. The microbiota detected in patients with tubular adenoma and villous/tubulovillous polyps is different from that in healthy controls and patients with hyperplastic polyps. Normalization of the microbiota is observed in patients after colorectal cancer treatment. Furthermore, the liver is exposed to microbiota-associated molecular patterns (MAMPs), bacterial metabolites, and toxins, as it is anatomically connected to the gut via the portal vein. Patients with cirrhosis have significantly higher plasma endotoxin levels than healthy controls. Helicobacter pylori is a well-established risk factor for gastric cancer. Some nitrosating bacteria convert nitrogen compounds in gastric fluid to potentially carcinogenic N-nitroso compounds, which also contribute to gastric cancer development. Growing evidence demonstrates that gut microbiota promotes carcinogenesis. In this review, we discuss the mechanisms and types of microbiota changes involved in these gastrointestinal cancers and the future treatment choices.}, }
@article {pmid30651577, year = {2019}, author = {Goethel, A and Turpin, W and Rouquier, S and Zanello, G and Robertson, SJ and Streutker, CJ and Philpott, DJ and Croitoru, K}, title = {Nod2 influences microbial resilience and susceptibility to colitis following antibiotic exposure.}, journal = {Mucosal immunology}, volume = {12}, number = {3}, pages = {720-732}, doi = {10.1038/s41385-018-0128-y}, pmid = {30651577}, issn = {1935-3456}, support = {THC-13523//CIHR/Canada ; }, abstract = {Inflammatory bowel disease (IBD) etiology involves genetic susceptibility, environmental triggers, and the gut microbiome. Antibiotic exposure is associated with IBD, both in early life and adulthood. Here, we investigated whether Nod2-deficiency influenced response of the gut microbiota to antibiotics and subsequent colitis susceptibility. Wild-type and Nod2-/- littermate mice were treated with amoxicillin as adults or neonates, and fecal samples were collected for 16S rRNA sequencing. Five weeks after antibiotic exposure, dextran sulfate sodium (DSS) colitis was induced. Antibiotic treatment altered the microbiota of adult WT and Nod2-/- mice, but recovery was delayed in Nod2-/- mice. Neonatal antibiotic treatment significantly changed the microbiota at weaning in WT and Nod2-/- littermates; however, Nod2-/- mice maintained reduced microbial diversity 14 days after cessation of antibiotics. Although treatment of adult mice did not influence susceptibility to colitis, neonatally treated Nod2-/- mice developed a more severe colitis. Moreover, the colitis phenotype was transferable through fecal transplantation into germ-free Nod2-/- recipients, and was associated with changes in intestinal T cells and the cytokine milieu following inflammation. These data demonstrate that neonatal antibiotic exposure has long-lasting influence on the microbiota and mucosal immunity, and may explain how NOD2 contributes to the risk of intestinal inflammation.}, }
@article {pmid30648128, year = {2019}, author = {Torres Soto, M and Hammond, S and Elshaboury, RH and Johnson, J and Hohmann, EL}, title = {Recurrent Relatively Resistant Salmonella infantis Infection in 2 Immunocompromised Hosts Cleared With Prolonged Antibiotics and Fecal Microbiota Transplantation.}, journal = {Open forum infectious diseases}, volume = {6}, number = {1}, pages = {ofy334}, doi = {10.1093/ofid/ofy334}, pmid = {30648128}, issn = {2328-8957}, abstract = {Two immunocompromised patients with relapsing gastrointestinal infection with relatively resistant Salmonella infantis were cured with prolonged ertapenem followed by encapsulated fecal transplant.}, }
@article {pmid30644982, year = {2019}, author = {Costello, SP and Hughes, PA and Waters, O and Bryant, RV and Vincent, AD and Blatchford, P and Katsikeros, R and Makanyanga, J and Campaniello, MA and Mavrangelos, C and Rosewarne, CP and Bickley, C and Peters, C and Schoeman, MN and Conlon, MA and Roberts-Thomson, IC and Andrews, JM}, title = {Effect of Fecal Microbiota Transplantation on 8-Week Remission in Patients With Ulcerative Colitis: A Randomized Clinical Trial.}, journal = {JAMA}, volume = {321}, number = {2}, pages = {156-164}, doi = {10.1001/jama.2018.20046}, pmid = {30644982}, issn = {1538-3598}, mesh = {Adult ; Anaerobiosis ; Colitis, Ulcerative/*therapy ; Colonoscopy ; Double-Blind Method ; Enema ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Gastrointestinal Microbiome ; Humans ; Male ; Metabolome ; Middle Aged ; Remission Induction/methods ; Surveys and Questionnaires ; Transplantation, Autologous ; Transplantation, Homologous ; Young Adult ; }, abstract = {Importance: High-intensity, aerobically prepared fecal microbiota transplantation (FMT) has demonstrated efficacy in treating active ulcerative colitis (UC). FMT protocols involving anaerobic stool processing methods may enhance microbial viability and allow efficacy with a lower treatment intensity.<br><br>Objective: To assess the efficacy of a short duration of FMT therapy to induce remission in UC using anaerobically prepared stool.<br><br>A total of 73 adults with mild to moderately active UC were enrolled in a multicenter, randomized, double-blind clinical trial in 3 Australian tertiary referral centers between June 2013 and June 2016, with 12-month follow-up until June 2017.<br><br>Interventions: Patients were randomized to receive either anaerobically prepared pooled donor FMT (n = 38) or autologous FMT (n = 35) via colonoscopy followed by 2 enemas over 7 days. Open-label therapy was offered to autologous FMT participants at 8 weeks and they were followed up for 12 months.<br><br>Main Outcomes and Measures: The primary outcome was steroid-free remission of UC, defined as a total Mayo score of ≤2 with an endoscopic Mayo score of 1 or less at week 8. Total Mayo score ranges from 0 to 12 (0 = no disease and 12 = most severe disease). Steroid-free remission of UC was reassessed at 12 months. Secondary clinical outcomes included adverse events.<br><br>Results: Among 73 patients who were randomized (mean age, 39 years; women, 33 [45%]), 69 (95%) completed the trial. The primary outcome was achieved in 12 of the 38 participants (32%) receiving pooled donor FMT compared with 3 of the 35 (9%) receiving autologous FMT (difference, 23% [95% CI, 4%-42%]; odds ratio, 5.0 [95% CI, 1.2-20.1]; P = .03). Five of the 12 participants (42%) who achieved the primary end point at week 8 following donor FMT maintained remission at 12 months. There were 3 serious adverse events in the donor FMT group and 2 in the autologous FMT group.<br><br>Conclusions and Relevance: In this preliminary study of adults with mild to moderate UC, 1-week treatment with anaerobically prepared donor FMT compared with autologous FMT resulted in a higher likelihood of remission at 8 weeks. Further research is needed to assess longer-term maintenance of remission and safety.<br><br>Trial Registration: anzctr.org.au Identifier: ACTRN12613000236796.}, }
@article {pmid30644970, year = {2019}, author = {Kelly, CR and Ananthakrishnan, AN}, title = {Manipulating the Microbiome With Fecal Transplantation to Treat Ulcerative Colitis.}, journal = {JAMA}, volume = {321}, number = {2}, pages = {151-152}, doi = {10.1001/jama.2018.20397}, pmid = {30644970}, issn = {1538-3598}, mesh = {*Colitis, Ulcerative ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Microbiota ; }, }
@article {pmid30643841, year = {2018}, author = {Tran, V and Phan, J and Nulsen, B and Huang, L and Kaneshiro, M and Weiss, G and Ho, W and Sack, J and Ha, C and Uslan, D and Sauk, JS}, title = {Severe Ileocolonic Crohn's Disease Flare Associated with Fecal Microbiota Transplantation Requiring Diverting Ileostomy.}, journal = {ACG case reports journal}, volume = {5}, number = {}, pages = {e97}, doi = {10.14309/crj.2018.97}, pmid = {30643841}, issn = {2326-3253}, abstract = {Patients with inflammatory bowel disease (IBD) are at increased risk of developing Clostridium difficile infection (CDI). Fecal microbiota transplantation (FMT) is an effective therapy with a high success rate in preventing recurrent CDI. However, patients with IBD have decreased response to FMT for recurrent CDI, with several reports also suggesting potential IBD flare post-FMT. We present a case of mild ileocolonic Crohn's disease in a patient treated with FMT for recurrent CDI who subsequently developed severe steroid-refractory flare requiring surgical intervention 1 week post-FMT. Greater understanding of risk factors associated with post-FMT IBD flare is indicated.}, }
@article {pmid30643289, year = {2019}, author = {Feehley, T and Plunkett, CH and Bao, R and Choi Hong, SM and Culleen, E and Belda-Ferre, P and Campbell, E and Aitoro, R and Nocerino, R and Paparo, L and Andrade, J and Antonopoulos, DA and Berni Canani, R and Nagler, CR}, title = {Healthy infants harbor intestinal bacteria that protect against food allergy.}, journal = {Nature medicine}, volume = {25}, number = {3}, pages = {448-453}, doi = {10.1038/s41591-018-0324-z}, pmid = {30643289}, issn = {1546-170X}, support = {UL1 TR000430/TR/NCATS NIH HHS/United States ; P30 DK042086/DK/NIDDK NIH HHS/United States ; P30 CA014599/CA/NCI NIH HHS/United States ; R56 AI134923/AI/NIAID NIH HHS/United States ; UL1 TR002389/TR/NCATS NIH HHS/United States ; R01 AI106302/AI/NIAID NIH HHS/United States ; }, mesh = {Anaphylaxis/*microbiology ; Animals ; Clostridiales/genetics ; *Fecal Microbiota Transplantation ; Female ; Food Hypersensitivity/microbiology ; Gastrointestinal Microbiome/*genetics ; Germ-Free Life ; Healthy Volunteers ; Humans ; Ileum/microbiology ; Infant ; Male ; Mice ; Milk Hypersensitivity/*microbiology ; }, abstract = {There has been a striking generational increase in life-threatening food allergies in Westernized societies1,2. One hypothesis to explain this rising prevalence is that twenty-first century lifestyle practices, including misuse of antibiotics, dietary changes, and higher rates of Caesarean birth and formula feeding have altered intestinal bacterial communities; early-life alterations may be particularly detrimental3,4. To better understand how commensal bacteria regulate food allergy in humans, we colonized germ-free mice with feces from healthy or cow's milk allergic (CMA) infants5. We found that germ-free mice colonized with bacteria from healthy, but not CMA, infants were protected against anaphylactic responses to a cow's milk allergen. Differences in bacterial composition separated the healthy and CMA populations in both the human donors and the colonized mice. Healthy and CMA colonized mice also exhibited unique transcriptome signatures in the ileal epithelium. Correlation of ileal bacteria with genes upregulated in the ileum of healthy or CMA colonized mice identified a clostridial species, Anaerostipes caccae, that protected against an allergic response to food. Our findings demonstrate that intestinal bacteria are critical for regulating allergic responses to dietary antigens and suggest that interventions that modulate bacterial communities may be therapeutically relevant for food allergy.}, }
@article {pmid30643227, year = {2019}, author = {Bajaj, JS}, title = {Alcohol, liver disease and the gut microbiota.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {16}, number = {4}, pages = {235-246}, doi = {10.1038/s41575-018-0099-1}, pmid = {30643227}, issn = {1759-5053}, mesh = {Anti-Bacterial Agents/therapeutic use ; Dysbiosis/*complications/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Liver Diseases, Alcoholic/*microbiology/physiopathology/psychology/therapy ; Probiotics ; }, abstract = {Alcoholic liver disease, which ranges from mild disease to alcoholic hepatitis and cirrhosis, is a leading cause of morbidity and mortality worldwide. Alcohol intake can lead to changes in gut microbiota composition, even before liver disease development. These alterations worsen with advancing disease and could be complicit in disease progression. Microbial function, especially related to bile acid metabolism, can modulate alcohol-associated injury even in the presence of cirrhosis and alcoholic hepatitis. Microbiota changes might also alter brain function, and the gut-brain axis might be a potential target to reduce alcoholic relapse risk. Gut microbiota manipulation including probiotics, faecal microbial transplant and antibiotics has been studied in alcoholic liver disease with varying success. Further investigation of the modulation of the gut-liver axis is relevant, as most of these patients are not candidates for liver transplantation. This Review focuses on clinical studies involving the gut microbiota in patients with alcoholic liver disease across the spectrum from alcoholic fatty liver to cirrhosis and alcoholic hepatitis. Specific alterations in the gut-liver-brain axis that are complicit in the interactions between the gut microbiota and alcohol addiction are also reviewed.}, }
@article {pmid30642269, year = {2019}, author = {Zhang, K and Beckett, P and Abouanaser, S and Stankus, V and Lee, C and Smieja, M}, title = {Prolonged oral vancomycin for secondary prophylaxis of relapsing Clostridium difficile infection.}, journal = {BMC infectious diseases}, volume = {19}, number = {1}, pages = {51}, doi = {10.1186/s12879-019-3676-1}, pmid = {30642269}, issn = {1471-2334}, mesh = {Administration, Oral ; Aged ; Aged, 80 and over ; Antibiotic Prophylaxis/*methods ; Clostridium Infections/*prevention &amp; control ; Clostridium difficile/*pathogenicity ; Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Treatment Outcome ; Vancomycin/*administration &amp; dosage/*therapeutic use ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is an important cause of diarrhea and continues to be a major burden within healthcare institutions and in the community. For a small subset of patients with frequently relapsing CDI who do not have access to fecal microbiota transplantation (FMT), or fail FMT, there are no clear treatment recommendations. We review our experience with prolonged oral vancomycin for secondary prophylaxis of relapsing CDI.<br><br>METHODS: We performed a retrospective chart review of cases from the C. difficile consultation service at our institution since 2013. The service had three primary physicians providing consultations and performing over 1000 FMTs over the five-year period. Patients with relapsing CDI who were not candidates for FMT, refused, or relapsed after FMT were treated with vancomycin, followed by long-term oral vancomycin at a dose of 125 mg once daily.<br><br>RESULTS: Twenty patients received at least 8 weeks of once-daily oral vancomycin for prophylaxis of relapsing CDI. Patients had a median age of 80 years, and experienced a median of four episodes of CDI prior to long-term vancomycin. Most were female and 75% had received FMT. Only a single case of C. difficile relapse occurred while on long-term vancomycin during 200 patient-months of follow-up. Amongst those who stopped long-term vancomycin, 31% relapsed within 6 weeks. No adverse events were observed.<br><br>CONCLUSIONS: For elderly patients with frequently relapsing C. difficile, prolonged vancomycin once daily at a dose of 125 mg orally was effective in preventing further relapse. Vancomycin secondary prophylaxis may be considered in patients who have failed FMT, or in cases where FMT is not available.}, }
@article {pmid30639376, year = {2019}, author = {Felizardo, RJF and Watanabe, IKM and Dardi, P and Rossoni, LV and Câmara, NOS}, title = {The interplay among gut microbiota, hypertension and kidney diseases: The role of short-chain fatty acids.}, journal = {Pharmacological research}, volume = {141}, number = {}, pages = {366-377}, doi = {10.1016/j.phrs.2019.01.019}, pmid = {30639376}, issn = {1096-1186}, abstract = {The bacteria community living in the gut maintains a symbiotic relationship with the host and its unbalance has been associated with progression of a wide range of intestinal and extra intestinal conditions. Hypertension and chronic kidney disease (CKD) are closely associated diseases with high incidence rates all over the world. Increasing data have supported the involvement of gut microbiome in the blood pressure regulation and the impairment of CKD prognosis. In hypertension, the reduced number of short-chain fatty acids (SCFAs) producing bacteria is associated with modifications in gut environment, involving reduction of the hypoxic gut profile and worsening of the microbial balance, leading to a loss of epithelial barrier integrity, development of gut inflammation and the reduction of SCFAs plasma levels. These modifications compromise the blood pressure regulation and, as a consequence, favor the end organ damage, also affecting the kidneys. In CKD, impaired renal function leads to accumulation of high levels of uremic toxins that reach the intestine and cause alterations in bacteria composition and fecal metabolite profile, inducing a positive feedback that allows translocation of endotoxins into the bloodstream, which enhances local kidney inflammation and exacerbate kidney injury, compromising even more CKD prognosis. In line with these data, the use of prebiotics, probiotics and fecal microbiota transplantation are becoming efficient therapies to improve the gut dysbiosis aiming hypertension and CKD treatment. This review describes how changes in gut microbiota composition can affect the development of hypertension and the progression of kidney diseases, highlighting the importance of the gut microbial composition uncovering to improve human health maintenance and, especially, for the development of new alternative therapies.}, }
@article {pmid30637223, year = {2018}, author = {Philips, CA and Augustine, P and Phadke, N}, title = {Healthy Donor Fecal Microbiota Transplantation for Recurrent Bacterial Cholangitis in Primary Sclerosing Cholangitis - A Single Case Report.}, journal = {Journal of clinical and translational hepatology}, volume = {6}, number = {4}, pages = {438-441}, doi = {10.14218/JCTH.2018.00033}, pmid = {30637223}, issn = {2225-0719}, abstract = {Recurrent acute bacterial cholangitis is a unique indication for liver transplantation in primary sclerosing cholangitis. We present the first report on utility of healthy donor fecal transplantation for management of recurrent acute bacterial cholangitis in a primary sclerosing cholangitis patient. We demonstrate the striking liver biochemistry, bile acid and bacterial community changes following intestinal microbiota transplantation associated with amelioration of recurrent cholangitis.}, }
@article {pmid30632438, year = {2019}, author = {Moutinho, BD and Baima, JP and Rigo, FF and Saad-Hossne, R and Rodrigues, J and Romeiro, FG and Sassaki, LY}, title = {Fecal microbiota transplantation in refractory ulcerative colitis - a case report.}, journal = {The Journal of international medical research}, volume = {47}, number = {2}, pages = {1072-1079}, doi = {10.1177/0300060518821790}, pmid = {30632438}, issn = {1473-2300}, mesh = {Adolescent ; Colitis, Ulcerative/drug therapy/pathology/*therapy ; *Drug Resistance ; *Fecal Microbiota Transplantation ; Humans ; Immunosuppressive Agents/*pharmacology ; Male ; Prognosis ; *Salvage Therapy ; }, abstract = {Studies comparing gut microbiota profiles of inflammatory bowel disease (IBD) patients have shown several changes in microbiota composition, with marked reduction of local biodiversity relative to that of healthy controls. Modulation of the bacterial community is a promising strategy to reduce the proportion of harmful microorganisms and increase the proportion of beneficial bacteria; this is expected to prevent or treat IBD. The exact mechanism of fecal microbiota transplantation (FMT) remains unknown; however, replacing the host microbiota can reestablish gut microbial composition and function in IBD patients. The present report describes an ulcerative colitis patient who underwent FMT. A 17-year-old male with moderate to severe clinical activity, which was refractory to mesalazine, azathioprine, and infliximab, underwent FMT as alternative therapy. The patient exhibited clinical improvement after the procedure; however, the symptoms returned. A second FMT was performed 8 months after the first procedure, but the patient did not improve. In conclusion, despite the FMT failure observed in this patient, the procedure is a promising therapeutic option for IBD patients, and more in-depth studies of this method are needed.}, }
@article {pmid30632052, year = {2019}, author = {Allegretti, JR and Kao, D and Phelps, E and Roach, B and Smith, J and Ganapini, VC and Kassam, Z and Xu, H and Fischer, M}, title = {Risk of Clostridium difficile Infection with Systemic Antimicrobial Therapy Following Successful Fecal Microbiota Transplant: Should We Recommend Anti-Clostridium difficile Antibiotic Prophylaxis?.}, journal = {Digestive diseases and sciences}, volume = {64}, number = {6}, pages = {1668-1671}, doi = {10.1007/s10620-018-5450-4}, pmid = {30632052}, issn = {1573-2568}, abstract = {INTRODUCTION: The risk of a new Clostridium difficile infection (CDI) after FMT is unknown if non-CDI antibiotics are required. It is uncertain if anti-CDI prophylaxis or probiotics would reduce risk. We therefore aimed to compare the risk of CDI with and without antibiotic exposure and the benefit of concomitant anti-CDI antibiotic or probiotic prophylaxis.<br><br>METHODS: This is a multicenter retrospective study carried out at three large FMT referral centers of patients who underwent FMT for recurrent CDI. Patients were assessed for antibiotic use, as well as concomitant use of prophylactic anti-CDI antibiotics or probiotics. Time to CDI recurrence after FMT was evaluated using the Kaplan-Meier method.<br><br>RESULTS: A total of 404 patients were included: 63% were females, with a mean age of 61.3 ± 18.8 years. Mean length of post-FMT follow-up was 18.1 ± 11.9 months (range 2.2-45.2). Among the entire cohort 8.1% (n = 33) experienced a CDI recurrence. Overall, 111 patients (27.4%) used a non-CDI antibiotic, of which 16.2% (n = 18) experienced a CDI recurrence. Patients who used non-CDI antibiotics were more likely to develop CDI (HR 8.44, 95% CI 4.21-16.93, p < 0.001). The risk of CDI recurrence was not different between patients who received anti-CDI antibiotic prophylaxis to those who did not (HR = 1.88, 95% CI 0.72-4.86, p = 0.2); however, probiotic prophylaxis was associated with a greater risk of CDI recurrence (HR = 2.65, 95% CI 1.02-6.86, p = 0.045).<br><br>CONCLUSION: Non-CDI antibiotic use was not uncommon after successful FMT and significantly increased the risk of a new episode of CDI. In this study, we found that the prophylactic use of anti-CDI antibiotics or probiotics was not protective.}, }
@article {pmid30630933, year = {2019}, author = {Jiang, X and Hall, AB and Arthur, TD and Plichta, DR and Covington, CT and Poyet, M and Crothers, J and Moses, PL and Tolonen, AC and Vlamakis, H and Alm, EJ and Xavier, RJ}, title = {Invertible promoters mediate bacterial phase variation, antibiotic resistance, and host adaptation in the gut.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6423}, pages = {181-187}, doi = {10.1126/science.aau5238}, pmid = {30630933}, issn = {1095-9203}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 AT009708/AT/NCCIH NIH HHS/United States ; }, abstract = {Phase variation, the reversible alternation between genetic states, enables infection by pathogens and colonization by commensals. However, the diversity of phase variation remains underexplored. We developed the PhaseFinder algorithm to quantify DNA inversion-mediated phase variation. A systematic search of 54,875 bacterial genomes identified 4686 intergenic invertible DNA regions (invertons), revealing an enrichment in host-associated bacteria. Invertons containing promoters often regulate extracellular products, underscoring the importance of surface diversity for gut colonization. We found invertons containing promoters regulating antibiotic resistance genes that shift to the ON orientation after antibiotic treatment in human metagenomic data and in vitro, thereby mitigating the cost of antibiotic resistance. We observed that the orientations of some invertons diverge after fecal microbiota transplant, potentially as a result of individual-specific selective forces.}, }
@article {pmid30627262, year = {2018}, author = {Tabbaa, OM and Aboelsoud, MM and Mattar, MC}, title = {Long-Term Safety and Efficacy of Fecal Microbiota Transplantation in the Treatment of Clostridium difficile Infection in Patients With and Without Inflammatory Bowel Disease: A Tertiary Care Center's Experience.}, journal = {Gastroenterology research}, volume = {11}, number = {6}, pages = {397-403}, doi = {10.14740/gr1091}, pmid = {30627262}, issn = {1918-2805}, abstract = {Background: Clostridium difficile infection (CDI) carries a large burden on the national public health with its high morbidity and mortality rates. Patients with inflammatory bowel disease (IBD) are generally at higher risk of infection, recurrence and complications. Therefore, the need for more reliable and safe therapy is necessary. Our study aims to evaluate long-term fecal microbiota transplant (FMT) outcomes in the general population compared to patients with IBD.<br><br>Methods: A single center long-term follow-up study was conducted to evaluate the outcomes of FMT in patients with and without IBD. Prior to FMT data including demographics, prior treatment of CDI and severity of symptoms were gathered via chart review. Post FMT, all patients were surveyed after 2 days, 30 days and > 1 year to assess clinical and laboratory response. Our study outcomes included primary cure rate (negative CDI testing > 1 year after single FMT), and secondary cure rate (negative CDI testing > 1 year after repeat FMT or after an additional course of antibiotic with or without repeat FMT).<br><br>Results: Seventy-eight patients with recurrent or refractory CDI and subsequent FMT treatment were included. Mean age was 57 years, and 69% were females and twenty-one (27%) had IBD. Primary cure rate was achieved in 77% of the cases while secondary cure rate reached 100% at the end of the study. IBD patients were younger with an average age of 47 years, and had more complains of abdominal pain (71%), and required escalation of therapy in 50% of patients.<br><br>Conclusions: FMT was effective in the eradication of CDI in patients with and without IBD, but with no significant symptoms improvement in patients with IBD. Future randomized control studies are needed to examine the long-term progression of IBD and quality of life in patients treated with FMT compared to standard therapy of antibiotics for recurrent CDI.}, }
@article {pmid30625497, year = {2019}, author = {de Clercq, NC and Frissen, MN and Davids, M and Groen, AK and Nieuwdorp, M}, title = {Weight Gain after Fecal Microbiota Transplantation in a Patient with Recurrent Underweight following Clinical Recovery from Anorexia Nervosa.}, journal = {Psychotherapy and psychosomatics}, volume = {88}, number = {1}, pages = {58-60}, doi = {10.1159/000495044}, pmid = {30625497}, issn = {1423-0348}, mesh = {Adult ; Anorexia Nervosa/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Thinness/microbiology/*therapy ; Weight Gain/*physiology ; }, }
@article {pmid30619136, year = {2018}, author = {Yang, H and Xiang, Y and Robinson, K and Wang, J and Zhang, G and Zhao, J and Xiao, Y}, title = {Gut Microbiota Is a Major Contributor to Adiposity in Pigs.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {3045}, doi = {10.3389/fmicb.2018.03045}, pmid = {30619136}, issn = {1664-302X}, abstract = {Different breeds of pigs vary greatly in their propensity for adiposity. Gut microbiota is known to play an important role in modulating host physiology including fat metabolism. However, the relative contribution of gut microbiota to lipogenic characteristics of pigs remains elusive. In this study, we transplanted fecal microbiota of adult Jinhua and Landrace pigs, two breeds of pigs with distinct lipogenic phenotypes, to antibiotic-treated mice. Our results indicated that, 4 weeks after fecal transplantation, the mice receiving Jinhua pigs' &quot;obese&quot; microbiota (JM) exhibited a different intestinal bacterial community structure from those receiving Landrace pigs' &quot;lean&quot; microbiota (LM). Notably, an elevated ratio of Firmicutes to Bacteroidetes and a significant diminishment of Akkermansia were observed in JM mice relative to LM mice. Importantly, mouse recipients resembled their respective porcine donors in many of the lipogenic characteristics. Similar to Jinhua pig donors, JM mice had elevated lipid and triglyceride levels and the lipoprotein lipase activity in the liver. Enhanced expression of multiple key lipogenic genes and reduced angiopoietin-like 4 (Angptl4) mRNA expression were also observed in JM mice, relative to those in LM mice. These results collectively suggested that gut microbiota of Jinhua pigs is more capable of enhancing lipogenesis than that of Landrace pigs. Transferability of the lipogenic phenotype across species further indicated that gut microbiota plays a major role in contributing to adiposity in pigs. Manipulation of intestinal microbiota will, therefore, have a profound impact on altering host metabolism and adipogenesis, with an important implication in the treatment of human overweight and obesity.}, }
@article {pmid30618824, year = {2018}, author = {Porras, D and Nistal, E and Martínez-Flórez, S and González-Gallego, J and García-Mediavilla, MV and Sánchez-Campos, S}, title = {Intestinal Microbiota Modulation in Obesity-Related Non-alcoholic Fatty Liver Disease.}, journal = {Frontiers in physiology}, volume = {9}, number = {}, pages = {1813}, doi = {10.3389/fphys.2018.01813}, pmid = {30618824}, issn = {1664-042X}, abstract = {Obesity and associated comorbidities, including non-alcoholic fatty liver disease (NAFLD), are a major concern to public well-being worldwide due to their high prevalence among the population, and its tendency on the rise point to as important threats in the future. Therapeutic approaches for obesity-associated disorders have been circumscribed to lifestyle modifications and pharmacological therapies have demonstrated limited efficacy. Over the last few years, different studies have shown a significant role of intestinal microbiota (IM) on obesity establishment and NAFLD development. Therefore, modulation of IM emerges as a promising therapeutic strategy for obesity-associated diseases. Administration of prebiotic and probiotic compounds, fecal microbiota transplantation (FMT) and exercise protocols have shown a modulatory action over the IM. In this review we provide an overview of current approaches targeting IM which have shown their capacity to counteract NAFLD and metabolic syndrome features in human patients and animal models.}, }
@article {pmid30616615, year = {2019}, author = {Sugita, K and Yanuma, N and Ohno, H and Takahashi, K and Kawano, K and Morita, H and Ohmori, K}, title = {Oral faecal microbiota transplantation for the treatment of Clostridium difficile-associated diarrhoea in a dog: a case report.}, journal = {BMC veterinary research}, volume = {15}, number = {1}, pages = {11}, doi = {10.1186/s12917-018-1754-z}, pmid = {30616615}, issn = {1746-6148}, mesh = {Animals ; Clostridium Infections/diagnosis/microbiology/therapy/*veterinary ; Clostridium difficile ; Diarrhea/microbiology/therapy/*veterinary ; Dog Diseases/diagnosis/microbiology/*therapy ; Dogs ; Fecal Microbiota Transplantation/*veterinary ; Male ; Real-Time Polymerase Chain Reaction/veterinary ; }, abstract = {BACKGROUND: Successful clinical outcomes of faecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection have been reported in humans and a marmoset. However, it has been unclear whether oral FMT was effective for the treatment of C. difficile-associated diarrhoea in dogs.<br><br>CASE PRESENTATION: An 8-month-old, intact male French bulldog was presented with a 4-month history of intermittent large bowel diarrhoea. Physical and clinical examinations did not identify any specific causes for diarrhoea. Real-time PCR analysis and immunochromatography detected C. difficile antigen and toxin A&amp;B genes and proteins in a faecal sample. Based on these findings, diarrhoea in the dog was considered to be induced by C. difficile-associated colitis. The dog was treated with oral FMT, in which a faecal solution obtained from a healthy beagle was orally administered to the subject. Stool consistency and frequency and faecal blood and mucus became normal 2-3 days after oral FMT, and real-time PCR analysis and immunochromatography was negative for C. difficile antigen and toxin A&amp;B genes and proteins. No adverse events were observed.<br><br>CONCLUSION: The present case report demonstrated that oral FMT was an effective treatment for C. difficile-associated diarrhoea in a dog. The findings in this report provide a rationale to evaluate clinical efficacy of oral FMT for other gastrointestinal diseases in dogs.}, }
@article {pmid30613670, year = {2018}, author = {Zhang, XY and Wang, YZ and Li, XL and Hu, H and Liu, HF and Li, D and Xiao, YM and Zhang, T}, title = {Safety of fecal microbiota transplantation in Chinese children: A single-center retrospective study.}, journal = {World journal of clinical cases}, volume = {6}, number = {16}, pages = {1121-1127}, doi = {10.12998/wjcc.v6.i16.1121}, pmid = {30613670}, issn = {2307-8960}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is the administration of fecal bacterial liquid from healthy donors to a recipient's digestive tract, which is recommended as a therapeutic method for recurrent Clostridium difficile infection (CDI). Many clinical trials focusing on different diseases are in progress. To date, scarce research and long-term follow-up have been conducted on FMT in children or on the proper guidelines. Our center first performed FMT to treat a 13-month-old boy with severe CDI in 2013. Until February 2018, our center had performed 114 pediatric FMT procedures in 49 subjects.<br><br>AIM: To investigate the safety of FMT in children.<br><br>METHODS: A retrospective study was conducted on 49 patients who underwent 114 FMT treatments at our hospital. All FMT processes followed uniform standards. Adverse events (AEs) related to FMT were divided into short-term (48 h post-FMT) and long-term (3 mo). All potential influencing factors for AEs, such as gender, age, time of FMT infusion, route of administration, disease type, immune function state, and donor relative genetic background, were analyzed as independent factors. The significant independent factors and risk ratio with 95% confidence interval (CI) were assessed by multivariate logistic regression analysis.<br><br>RESULTS: Forty-nine patients (mean age 68.1 mo, range 4 to 193 mo) were recruited. Their average follow-up time after the first FMT was 23.1 mo. The incidence of short-term AEs was 26.32% (30/114). The most common short-term AEs were abdominal pain, diarrhea, fever, and vomiting, which were all self-limited and symptom-free within 48 h. Two severe AEs occurred, and one patient died in the fourth week after FMT. All-cause mortality was 2.04%. As independent factors, age (P = 0.006) and immune state (P = 0.002) had significant effects. Age greater than 72 mo seemed to be correlated with more AEs than age 13 to 36 mo (P = 0.04). In multivariate logistic regression analysis, immune state was an independent risk factor for AE occurrence (P = 0.035), and the risk ratio in immunodeficient patients was 3.105 (95%CI: 1.080-8.923).<br><br>CONCLUSION: Although FMT was proven to be tolerated in children, we need to be more cautious with immunodeficient patients. The effect on children's long-term health is unpredictable.}, }
@article {pmid30613005, year = {2018}, author = {Guirong, YE and Minjie, Z and Lixin, YU and Junsheng, YE and Lin, Y and Lisha, S}, title = {[Gut microbiota in renal transplant recipients, patients with chronic kidney disease and healthy subjects].}, journal = {Nan fang yi ke da xue xue bao = Journal of Southern Medical University}, volume = {38}, number = {12}, pages = {1401-1408}, doi = {10.12122/j.issn.1673-4254.2018.12.01}, pmid = {30613005}, issn = {1673-4254}, mesh = {Feces/*microbiology ; Gastrointestinal Microbiome/*physiology ; *Healthy Volunteers ; Humans ; *Kidney ; Kidney Transplantation ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; Renal Insufficiency, Chronic/*microbiology ; *Transplant Recipients ; }, abstract = {OBJECTIVE: Recent studies have shown that gut microbiota is associated with immunomodulation in transplant recipients, but the composition and function of gut microbiota in renal transplant recipients have not been understood.<br><br>METHODS: We analyzed the composition and function of gut microbiota in the fecal samples from 16 renal transplant (RT) recipients by deep sequencing of the 16S rRNA V3 variable region. The gut microbiota of RT recipients was compared to that of 84 patients with chronic kidney disease (CKD) and 53 healthy subjects.<br><br>RESULTS: The overall microbial structure of RT recipients was similar to that of CKD. The abundance of Firmicutes, Lachnospiraceae, Ruminococcaceae and Faecalibacterium was decreased and that of Bacteroidetes, Proteobacteria, Clostridiales, and Enterobacteriaceae was increased significantly in RT recipients and CKD patients compared with the healthy control subjects. Functional comparison revealed significantly enhanced carbohydrate metabolism and decreased metabolism of cofactors, vitamins, cell motility and genetic information processing in RT recipients and CKD patients. RT recipients and CKD patients also showed slight differences in that the abundance of Proteobacteria and Enterobacteriaceae and the pathways involving transport system members and carbohydrate metabolism were much greater in the former. We found that several beneficial genera in the Lachnospiraceae and Veillonellaceae were negatively correlated with such clinical markers as serum creatinine and blood urea nitrogen.<br><br>CONCLUSIONS: Our results suggested that alterations in the composition and function of gut microbiota are significantly correlated with the clinical conditions of in RT recipients, and future prospective studies of these correlations may provide evidence for predicting the clinical outcomes of RT recipients.}, }
@article {pmid30611533, year = {2019}, author = {Bermejo Boixareu, C and Ramos Martínez, A and Tutor-Ureta, P}, title = {Ninety-eight years old female treated with fecal microbiota transplantation after recurrent Clostridium difficile infection.}, journal = {Medicina clinica}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.medcli.2018.11.024}, pmid = {30611533}, issn = {1578-8989}, }
@article {pmid30610862, year = {2019}, author = {Hvas, CL and Dahl Jørgensen, SM and Jørgensen, SP and Storgaard, M and Lemming, L and Hansen, MM and Erikstrup, C and Dahlerup, JF}, title = {Fecal Microbiota Transplantation Is Superior to Fidaxomicin for Treatment of Recurrent Clostridium difficile Infection.}, journal = {Gastroenterology}, volume = {156}, number = {5}, pages = {1324-1332.e3}, doi = {10.1053/j.gastro.2018.12.019}, pmid = {30610862}, issn = {1528-0012}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Clostridium Infections/diagnosis/microbiology/*therapy ; Clostridium difficile/*drug effects/pathogenicity ; Denmark ; *Fecal Microbiota Transplantation/adverse effects ; Female ; Fidaxomicin/adverse effects/*therapeutic use ; Humans ; Male ; Middle Aged ; Recurrence ; Remission Induction ; Time Factors ; Treatment Outcome ; Vancomycin/adverse effects/*therapeutic use ; Young Adult ; }, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) is recommended for treatment of recurrent Clostridium difficile infection (rCDI). We performed a single-center randomized trial to compare the effects of FMT with those of fidaxomicin and vancomycin.<br><br>METHODS: We studied consecutive adults with rCDI seen at a gastroenterology clinic in Denmark from April 5, 2016 through June 10, 2018. Patients were randomly assigned to a group that received FMT, applied by colonoscopy or nasojejunal tube, after 4-10 days of vancomycin (125 mg 4 times daily; FMTv; n = 24), 10 days of fidaxomicin (200 mg twice daily; n = 24), or 10 days of vancomycin (125 mg 4 times daily; n = 16). Patients who had rCDI after this course of treatment and patients who could not be randomly assigned to groups were offered rescue FMTv. The primary outcome was combined clinical resolution and a negative result from a polymerase chain reaction test for Clostridium difficile (CD) toxin 8 weeks after the allocated treatment. Secondary end points included clinical resolution at week 8.<br><br>RESULTS: All 64 patients received their assigned treatment. The combination of clinical resolution and negative results from the test for CD were observed in 17 patients given FMTv (71%), 8 patients given fidaxomicin (33%), and 3 patients given vancomycin (19%; P = .009 for FMTv vs fidaxomicin; P = .001 for FMTv vs vancomycin; P = .31 for fidaxomicin vs vancomycin). Clinical resolution was observed in 22 patients given FMTv (92%), 10 patients given fidaxomicin (42%), and 3 patients given vancomycin (19%; P = .0002; P < .0001; P = .13). Results did not differ significantly between patients who received FMTv as their initial therapy and patients who received rescue FMTv. There was 1 serious adverse event that might have been related to FMTv.<br><br>CONCLUSIONS: In a randomized trial of patients with rCDI, we found the FMTv combination superior to fidaxomicin or vancomycin based on end points of clinical and microbiological resolution or clinical resolution alone. ClinicalTrials.gov, number NCT02743234; EudraCT, j.no 2015-003004-24.}, }
@article {pmid30606236, year = {2019}, author = {Dai, M and Zhang, T and Li, Q and Cui, B and Xiang, L and Ding, X and Rong, R and Bai, J and Zhu, J and Zhang, F}, title = {The bowel preparation for magnetic resonance enterography in patients with Crohn's disease: study protocol for a randomized controlled trial.}, journal = {Trials}, volume = {20}, number = {1}, pages = {1}, doi = {10.1186/s13063-018-3101-x}, pmid = {30606236}, issn = {1745-6215}, mesh = {Adult ; Colonoscopy/*methods ; Crohn Disease/*diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Male ; Multicenter Studies as Topic ; Outcome Assessment (Health Care) ; Randomized Controlled Trials as Topic ; Research Design ; }, abstract = {BACKGROUND: Adequate bowel preparation is required for magnetic resonance enterography (MRE), which can be achieved by administering contrast solution after mid-gut tubing or taking contrast solution orally. We present the design of randomized controlled trial (RCT) to compare the efficacy and compliance of bowel preparation between mid-gut tubing and oral administering for MRE in patients with Crohn's disease (CD).<br><br>METHODS/DESIGN: This is an open-label, multicenter RCT. Ninety-six patients with CD in need of MRE examination and mid-gut tubing (prepared for fecal microbiota transplantation and/or enteral nutrition), aged ≥ 14 years, will be included. Patients will be randomized 1:1 into either bowel preparation by oral administering (oral group) or bowel preparation through mid-gut transendoscopic enteral tubing (TET) (tubing group). The primary outcome measures are: (1) degree of discomfort before/during/after bowel preparation for MRE using a visual 5-grade scale (1 = few, 5 = very severe); and (2) grade of bowel distention evaluated by a 5-grade scale (1 = 0-20% segmental distention, 2 = 20-40% distention, 3 = 40-60% distention, 4 = 60-80% distention, 5 = 80-100% distention). The secondary outcome measure is the accuracy of lesion detection through MRE confirmed by colonoscopy which is evaluated by a 5-point scale.<br><br>DISCUSSION: The outcome of this study is expected to provide a novel effective clinical protocol of bowel preparation for MRE in patients with CD. We hope to highlight the concept of physician-patient satisfaction based on different methods of bowel preparation for MRE.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, NCT03541733 . Registered on 30 May 2018.}, }
@article {pmid30602276, year = {Wint}, author = {Stebel, R and Svačinka, R and Vojtilová, L and Freibergerová, M and Husa, P}, title = {Fecal bacteriotherapy in the treatment of Clostridium difficile infection.}, journal = {Epidemiologie, mikrobiologie, imunologie : casopis Spolecnosti pro epidemiologii a mikrobiologii Ceske lekarske spolecnosti J.E. Purkyne}, volume = {67}, number = {3}, pages = {104-109}, pmid = {30602276}, issn = {1210-7913}, mesh = {*Clostridium Infections/complications/therapy ; Clostridium difficile ; Czech Republic ; *Enterocolitis, Pseudomembranous/etiology/therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Prospective Studies ; Treatment Outcome ; }, abstract = {AIM: Using a prospective analysis to assess the success of faecal bacteriotherapy (FBT) in antibiotic-associated colitis due to Clostridium difficile. To analyse whether any of the factors according to which the treated patients can be categorized has a statistically significant effect on the therapeutic outcome.<br><br>MATERIALS AND METHODS: During the 2-year study period (2015-2016), 71 patients received FBT. After treatment, the patients were followed up by means of clinic visits or by phone. If colitis did not recur within eight weeks of follow-up, the treatment was considered successful.<br><br>RESULTS: The overall success rate was 76%, with statistically insignificant decline in recurrences. Subgroup analysis did not show any statistically significant difference in the success rate between the routes of administration, i.e. through a naso-enteral feeding tube and rectal enema. Likewise, there were no statistically significant differences in the success rate between the types of prior antibiotic therapy or between using fresh and cryo-stored stool suspension. No unexpected adverse event or lethality occurred during the study period.<br><br>CONCLUSIONS: Faecal bacteriotherapy is a successful and safe therapeutic alternative for recurrent C. difficile infections.}, }
@article {pmid30601771, year = {2019}, author = {Mankal, PK and Abed, J and Latte-Naor, S and Grinspan, A and Kotler, DP}, title = {Fidaxomicin and Fecal Microbiota Transplants for Severe Clostridium difficile Colitis.}, journal = {American journal of therapeutics}, volume = {26}, number = {1}, pages = {e115-e117}, doi = {10.1097/MJT.0000000000000573}, pmid = {30601771}, issn = {1536-3686}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridium difficile/*isolation &amp; purification ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Fidaxomicin/*therapeutic use ; Humans ; Male ; Middle Aged ; Treatment Outcome ; }, }
@article {pmid30598589, year = {2019}, author = {Ramai, D and Zakhia, K and Ofosu, A and Ofori, E and Reddy, M}, title = {Fecal microbiota transplantation: donor relation, fresh or frozen, delivery methods, cost-effectiveness.}, journal = {Annals of gastroenterology}, volume = {32}, number = {1}, pages = {30-38}, doi = {10.20524/aog.2018.0328}, pmid = {30598589}, issn = {1108-7471}, support = {T32 DK007356/DK/NIDDK NIH HHS/United States ; }, abstract = {Fecal microbiota transplantation (FMT) has evolved into a robust and efficient means for treating recurrent Clostridium difficile infection (CDI). Our narrative review looks at the donor selection, preparation, delivery techniques and cost-effectiveness of FMT. We searched electronic databases, including PubMed, MEDLINE, Google Scholar, and Cochrane Databases, for studies that compared the biological effects of donor selection, fresh or frozen fecal preparation, and various delivery techniques. We also evaluated the cost-effectiveness and manually searched references to identify additional relevant studies. Overall, there is a paucity of studies that directly compare outcomes associated with related and non-related stool donors. However, inferences from prior studies indicate that the success of FMT does not depend on the donor-patient relationship. Over time, the use of unrelated donors has increased because of the formation of stool banks and the need to save processing time and capital. However, longitudinal studies are needed to clarify the optimal freezing time before microbial function declines. Several FMT techniques have been developed, such as colonoscopy, enema, nasogastric or nasojejunal tubes, and capsules. The comparable and high efficacy of FMT capsules, combined with their convenience, safety and aesthetically tolerable mode of delivery, makes it an attractive option for many patients. Cost-effective models comparing these various approaches support the use of FMT via colonoscopy as being the best strategy for the treatment of recurrent CDI.}, }
@article {pmid30598584, year = {2018}, author = {Greenberg, SA and Youngster, I and Cohen, NA and Livovsky, DM and Strahilevitz, J and Israeli, E and Melzer, E and Paz, K and Fliss-Isakov, N and Maharshak, N}, title = {Five years of fecal microbiota transplantation - an update of the Israeli experience.}, journal = {World journal of gastroenterology}, volume = {24}, number = {47}, pages = {5403-5414}, doi = {10.3748/wjg.v24.i47.5403}, pmid = {30598584}, issn = {2219-2840}, mesh = {Aged ; Aged, 80 and over ; Capsules ; Clostridium Infections/diagnosis/microbiology/*therapy ; Clostridium difficile/*isolation &amp; purification ; Diarrhea/diagnosis/microbiology/*therapy ; Fecal Microbiota Transplantation/instrumentation/*methods ; Female ; Humans ; Israel ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {AIM: To evaluate and describe the efficacy of fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in a national Israeli cohort.<br><br>METHODS: All patients who received FMT for recurrent (recurrence within 8 wk of the previous treatment) or refractory CDI from 2013 through 2017 in all the five medical centers in Israel currently performing FMT were included. Stool donors were screened according to the Israeli Ministry of Health guidelines. Clinical and laboratory data of patients were collected from patients' medical files, and they included indications for FMT, risk factors for CDI and disease severity. Primary outcome was FMT success (at least 2 mo free of CDI-related diarrhea post-FMT). Secondary outcomes included initial response to FMT (cessation of diarrhea within 7 d) and recurrence at 6 mo.<br><br>RESULTS: There were 111 FMTs for CDI, with a median age of 70 years [interquartile range (IQR): 53-82], and 42% (47) males. Fifty patients (45%) were treated via the lower gastrointestinal (LGI, represented only by colonoscopy) route, 37 (33%) via capsules, and 24 (22%) via the upper gastrointestinal (UGI) route. The overall success rate was 87.4% (97 patients), with no significant difference between routes of administration (P = 0.338). In the univariant analysis, FMT success correlated with milder disease (P = 0.01), ambulatory setting (P < 0.05) and lower Charlson comorbidity score (P < 0.05). In the multivariant analysis, only severe CDI [odd ratio (OR) = 0.14, P < 0.05] and inpatient FMT (OR = 0.19, P < 0.05) were each independently inversely related to FMT success. There were 35 (32%) patients younger than 60 years of age, and 14 (40%) of them had a background of inflammatory bowel disease.<br><br>CONCLUSION: FMT is a safe and effective treatment for CDI, with capsules emerging as a successful and well-tolerated route. Severe CDI is less likely to respond to FMT.}, }
@article {pmid30593419, year = {2019}, author = {Liptak, R and Gromova, B and Maronek, M and Gardlik, R}, title = {Reverse phenotype transfer via fecal microbial transplantation in inflammatory bowel disease.}, journal = {Medical hypotheses}, volume = {122}, number = {}, pages = {41-44}, doi = {10.1016/j.mehy.2018.10.017}, pmid = {30593419}, issn = {1532-2777}, mesh = {Animals ; Colitis/*therapy ; Colon/pathology ; Dextran Sulfate/chemistry ; Dysbiosis/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*therapy ; Mice ; Permeability ; Phenotype ; }, abstract = {Inflammatory bowel disease (IBD) is characterized by a disbalance in the composition of intestinal microbiota. It is not clear whether such dysbiosis is a cause or a consequence of a disease state. Fecal microbiota transplantation (FMT) from a healthy donor to a patient or diseased animal is a valuable tool for targeted modification of microbiome leading to therapeutic response. Positive effect has been shown in therapy of a number of gastrointestinal as well as non-gastrointestinal diseases. In addition, FMT has been successfully used to transfer the diseased phenotype form a donor with the disease to a healthy recipient. However, targeted modification of the microbiome before the onset of colitis has not been shown previously. Based on our preliminary results, we propose the hypothesis of so called reverse phenotype transfer in IBD. This term describes the phenomenon, in which the transplantation of gut microbiota from a donor more sensitive to IBD to a healthy recipient leads to resistance of the recipient to IBD and vice versa. Mice that received FMT from donors with severe colitis have shown improved colitis score compared with mice that received FMT from donors more resistant to development of colitis. Such reverse phenotype transfer has broad implications, especially in terms of preventive medicine. However, detailed mechanisms need to be elucidated to conclude the validity of the phenomenon.}, }
@article {pmid30586712, year = {2019}, author = {Tang, TWH and Chen, HC and Chen, CY and Yen, CYT and Lin, CJ and Prajnamitra, RP and Chen, LL and Ruan, SC and Lin, JH and Lin, PJ and Lu, HH and Kuo, CW and Chang, CM and Hall, AD and Vivas, EI and Shui, JW and Chen, P and Hacker, TA and Rey, FE and Kamp, TJ and Hsieh, PCH}, title = {Loss of Gut Microbiota Alters Immune System Composition and Cripples Postinfarction Cardiac Repair.}, journal = {Circulation}, volume = {139}, number = {5}, pages = {647-659}, doi = {10.1161/CIRCULATIONAHA.118.035235}, pmid = {30586712}, issn = {1524-4539}, abstract = {BACKGROUND: The impact of gut microbiota on the regulation of host physiology has recently garnered considerable attention, particularly in key areas such as the immune system and metabolism. These areas are also crucial for the pathophysiology of and repair after myocardial infarction (MI). However, the role of the gut microbiota in the context of MI remains to be fully elucidated.<br><br>METHODS: To investigate the effects of gut microbiota on cardiac repair after MI, C57BL/6J mice were treated with antibiotics 7 days before MI to deplete mouse gut microbiota. Flow cytometry was applied to examine the changes in immune cell composition in the heart. 16S rDNA sequencing was conducted as a readout for changes in gut microbial composition. Short-chain fatty acid (SCFA) species altered after antibiotic treatment were identified by high-performance liquid chromatography. Fecal reconstitution, transplantation of monocytes, or dietary SCFA or Lactobacillus probiotic supplementation was conducted to evaluate the cardioprotective effects of microbiota on the mice after MI.<br><br>RESULTS: Antibiotic-treated mice displayed drastic, dose-dependent mortality after MI. We observed an association between the gut microbiota depletion and significant reductions in the proportion of myeloid cells and SCFAs, more specifically acetate, butyrate, and propionate. Infiltration of CX3CR1+ monocytes to the peri-infarct zone after MI was also reduced, suggesting impairment of repair after MI. Accordingly, the physiological status and survival of mice were significantly improved after fecal reconstitution, transplantation of monocytes, or dietary SCFA supplementation. MI was associated with a reorganization of the gut microbial community such as a reduction in Lactobacillus. Supplementing antibiotic-treated mice with a Lactobacillus probiotic before MI restored myeloid cell proportions, yielded cardioprotective effects, and shifted the balance of SCFAs toward propionate.<br><br>CONCLUSIONS: Gut microbiota-derived SCFAs play an important role in maintaining host immune composition and repair capacity after MI. This suggests that manipulation of these elements may provide opportunities to modulate pathological outcome after MI and indeed human health and disease as a whole.}, }
@article {pmid30585500, year = {2019}, author = {Vigvári, S and Vincze, Á and Solt, J and Sipos, D and Feiszt, Z and Kovács, B and Kappéter, Á and Péterfi, Z}, title = {Experiences with fecal microbiota transplantation in Clostridium difficile infections via upper gastrointestinal tract.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {66}, number = {2}, pages = {179-188}, doi = {10.1556/030.65.2018.051}, pmid = {30585500}, issn = {1588-2640}, abstract = {Dramatic changes in the epidemiology of Clostridium difficile infections have been reported from the western world in the past decade. The proportion of severe cases is significantly elevating and clinicians now have to contend with the problem of additional and more frequent episodes of recurrences including an upward trend in the mortality rate. This situation led us to investigate the possibility of the fecal microbiota transplantation (FMT). An amount of 100 ml of fecal microbiota solution was instilled into a nasojejunal (NJ) tube in 16 cases and into a nasogastric (NG) tube in 44 cases. In all of the cases, where the solution was instilled via nasojejunal tubes, the symptoms resolved within 24 h. We did not note any recurrences in this group. When the material was flushed in through nasogastric tubes, the symptoms resolved in 39 (88.64%) cases within 24 h. In this group, we have experienced a recurrent episode of C. difficile infection in five (11.36%) cases. Three of them were cured with a second transplantation. We have found that in our practice the upper gastrointestinal tract methods had the primary cure rate of 91.67%, whereas the secondary cure rate is 96.67%. When we compared the NJ and NG methods, we have found that the differences in the outcomes are not significant statistically (p = 0.3113 using Fisher's exact probability test). In conclusion, FMT proved to be very effective, particularly in recurrent infections and in cases where conventional treatment had failed.}, }
@article {pmid30582442, year = {2019}, author = {Brandsma, E and Kloosterhuis, NJ and Koster, M and Dekker, DC and Gijbels, MJJ and van der Velden, S and Ríos-Morales, M and van Faassen, MJR and Loreti, MG and de Bruin, A and Fu, J and Kuipers, F and Bakker, BM and Westerterp, M and de Winther, MPJ and Hofker, MH and van de Sluis, B and Koonen, DPY}, title = {A Proinflammatory Gut Microbiota Increases Systemic Inflammation and Accelerates Atherosclerosis.}, journal = {Circulation research}, volume = {124}, number = {1}, pages = {94-100}, doi = {10.1161/CIRCRESAHA.118.313234}, pmid = {30582442}, issn = {1524-4571}, abstract = {RATIONALE: Several studies have suggested a role for the gut microbiota in inflammation and atherogenesis. A causal relation relationship between gut microbiota, inflammation, and atherosclerosis has not been explored previously.<br><br>OBJECTIVE: Here, we investigated whether a proinflammatory microbiota from Caspase1-/- (Casp1-/-) mice accelerates atherogenesis in Ldlr-/- mice.<br><br>METHOD AND RESULTS: We treated female Ldlr-/- mice with antibiotics and subsequently transplanted them with fecal microbiota from Casp1-/- mice based on a cohousing approach. Autologous transplantation of fecal microbiota of Ldlr-/- mice served as control. Mice were cohoused for 8 or 13 weeks and fed chow or high-fat cholesterol-rich diet. Fecal samples were collected, and factors related to inflammation, metabolism, intestinal health, and atherosclerotic phenotypes were measured. Unweighted Unifrac distances of 16S rDNA (ribosomal DNA) sequences confirmed the introduction of the Casp1-/- and Ldlr-/- microbiota into Ldlr-/- mice (referred to as Ldlr-/-(Casp1-/-) or Ldlr-/-(Ldlr-/-) mice). Analysis of atherosclerotic lesion size in the aortic root demonstrated a significant 29% increase in plaque size in 13-week high-fat cholesterol-fed Ldlr-/-(Casp1-/-) mice compared with Ldlr-/-(Ldlr-/-) mice. We found increased numbers of circulating monocytes and neutrophils and elevated proinflammatory cytokine levels in plasma in high-fat cholesterol-fed Ldlr-/-(Casp1-/-) compared with Ldlr-/-(Ldlr-/-) mice. Neutrophil accumulation in the aortic root of Ldlr-/-(Casp1-/-) mice was enhanced compared with Ldlr-/-(Ldlr-/-) mice. 16S-rDNA-encoding sequence analysis in feces identified a significant reduction in the short-chain fatty acid-producing taxonomies Akkermansia, Christensenellaceae, Clostridium, and Odoribacter in Ldlr-/-(Casp1-/-) mice. Consistent with these findings, cumulative concentrations of the anti-inflammatory short-chain fatty acids propionate, acetate and butyrate in the cecum were significantly reduced in 13-week high-fat cholesterol-fed Ldlr-/-(Casp1-/-) compared with Ldlr-/-(Ldlr-/-) mice.<br><br>CONCLUSIONS: Introduction of the proinflammatory Casp1-/- microbiota into Ldlr-/- mice enhances systemic inflammation and accelerates atherogenesis.}, }
@article {pmid30580506, year = {2018}, author = {Xu, Z and Liu, Z and Dong, X and Hu, T and Wang, L and Li, J and Liu, X and Sun, J}, title = {Fecal Microbiota Transplantation from Healthy Donors Reduced Alcohol-induced Anxiety and Depression in an Animal Model of Chronic Alcohol Exposure.}, journal = {The Chinese journal of physiology}, volume = {61}, number = {6}, pages = {360-371}, doi = {10.4077/CJP.2018.BAH633}, pmid = {30580506}, issn = {0304-4920}, support = {NO. 81671320//Natural Science Foundation of China/International ; NO. 2016GSF201054//Key Research Plan of Shandong Province/International ; }, mesh = {Animals ; Anxiety ; *Depression ; Ethanol ; *Fecal Microbiota Transplantation ; Feces ; Mice ; }, }
@article {pmid30578461, year = {2019}, author = {Nobili, V and Mosca, A and Alterio, T and Cardile, S and Putignani, L}, title = {Fighting Fatty Liver Diseases with Nutritional Interventions, Probiotics, Symbiotics, and Fecal Microbiota Transplantation (FMT).}, journal = {Advances in experimental medicine and biology}, volume = {1125}, number = {}, pages = {85-100}, doi = {10.1007/5584_2018_318}, pmid = {30578461}, issn = {0065-2598}, abstract = {Pediatric obesity is rising worldwide leading the worrying phenomenon of nonalcoholic fatty liver disease (NAFLD) to shift into one of the most frequent causes of chronic liver illness in childhood. Occurrence of NAFLD depends on several factors such as the geographical area and the diagnostic modalities used; overall it ranges between 3% and 10% of pediatric population, increasing up to 70% in patients with metabolic comorbidities (Manco M, Bottazzo G, DeVito R et al, J Am Coll Nutr 27:667-676, 2008).Recent findings have related the intestinal microbiota to a plethora of pathological conditions, including type 2 diabetes (T2D), obesity, and nonalcoholic steatohepatitis (NASH). One of the emerging areas of the study is the link between liver diseases and gut microbiome, which has added new information to the understanding of the so-called gut-liver axis.In order to address the role of gut microbiome in NAFLD onset and progression, it is necessary to &quot;decipher&quot; operational codes for microbiome investigation within the context of advanced laboratory medicine to capture microbiome features and, hence, to address the function of the intestinal microbiome within the gut microbiota-liver axis.Results of these investigations have allowed the beginning of implementing the usage of probiotics and symbiotics in the medical approach of obesity and NAFLD in adults and children. Several randomized clinical trials (RCTs) have been already published on fecal microbiota transplantation (FMT), T2D, NASH, and inflammatory bowel disease (IBD).This review proposes to describe the current state of knowledge on the ways fatty liver diseases can be addressed with nutritional interventions, probiotics, symbiotics, and FMT.}, }
@article {pmid30576642, year = {2019}, author = {Singh, S and Feuerstein, JD and Binion, DG and Tremaine, WJ}, title = {AGA Technical Review on the Management of Mild-to-Moderate Ulcerative Colitis.}, journal = {Gastroenterology}, volume = {156}, number = {3}, pages = {769-808.e29}, doi = {10.1053/j.gastro.2018.12.008}, pmid = {30576642}, issn = {1528-0012}, mesh = {Adult ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Colitis, Ulcerative/*diagnosis/*drug therapy ; Disease Management ; Disease Progression ; Female ; Gastroenterology/*standards ; Humans ; Male ; Mesalamine/therapeutic use ; Prognosis ; Risk Assessment ; Severity of Illness Index ; Societies, Medical ; Sulfasalazine/therapeutic use ; Treatment Outcome ; United States ; }, abstract = {Most patients with ulcerative colitis (UC) have mild-to-moderate disease activity, with low risk of colectomy, and are managed by primary care physicians or gastroenterologists. Optimal management of these patients decreases the risk of relapse and proximal disease extension, and may prevent disease progression, complications, and need for immunosuppressive therapy. With several medications (eg, sulfasalazine, diazo-bonded 5-aminosalicylates [ASA], mesalamines, and corticosteroids, including budesonide) and complex dosing formulations, regimens, and routes, to treat a disease with variable anatomic extent, there is considerable practice variability in the management of patients with mild-moderate UC. Hence, the American Gastroenterological Association prioritized clinical guidelines on this topic. To inform clinical guidelines, this technical review was developed in accordance with the Grading of Recommendations Assessment, Development and Evaluation framework for interventional studies. Focused questions included the following: (1) comparative effectiveness and tolerability of different oral 5-ASA therapies (sulfalsalazine vs diazo-bonded 5-ASAs vs mesalamine; low- (<2 g) vs standard (2-3 g/d) vs high-dose (>3 g/d) mesalamine); (2) comparison of different dosing regimens (once-daily vs multiple times per day dosing) and routes (oral vs rectal vs both oral and rectal); (3) role of oral budesonide in patients mild-moderate UC; (4) comparative effectiveness and tolerability of rectal 5-ASA and corticosteroid formulations in patients with distal colitis; and (5) role of alternative therapies like probiotics, curcumin, and fecal microbiota transplantation in the management of mild-moderate UC.}, }
@article {pmid30575732, year = {2018}, author = {Coryell, M and McAlpine, M and Pinkham, NV and McDermott, TR and Walk, ST}, title = {The gut microbiome is required for full protection against acute arsenic toxicity in mouse models.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {5424}, doi = {10.1038/s41467-018-07803-9}, pmid = {30575732}, issn = {2041-1723}, support = {F31 ES026884/ES/NIEHS NIH HHS/United States ; R01 CA215784/CA/NCI NIH HHS/United States ; R21 ES026411/ES/NIEHS NIH HHS/United States ; }, mesh = {Adult ; Animals ; Arsenic/metabolism ; Arsenic Poisoning/*prevention &amp; control ; Faecalibacterium prausnitzii/*physiology ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; *Germ-Free Life ; Humans ; Inactivation, Metabolic ; Male ; Methyltransferases/physiology ; Mice, Inbred C57BL ; Mice, Transgenic ; Young Adult ; }, abstract = {Arsenic poisons an estimated 200 million people worldwide through contaminated food and drinking water. Confusingly, the gut microbiome has been suggested to both mitigate and exacerbate arsenic toxicity. Here, we show that the microbiome protects mice from arsenic-induced mortality. Both antibiotic-treated and germ-free mice excrete less arsenic in stool and accumulate more arsenic in organs compared to control mice. Mice lacking the primary arsenic detoxification enzyme (As3mt) are hypersensitive to arsenic after antibiotic treatment or when derived germ-free, compared to wild-type and/or conventional counterparts. Human microbiome (stool) transplants protect germ-free As3mt-KO mice from arsenic-induced mortality, but protection depends on microbiome stability and the presence of specific bacteria, including Faecalibacterium. Our results demonstrate that both a functional As3mt and specific microbiome members are required for protection against acute arsenic toxicity in mouse models. We anticipate that the gut microbiome will become an important explanatory factor of disease (arsenicosis) penetrance in humans, and a novel target for prevention and treatment strategies.}, }
@article {pmid30563199, year = {2018}, author = {Lin, C and Wan, J and Su, Y and Zhu, W}, title = {Effects of Early Intervention with Maternal Fecal Microbiota and Antibiotics on the Gut Microbiota and Metabolite Profiles of Piglets.}, journal = {Metabolites}, volume = {8}, number = {4}, pages = {}, doi = {10.3390/metabo8040089}, pmid = {30563199}, issn = {2218-1989}, support = {31572414 and 31872362//the National Natural Science Foundation of China/ ; KYCYL201502-2//the Fundamental Research Funds for the Central Universities/ ; }, abstract = {We investigated the effects of early intervention with maternal fecal microbiota and antibiotics on gut microbiota and the metabolites. Five litters of healthy neonatal piglets (Duroc × Landrace × Yorkshire, nine piglets in each litter) were used. Piglets in each litter were orally treated with saline (CO), amoxicillin treatment (AM), or maternal fecal microbiota transplantation (MFMT) on days 1⁻6, with three piglets in each treatment. Results were compared to the CO group. MFMT decreased the relative abundances of Clostridium sensu stricto and Parabacteroides in the colon on day 7, whereas the abundance of Blautia increased, and the abundance of Corynebacterium in the stomach reduced on day 21. AM reduced the abundance of Arcanobacterium in the stomach on day 7 and reduced the abundances of Streptococcus and Lachnoclostridium in the ileum and colon on day 21, respectively. The metabolite profile indicated that MFMT markedly influenced carbohydrate metabolism and amino acid (AA) metabolism on day 7. On day 21, carbohydrate metabolism and AA metabolism were affected by AM. The results suggest that MFMT and AM discriminatively modulate gastrointestinal microflora and alter the colonic metabolic profiles of piglets and show different effects in the long-term. MFMT showed a location-specific influence on the gastrointestinal microbiota.}, }
@article {pmid30563034, year = {2018}, author = {Moelling, K and Broecker, F and Willy, C}, title = {A Wake-Up Call: We Need Phage Therapy Now.}, journal = {Viruses}, volume = {10}, number = {12}, pages = {}, doi = {10.3390/v10120688}, pmid = {30563034}, issn = {1999-4915}, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Bacterial Infections/*therapy ; Bacteriophages/physiology ; Clinical Trials as Topic ; Fecal Microbiota Transplantation ; History, 20th Century ; History, 21st Century ; Humans ; Mice ; Phage Therapy/adverse effects/history/*methods ; }, abstract = {The rise of multidrug-resistant bacteria has resulted in an increased interest in phage therapy, which historically preceded antibiotic treatment against bacterial infections. To date, there have been no reports of serious adverse events caused by phages. They have been successfully used to cure human diseases in Eastern Europe for many decades. More recently, clinical trials and case reports for a variety of indications have shown promising results. However, major hurdles to the introduction of phage therapy in the Western world are the regulatory and legal frameworks. Present regulations may take a decade or longer to be fulfilled. It is of urgent need to speed up the availability of phage therapy.}, }
@article {pmid30561131, year = {2019}, author = {Limketkai, BN and Hendler, S and Ting, PS and Parian, AM}, title = {Fecal Microbiota Transplantation for the Critically Ill Patient.}, journal = {Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition}, volume = {34}, number = {1}, pages = {73-79}, doi = {10.1002/ncp.10228}, pmid = {30561131}, issn = {1941-2452}, mesh = {Critical Illness/*therapy ; Diarrhea/therapy ; Dysbiosis/therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; }, abstract = {The gut microbiome has been implicated in a diversity of diseases, such as irritable bowel syndrome, inflammatory bowel disease, hepatic steatosis, metabolic syndrome, obesity, and anxiety. Current research also suggests the presence of a bidirectional relationship between the composition of the gut microbiome and critical illness. In the critical care setting, multiple factors (eg, use of antibiotics, aberrant nutrition, bloodstream infections, bowel ischemia, and abnormal bowel motility) strongly contribute to intestinal dysbiosis. Conversely, early studies have associated intestinal dysbiosis with worse clinical outcomes in the intensive care unit (ICU), such as infection, organ failure, and mortality. The possibility of intestinal dysbiosis influencing these clinical outcomes has prompted the question of whether microbiome manipulation strategies, such as fecal microbiota transplantation (FMT), may have a role in the management of critical illness. After a literature search of FMT used in the ICU for indications other than Clostridium difficile infections, we found 4 case reports that describe the use of FMT in 5 critically ill patients with systemic inflammatory responses and no clear source of infection. This review discusses the relationship between the gut microbiome and critical illness, early data on the use of FMT in critical care, and safety considerations of FMT in the critically ill and immunocompromised populations.}, }
@article {pmid30558014, year = {2018}, author = {Cai, TT and Ye, XL and Yong, HJ and Song, B and Zheng, XL and Cui, BT and Zhang, FM and Lu, YB and Miao, H and Ding, DF}, title = {Fecal microbiota transplantation relieve painful diabetic neuropathy: A case report.}, journal = {Medicine}, volume = {97}, number = {50}, pages = {e13543}, doi = {10.1097/MD.0000000000013543}, pmid = {30558014}, issn = {1536-5964}, mesh = {Diabetic Neuropathies/microbiology/*surgery ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Middle Aged ; Remission Induction/methods ; }, abstract = {RATIONALE: Fecal microbiota transplantation (FMT) has been used in a wide variety of diseases. In this article, we reported a 46-year-old female with diabetic neuropathy (DN) achieved remission by the treatment of FMT.<br><br>PATIENT CONCERNS: The patient with an 8-year history of diabetes and hypertension was admitted to hospital due to sensitive pain of her right thigh and poor blood glucose control. The traditional hypoglycemic and analgesic treatment were useless to her symptoms.<br><br>DIAGNOSIS: Diabetic-induced neuropathy was considered.<br><br>INTERVENTIONS: This patient received twice FMTs for 3 months.<br><br>OUTCOMES: After twice FMTs, the clinical response of patient was pleasant. The glycemic control was improved, with a remarkable relief of the symptoms of painful DN in particular. No obvious adverse effects were observed during the FMTs and follow-up observation-testing.<br><br>LESSONS: We proposed that FMT could be a promising treatment in patients with diabetes or diabetes-related complications like DN. FMT also appeared to be definitely safer and more tolerable than the pharmacologic treatment in patients with DN.}, }
@article {pmid30554391, year = {2019}, author = {Bianchi, F and Duque, ALRF and Saad, SMI and Sivieri, K}, title = {Gut microbiome approaches to treat obesity in humans.}, journal = {Applied microbiology and biotechnology}, volume = {103}, number = {3}, pages = {1081-1094}, doi = {10.1007/s00253-018-9570-8}, pmid = {30554391}, issn = {1432-0614}, support = {(2013/50506-8; 2015/13965-0; 2015/08228-6)//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, mesh = {Exercise ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Obesity/*therapy ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {The rising worldwide prevalence of obesity has become a major concern having many implications for the public health and the economy. It is well known that many factors such as lifestyle, increased intake of foods high in fat and sugar and a host's genetic profile can lead to obesity. Besides these factors, recent studies have pointed to the gut microbiota composition as being responsible for the development of obesity. Since then, many efforts have been made to understand the link between the gut microbiota composition and obesity, as well as the role of food ingredients, such as pro- and prebiotics, in the modulation of the gut microbiota. Studies involving the gut microbiota composition of obese individuals are however still controversial, making it difficult to treat obesity. In this sense, this mini-review deals with obesity and the relationship with gut microbiota, summarising the principal findings on gut microbiome approaches for treating obesity in humans.}, }
@article {pmid30551119, year = {2019}, author = {McClave, SA and Martindale, RG}, title = {Why do current strategies for optimal nutritional therapy neglect the microbiome?.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {60}, number = {}, pages = {100-105}, doi = {10.1016/j.nut.2018.09.024}, pmid = {30551119}, issn = {1873-1244}, abstract = {Strategies for providing optimal nutritional therapy have evolved over time, with the emphasis on specific directives (such as route, use of immunonutrition, high protein, organ-specific formulas, etc.), achieving variable degrees of success for improving outcomes in the intensive care unit. As the largest immune organ in the body comprising the largest interface between the host and the external environment, the gut can have an amplifying effect on a pattern of dysbiosis, immune dysregulation, and multiple organ failure seen in the critically ill patient. Conversely, maintenance of gut integrity can serve to restore a pattern of homeostasis, appropriate immune responses, symbiosis, and clinical recovery. Simply providing refined polymeric formulas as enteral nutrition may not take full advantage of the potential for optimal outcome that could be derived by giving therapy designed to directly stimulate gut defenses and support the intestinal microbiota. This article describes a series of strategies (such as use of intact whole food formulas, soluble fiber, fecal microbial transplantation, serum bovine immunoglobulin, or agents to promote commensal behavior) that should modulate the gut microbiome and shift the critically ill patient toward a pattern of health and recovery.}, }
@article {pmid30546094, year = {2019}, author = {Libertucci, J and Young, VB}, title = {The role of the microbiota in infectious diseases.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {35-45}, doi = {10.1038/s41564-018-0278-4}, pmid = {30546094}, issn = {2058-5276}, mesh = {Communicable Disease Control/*methods ; Communicable Diseases/microbiology/transmission ; Disease Susceptibility/*microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Tract/microbiology ; Humans ; Metagenome/genetics ; Microbiota/*genetics ; Prebiotics/*microbiology ; Probiotics/*therapeutic use ; Respiratory Mucosa/microbiology ; }, abstract = {The human body is colonized by a diverse community of microorganisms collectively referred to as the microbiota. Here, we describe how the human microbiota influences susceptibility to infectious diseases using examples from the respiratory, gastrointestinal and female reproductive tract. We will discuss how interactions between the host, the indigenous microbiota and non-native microorganisms, including bacteria, viruses and fungi, can alter the outcome of infections. This Review Article will highlight the complex mechanisms by which the microbiota mediates colonization resistance, both directly and indirectly, against infectious agents. Strategies for the therapeutic modulation of the microbiota to prevent or treat infectious diseases will be discussed, and we will review potential therapies that directly target the microbiota, including prebiotics, probiotics, synbiotics and faecal microbiota transplantation.}, }
@article {pmid30543777, year = {2018}, author = {Hu, J and Ma, L and Nie, Y and Chen, J and Zheng, W and Wang, X and Xie, C and Zheng, Z and Wang, Z and Yang, T and Shi, M and Chen, L and Hou, Q and Niu, Y and Xu, X and Zhu, Y and Zhang, Y and Wei, H and Yan, X}, title = {A Microbiota-Derived Bacteriocin Targets the Host to Confer Diarrhea Resistance in Early-Weaned Piglets.}, journal = {Cell host &amp; microbe}, volume = {24}, number = {6}, pages = {817-832.e8}, doi = {10.1016/j.chom.2018.11.006}, pmid = {30543777}, issn = {1934-6069}, mesh = {Animals ; Bacteriocins/*metabolism ; Cell Line ; Cell Membrane/metabolism ; Diarrhea/microbiology/*prevention &amp; control/*veterinary ; Enterocytes/metabolism ; Feces/microbiology ; *Gastrointestinal Microbiome ; Keratin-19/genetics/metabolism ; Lactobacillus gasseri/*metabolism ; Mice ; Specific Pathogen-Free Organisms ; Swine/*microbiology ; Weaning ; }, abstract = {Alternatives to antibiotics for preventing diarrhea in early-weaned farm animals are sorely needed. CM piglets (a native Chinese breed) are more resistant to early-weaning stress-induced diarrhea than the commercial crossbred LY piglets. Transferring fecal microbiota, but not saline, from healthy CM into LY piglets by oral administration prior to early weaning conferred diarrhea resistance. By comparing the relative abundance of intestinal microbiota in saline and microbiota transferred LY piglets, we identified and validated Lactobacillus gasseri LA39 and Lactobacillus frumenti as two bacterial species that mediate diarrhea resistance. Diarrhea resistance depended on the bacterial secretory circular peptide gassericin A, a bacteriocin. The binding of gassericin A to Keratin 19 (KRT19) on the plasma membrane of intestinal epithelial cells was essential for enhancement of fluid absorption and decreased secretion. These findings suggest the use of L. gasseri LA39 and L. frumenti as antibiotic alternatives for preventing diarrhea in mammals.}, }
@article {pmid30540704, year = {2019}, author = {Davidovics, ZH and Michail, S and Nicholson, MR and Kociolek, LK and Pai, N and Hansen, R and Schwerd, T and Maspons, A and Shamir, R and Szajewska, H and Thapar, N and de Meij, T and Mosca, A and Vandenplas, Y and Kahn, SA and Kellermayer, R and , }, title = {Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection and Other Conditions in Children: A Joint Position Paper From the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {68}, number = {1}, pages = {130-143}, doi = {10.1097/MPG.0000000000002205}, pmid = {30540704}, issn = {1536-4801}, support = {R01 HD081197/HD/NICHD NIH HHS/United States ; }, abstract = {Fecal microbiota transplantation (FMT) is becoming part of the treatment algorithms against recurrent Clostridium difficile infection (rCDI) both in adult and pediatric gastroenterology practice. With our increasing recognition of the critical role the microbiome plays in human health and disease, FMT is also being considered as a potential therapy for other disorders, including inflammatory bowel disease (Crohn disease, ulcerative colitis), graft versus host disease, neuropsychiatric diseases, and metabolic syndrome. Controlled trials with FMT for rCDI have not been performed in children, and numerous clinical and regulatory considerations have to be considered when using this untraditional therapy. This report is intended to provide guidance for FMT in the treatment of rCDI in pediatric patients.}, }
@article {pmid30539026, year = {2018}, author = {Leustean, AM and Ciocoiu, M and Sava, A and Costea, CF and Floria, M and Tarniceriu, CC and Tanase, DM}, title = {Implications of the Intestinal Microbiota in Diagnosing the Progression of Diabetes and the Presence of Cardiovascular Complications.}, journal = {Journal of diabetes research}, volume = {2018}, number = {}, pages = {5205126}, pmid = {30539026}, issn = {2314-6753}, mesh = {Cardiovascular Diseases/complications/microbiology/*pathology ; Diabetes Mellitus, Type 2/complications/microbiology/*pathology ; Disease Progression ; *Gastrointestinal Microbiome ; Humans ; Insulin Resistance ; }, abstract = {The prevalence of diabetes is steadily rising, and once it occurs, it can cause multiple complications with a negative impact on the whole organism. Complications of diabetes may be macrovascular: such as stroke and ischemic heart disease as well as peripheral vascular and microvascular diseases-retinopathy, nephropathy, and neuropathy. Key factors that cause cardiovascular disease in people with diabetes include hyperglycemia, dyslipidemia, obesity, insulin resistance, inflammation, hypertension, autonomic dysfunction, and decreased vascular response capacity. Microbes can be considered a complex endocrine system capable of ensuring the proper functioning of the body but are also responsible for the development of numerous pathologies (diabetes, coronary syndromes, peripheral arterial disease, neoplasia, Alzheimer's disease, and hepatic steatosis). Changes in the intestinal microbiota may influence the host's sensitivity to insulin, body weight, and lipid and carbohydrate metabolism. Dysbiosis causes activation of proinflammatory mechanisms, metabolic toxicity, and insulin resistance. Trimethylamine N-oxide (TMAO) is a microbial organic compound generated by the large intestine, and its concentration increases in the blood after ingestion of foods rich in L-carnitine and choline, such as red meat, eggs, and fish. The interest for TMAO in cardiometabolic research has recently emerged, given the preclinical evidence that reveals a link between TMAO, diabetes, and cardiovascular complications. Intestinal microbiota can be modulated by changing one's lifestyle but also by antibiotic, probiotic, prebiotic, and fecal transplantation. The purpose of this article is to highlight issues related to the involvement of microbiota and trimethylamine N-oxide in the pathogenesis of diabetes mellitus and cardiovascular disease. Better appreciation of the interactions between food intake and intestinal floral-mediated metabolism can provide clinical insights into the definition of individuals with diabetic risk and cardiometabolic disease as well as potential therapeutic targets for reducing the risk of progression of the disease.}, }
@article {pmid30534963, year = {2019}, author = {Kalla, R and Pitt, M and Sharma, A}, title = {The Role of Autologous Fecal Microbiota Transplantation in Diversion Colitis: A Case Report.}, journal = {Inflammatory bowel diseases}, volume = {25}, number = {4}, pages = {e29-e30}, doi = {10.1093/ibd/izy270}, pmid = {30534963}, issn = {1536-4844}, }
@article {pmid30534859, year = {2018}, author = {Quera, R and Ibáñez, P and Simian, D and Rivera, D and Acuña, G and Espinoza, R}, title = {[Fecal microbiota transplantation through colonoscopy for Clostridium difficile recurrent infection. Report of eight cases].}, journal = {Revista medica de Chile}, volume = {146}, number = {8}, pages = {823-830}, doi = {10.4067/s0034-98872018000800823}, pmid = {30534859}, issn = {0717-6163}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/classification/therapeutic use ; Clostridium Infections/*therapy ; Clostridium difficile ; *Colonoscopy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Most cases of Clostridium difficile infection (CDI) respond to a standard course of antibiotics, however recurrent CDI is becoming common and alternative therapeutic strategies are needed. In this scenario, fecal microbiota transplantation (FMT) has been suggested.<br><br>AIM: To describe the efficacy and safety of FMT for the treatment of recurrent CDI.<br><br>PATIENTS AND METHODS: Review of medical records of all patients with recurrent CDI treated with FMT between April 2013 and April 2017. Demographic and clinical data were abstracted including details of treatment prior to FMT, rate of FMT treatment success and clinical course during follow-up period. Telephone surveys were conducted to determine patient satisfaction.<br><br>RESULTS: Eight patients aged 19 to 82 years (six women) underwent FMT. They experienced a median of four previous episodes of CDI (range 3-8). The mean duration of CDI was 18 days (range 3-36) before FMT. All procedures were performed by colonoscopy. Effectiveness with one session of FMT was 100%. During the follow-up period (median 24 months, range 7-55), two patients developed CDI, one of them after using antibiotics. Adverse events were reported in three patients. Two had bloating and one patient with Crohn's disease and a history of bacteremia had an episode of Escherichia coli bacteremia. All patients would use FMT again if necessary.<br><br>CONCLUSIONS: FMT through colonoscopy appears to be a safe, effective and long-lasting therapy in cases of recurrent CDI.}, }
@article {pmid30534630, year = {2018}, author = {Lindheim, L and Manti, M and Fornes, R and Bashir, M and Czarnewski, P and Diaz, OE and Seifert, M and Engstrand, L and Villablanca, EJ and Obermayer-Pietsch, B and Stener-Victorin, E}, title = {Reproductive and Behavior Dysfunction Induced by Maternal Androgen Exposure and Obesity Is Likely Not Gut Microbiome-Mediated.}, journal = {Journal of the Endocrine Society}, volume = {2}, number = {12}, pages = {1363-1380}, pmid = {30534630}, issn = {2472-1972}, abstract = {Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder of unclear etiology in women and is characterized by androgen excess, insulin resistance, and mood disorders. The gut microbiome is known to influence conditions closely related with PCOS, and several recent studies have observed changes in the stool microbiome of women with PCOS. The mechanism by which the gut microbiome interacts with PCOS is still unknown. We used a mouse model to investigate if diet-induced maternal obesity and maternal DHT exposure, mimicking the lean and obese PCOS women, cause lasting changes in the gut microbiome of offspring. Fecal microbiome profiles were assessed using Illumina paired-end sequencing of 16S rRNA gene V4 amplicons. We found sex-specific effects of maternal and offspring diet, and maternal DHT exposure on fecal bacterial richness and taxonomic composition. Female offspring exposed to maternal obesity and DHT displayed reproductive dysfunction and anxietylike behavior. Fecal microbiota transplantation from DHT and diet-induced obesity exposed female offspring to wild-type mice did not transfer reproductive dysfunction and did not cause the expected increase in anxietylike behavior in recipients. Maternal obesity and androgen exposure affect the gut microbiome of offspring, but the disrupted estrous cycles and anxietylike behavior are likely not microbiome-mediated.}, }
@article {pmid30529583, year = {2019}, author = {Paramsothy, S and Nielsen, S and Kamm, MA and Deshpande, NP and Faith, JJ and Clemente, JC and Paramsothy, R and Walsh, AJ and van den Bogaerde, J and Samuel, D and Leong, RWL and Connor, S and Ng, W and Lin, E and Borody, TJ and Wilkins, MR and Colombel, JF and Mitchell, HM and Kaakoush, NO}, title = {Specific Bacteria and Metabolites Associated With Response to Fecal Microbiota Transplantation in Patients With Ulcerative Colitis.}, journal = {Gastroenterology}, volume = {156}, number = {5}, pages = {1440-1454.e2}, doi = {10.1053/j.gastro.2018.12.001}, pmid = {30529583}, issn = {1528-0012}, mesh = {Bacteria/classification/genetics/growth &amp; development/*metabolism ; Biomarkers/metabolism ; Colitis, Ulcerative/diagnosis/microbiology/*therapy ; Double-Blind Method ; Fecal Microbiota Transplantation/adverse effects ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Metabolomics ; New South Wales ; Remission Induction ; Ribotyping ; Time Factors ; Treatment Outcome ; }, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis (UC). In a randomized controlled trial of FMT in patients with active UC, we aimed to identify bacterial taxonomic and functional factors associated with response to therapy.<br><br>METHODS: We performed a double-blind trial of 81 patients with active UC randomly assigned to groups that received an initial colonoscopic infusion and then intensive multidonor FMT or placebo enemas, 5 d/wk for 8 weeks. Patients in the FMT group received blended homogenized stool from 3-7 unrelated donors. Patients in the placebo group were eligible to receive open-label FMT after the double-blind study period. We collected 314 fecal samples from the patients at screening, every 4 weeks during treatment, and 8 weeks after the blinded or open-label FMT therapy. We also collected 160 large-bowel biopsy samples from the patients at study entry, at completion of 8 weeks of blinded therapy, and at the end of open-label FMT, if applicable. We analyzed 105 fecal samples from the 14 individual donors (n = 55), who in turn contributed to 21 multidonor batches (n = 50). Bacteria in colonic and fecal samples were analyzed by both 16S ribosomal RNA gene and transcript amplicon sequencing; 285 fecal samples were analyzed by shotgun metagenomics, and 60 fecal samples were analyzed for metabolome features.<br><br>RESULTS: FMT increased microbial diversity and altered composition, based on analyses of colon and fecal samples collected before vs after FMT. Diversity was greater in fecal and colon samples collected before and after FMT treatment from patients who achieved remission compared with patients who did not. Patients in remission after FMT had enrichment of Eubacterium hallii and Roseburia inulivorans compared with patients who did not achieve remission after FMT and had increased levels of short-chain fatty acid biosynthesis and secondary bile acids. Patients who did not achieve remission had enrichment of Fusobacterium gonidiaformans, Sutterella wadsworthensis, and Escherichia species and increased levels of heme and lipopolysaccharide biosynthesis. Bacteroides in donor stool were associated with remission in patients receiving FMT, and Streptococcus species in donor stool was associated with no response to FMT.<br><br>CONCLUSIONS: In an analysis of fecal and colonic mucosa samples from patients receiving FMT for active UC and stool samples from donors, we associated specific bacteria and metabolic pathways with induction of remission. These findings may be of value in the design of microbe-based therapies for UC. ClinicalTrials.gov, Number NCT01896635.}, }
@article {pmid30526683, year = {2018}, author = {Draper, LA and Ryan, FJ and Smith, MK and Jalanka, J and Mattila, E and Arkkila, PA and Ross, RP and Satokari, R and Hill, C}, title = {Long-term colonisation with donor bacteriophages following successful faecal microbial transplantation.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {220}, pmid = {30526683}, issn = {2049-2618}, mesh = {Bacteriophages/*classification/isolation &amp; purification ; Clostridium Infections/*therapy/virology ; Fecal Microbiota Transplantation/*methods ; Feces/virology ; Humans ; Metagenomics ; Phylogeny ; Tissue Donors ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is used in the treatment of recurrent Clostridium difficile infection. Its success is typically attributed to the restoration of a diverse microbiota. Viruses (including bacteriophages) are the most numerically dominant and potentially the most diverse members of the microbiota, but their fate following FMT has not been well studied.<br><br>RESULTS: We studied viral transfer following FMT from 3 donors to 14 patients. Recipient viromes resembled those of their donors for up to 12 months. Tracking individual bacteriophage colonisation revealed that engraftment of individual bacteriophages was dependent on specific donor-recipient pairings. Specifically, multiple recipients from a single donor displayed highly individualised virus colonisation patterns.<br><br>CONCLUSIONS: The impact of viruses on long-term microbial dynamics is a factor that should be reviewed when considering FMT as a therapeutic option.}, }
@article {pmid30525949, year = {2019}, author = {Wing, AC and Kremenchutzky, M}, title = {Multiple sclerosis and faecal microbiome transplantation: are you going to eat that?.}, journal = {Beneficial microbes}, volume = {10}, number = {1}, pages = {27-32}, doi = {10.3920/BM2018.0029}, pmid = {30525949}, issn = {1876-2891}, mesh = {Dysbiosis/immunology/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Host Microbial Interactions/immunology ; Humans ; Intestines/immunology/microbiology ; Multiple Sclerosis/immunology/microbiology/*therapy ; Probiotics/therapeutic use ; }, abstract = {Gut microbiome interaction goes beyond commensal function as vitamin production or support nutrients digestion. It also interplays with the host immune system and may be related to the development of immune-mediated diseases. Multiple sclerosis patients have dysbiosis compared to healthy individuals. But how this relates to disease development and severity is still uncertain. Dietary change including probiotic mixtures or ketogenic regimen has proven to change microbiome in multiple sclerosis (MS) subjects to one similar to healthy controls. However, proof of clinical benefits is lacking. We dissert on current knowledge about immune system and gut bacteria interactions. We discuss faecal microbial transplantation as a potential intervention to ameliorate gut dysbiosis in MS as well as the caveats of a clinical trial design.}, }
@article {pmid30521978, year = {2019}, author = {Huang, C and Yang, X and Zeng, B and Zeng, L and Gong, X and Zhou, C and Xia, J and Lian, B and Qin, Y and Yang, L and Liu, L and Xie, P}, title = {Proteomic analysis of olfactory bulb suggests CACNA1E as a promoter of CREB signaling in microbiota-induced depression.}, journal = {Journal of proteomics}, volume = {194}, number = {}, pages = {132-147}, doi = {10.1016/j.jprot.2018.11.023}, pmid = {30521978}, issn = {1876-7737}, abstract = {Major depressive disorders impact approximately 17% of the population worldwide, whose high morbidity and considerable adversity have resulted in enormous social and economic burden. In addition, clinically depressed patients often show reduced volume of olfactory bulb (OB) and decreased olfactory sensitivity. Although mounting evidence conveyed that the gut microbiota may implicate the pathophysiology of major depressive disorder (MDD) via the microbe-gut-brain axis, knowledge about its distinctive molecular mechanism is rudimentary. Herein, iTRAQ coupled with LC-MS/MS was applied to compare the OB proteome between &quot;pathological microbiota&quot; and &quot;healthy microbiota&quot; germ-free mice. A set of 367 proteins were differentially identified in the OB, including 119 up-regulated and 248 down-regulated proteins compared with the levels in controls. A combined analysis with significantly changed OB proteins from CUMS depression model supported the role of CREB signaling, whose dysregulation is likely to disrupt the axonogenesis of OB under microbiota condition. With that, the down-regulated CACNA1E and its downstream proteins (CALM/ CaMKII/ CREB/ BDNF) in CREB pathway were validated by Western blot. Meanwhile, the canonical pathways involved Nuclear Receptor Signaling highlighted the fecal microbiota transplantation (FMT) model, which would be a new breakthrough for depressive research. These findings enrich the previous research achievements about the gut microbiota in psychiatric disorders, providing a creative insight into the intricate mechanisms of OB dysfunction in depression. SIGNIFICANCE: Emerging evidence has shown that gut microbiota can greatly influence brain functions and even behaviors. As one of the post-developmental neurogenesis areas for the adult brain, the OB is becoming increasingly important in the study of the pathogenesis of depression. Using an iTRAQ-based proteomics, we identified 367 altered proteins in the OB of fecal microbiota transplanted mouse, which provide a novel insight for further research of the &quot;microbiota-gut-brain axis&quot;. In addition, combined analyses with the CUMS depression model and the validation of key proteins by Western blot may assist in the investigation of OB dysfunction in mental sickness.}, }
@article {pmid30521856, year = {2019}, author = {Kaako, A and Al-Amer, M and Abdeen, Y}, title = {Bezlotoxumab use as adjunctive therapy with the third fecal microbiota transplant in refractory recurrent Clostridium difficile colitis; a case report and concise literature review.}, journal = {Anaerobe}, volume = {55}, number = {}, pages = {112-116}, doi = {10.1016/j.anaerobe.2018.11.010}, pmid = {30521856}, issn = {1095-8274}, mesh = {Antibodies, Monoclonal/*administration &amp; dosage ; Antibodies, Neutralizing/*administration &amp; dosage ; Antitoxins/*administration &amp; dosage ; Clostridium Infections/*therapy ; Clostridium difficile/isolation &amp; purification ; Combined Modality Therapy/methods ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Middle Aged ; Treatment Outcome ; }, abstract = {Clostridium difficile is the most commonly reported pathogen to cause nosocomial infections in the United States with a high burden affecting morbidity, mortality and healthcare expenditure. The use of Fecal Microbiota Transplantation (FMT) is one of the current standard therapies for recurrent C. difficile infection (CDIr). One emerging promising approach is the use of monoclonal antibodies that bind to and neutralize C. difficile toxins such as Bezlotoxumab. We present the first case report on combining the third FMT with bezlotoxumab after the failure of standard-of-care antibiotics and two trials of FMT alone, with subsequent success in preventing the recurrence of refractory CDI for 12 weeks following treatment. This case highlights the need for further studies and guidelines to recommend the best combination among different treatment options and modalities.}, }
@article {pmid30519847, year = {2019}, author = {Allegretti, JR and Fischer, M and Sagi, SV and Bohm, ME and Fadda, HM and Ranmal, SR and Budree, S and Basit, AW and Glettig, DL and de la Serna, EL and Gentile, A and Gerardin, Y and Timberlake, S and Sadovsky, R and Smith, M and Kassam, Z}, title = {Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Lose Dose.}, journal = {Digestive diseases and sciences}, volume = {64}, number = {6}, pages = {1672-1678}, doi = {10.1007/s10620-018-5396-6}, pmid = {30519847}, issn = {1573-2568}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium. difficile infection (rCDI). FMT capsules have emerged, and it is unknown if delivery location and dose impact efficacy.<br><br>METHODS: We compared two cohorts of patients receiving two capsule formulations: gastric release (FMTgr) and targeted colonic release (FMTcr) at two different sites. Cohort A received FMTgr at (1) high dose: 60 capsules and low dose: 30 capsules. Patients in Cohort B received FMTcr at (1) high dose: 30 capsules (2) low dose: 10 capsules. Clinical cure rates and adverse events were monitored through week 8. Paired t-tests were used to compare diversity pre- and post-FMT.<br><br>RESULTS: 51 rCDI patients were enrolled. Cohort A contained n = 20 and Cohort B contained n = 31. Overall cure at week 8 for FMTgr was 75% (15/20) compared to 80.6% for FMTcr, (25/31), p = 0.63. Both formulations were safe with no serious adverse events. FMTcr was superior at increasing gut microbial diversity.<br><br>DISCUSSION: To our knowledge, this is the first study to compare targeted delivery of FMT capsules. While both capsules were safe and efficacious, microbial engraftment patterns were superior in FMTcr.}, }
@article {pmid30519748, year = {2019}, author = {Zhu, Y and He, C and Li, X and Cai, Y and Hu, J and Liao, Y and Zhao, J and Xia, L and He, W and Liu, L and Luo, C and Shu, X and Cai, Q and Chen, Y and Lu, N}, title = {Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice.}, journal = {Journal of gastroenterology}, volume = {54}, number = {4}, pages = {347-358}, doi = {10.1007/s00535-018-1529-0}, pmid = {30519748}, issn = {1435-5922}, support = {81760120//National Natural Science Foundation of China/ ; 81460116//National Natural Science Foundation of China/ ; 20171BBG70084//Science and Technology Department of Jiangxi Province/ ; }, abstract = {BACKGROUND: The gut is implicated in the pathogenesis of acute pancreatitis (AP) and the infectious complications of AP are commonly associated with enteric bacteria, yet whether gut microbiota dysbiosis participants in AP severity remains largely unknown.<br><br>METHODS: We collected clinical information and fecal samples from 165 adult participants, including 41 with mild AP (MAP), 59 with moderately severe AP (MSAP), 30 with severe AP (SAP) and 35 healthy controls (HC). The serum inflammatory cytokines and gut barrier indexes were detected. Male C57BL/6 mice with AP were established and injuries of pancreas were evaluated in antibiotic-treated mice, germ-free mice as well as those transplanted with fecal microbiota. The gut microbiota was analyzed by 16S rRNA gene sequencing.<br><br>RESULTS: The structure of gut microbiota was significantly different between AP and HC, and the disturbed microbiota was closely correlated with systematic inflammation and gut barrier dysfunction. Notably, the microbial composition changed further with the worsening of AP and the abundance of beneficial bacteria such as Blautia was decreased in SAP compared with MAP and MSAP. The increased capacity for the inferred pathway, bacterial invasion of epithelial cells in AP, highly correlated with the abundance of Escherichia-Shigella. Furthermore, the antibiotic-treated mice and germ-free mice exhibited alleviated pancreatic injury after AP induction and subsequent fecal microbiota transplantation in turn exacerbated the disease.<br><br>CONCLUSIONS: This study identifies the gut microbiota as an important mediator during AP and its dysbiosis is associated with AP severity, which suggests its role as potential therapeutic target.}, }
@article {pmid30518790, year = {2018}, author = {Burrello, C and Garavaglia, F and Cribiù, FM and Ercoli, G and Lopez, G and Troisi, J and Colucci, A and Guglietta, S and Carloni, S and Guglielmetti, S and Taverniti, V and Nizzoli, G and Bosari, S and Caprioli, F and Rescigno, M and Facciotti, F}, title = {Therapeutic faecal microbiota transplantation controls intestinal inflammation through IL10 secretion by immune cells.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {5184}, doi = {10.1038/s41467-018-07359-8}, pmid = {30518790}, issn = {2041-1723}, mesh = {Adaptive Immunity ; Animals ; Antigen-Presenting Cells/immunology ; CD4-Positive T-Lymphocytes/immunology ; Colitis/genetics/immunology/microbiology/*therapy ; Dendritic Cells/immunology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Immunity, Innate ; Interleukin-10/genetics/*immunology ; Intestinal Mucosa/*immunology/*microbiology ; Macrophages/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Natural Killer T-Cells/immunology ; }, abstract = {Alteration of the gut microbiota has been associated with different gastrointestinal disorders. Normobiosis restoration by faecal microbiota transplantation (FMT) is considered a promising therapeutic approach, even if the mechanisms underlying its efficacy are at present largely unknown. Here we sought to elucidate the functional effects of therapeutic FMT administration during experimental colitis on innate and adaptive immune responses in the intestinal mucosa. We show that therapeutic FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis through the simultaneous activation of different immune-mediated pathways, ultimately leading to IL-10 production by innate and adaptive immune cells, including CD4+ T cells, iNKT cells and Antigen Presenting Cells (APC), and reduces the ability of dendritic cells, monocytes and macrophages to present MHCII-dependent bacterial antigens to colonic T cells. These results demonstrate the capability of FMT to therapeutically control intestinal experimental colitis and poses FMT as a valuable therapeutic option in immune-related pathologies.}, }
@article {pmid30518356, year = {2018}, author = {Bin, P and Tang, Z and Liu, S and Chen, S and Xia, Y and Liu, J and Wu, H and Zhu, G}, title = {Intestinal microbiota mediates Enterotoxigenic Escherichia coli-induced diarrhea in piglets.}, journal = {BMC veterinary research}, volume = {14}, number = {1}, pages = {385}, pmid = {30518356}, issn = {1746-6148}, mesh = {Animals ; Bacteria/classification/genetics ; Diarrhea/microbiology/*veterinary ; Dysbiosis/immunology/microbiology/*veterinary ; Enterotoxigenic Escherichia coli/immunology/physiology ; Escherichia coli Infections/veterinary ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*genetics/*immunology ; Intestinal Diseases/immunology/microbiology/*veterinary ; Metagenomics ; RNA, Ribosomal, 16S/genetics ; Swine ; Swine Diseases/immunology/*microbiology ; }, abstract = {BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) causes diarrhea in humans, cows, and pigs. The gut microbiota underlies pathology of several infectious diseases yet the role of the gut microbiota in the pathogenesis of ETEC-induced diarrhea is unknown.<br><br>RESULTS: By using an ETEC induced diarrheal model in piglet, we profiled the jejunal and fecal microbiota using metagenomics and 16S rRNA sequencing. A jejunal microbiota transplantation experiment was conducted to determine the role of the gut microbiota in ETEC-induced diarrhea. ETEC-induced diarrhea influenced the structure and function of gut microbiota. Diarrheal piglets had lower Bacteroidetes: Firmicutes ratio and microbiota diversity in the jejunum and feces, and lower percentage of Prevotella in the feces, but higher Lactococcus in the jejunum and higher Escherichia-Shigella in the feces. The transplantation of the jejunal microbiota from diarrheal piglets to uninfected piglets leaded to diarrhea after transplantation. Microbiota transplantation experiments also supported the notion that dysbiosis of gut microbiota is involved in the immune responses in ETEC-induced diarrhea.<br><br>CONCLUSION: We conclude that ETEC infection influences the gut microbiota and the dysbiosis of gut microbiota after ETEC infection mediates the immune responses in ETEC infection.}, }
@article {pmid30518033, year = {2018}, author = {Huang, E and Kang, S and Park, H and Park, S and Ji, Y and Holzapfel, WH}, title = {Differences in Anxiety Levels of Various Murine Models in Relation to the Gut Microbiota Composition.}, journal = {Biomedicines}, volume = {6}, number = {4}, pages = {}, doi = {10.3390/biomedicines6040113}, pmid = {30518033}, issn = {2227-9059}, abstract = {Psychobiotics are probiotic strains that confer mental health benefits to the host through the modulation of the gut microbial population. Mounting evidence shows that the gut microbiota play an important role in communication within the gut⁻brain axis. However, the relationship between the host genetics and the gut microbiota and their influence on anxiety are still not fully understood. Hence, in our research, we attempted to draw a connection between host genetics, microbiota composition, and anxiety by performing an elevated plus maze (EPM) test on four genetically different mice. Four different breeds of 5-week-old mice were used in this experiment: Balb/c, Orient C57BL/6N, Taconic C57BL/6N, and Taconic C57BL/6J. After 1 week of adaptation, their initial anxiety level was monitored using the EPM test via an EthoVision XT, a standardized software used for behavorial testing. Significant differences in the initial anxiety level and microbial composition were detected. Subsequently, the microbiota of each group was modulated by the administration of either a probiotic, fecal microbiota transplantation, or antibiotics. Changes were observed in host anxiety levels in correlation to the shift of the gut microbiota. Our results suggest that the microbiota, host genetics, and psychological symptoms are strongly related, yet the deeper mechanistic links need further exploration.}, }
@article {pmid30508676, year = {2019}, author = {Hu, XF and Zhang, WY and Wen, Q and Chen, WJ and Wang, ZM and Chen, J and Zhu, F and Liu, K and Cheng, LX and Yang, J and Shu, YW}, title = {Fecal microbiota transplantation alleviates myocardial damage in myocarditis by restoring the microbiota composition.}, journal = {Pharmacological research}, volume = {139}, number = {}, pages = {412-421}, doi = {10.1016/j.phrs.2018.11.042}, pmid = {30508676}, issn = {1096-1186}, mesh = {Animals ; Dysbiosis/microbiology/pathology/*therapy ; *Fecal Microbiota Transplantation ; Male ; Mice, Inbred BALB C ; Microbiota ; Myocarditis/microbiology/pathology/*therapy ; Myocardium/pathology ; }, abstract = {Myocarditis can be caused by several infectious and noninfectious causes. Treatment for myocarditis is still a difficult task in clinical practice. The gut microbiota is related to cardiovascular diseases such as atherosclerosis and hypertension. However, little is known about the role of the gut microbiota in myocarditis. In our study, we tested the hypothesis that gut dysbiosis is associated with myocarditis. We focused on whether fecal microbiota transplantation (FMT) can be used as an effective treatment for myocarditis. We used an experimental autoimmune myocarditis (EAM) mouse model. Fecal samples were isolated from the control and EAM groups for bacterial genome analysis. We observed an increase in microbial richness and diversity in the myocarditis mice. These changes were accompanied by an increased Firmicutes/Bacteroidetes ratio. We also evaluated the efficacy of FMT for the treatment of myocarditis. EAM mouse guts were repopulated with fecal contents from an untreated male mouse donor. We found that myocardial injury was improved by diminished inflammatory infiltration, showing that IFN-γ gene expression in the heart tissue and CD4+IFN-γ+ cells in the spleen were decreased after FMT in EAM mice. We also found that FMT was able to rebalance the gut microbiota by restoring the Bacteroidetes population and reshaping the microbiota composition. Myocarditis is associated with gut microbiota dysbiosis and characterized by an increased F/B ratio. FMT treatment can rebalance the gut microbiota and attenuate myocarditis. Thus, FMT may be a potential therapeutic strategy for the treatment of myocarditis.}, }
@article {pmid30506900, year = {2019}, author = {Leedahl, DD and Personett, HA and Nagpal, A and Barreto, EF}, title = {Prevention of Clostridium difficile Infection in Critically Ill Adults.}, journal = {Pharmacotherapy}, volume = {39}, number = {3}, pages = {399-407}, doi = {10.1002/phar.2200}, pmid = {30506900}, issn = {1875-9114}, abstract = {The incidence and severity of Clostridium difficile infection (CDI) remain high across intensive care units in the United States despite national efforts to decrease this escalating health care burden. Most published literature and guidelines address treatment rather than prevention, yet this approach may be too downstream to limit morbidity and mortality from the disease and its complications. Mechanisms to prevent CDI successfully include reducing modifiable risk factors and minimizing horizontal transmission of C. difficile spores between patients and the health care environment. Because CDI prevention is characterized by a bundled approach, it is difficult to quantify the individual impact of any one element; however, a number of patient- and facility-level strategies can be considered for CDI prevention. Robust hygiene strategies, diagnostic and antimicrobial stewardship, and particular prophylaxis maneuvers such as continuation of oral vancomycin or fidaxomicin in the setting of systemic antibiotics have all demonstrated benefit. The preventive roles of deprescribing acid suppressants, routine use of probiotics, or early fecal microbiota transplantation remain unclear. The focus of this review is to summarize the evidence related to primary and secondary CDI prevention in critically ill adults and provide a concise implementation pathway for clinicians and policymakers.}, }
@article {pmid30506577, year = {2019}, author = {Gong, S and Yan, Z and Liu, Z and Niu, M and Fang, H and Li, N and Huang, C and Li, L and Chen, G and Luo, H and Chen, X and Zhou, H and Hu, J and Yang, W and Huang, Q and Schnabl, B and Chang, P and Billiar, TR and Jiang, Y and Chen, P}, title = {Intestinal Microbiota Mediates the Susceptibility to Polymicrobial Sepsis-Induced Liver Injury by Granisetron Generation in Mice.}, journal = {Hepatology (Baltimore, Md.)}, volume = {69}, number = {4}, pages = {1751-1767}, doi = {10.1002/hep.30361}, pmid = {30506577}, issn = {1527-3350}, support = {2016A030306043//Natural Science Funds for Distinguished Young Scholar of Guangdong province/ ; 201804//the funding from State Key Laboratory of Organ Failure Research/ ; U1601225//NSFC-Guangdong Joint Foundation of China/ ; 201607020016//Key Scientific and Technological Program of Guangzhou City/ ; 81372030//National Natural Science Foundation of China/ ; N/A//the award of Young Pearl Scholars of Guangdong province/ ; 201804//funding from State Key Laboratory of Organ Failure Research/ ; N/A//THE award of Young Pearl Scholars of Guangdong province/ ; }, abstract = {Sepsis-induced liver injury is recognized as a key problem in intensive care units. The gut microbiota has been touted as an important mediator of liver disease development; however, the precise roles of gut microbiota in regulating sepsis-induced liver injury are unknown. Here, we aimed to investigate the role of the gut microbiota in sepsis-induced liver injury and the underlying mechanism. Cecal ligation and puncture (CLP) was used to induce polymicrobial sepsis and related liver injury. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in these pathologies. Metabolomics analysis was performed to characterize the metabolic profile differences between sepsis-resistant (Res; survived to 7 days after CLP) and sepsis-sensitive (Sen; moribund before or approximately 24 hours after CLP) mice. Mice gavaged with feces from Sen mice displayed more-severe liver damage than did mice gavaged with feces from Res mice. The gut microbial metabolic profile between Sen and Res mice was different. In particular, the microbiota from Res mice generated more granisetron, a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, than the microbiota from Sen mice. Granisetron protected mice against CLP-induced death and liver injury. Moreover, proinflammatory cytokine expression by macrophages after lipopolysaccharide (LPS) challenge was markedly reduced in the presence of granisetron. Both treatment with granisetron and genetic knockdown of the 5-HT3A receptor in cells suppressed nuclear factor kappa B (NF-кB) transactivation and phosphorylated p38 (p-p38) accumulation in macrophages. Gut microbial granisetron levels showed a significantly negative correlation with plasma alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels in septic patients. Conclusion: Our study indicated that gut microbiota plays a key role in the sensitization of sepsis-induced liver injury and associates granisetron as a hepatoprotective compound during sepsis development.}, }
@article {pmid30502914, year = {2018}, author = {Niederwerder, MC}, title = {Fecal microbiota transplantation as a tool to treat and reduce susceptibility to disease in animals.}, journal = {Veterinary immunology and immunopathology}, volume = {206}, number = {}, pages = {65-72}, doi = {10.1016/j.vetimm.2018.11.002}, pmid = {30502914}, issn = {1873-2534}, mesh = {Animals ; *Disease Susceptibility ; *Fecal Microbiota Transplantation ; Veterinary Medicine ; }, abstract = {Fecal microbiota transplantation (FMT) is the process by which fecal microbiota are donated from a healthy individual and subsequently transplanted into a diseased or young individual. The mechanism by which FMT is effective is believed to be due to enhanced beneficial microbes, increased microbiome diversity, and restored normal flora. Beneficial gut microorganisms not only play a role in maintaining an intestinal barrier and metabolizing nutrients, but importantly, these microbes help regulate local and systemic immune function. Although FMT has been described for several centuries, only recently has it been utilized as a mainstream therapy in humans and significantly considered for applications in other species. In humans and animals, gastrointestinal diseases are by far the most widely accepted FMT-treatable conditions; however, recent research has shown exceptional promise for FMT being used to treat or prevent other conditions, including those outside of the gastrointestinal tract. Overall, FMT is likely an underutilized, widely-available, and inexpensive tool for improving the health and response to disease in animals. In this review, the effects of FMT on veterinary diseases and potential applications for FMT in animals are discussed.}, }
@article {pmid30502308, year = {2019}, author = {Davido, B and Batista, R and Fessi, H and Michelon, H and Escaut, L and Lawrence, C and Denis, M and Perronne, C and Salomon, J and Dinh, A}, title = {Fecal microbiota transplantation to eradicate vancomycin-resistant enterococci colonization in case of an outbreak.}, journal = {Medecine et maladies infectieuses}, volume = {49}, number = {3}, pages = {214-218}, doi = {10.1016/j.medmal.2018.11.002}, pmid = {30502308}, issn = {1769-6690}, abstract = {OBJECTIVE: A rapid and worrying emergence of vancomycin-resistant enterococci (VRE) gut colonization is occurring worldwide and may be responsible for outbreaks, especially in healthcare facilities. While no efficient decolonization strategies are recommended, we assessed fecal microbiota transplantation (FMT) to eradicate VRE colonization.<br><br>PATIENTS AND METHOD: Our main objective was to measure the impact of FMT on decolonization of VRE carriers, confirmed by at least two consecutive negative rectal swabs at one-week interval during a 3-month follow-up period. Patients received no antibiotic prior to the FMT.<br><br>RESULTS: After a month only three patients remained colonized with VRE. Decolonization was associated with 87.5% (n=7) of success after three months as only one patient remained colonized.<br><br>CONCLUSION: Our first results confirm that the FMT seems to be safe, with an impact on VRE colonization over time that may help control outbreaks.}, }
@article {pmid30513674, year = {2018}, author = {Carrera-Quintanar, L and Ortuño-Sahagún, D and Franco-Arroyo, NN and Viveros-Paredes, JM and Zepeda-Morales, AS and Lopez-Roa, RI}, title = {The Human Microbiota and Obesity: A Literature Systematic Review of In Vivo Models and Technical Approaches.}, journal = {International journal of molecular sciences}, volume = {19}, number = {12}, pages = {}, doi = {10.3390/ijms19123827}, pmid = {30513674}, issn = {1422-0067}, support = {CB-2015-256736//Consejo Nacional de Ciencia y Tecnología/ ; CB-2017-A1-S-51026//Consejo Nacional de Ciencia y Tecnología/ ; 620112//Consejo Nacional de Ciencia y Tecnología/ ; UDG-PTC-1313//SEP PRODEP/ ; }, mesh = {Animals ; Gastrointestinal Microbiome/physiology ; Humans ; Inflammation/immunology/microbiology ; Microbiota/*physiology ; Obesity/immunology/*microbiology ; }, abstract = {Obesity is a noncommunicable disease that affects a considerable part of humanity. Recently, it has been recognized that gut microbiota constitutes a fundamental factor in the triggering and development of a large number of pathologies, among which obesity is one of the most related to the processes of dysbiosis. In this review, different animal model approaches, methodologies, and genome scale metabolic databases were revisited to study the gut microbiota and its relationship with metabolic disease. As a data source, PubMed for English-language published material from 1 January 2013, to 22 August 2018, were screened. Some previous studies were included if they were considered classics or highly relevant. Studies that included innovative technical approaches or different in vivo or in vitro models for the study of the relationship between gut microbiota and obesity were selected after a 16-different-keyword exhaustive search. A clear panorama of the current available options for the study of microbiota's influence on obesity, both for animal model election and technical approaches, is presented to the researcher. All the knowledge generated from the study of the microbiota opens the possibility of considering fecal transplantation as a relevant therapeutic alternative for obesity and other metabolic disease treatment.}, }
@article {pmid30510995, year = {2019}, author = {Kiyohara, H and Sujino, T and Teratani, T and Miyamoto, K and Arai, MM and Nomura, E and Harada, Y and Aoki, R and Koda, Y and Mikami, Y and Mizuno, S and Naganuma, M and Hisamatsu, T and Kanai, T}, title = {Toll-Like Receptor 7 Agonist-Induced Dermatitis Causes Severe Dextran Sulfate Sodium Colitis by Altering the Gut Microbiome and Immune Cells.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {7}, number = {1}, pages = {135-156}, pmid = {30510995}, issn = {2352-345X}, mesh = {Animals ; B-Lymphocytes/immunology ; Cell Movement ; Colitis/chemically induced/*immunology/*microbiology/pathology ; Dermatitis/*complications/immunology ; Dextran Sulfate ; Disease Progression ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Hematopoietic Stem Cells/metabolism ; Imiquimod/adverse effects ; Immunoglobulin D/metabolism ; Immunoglobulin M/metabolism ; Intestines/immunology/pathology ; Lactobacillus/physiology ; Lymph Nodes/pathology ; Lymphocyte Depletion ; Mice, Inbred C57BL ; Permeability ; Psoriasis/complications/immunology ; Toll-Like Receptor 7/*agonists ; }, abstract = {Background &amp; Aims: Psoriasis and inflammatory bowel disease (IBD) are both chronic inflammatory diseases occurring in the skin and gut, respectively. It is well established that psoriasis and IBD have high concordance rates, and similar changes in immune cells and microbiome composition have been reported in both conditions. To study this connection, we used a combination murine model of psoriatic dermatitis and colitis in which mice were treated topically with the Toll-like receptor 7 agonist imiquimod (IMQ) and fed dextran sulfate sodium (DSS).<br><br>Methods: We applied IMQ topically to B6 mice (IMQ mice) and subsequently fed them 2% DSS in their drinking water. Disease activity and immune cell phenotypes were analyzed, and the microbial composition of fecal samples was investigated using 16S ribosomal RNA sequencing. We transplanted feces from IMQ mice to germ-free IQI/Jic (IQI) mice and fed them DSS to assess the effect of the gut microbiome on disease.<br><br>Results: We first confirmed that IMQ mice showed accelerated DSS colitis. IMQ mice had decreased numbers of IgD+ and IgM+ B cells and increased numbers of non-cytokine-producing macrophages in the gut. Moreover, the gut microbiomes of IMQ mice were perturbed, with significant reductions of Lactobacillus johnsonii and Lactobacillus reuteri populations. Germ-free mice transplanted with feces from IMQ mice, but not with feces from untreated mice, also developed exacerbated DSS colitis.<br><br>Conclusions: These results suggest that skin inflammation may contribute to pathogenic conditions in the gut via immunologic and microbiological changes. Our finding of a novel potential skin-gut interaction provides new insights into the coincidence of psoriasis and IBD.}, }
@article {pmid30510291, year = {2019}, author = {Thomas, H}, title = {FMT for drug-induced colitis.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {16}, number = {1}, pages = {4}, doi = {10.1038/s41575-018-0092-8}, pmid = {30510291}, issn = {1759-5053}, mesh = {*Colitis ; *Colitis, Ulcerative ; Fecal Microbiota Transplantation ; Humans ; }, }
@article {pmid30498879, year = {2019}, author = {Mathias, F and Curti, C and Montana, M and Bornet, C and Vanelle, P}, title = {Management of adult Clostridium difficile digestive contaminations: a literature review.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {38}, number = {2}, pages = {209-231}, doi = {10.1007/s10096-018-3419-z}, pmid = {30498879}, issn = {1435-4373}, mesh = {Adult ; Anti-Bacterial Agents/standards/*therapeutic use ; Clostridium Infections/complications/microbiology/*therapy ; Clostridium difficile/drug effects/*isolation &amp; purification ; Disease Management ; Drug Resistance, Bacterial ; Fecal Microbiota Transplantation ; Gastroenteritis/complications/*microbiology/therapy ; Humans ; Recurrence ; }, abstract = {Clostridium difficile infections (CDI) dramatically increased during the last decade and cause a major public health problem. Current treatments are limited by the high disease recurrence rate, severity of clinical forms, disruption of the gut microbiota, and colonization by vancomycin-resistant enterococci (VRE). In this review, we resumed current treatment options from official recommendation to promising alternatives available in the management of adult CDI, with regard to severity and recurring or non-recurring character of the infection. Vancomycin remains the first-line antibiotic in the management of mild to severe CDI. The use of metronidazole is discussed following the latest US recommendations that replaced it by fidaxomicin as first-line treatment of an initial episode of non-severe CDI. Fidaxomicin, the most recent antibiotic approved for CDI in adults, has several advantages compared to vancomycin and metronidazole, but its efficacy seems limited in cases of multiple recurrences. Innovative therapies such as fecal microbiota transplantation (FMT) and antitoxin antibodies were developed to limit the occurrence of recurrence of CDI. Research is therefore very active, and new antibiotics are being studied as surotomycin, cadazolid, and rinidazole.}, }
@article {pmid30489686, year = {2019}, author = {Takahashi, M and Ishikawa, D and Sasaki, T and Lu, YJ and Kuwahara-Arai, K and Kamei, M and Shibuya, T and Osada, T and Hiramatsu, K and Nagahara, A}, title = {Faecal freezing preservation period influences colonization ability for faecal microbiota transplantation.}, journal = {Journal of applied microbiology}, volume = {126}, number = {3}, pages = {973-984}, doi = {10.1111/jam.14167}, pmid = {30489686}, issn = {1365-2672}, support = {JP16K09328//JSPS KAKENHI/ ; S1201013//Japanese Ministry of Education, Culture, Sports, Science and Technology/ ; }, mesh = {*Cryopreservation ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; *Microbial Viability ; }, abstract = {AIMS: There has been growing interest in faecal microbiota transplantation (FMT) as treatment. Although, frozen donor faeces preserved at -20°C has been widely used for practical advantages, freezing at -20°C can affect bacterial viability. Adequacy evaluation of fresh and frozen faeces as the transplant is necessary for the methodological improvement of FMT.<br><br>METHODS AND RESULTS: The viable bacterial compositions of faecal specimens under fresh and freezing conditions were compared by a microbiome analysis using propidium monoazide (PMA microbiome). In addition, recovery abilities from bacterial reduction by antibiotics were compared between fresh and frozen FMT using a murine model. PMA microbiome results suggested that freezing and freeze-thawing did not significantly affect in vitro faecal bacterial viability. However, the recovery effect from antimicrobial cleansing in frozen FMT was reduced in a freezing time-dependent manner, especially prominent in Actinobacteria and Bacteroidetes phyla.<br><br>CONCLUSIONS: Short-term freezing preservation of faeces exhibited maintenance of enteric colonization ability in frozen FMT in comparison to 1 month -20°C-preservation.<br><br>Long-term -20°C-preservation of transplanted faeces can result in instability of the clinical outcome in FMT therapy. The standardization of practical procedures of FMT therapy according to disease types is desirable.}, }
@article {pmid30486338, year = {2018}, author = {Amedei, A and Boem, F}, title = {I've Gut A Feeling: Microbiota Impacting the Conceptual and Experimental Perspectives of Personalized Medicine.}, journal = {International journal of molecular sciences}, volume = {19}, number = {12}, pages = {}, doi = {10.3390/ijms19123756}, pmid = {30486338}, issn = {1422-0067}, support = {FAS SALUTE 2014//Regione Toscana/ ; P2016.0808//Ente Cassa di Risparmio di Firenze/ ; }, mesh = {Animals ; Biodiversity ; Biological Therapy ; Disease Susceptibility ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Genomics/methods ; Humans ; Metagenomics/methods ; Microbiota ; Organ Specificity ; *Precision Medicine/methods ; Research ; Symbiosis ; }, abstract = {In recent years, the human microbiota has gained increasing relevance both in research and clinical fields. Increasing studies seem to suggest the centrality of the microbiota and its composition both in the development and maintenance of what we call &quot;health&quot; and in generating and/or favoring (those cases in which the microbiota's complex relational architecture is dysregulated) the onset of pathological conditions. The complex relationships between the microbiota and human beings, which invest core notions of biomedicine such as &quot;health&quot; and &quot;individual,&quot; do concern not only problems of an empirical nature but seem to require the need to adopt new concepts and new perspectives in order to be properly analysed and utilized, especially for their therapeutic implementation. In this contribution we report and discuss some of the theoretical proposals and innovations (from the ecological component to the notion of polygenomic organism) aimed at producing this change of perspective. In conclusion, we summarily analyze what impact and what new challenges these new approaches might have on personalized/person centred/precision medicine.}, }
@article {pmid30483574, year = {2018}, author = {Shi, YC and Yang, YS}, title = {Fecal microbiota transplantation: Current status and challenges in China.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {2}, number = {4}, pages = {114-116}, pmid = {30483574}, issn = {2397-9070}, }
@article {pmid30480772, year = {2018}, author = {Imdad, A and Nicholson, MR and Tanner-Smith, EE and Zackular, JP and Gomez-Duarte, OG and Beaulieu, DB and Acra, S}, title = {Fecal transplantation for treatment of inflammatory bowel disease.}, journal = {The Cochrane database of systematic reviews}, volume = {11}, number = {}, pages = {CD012774}, doi = {10.1002/14651858.CD012774.pub2}, pmid = {30480772}, issn = {1469-493X}, mesh = {Colitis, Ulcerative/*therapy ; Crohn Disease/*therapy ; Dysbiosis/complications/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Humans ; Randomized Controlled Trials as Topic ; Recurrence ; Remission Induction ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal tract that is thought to be associated with a complex interplay between microbes and the immune system, leading to an abnormal inflammatory response in genetically susceptible individuals. Dysbiosis, characterized by the alteration of the composition of the resident commensal bacteria in a host compared to healthy individuals, is thought to play a major role in the pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD), two subtypes of IBD. There is growing interest to correct the underlying dysbiosis through the use of fecal microbiota transplantation (FMT) for the treatment of IBD.<br><br>OBJECTIVES: The objective of this systematic review was to assess the efficacy and safety of FMT for the treatment of IBD.<br><br>SEARCH METHODS: We searched the MEDLINE, Embase, Cochrane Library, and Cochrane IBD Group Specialized Register databases from inception to 19 March 2018. We also searched ClinicalTrials.gov, ISRCTN metaRegister of Controlled Trials, and the Conference Proceedings Citation Index.<br><br>SELECTION CRITERIA: Only randomized trials or non-randomized studies with a control arm were considered for inclusion. Adults or pediatric participants with UC or CD were eligible for inclusion. Eligible interventions were FMT defined as the administration of fecal material containing distal gut microbiota from a healthy donor to the gastrointestinal tract of a someone with UC or CD. The comparison group included participants who did not receive FMT and were given placebo, autologous FMT, or no intervention.<br><br>DATA COLLECTION AND ANALYSIS: Two authors independently screened the titles and extracted data from the included studies. We used the Cochrane risk of bias tool to assess study bias. The primary outcomes were induction of clinical remission, clinical relapse, and serious adverse events. Secondary outcomes included clinical response, endoscopic remission and endoscopic response, quality of life scores, laboratory measures of inflammation, withdrawals, and microbiome outcomes. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes and the mean difference and 95% CI for continuous outcomes. Random-effects meta-analysis models were used to synthesize effect sizes across trials. The overall certainty of the evidence supporting the primary and selected secondary outcomes was rated using the GRADE criteria.<br><br>MAIN RESULTS: Four studies with a total of 277 participants were included. These studies assessed the efficacy of FMT for treatment of UC in adults; no eligible trials were found for the treatment of CD. Most participants had mild to moderate UC. Two studies were conducted in Australia, one study was conducted in Canada, and another in the Netherlands. Three of the included studies administered FMT via the rectal route and one study administered FMT via the nasoduodenal route. Three studies were rated as low risk of bias. One study (abstract publication) was rated as unclear risk of bias. Combined results from four studies (277 participants) suggest that FMT increases rates of clinical remission by two-fold in patients with UC compared to controls. At 8 weeks, 37% (52/140) of FMT participants achieved remission compared to 18% (24/137) of control participants (RR 2.03, 95 % CI, 1.07 to 3.86; I² = 50%; low certainty evidence). One study reported data on relapse at 12 weeks among participants who achieved remission. None of the FMT participants (0/7) relapsed at 12 weeks compared to 20% of control participants (RR 0.28, 95% CI 0.02 to 4.98, 17 participants, very low certainty evidence). It is unclear whether there is a difference in serious adverse event rates between the intervention and control groups. Seven per cent (10/140) of FMT participants had a serious adverse event compared to 5% (7/137) of control participants (RR 1.40, 95% CI 0.55 to 3.58; 4 studies; I² = 0%; low certainty evidence). Serious adverse events included worsening of UC necessitating intravenous steroids or surgery; infection such as Clostridium difficile and cytomegalovirus, small bowel perforation and pneumonia. Adverse events were reported by two studies and the pooled data did not show any difference between the study groups. Seventy-eight per cent (50/64) of FMT participants had an adverse event compared to 75% (49/65) of control participants (RR 1.03, 95% CI 0.81 to 1.31; I² = 31%; moderate certainty evidence). Common adverse events included abdominal pain, nausea, flatulence, bloating, upper respiratory tract infection, headaches, dizziness, and fever. Four studies reported on clinical response at 8 weeks. Forty-nine per cent (68/140) of FMT participants had a clinical response compared to 28% (38/137) of control participants (RR 1.70, 95% CI 0.98 to 2.95, I² = 50%, low certainty evidence). Endoscopic remission at 8 weeks was reported by three studies and the combined results favored FMT over the control group. Thirty per cent (35/117) of FMT participants achieved endoscopic remission compared to 10% (11/112) of control participants (RR 2.96, 95 % CI 1.60 to 5.48, I² = 0%; low certainty evidence).<br><br>AUTHORS' CONCLUSIONS: Fecal microbiota transplantation may increase the proportion of participants achieving clinical remission in UC. However, the number of identified studies was small and the quality of evidence was low. There is uncertainty about the rate of serious adverse events. As a result, no solid conclusions can be drawn at this time. Additional high-quality studies are needed to further define the optimal parameters of FMT in terms of route, frequency, volume, preparation, type of donor and the type and disease severity. No studies assessed efficacy of FMT for induction of remission in CD or in pediatric participants. In addition, no studies assessed long-term maintenance of remission in UC or CD. Future studies are needed to address the therapeutic benefit of FMT in CD and the long-term FMT-mediated maintenance of remission in UC or CD.}, }
@article {pmid30479380, year = {2019}, author = {Wang, Y and Wiesnoski, DH and Helmink, BA and Gopalakrishnan, V and Choi, K and DuPont, HL and Jiang, ZD and Abu-Sbeih, H and Sanchez, CA and Chang, CC and Parra, ER and Francisco-Cruz, A and Raju, GS and Stroehlein, JR and Campbell, MT and Gao, J and Subudhi, SK and Maru, DM and Blando, JM and Lazar, AJ and Allison, JP and Sharma, P and Tetzlaff, MT and Wargo, JA and Jenq, RR}, title = {Author Correction: Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis.}, journal = {Nature medicine}, volume = {25}, number = {1}, pages = {188}, doi = {10.1038/s41591-018-0305-2}, pmid = {30479380}, issn = {1546-170X}, abstract = {In the version of this article originally published, an author was missing from the author list. Alexander J. Lazar should have been included between Jorge M. Blando and James P. Allison. The author has been added to the list, and the author contributions section has been updated to include Alexander J. Lazar's contribution to the study. The error has been corrected in the print, PDF and HTML versions of the manuscript.}, }
@article {pmid30474827, year = {2018}, author = {Mehta, R and Kabrawala, M and Nandwani, S and Kalra, P and Patel, C and Desai, P and Parekh, K}, title = {Preliminary experience with single fecal microbiota transplant for treatment of recurrent overt hepatic encephalopathy-A case series.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {37}, number = {6}, pages = {559-562}, doi = {10.1007/s12664-018-0906-1}, pmid = {30474827}, issn = {0975-0711}, mesh = {Adult ; Aged ; Dysbiosis/microbiology/therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Hepatic Encephalopathy/*therapy ; Humans ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Time Factors ; Treatment Outcome ; }, abstract = {Experimental studies demonstrated that fecal microbiota transplant (FMT) may reverse intestinal microbial dysbiosis. In this retrospective case series, we share our experience of treating recurrent overt hepatic encephalopathy (HE) with single FMT treatment. A total of 10 patients, age ranged from 25 to 65 years, were treated with single FMT through colonoscopy using fecal material received from rigorously screened patient-identified donors. There was sustained clinical response with single FMT treatment in 6 patients at post-treatment week 20. Arterial ammonia concentration decreased considerably (96 [87.25-117.75] vs. 74 [70-82]; p = 0.024) at post-treatment week 20. Moreover, there was statistically significant decrease in Child-Turcotte-Pugh (CTP) score (9.5 [9-10.75] vs. 8 [7-8]; p = 0.005) and model for end-stage liver disease (MELD) score (18 [16.25-19] vs. 15 [14-16]; p = 0.008). Four patients experienced six adverse-events. Overt HE and re-hospitalization were observed in 3 and 2 patients, respectively. One patient (who also experienced overt HE) died within 2 months of the index procedure.}, }
@article {pmid30474116, year = {2018}, author = {Dai, Z and Zhang, J and Wu, Q and Chen, J and Liu, J and Wang, L and Chen, C and Xu, J and Zhang, H and Shi, C and Li, Z and Fang, H and Lin, C and Tang, D and Wang, D}, title = {The role of microbiota in the development of colorectal cancer.}, journal = {International journal of cancer}, volume = {}, number = {}, pages = {}, doi = {10.1002/ijc.32017}, pmid = {30474116}, issn = {1097-0215}, support = {BE2015664//Standardized diagnosis and treatment of key diseases in Jiangsu Province: standardized diagnosis and treatment of rectal cancer and rectal cancer liver metastasis and its clinical application/ ; QNRC2016330//training project of key talents of youth medicine in Jiangsu province, China/ ; YZ2018087//Yangzhou Science and Technology Bureau Social Development Project/ ; }, abstract = {Colorectal cancer is the third largest cancer in worldwide and has been proven to be closely related to the intestinal microbiota. Many reports and clinical studies have shown that intestinal microbial behavior may lead to pathological changes in the host intestines. The changes can be divided into epigenetic changes and carcinogenic changes at the gene level, which ultimately promote the production and development of colorectal cancer. This article reviews the pathways of microbial signaling in the intestinal epithelial barrier, the role of microbiota in inflammatory colorectal tumors, and typical microbial carcinogenesis. Finally, by gaining a deeper understanding of the intestinal microbiota, we hope to achieve the goal of treating colorectal cancer using current microbiota technologies, such as fecal microbiological transplantation.}, }
@article {pmid30470860, year = {2019}, author = {Tillmann, S and Abildgaard, A and Winther, G and Wegener, G}, title = {Altered fecal microbiota composition in the Flinders sensitive line rat model of depression.}, journal = {Psychopharmacology}, volume = {236}, number = {5}, pages = {1445-1457}, doi = {10.1007/s00213-018-5094-2}, pmid = {30470860}, issn = {1432-2072}, abstract = {RATIONALE: The gut microbiota is increasingly recognized as a potential mediator of psychiatric diseases. Depressed patients have been shown to have a different microbiota composition compared with healthy controls, and several lines of research now aim to restore this dysbiosis. To develop novel treatments, preclinical models may provide novel mechanistic insights.<br><br>OBJECTIVE AND METHODS: We characterized the gut microbiota of male adult Flinders sensitive line (FSL) rats, an animal model of depression, and their controls, Flinders resistant line (FRL) rats using 16S rRNA amplicon sequencing. Moreover, we performed fecal microbiota transplantation (using saline or pooled FRL/FSL feces) to study if the potential strain-specific differences could be transferred from one strain to the other, and if these differences were reflected in their depressive-like behavior in the forced swim test.<br><br>RESULTS: FSL rats tended to have lower bacterial richness and altered relative abundances of several bacterial phyla, families, and species, including higher Proteobacteria and lower Elusimicrobia and Saccharibacteria. There was a clear separation between FRL and FSL rat strains, but no effect of treatment, i.e., the bacterial composition of FSL rats receiving FRL feces was still more similar to FSL and not FRL rats. Similarly, the transplantation did not reverse behavioral differences in the forced swim test, although FSL feces significantly increased immobility compared with saline.<br><br>CONCLUSIONS: Our study showed that the gut microbiota composition of the depressive-like rats markedly differed from their controls, which may be of value for future microbiota-targeted work in this and similar animal models.}, }
@article {pmid30467295, year = {2018}, author = {Ganesan, K and Chung, SK and Vanamala, J and Xu, B}, title = {Causal Relationship between Diet-Induced Gut Microbiota Changes and Diabetes: A Novel Strategy to Transplant Faecalibacterium prausnitzii in Preventing Diabetes.}, journal = {International journal of molecular sciences}, volume = {19}, number = {12}, pages = {}, doi = {10.3390/ijms19123720}, pmid = {30467295}, issn = {1422-0067}, support = {R201714//Beijing Normal University-Hong Kong Baptist University United International College/ ; }, mesh = {Butyrates/metabolism ; Diabetes Mellitus/immunology/*microbiology/pathology/prevention &amp; control ; Diet/methods ; Dietary Fiber/administration &amp; dosage ; Dysbiosis/immunology/*microbiology/pathology/therapy ; Faecalibacterium prausnitzii/*physiology ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; Probiotics/*therapeutic use ; Symbiosis/*physiology ; }, abstract = {The incidence of metabolic disorders, including diabetes, has elevated exponentially during the last decades and enhanced the risk of a variety of complications, such as diabetes and cardiovascular diseases. In the present review, we have highlighted the new insights on the complex relationships between diet-induced modulation of gut microbiota and metabolic disorders, including diabetes. Literature from various library databases and electronic searches (ScienceDirect, PubMed, and Google Scholar) were randomly collected. There exists a complex relationship between diet and gut microbiota, which alters the energy balance, health impacts, and autoimmunity, further causes inflammation and metabolic dysfunction, including diabetes. Faecalibacterium prausnitzii is a butyrate-producing bacterium, which plays a vital role in diabetes. Transplantation of F. prausnitzii has been used as an intervention strategy to treat dysbiosis of the gut's microbial community that is linked to the inflammation, which precedes autoimmune disease and diabetes. The review focuses on literature that highlights the benefits of the microbiota especially, the abundant of F. prausnitzii in protecting the gut microbiota pattern and its therapeutic potential against inflammation and diabetes.}, }
@article {pmid30463925, year = {2018}, author = {Bulow, C and Langdon, A and Hink, T and Wallace, M and Reske, KA and Patel, S and Sun, X and Seiler, S and Jones, S and Kwon, JH and Burnham, CA and Dantas, G and Dubberke, ER}, title = {Impact of Amoxicillin-Clavulanate followed by Autologous Fecal Microbiota Transplantation on Fecal Microbiome Structure and Metabolic Potential.}, journal = {mSphere}, volume = {3}, number = {6}, pages = {}, pmid = {30463925}, issn = {2379-5042}, support = {KL2 TR002346/TR/NCATS NIH HHS/United States ; T32 HG000045/HG/NHGRI NIH HHS/United States ; TL1 TR000449/TR/NCATS NIH HHS/United States ; TL1 TR002344/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Amoxicillin-Potassium Clavulanate Combination/*administration &amp; dosage ; Anti-Bacterial Agents/*administration &amp; dosage ; Enema ; Fecal Microbiota Transplantation/*methods ; Female ; *Gastrointestinal Microbiome ; Healthy Volunteers ; Humans ; Male ; *Metabolism ; *Microbiota ; Middle Aged ; Treatment Outcome ; Young Adult ; beta-Lactamase Inhibitors/*administration &amp; dosage ; }, abstract = {Strategies to prevent multidrug-resistant organism (MDRO) infections are scarce, but autologous fecal microbiota transplantation (autoFMT) may limit gastrointestinal MDRO expansion. AutoFMT involves banking one's feces during a healthy state for later use in restoring gut microbiota following perturbation. This pilot study evaluated the effect of autoFMT on gastrointestinal microbiome taxonomic composition, resistance gene content, and metabolic capacity after exposure to amoxicillin-clavulanic acid (Amox-Clav). Ten healthy participants were enrolled. All received 5 days of Amox-Clav. Half were randomized to autoFMT, derived from stool collected pre-antimicrobial exposure, by enema, and half to saline enema. Participants submitted stool samples pre- and post-Amox-Clav and enema and during a 90-day follow-up period. Shotgun metagenomic sequencing revealed taxonomic composition, resistance gene content, and metabolic capacity. Amox-Clav significantly altered gut taxonomic composition in all participants (n = 10, P < 0.01); however, only three participants exhibited major changes at the phylum level following exposure. In the cohort as a whole, beta-lactamase genes were enriched following Amox-Clav (P < 0.05), and predicted metabolic capacity was significantly altered (P < 0.01). Species composition, metabolic capacity, and beta-lactamase abundance returned to pre-antimicrobial exposure state 7 days after either autoFMT or saline enema (P > 0.05, compared to enrollment). Alterations to microbial metabolic capacity occurred following antimicrobial exposure even in participants without substantial taxonomic disruption, potentially creating open niches for pathogen colonization. Our findings suggest that metabolic potential is an important consideration for complete assessment of antimicrobial impact on the microbiome. AutoFMT was well tolerated and may have contributed to phylogenetic recovery. (This study has been registered at ClinicalTrials.gov under identifier NCT02046525.)IMPORTANCE The spread of multidrug resistance among pathogenic organisms threatens the efficacy of antimicrobial treatment options. The human gut serves as a reservoir for many drug-resistant organisms and their resistance genes, and perturbation of the gut microbiome by antimicrobial exposure can open metabolic niches to resistant pathogens. Once established in the gut, antimicrobial-resistant bacteria can persist even after antimicrobial exposure ceases. Strategies to prevent multidrug-resistant organism (MDRO) infections are scarce, but autologous fecal microbiota transplantation (autoFMT) may limit gastrointestinal MDRO expansion. AutoFMT involves banking one's feces during a healthy state for later use in restoring gut microbiota following perturbation. This pilot study evaluated the effect of amoxicillin-clavulanic acid (Amox-Clav) exposure and autoFMT on gastrointestinal microbiome taxonomic composition, resistance gene content, and metabolic capacity. Importantly, we found that metabolic capacity was perturbed even in cases where gross phylogeny remained unchanged and that autoFMT was safe and well tolerated.}, }
@article {pmid30458058, year = {2018}, author = {Chen, D and Wu, J and Jin, D and Wang, B and Cao, H}, title = {Fecal microbiota transplantation in cancer management: Current status and perspectives.}, journal = {International journal of cancer}, volume = {}, number = {}, pages = {}, doi = {10.1002/ijc.32003}, pmid = {30458058}, issn = {1097-0215}, support = {17JCYBJC24900//Tianjin Research Program of Application Foundation and Advanced Technology of China/ ; 81741075//National Natural Science Foundation of China/ ; 81570478//National Natural Science Foundation of China/ ; }, abstract = {The human gut is home to a large and diverse microbial community, comprising about 1,000 bacterial species. The gut microbiota exists in a symbiotic relationship with its host, playing a decisive role in the host's nutrition, immunity and metabolism. Accumulating studies have revealed the associations between gut dysbiosis or some special bacteria and various cancers. Emerging data suggest that gut microbiota can modulate the effectiveness of cancer therapies, especially immunotherapy. Manipulating the microbial populations with therapeutic intent has become a hot topic of cancer research, and the most dramatic manipulation of gut microbiota refers to fecal microbiota transplantation (FMT) from healthy individuals to patients. FMT has demonstrated remarkable clinical efficacy against Clostridium difficile infection (CDI) and it is highly recommended for the treatment of recurrent or refractory CDI. Lately, interest is growing in the therapeutic potential of FMT for other diseases, including cancers. We briefly reviewed the current researches about gut microbiota and its link to cancer, and then summarized the recent preclinical and clinical evidence to indicate the potential of FMT in cancer management as well as cancer-treatment associated complications. We also presented the rationale of FMT for cancer management such as reconstruction of intestinal microbiota, amelioration of bile acid metabolism, and modulation of immunotherapy efficacy. This article would help to better understand this new therapeutic approach for cancer patients by targeting gut microbiota.}, }
@article {pmid30455884, year = {2018}, author = {Ohara, T and Suzutani, T}, title = {Efficacy of fecal microbiota transplantation in a patient with chronic intractable constipation.}, journal = {Clinical case reports}, volume = {6}, number = {11}, pages = {2029-2032}, pmid = {30455884}, issn = {2050-0904}, abstract = {We have presented the first case report of FMT therapy for a patient with chronic intractable constipation. This therapy resulted in good, medium-term outcomes. Follow-up analysis of the intestinal flora suggested that transplanted microbes from the donor, particularly Bifidobacterium and Clostridium cluster IX, may have been incorporated into the recipient.}, }
@article {pmid30455339, year = {2018}, author = {Weis, M}, title = {Impact of the gut microbiome in cardiovascular and autoimmune diseases.}, journal = {Clinical science (London, England : 1979)}, volume = {132}, number = {22}, pages = {2387-2389}, doi = {10.1042/CS20180410}, pmid = {30455339}, issn = {1470-8736}, abstract = {The gut microbiome functions like an endocrine organ, generating enzymes and bioactive metabolites, which affect host physiology. In addition metabolism-independent processes like impaired intestinal barrier function may result in bacterial translocation and an increased inflammation. Specific microbe-associated molecular patterns (MAMPs) have been detected that induce immune activation via cognate pattern-recognition receptors on host immune cells, with subsequent consequences on inflammatory-induced endothelial dysfunction. Alterations in intestinal microbial and metabolic composition play an important role in human health and disease, including cardiovascular and autoimmune diseases. Changes in the composition of gut microbiota (dysbiosis) are linked to chronic inflammation, thrombosis, atherogenesis, chronic heart, and kidney disease, as well as to autoimmune diseases like systemic lupus erythematodes. Although non-selective approaches that broadly alter microbial community structure, such as prebiotics, probiotics, and fecal microbial transplantation, may have some promise, targeting defined microbial pathways and adjacent host immune responses may be the ultimate scientific goal.}, }
@article {pmid30450088, year = {2018}, author = {Li, X and Gao, X and Hu, H and Xiao, Y and Li, D and Yu, G and Yu, D and Zhang, T and Wang, Y}, title = {Clinical Efficacy and Microbiome Changes Following Fecal Microbiota Transplantation in Children With Recurrent Clostridium Difficile Infection.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2622}, pmid = {30450088}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) has been shown as an effective treatment for recurrent clostridium difficile infection (RCDI) in adults. In this study, we aim to evaluate the clinical efficacy of FMT in treating children with RCDI, and explore fecal microbiota changes during FMT treatment. A total of 11 RCDI subjects with a median age of 3.5 years were enrolled in this single-center prospective pilot study. All patients were cured (11/11, 100%) by FMT either through upper gastrointestinal tract route with a nasointestinal tube (13/16, 81.2%) or lower gastrointestinal tract route with a rectal tube (3/16, 18.8%). The cure rate of single FMT was 63.6% (7/11), and 4 (4/11, 36.4%) cases were performed with 2 or 3 times of FMT. Mild adverse events were reported in 4 children (4/11, 36.4%), including transient diarrhea, mild abdominal pain, transient fever and vomit. Gut microbiota composition analysis of 59 fecal samples collected from 34 participants (9 RCDI children, 9 donors and 16 health controls) showed that the alpha diversity was lower in pediatric RCDI patients before FMT than the healthy controls and donors, and fecal microbial community of pre-FMT samples (beta diversity) was apart from that of healthy controls and donors. No significant differences in alpha diversity, beta diversity or phylogenetic distance were detected between donors and healthy controls. Both the richness and diversity of gut microbiota were improved in the pediatric RCDI patients after FMT, and the bacteria community was shifted closer to the donor and healthy control group. Furthermore, FMT re-directed gut microbiome functions of pediatric RCDI toward a health state. Our results indicate that it is safe and tolerant to use FMT in treating pediatric RCDI. FMT shifted the gut microbiome composition and function in children with RCDI toward a healthy state.}, }
@article {pmid30449078, year = {2019}, author = {Sood, A and Mahajan, R and Juyal, G and Midha, V and Grewal, CS and Mehta, V and Singh, A and Joshi, MC and Narang, V and Kaur, K and Sidhu, H}, title = {Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: a real world intention-to-treat analysis.}, journal = {Intestinal research}, volume = {17}, number = {1}, pages = {78-86}, doi = {10.5217/ir.2018.00089}, pmid = {30449078}, issn = {1598-9100}, abstract = {BACKGROUND/AIMS: Four high-quality randomized controlled trials have proven the efficacy of fecal microbiota transplantation (FMT) in active ulcerative colitis (UC). We assessed the efficacy of FMT in a real-world setting involving steroid-dependent patients with UC.<br><br>METHODS: This was a single-center prospective analysis of data from steroid-dependent patients with UC treated with FMT from September 2015 to September 2017 at the Dayanand Medical College, a tertiary care center in India. Fecal samples from random unrelated donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. The primary outcome was achievement of steroid-free clinical remission, and the secondary outcomes were clinical response and endoscopic remission at 24 weeks. Modified intention-to-treat analysis was performed, which included subjects who underwent at least 1 FMT.<br><br>RESULTS: Of 345 patients with UC treated during the study period, 49 (14.2%) had steroid-dependent UC. Of these 49 patients, 41 underwent FMT: 33 completed 7 sessions over 22 weeks according to the protocol, and 8 discontinued treatment (non-response, 5; lost to follow-up, 2; and fear of adverse effects, 1). At week 24, steroid-free clinical remission was achieved in 19 out of 41 (46.3%) patients, whereas clinical response and endoscopic remission were achieved in 31 out of 41 (75.6%) and 26 out of 41 (63.4%) patients, respectively. All patients with clinical response were able to withdraw steroids. There were no serious adverse events necessitating discontinuation.<br><br>CONCLUSIONS: A multisession FMT via the colonoscopic route is a promising therapeutic option for patients with steroid-dependent UC, as it can induce clinical remission and aid in steroid withdrawal.}, }
@article {pmid30446486, year = {2018}, author = {Kaito, S and Toya, T and Yoshifuji, K and Kurosawa, S and Inamoto, K and Takeshita, K and Suda, W and Kakihana, K and Honda, K and Hattori, M and Ohashi, K}, title = {Fecal microbiota transplantation with frozen capsules for a patient with refractory acute gut graft-versus-host disease.}, journal = {Blood advances}, volume = {2}, number = {22}, pages = {3097-3101}, pmid = {30446486}, issn = {2473-9537}, }
@article {pmid30442907, year = {2019}, author = {Zhou, W and Chow, KH and Fleming, E and Oh, J}, title = {Selective colonization ability of human fecal microbes in different mouse gut environments.}, journal = {The ISME journal}, volume = {13}, number = {3}, pages = {805-823}, doi = {10.1038/s41396-018-0312-9}, pmid = {30442907}, issn = {1751-7370}, support = {1 DP2 GM126893-01//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/International ; DP2 GM126893/GM/NIGMS NIH HHS/United States ; K22 AI119231/AI/NIAID NIH HHS/United States ; }, abstract = {Mammalian hosts constantly interact with diverse exogenous microbes, but only a subset of the microbes manage to colonize due to selective colonization resistance exerted by host genetic factors as well as the native microbiota of the host. An important question in microbial ecology and medical science is if such colonization resistance can discriminate closely related microbial species, or even closely related strains of the same species. Using human-mouse fecal microbiota transplantation and metagenomic shotgun sequencing, we reconstructed colonization patterns of human fecal microbes in mice with different genotypes (C57BL6/J vs. NSG) and with or without an intact gut microbiota. We found that mouse genotypes and the native mouse gut microbiota both exerted different selective pressures on exogenous colonizers: human fecal Bacteroides successfully established in the mice gut, however, different species of Bacteroides selectively enriched under different gut conditions, potentially due to a multitude of functional differences, ranging from versatility in nutrient acquisition to stress responses. Additionally, different clades of Bacteroides cellulosilyticus strains were selectively enriched in different gut conditions, suggesting that the fitness of conspecific microbial strains in a novel host environment could differ.}, }
@article {pmid30431239, year = {2019}, author = {Berry, D}, title = {Up-close-and-personal with the human microbiome.}, journal = {Environmental microbiology reports}, volume = {11}, number = {1}, pages = {17-19}, doi = {10.1111/1758-2229.12709}, pmid = {30431239}, issn = {1758-2229}, mesh = {Diet Therapy ; Drug Design ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/genetics/*physiology ; Genomics ; Humans ; Microbiota/drug effects/genetics/*physiology ; Phage Therapy ; }, }
@article {pmid30427836, year = {2018}, author = {Mazzawi, T and Lied, GA and Sangnes, DA and El-Salhy, M and Hov, JR and Gilja, OH and Hatlebakk, JG and Hausken, T}, title = {The kinetics of gut microbial community composition in patients with irritable bowel syndrome following fecal microbiota transplantation.}, journal = {PloS one}, volume = {13}, number = {11}, pages = {e0194904}, pmid = {30427836}, issn = {1932-6203}, mesh = {Adolescent ; Adult ; Aged ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Irritable Bowel Syndrome/microbiology/*therapy ; Male ; *Microbiota ; Middle Aged ; Quality of Life ; Young Adult ; }, abstract = {BACKGROUND: Gut microbiota alterations are important in irritable bowel syndrome (IBS). The aim was to investigate the effect of fecal microbiota transplantation (FMT) on gut microbiota and the symptoms in patients with IBS.<br><br>MATERIAL AND METHODS: The study included 13 IBS patients according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered to the descending part of the duodenum via a gastroscope. Feces were collected from donors and patients before FMT, and from the patients at 1, 3 and 12 weeks and donors and patients at 20/28 weeks after FMT. Microbiota analysis was performed using GA-map Dysbiosis test (Genetic Analysis AS, Oslo, Norway). The patients completed the following questionnaires before and at the aforementioned weeks after FMT: IBS Symptom Questionnaire (IBS-SQ), IBS-Symptom Severity Scoring system (IBS-SSS), Short Form of Nepean Dyspepsia Index (SF-NDI), Bristol stool form scale, the Eysenck Personality Questionnaire-Neuroticism and Hospital Anxiety and Depression.<br><br>RESULTS: Donors and IBS patients had significantly different bacterial strain signals before FMT (Ruminococcus gnavus, Actinobacteria and Bifidobacteria) that became non-significant after 3 weeks following FMT. The changes in gut microbiota were similar between donors and patients at 20/28 weeks after FMT. Thus, patients' microbiota profiles became more-or-less similar to donors. The scores of all the questionnaires were significantly improved at all time points following FMT. No reported adverse effects.<br><br>CONCLUSIONS: FMT was associated with a change in gut microbiota and improvement in IBS symptoms and quality of life lasting for up to 28 weeks.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03333291.}, }
@article {pmid30424806, year = {2018}, author = {Kaliannan, K and Robertson, RC and Murphy, K and Stanton, C and Kang, C and Wang, B and Hao, L and Bhan, AK and Kang, JX}, title = {Estrogen-mediated gut microbiome alterations influence sexual dimorphism in metabolic syndrome in mice.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {205}, pmid = {30424806}, issn = {2049-2618}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; }, mesh = {Alkaline Phosphatase/biosynthesis ; Animals ; Bacterial Load ; Estradiol/*pharmacology ; Estrogens/*pharmacology ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Isoflavones/pharmacology ; Lipopolysaccharides/biosynthesis ; Male ; Metabolic Syndrome/*prevention &amp; control ; Mice ; Mice, Inbred C57BL ; Proteobacteria/*metabolism ; *Sex Characteristics ; }, abstract = {BACKGROUND: Understanding the mechanism of the sexual dimorphism in susceptibility to obesity and metabolic syndrome (MS) is important for the development of effective interventions for MS.<br><br>RESULTS: Here we show that gut microbiome mediates the preventive effect of estrogen (17β-estradiol) on metabolic endotoxemia (ME) and low-grade chronic inflammation (LGCI), the underlying causes of MS and chronic diseases. The characteristic profiles of gut microbiome observed in female and 17β-estradiol-treated male and ovariectomized mice, such as decreased Proteobacteria and lipopolysaccharide biosynthesis, were associated with a lower susceptibility to ME, LGCI, and MS in these animals. Interestingly, fecal microbiota-transplant from male mice transferred the MS phenotype to female mice, while antibiotic treatment eliminated the sexual dimorphism in MS, suggesting a causative role of the gut microbiome in this condition. Moreover, estrogenic compounds such as isoflavones exerted microbiome-modulating effects similar to those of 17β-estradiol and reversed symptoms of MS in the male mice. Finally, both expression and activity of intestinal alkaline phosphatase (IAP), a gut microbiota-modifying non-classical anti-microbial peptide, were upregulated by 17β-estradiol and isoflavones, whereas inhibition of IAP induced ME and LGCI in female mice, indicating a critical role of IAP in mediating the effects of estrogen on these parameters.<br><br>CONCLUSIONS: In summary, we have identified a previously uncharacterized microbiome-based mechanism that sheds light upon sexual dimorphism in the incidence of MS and that suggests novel therapeutic targets and strategies for the management of obesity and MS in males and postmenopausal women.}, }
@article {pmid30420754, year = {2018}, author = {Wang, Y and Wiesnoski, DH and Helmink, BA and Gopalakrishnan, V and Choi, K and DuPont, HL and Jiang, ZD and Abu-Sbeih, H and Sanchez, CA and Chang, CC and Parra, ER and Francisco-Cruz, A and Raju, GS and Stroehlein, JR and Campbell, MT and Gao, J and Subudhi, SK and Maru, DM and Blando, JM and Lazar, AJ and Allison, JP and Sharma, P and Tetzlaff, MT and Wargo, JA and Jenq, RR}, title = {Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis.}, journal = {Nature medicine}, volume = {24}, number = {12}, pages = {1804-1808}, doi = {10.1038/s41591-018-0238-9}, pmid = {30420754}, issn = {1546-170X}, support = {R01 CA219896/CA/NCI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; T32 CA009599/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; CTLA-4 Antigen/antagonists &amp; inhibitors/immunology/therapeutic use ; Colitis/chemically induced/immunology/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/*drug effects/immunology ; Humans ; Immune System/drug effects/microbiology ; Intestinal Mucosa/immunology/microbiology/pathology ; Ipilimumab/*adverse effects ; Male ; Middle Aged ; Programmed Cell Death 1 Receptor/antagonists &amp; inhibitors/immunology/therapeutic use ; T-Lymphocytes, Regulatory/drug effects/immunology/microbiology ; }, abstract = {We report the first case series of immune checkpoint inhibitors (ICI)-associated colitis successfully treated with fecal microbiota transplantation, with reconstitution of the gut microbiome and a relative increase in the proportion of regulatory T-cells within the colonic mucosa. These preliminary data provide evidence that modulation of the gut microbiome may abrogate ICI-associated colitis.}, }
@article {pmid30415447, year = {2019}, author = {Fang, X}, title = {Microbial treatment: the potential application for Parkinson's disease.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {40}, number = {1}, pages = {51-58}, doi = {10.1007/s10072-018-3641-6}, pmid = {30415447}, issn = {1590-3478}, support = {81660203//National Natural Science Foundation of China/ ; 20142BAB205092//Natural Science Foundation of Jiangxi Province (CN)/ ; 20181BAB205030//Natural Science Foundation of Jiangxi Province (CN)/ ; }, mesh = {Animals ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Parkinson Disease/microbiology/*therapy ; Probiotics/*administration &amp; dosage ; Treatment Outcome ; }, abstract = {Alterations in the composition of the intestinal flora are associated with the pathophysiology of Parkinson's disease (PD). More importantly, the possible cause-effect links between gut flora and PD pathogenesis have been identified using PD animal models. Recent studies have found that probiotics improve the symptoms associated with constipation in PD patients. In addition, fecal microbiota transplantation (FMT) was recently shown to provide a protective effect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice. Effective microbial therapy for PD includes probiotics and FMT. Therefore, microbial therapy may be a useful and novel approach for treatment of PD. In this review, I discuss the use of microbial treatment in PD.}, }
@article {pmid30414693, year = {2018}, author = {Prado, C and Michels, M and Ávila, P and Burger, H and Milioli, MVM and Dal-Pizzol, F}, title = {The protective effects of fecal microbiota transplantation in an experimental model of necrotizing enterocolitis.}, journal = {Journal of pediatric surgery}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jpedsurg.2018.10.045}, pmid = {30414693}, issn = {1531-5037}, abstract = {BACKGROUND: Necrotizing enterocolitis (NEC) is a serious disease that affects premature neonates, causing high mortality. In the search for new options of treatment it was investigated whether fecal microbiota transplantation (FMT) decreased the inflammatory response during NEC development in experimental model.<br><br>METHODS: Wistar rats were used and divided as follows: naïve, control (NEC induction), FMT-before (transplantation of microbiota before insult) and FMT-after (microbiota transplantation after insult). The microbiota transplantation was performed by administering a feces solution obtained from an adult donor rat. The induction of enterocolitis involves feeding by artificial formula, hypothermia, hypoxia and endotoxin administration. MPO activity, TNF-α, IL-1β and IL-6 levels, oxidative and nitrosative damage and the grade of intestinal mucosa lesion were analyzed.<br><br>RESULTS: The control group had a significant increase of inflammatory and oxidative parameters when compared to naive animals. Both FMT-before and after decreased all inflammatory and oxidative damage parameters when compared to control group. This was also true to the intestinal mucosa damage.<br><br>CONCLUSION: FMT administered just before or after NEC induction improved gut and systemic inflammation, and gut oxidative damage and intestinal injury.}, }
@article {pmid30409169, year = {2018}, author = {Ma, C and Sun, Z and Zeng, B and Huang, S and Zhao, J and Zhang, Y and Su, X and Xu, J and Wei, H and Zhang, H}, title = {Cow-to-mouse fecal transplantations suggest intestinal microbiome as one cause of mastitis.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {200}, pmid = {30409169}, issn = {2049-2618}, mesh = {Animals ; Bacteria/classification/genetics ; Cattle ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Mammary Glands, Animal/*microbiology ; Mastitis, Bovine/drug therapy/*microbiology ; Mice ; Probiotics/*therapeutic use ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Mastitis, which affects nearly all lactating mammals including human, is generally thought to be caused by local infection of the mammary glands. For treatment, antibiotics are commonly prescribed, which however are of concern in both treatment efficacy and neonate safety. Here, using bovine mastitis which is the most costly disease in the dairy industry as a model, we showed that intestinal microbiota alone can lead to mastitis.<br><br>RESULTS: Fecal microbiota transplantation (FMT) from mastitis, but not healthy cows, to germ-free (GF) mice resulted in mastitis symptoms in mammary gland and inflammations in serum, spleen, and colon. Probiotic intake in parallel with FMT from diseased cows led to relieved mastitis symptoms in mice, by shifting the murine intestinal microbiota to a state that is functionally distinct from either healthy or diseased microbiota yet structurally similar to the latter. Despite conservation in mastitis symptoms, diseased cows and mice shared few mastitis-associated bacterial organismal or functional markers, suggesting striking divergence in mastitis-associated intestinal microbiota among lactating mammals. Moreover, an &quot;amplification effect&quot; of disease-health distinction in both microbiota structure and function was apparent during the cow-to-mouse FMT.<br><br>CONCLUSIONS: Hence, dysbiosis of intestinal microbiota may be one cause of mastitis, and probiotics that restore intestinal microbiota function are an effective and safe strategy to treat mastitis.}, }
@article {pmid30408565, year = {2019}, author = {DeFilipp, Z and Hohmann, E and Jenq, RR and Chen, YB}, title = {Fecal Microbiota Transplantation: Restoring the Injured Microbiome after Allogeneic Hematopoietic Cell Transplantation.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {25}, number = {1}, pages = {e17-e22}, doi = {10.1016/j.bbmt.2018.10.022}, pmid = {30408565}, issn = {1523-6536}, abstract = {Disruption of the intestinal microbiome early after allogeneic hematopoietic cell transplantation (allo-HCT) has been linked to adverse outcomes in transplant recipients. To date, whether microbiome-directed interventions will be able to impact important clinical endpoints remains unknown. Fecal microbiota transplantation (FMT) is a compelling intervention to restore healthy diversity to the intestinal microenvironment after allo-HCT, but currently has no established role in transplant recipients. In this review, we examine the use of FMT as treatment for Clostridium difficile infection and acute graft-versus-host disease, and also as a restorative intervention early after allo-HCT. Ongoing and planned studies will help determine the ultimate role of FMT in allo-HCT recipients.}, }
@article {pmid30405910, year = {2018}, author = {Niccum, BA and Stein, DJ and Behm, BW and Hays, RA}, title = {Zinc Deficiency and the Recurrence of Clostridium difficile Infection after Fecal Microbiota Transplant: A Retrospective Cohort Study.}, journal = {Journal of nutrition and metabolism}, volume = {2018}, number = {}, pages = {9682975}, pmid = {30405910}, issn = {2090-0724}, abstract = {Background: Fecal microbiota transplant (FMT) is an effective therapy for recurrent Clostridium difficile infection (CDI). However, in 12% of patients treated with FMT, CDI recurs within one month. Zinc deficiency predicts increased diarrheal frequency in malnourished children, but little is known about its association with FMT outcome. We hypothesized that zinc levels were an independent predictor of CDI recurrence after FMT.<br><br>Methods: We performed a retrospective cohort study of 80 patients (mean age, 66; 59 women) receiving FMT for CDI from 9/2013-9/2016 at a tertiary care center. Zinc levels were measured within 90 days before FMT. The primary outcome was CDI recurrence within 90 days after FMT. We controlled for risk factors for FMT failure using Cox regression. We also analyzed the effect of zinc supplementation in individuals with deficiency.<br><br>Results: Forty-nine subjects had a normal zinc level, and 31 had a low level (<0.66 µg/mL). CDI recurred in 3/49 (6%) patients with normal zinc and 5/31 (16%) patients with low zinc (HR = 11.327, 95% CI = 2.162-59.336, p=0.004). Among low zinc subjects, 2 of 25 (8%) that received zinc supplements and 3 of 6 (50%) that did not receive zinc supplements had recurrence of CDI (HR = 0.102, 95% CI = 0.015-0.704, p=0.021).<br><br>Conclusion: Zinc deficiency was associated with increased CDI recurrence after FMT. Among zinc-deficient patients, supplementation was associated with reduced recurrence. Further study is needed to determine whether zinc deficiency represents a pathophysiologic mechanism and target for therapy.}, }
@article {pmid30404941, year = {2019}, author = {Morand, A and Cornu, F and Dufour, JC and Tsimaratos, M and Lagier, JC and Raoult, D}, title = {Human Bacterial Repertoire of the Urinary Tract: a Potential Paradigm Shift.}, journal = {Journal of clinical microbiology}, volume = {57}, number = {3}, pages = {}, doi = {10.1128/JCM.00675-18}, pmid = {30404941}, issn = {1098-660X}, abstract = {The aim of this article is to review the human repertoire of bacteria in urine already described by culture and metagenomic techniques and published in the literature. Our study led us to compare this repertoire with other available human repertoires. We followed automatic and manual bibliographical methods and found 562 bacterial species reported in the literature as part of the human urinary microbiota. Of the 562 species, 322 were described only by culture, 101 by both culture and metagenomics, and 139 only by metagenomics. A total of 352 species (62.6%) have been associated with at least one case report of human infection, of which 225 (40.0%) have been described as causative agents of urinary tract infection. The urinary tract bacterial repertoire contains 21.4% of the known prokaryotic diversity associated with human beings (464 species in common), and it shares 23.6% species with the human gut microbiota (350 species in common, 62.3% of the urine species). The urinary repertoire shares a significant difference in aerointolerant species compared with those of the gut microbiota (100/562 [17.8%] and 505/1,484 [34.0%], respectively; P < 0.001; odds ratio [OR] = 9.0 [7.0 to 11.4]). Studies using high-throughput sequencing show a higher proportion of aerointolerant bacteria in urine (74/240 [30.8%]) than studies using culture techniques (40/423 [9.5%]). Most pathogenic bacteria are part of the commensal human urinary tract bacteria, and their pathogenicity may occur following any imbalance of this microbiota. The restoration of urinary tract health can occur following a fecal transplantation. The potential gut origin of the human bacterial microbiota has to be explored.}, }
@article {pmid30403550, year = {2019}, author = {Ooijevaar, RE and Terveer, EM and Verspaget, HW and Kuijper, EJ and Keller, JJ}, title = {Clinical Application and Potential of Fecal Microbiota Transplantation.}, journal = {Annual review of medicine}, volume = {70}, number = {}, pages = {335-351}, doi = {10.1146/annurev-med-111717-122956}, pmid = {30403550}, issn = {1545-326X}, abstract = {Fecal microbiota transplantation (FMT) is a well-established treatment for recurrent Clostridioides difficile infection. FMT has become a more readily available and useful new treatment option as a result of stool banks. The current state of knowledge indicates that dysbiosis of the gut microbiota is implicated in several disorders in addition to C. difficile infection. Randomized controlled studies have shown FMT to be somewhat effective in treating ulcerative colitis, irritable bowel syndrome, and hepatic encephalopathy. In addition, FMT has been beneficial in treating several other conditions, such as the eradication of multidrug-resistant organisms and graft-versus-host disease. We expect that FMT will soon be implemented as a treatment strategy for several new indications, although further studies are needed.}, }
@article {pmid30400734, year = {2019}, author = {Song, JH and Kim, YS}, title = {Recurrent Clostridium difficile Infection: Risk Factors, Treatment, and Prevention.}, journal = {Gut and liver}, volume = {13}, number = {1}, pages = {16-24}, doi = {10.5009/gnl18071}, pmid = {30400734}, issn = {2005-1212}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridium Infections/etiology/prevention &amp; control/*therapy ; *Clostridium difficile ; Enterocolitis, Pseudomembranous/etiology/prevention &amp; control/*therapy ; Fecal Microbiota Transplantation/methods ; Humans ; Recurrence ; Risk Factors ; Secondary Prevention/*methods ; }, abstract = {The most common cause of antibiotic-associated diarrhea is Clostridium difficile infection (CDI). Recurrent C. difficile infection (rCDI) often occurs after successful treatment of CDI. Due to the increased incidence and the difficulty in treating rCDI, it is becoming an important clinical issue. Identifying risk factors is helpful for early detection, treatment, and prevention of rCDI. Advanced age, use of antibiotics, gastric acid suppression, and infection with a hypervirulent strain are currently regarded as the major risk factors for rCDI. Several treatment modalities, including vancomycin, fidaxomicin, and fecal microbiota transplant (FMT), are suggested for rCDI treatment. However, there is currently no definitive treatment method with sufficient evidence for rCDI. Recent studies have focused on FMT and have shown positive results for rCDI. Prevention of rCDI by measures such as hand washing and isolation of patients is very important. However, these preventive measures are often overlooked in clinical practice. Here, we review the risk factors, treatment, and prevention of rCDI.}, }
@article {pmid30388112, year = {2018}, author = {Jiang, ZD and Jenq, RR and Ajami, NJ and Petrosino, JF and Alexander, AA and Ke, S and Iqbal, T and DuPont, AW and Muldrew, K and Shi, Y and Peterson, C and Do, KA and DuPont, HL}, title = {Safety and preliminary efficacy of orally administered lyophilized fecal microbiota product compared with frozen product given by enema for recurrent Clostridium difficile infection: A randomized clinical trial.}, journal = {PloS one}, volume = {13}, number = {11}, pages = {e0205064}, pmid = {30388112}, issn = {1932-6203}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; }, mesh = {Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Capsules ; Clostridium Infections/*therapy ; Clostridium difficile/*isolation &amp; purification ; Cryopreservation ; Enema/adverse effects/*methods ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; Freeze Drying ; Humans ; Male ; Middle Aged ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) via colonoscopy or enema has become a commonly used treatment of recurrent C. difficile infection (CDI).<br><br>AIMS: To compare the safety and preliminary efficacy of orally administered lyophilized microbiota product compared with frozen product by enema.<br><br>METHODS: In a single center, adults with ≥ 3 episodes of recurrent CDI were randomized to receive encapsulated lyophilized fecal microbiota from 100-200 g of donor feces (n = 31) or frozen FMT from 100 g of donor feces (n = 34) by enema. Safety during the three months post FMT was the primary study objective. Prevention of CDI recurrence during the 60 days after FMT was a secondary objective. Fecal microbiome changes were examined in first 39 subjects studied.<br><br>RESULTS: Adverse experiences were commonly seen in equal frequency in both groups and did not appear to relate to the route of delivery of FMT. CDI recurrence was prevented in 26 of 31 (84%) subjects randomized to capsules and in 30 of 34 (88%) receiving FMT by enema (p = 0.76). Both products normalized fecal microbiota diversity while the lyophilized orally administered product was less effective in repleting Bacteroidia and Verrucomicrobia classes compared to frozen product via enema.<br><br>CONCLUSIONS: The route of delivery, oral or rectal, did not influence adverse experiences in FMT. In preliminary evaluation, both routes appeared to show equivalent efficacy, although the dose may need to be higher for lyophilized product. Spore-forming bacteria appear to be the most important engrafting organisms in FMT by the oral route using lyophilized product.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT02449174.}, }
@article {pmid30385177, year = {2018}, author = {Peng, J and Xiao, X and Hu, M and Zhang, X}, title = {Interaction between gut microbiome and cardiovascular disease.}, journal = {Life sciences}, volume = {214}, number = {}, pages = {153-157}, doi = {10.1016/j.lfs.2018.10.063}, pmid = {30385177}, issn = {1879-0631}, mesh = {Cardiovascular Diseases/etiology/*microbiology/therapy ; Fatty Acids, Volatile/*metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Methylamines/*metabolism ; Probiotics/therapeutic use ; }, abstract = {Traditional cardiovascular risk factors do not underlie all incidence of cardiovascular disease. In recent years, accumulating evidence has demonstrated that gut microbiota and its metabolites also play a pivotal role in the onset and development of cardiovascular disease, including atherosclerosis, hypertension, heart failure, atrial fibrillation and myocardial fibrosis. Trillions of bacteria indwell the gastrointestinal tract and metabolize nutrients into trimethylamine-N-oxide, short-chain fatty acids and so on. Targeting these microorganisms and relevant metabolic pathways has beneficial effects in cardiovascular disease. This review will summarize the role of gut microbiota and its metabolites, mainly trimethylamine-N-oxide, in the pathogenesis of cardiovascular diseases, and discuss the possible mechanisms that drive cardiovascular diseases and highlight potential therapies in this field.}, }
@article {pmid30384952, year = {2018}, author = {Gopalsamy, SN and Woodworth, MH and Wang, T and Carpentieri, CT and Mehta, N and Friedman-Moraco, RJ and Mehta, AK and Larsen, CP and Kraft, CS}, title = {The Use of Microbiome Restoration Therapeutics to Eliminate Intestinal Colonization With Multidrug-Resistant Organisms.}, journal = {The American journal of the medical sciences}, volume = {356}, number = {5}, pages = {433-440}, doi = {10.1016/j.amjms.2018.08.015}, pmid = {30384952}, issn = {1538-2990}, support = {UL1 TR000454/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UM1 AI104681/AI/NIAID NIH HHS/United States ; }, abstract = {Antibiotic resistance (AR) has been described by the World Health Organization as an increasingly serious threat to global public health. Many mechanisms of AR have become widespread due to global selective pressures such as widespread antibiotic use. The intestinal tract is an important reservoir for many multidrug-resistant organisms (MDROs), and next-generation sequencing has expanded understanding of the resistome, defined as the comprehensive sum of genetic determinants of AR. Intestinal decolonization has been explored as a strategy to eradicate MDROs with selective digestive tract decontamination and probiotics being notable examples with mixed results. This review focuses on fecal microbiota transplantation and the early evidence supporting its efficacy in decolonizing MDROs and potential mechanisms of action to reduce AR genes. Current evidence suggests that fecal microbiota transplantation may have promise in restoring healthy microbial diversity and reducing AR, and clinical trials are underway to better characterize its safety and efficacy.}, }
@article {pmid30384951, year = {2018}, author = {Stripling, J and Rodriguez, M}, title = {Current Evidence in Delivery and Therapeutic Uses of Fecal Microbiota Transplantation in Human Diseases-Clostridium difficile Disease and Beyond.}, journal = {The American journal of the medical sciences}, volume = {356}, number = {5}, pages = {424-432}, doi = {10.1016/j.amjms.2018.08.010}, pmid = {30384951}, issn = {1538-2990}, abstract = {The use of fecal microbiota transplantation (FMT) was first described in China in the 4th century by Ge Hong when &quot;yellow soup,&quot; a fecal slurry, was administered for the treatment of severe food poisoning and diarrhea, a practice that continued for centuries. Bedouin groups also consumed stools of their camels as a remedy for dysentery. FMT was also applied in veterinary medicine in Europe in the 16th century. Additional therapeutic use of human excretions was described in Europe in the 18th and 19th century and in World War II, when gut bacteria were administered to German soldiers suffering from dysentery in the North African campaign. More scientifically, Eismann, in 1958, utilized fecal transplantation via enema in 4 patients for the treatment of severe pseudomembranous colitis with success. Following this report a number of isolated cases were published describing the use of FMT by different delivery routes for the treatment of a variety of illnesses.}, }
@article {pmid30376869, year = {2018}, author = {Khoruts, A}, title = {Targeting the microbiome: from probiotics to fecal microbiota transplantation.}, journal = {Genome medicine}, volume = {10}, number = {1}, pages = {80}, pmid = {30376869}, issn = {1756-994X}, mesh = {Dietary Supplements ; *Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Molecular Targeted Therapy ; Probiotics/pharmacology ; }, abstract = {The modern techniques of microbiome science can be applied to the development and evaluation of all microbiota-directed products, including probiotics and fecal microbiota transplantation.}, }
@article {pmid30373736, year = {2018}, author = {Hassoun, A}, title = {Clostridium difficile associated disease.}, journal = {BMJ (Clinical research ed.)}, volume = {363}, number = {}, pages = {k4369}, doi = {10.1136/bmj.k4369}, pmid = {30373736}, issn = {1756-1833}, mesh = {Abdominal Pain/diagnosis ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/diagnosis/microbiology/therapy ; *Clostridium difficile ; Diarrhea/diagnosis ; Digestive System Surgical Procedures ; Fecal Microbiota Transplantation ; Humans ; Practice Guidelines as Topic ; Recurrence ; Risk Factors ; }, }
@article {pmid30372516, year = {2018}, author = {Zare, A and Johansson, AM and Karlsson, E and Delhomme, N and Stenberg, P}, title = {The gut microbiome participates in transgenerational inheritance of low-temperature responses in Drosophila melanogaster.}, journal = {FEBS letters}, volume = {592}, number = {24}, pages = {4078-4086}, doi = {10.1002/1873-3468.13278}, pmid = {30372516}, issn = {1873-3468}, mesh = {Adaptation, Physiological/*genetics ; Animals ; *Cold Temperature ; Drosophila melanogaster/*genetics/microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*genetics ; Gene Expression Profiling ; Inheritance Patterns/*genetics ; Male ; }, abstract = {Environmental perturbations induce transcriptional changes, some of which may be inherited even in the absence of the initial stimulus. Previous studies have focused on transfers through the germline although microbiota is also passed on to the offspring. Thus, we inspected the involvement of the gut microbiome in transgenerational inheritance of environmental exposures in Drosophila melanogaster. We grew flies in the cold versus control temperatures and compared their transcriptional patterns in both conditions as well as in their offspring. F2 flies grew in control temperature, while we controlled their microbiota acquisition from either F1 sets. Transcriptional status of some genes was conserved transgenerationally, and a subset of these genes, mainly expressed in the gut, was transcriptionally dependent on the acquired microbiome.}, }
@article {pmid30370307, year = {2018}, author = {Sun, W and Guo, Y and Zhang, S and Chen, Z and Wu, K and Liu, Q and Liu, K and Wen, L and Wei, Y and Wang, B and Chen, D}, title = {Fecal Microbiota Transplantation Can Alleviate Gastrointestinal Transit in Rats with High-Fat Diet-Induced Obesity via Regulation of Serotonin Biosynthesis.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {8308671}, pmid = {30370307}, issn = {2314-6141}, mesh = {Animals ; Bile Acids and Salts/metabolism ; Diet, High-Fat/*adverse effects ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Transit/*physiology ; Male ; Obesity/*metabolism ; Rats ; Rats, Sprague-Dawley ; Serotonin/*metabolism ; }, abstract = {Aim: We tested the hypothesis that fecal microbiota transplantation (FMT) could regulate the biotransformation of bile acids, such as deoxycholic acid (DCA) and cholic acid (CA), which in turn regulate the biosynthesis of serotonin in the gut and relieve gastrointestinal dysmotility in high-fat diet- (HFD-) induced obesity in rats.<br><br>Methods: Male Sprague-Dawley rats were randomly divided into the control diet group, HFD group, and HFD-fed with receiving FMT. HFD was fed for 12 weeks. At the end of two-week HFD, FMT was carried out for two weeks. The gastrointestinal transit, serotonin concentration, the expression of tryptophan hydroxylase 1 (TPH1) and serotonin reuptake transporter (SERT), and the levels of bile acids in intestinal contents were examined.<br><br>Results: Compared with the control group, the gastrointestinal transit and small intestinal serotonin concentration of HFD-fed rats were increased. In HFD-fed rats, TPH1 protein expression was increased significantly, while SERT protein expression was decreased, but not significant. The levels of CA and DCA in intestinal contents were also significantly increased in HFD-fed rats compared with the control group. After HFD-fed rats receiving FMT treatment, the gastrointestinal transit, small intestinal serotonin concentration, and TPH1 expression were decreased, while SERT expression was not affected. Moreover, the levels of CA and DCA in intestinal contents were also decreased.<br><br>Conclusions: FMT could alleviate small intestinal transit in the HFD-fed rats by regulating the serotonin biosynthesis. In this process, CA and DCA may be related to the regulation of synthesis of serotonin.}, }
@article {pmid30367124, year = {2019}, author = {Brunse, A and Martin, L and Rasmussen, TS and Christensen, L and Skovsted Cilieborg, M and Wiese, M and Khakimov, B and Pieper, R and Nielsen, DS and Sangild, PT and Thymann, T}, title = {Effect of fecal microbiota transplantation route of administration on gut colonization and host response in preterm pigs.}, journal = {The ISME journal}, volume = {13}, number = {3}, pages = {720-733}, doi = {10.1038/s41396-018-0301-z}, pmid = {30367124}, issn = {1751-7370}, abstract = {This study examined gut colonization patterns and host responses to fecal microbiota transplantation (FMT) by different administration routes after preterm birth. In two separate experiments, cesarean-delivered, preterm pigs were administered combined oral + rectal, or exclusively rectal donor feces, and compared with saline controls. After 5 days, stomach and colon bacterial compositions were determined by 16S rRNA gene amplicon sequencing, and organic acid metabolites measured. Further, gut pathology, mucosa bacterial adherence, and goblet cell density were assessed. FMT increased the relative abundance of obligate anaerobes in the colon without affecting total bacterial load. Bacteroides colonized recipients despite low abundance in the donor feces, whereas highly abundant Prevotella and Ruminococcaceae did not. Further, FMT changed carbohydrate metabolism from lactate to propionate production thereby increasing colonic pH. Besides, FMT preserved goblet cell mucin stores and reduced necrotizing enterocolitis incidence. Only rectal FMT increased the stomach-to-colon pH gradient and resistance to mucosa bacterial adhesion. Conversely, oral + rectal FMT increased bacterial adhesion, internal organ colonization, and overall mortality. Our results uncovered distinctions in bacterial colonization patterns along the gastrointestinal tract, as well as host tolerability between oral and rectal FMT administration in preterm newborns. Besides, FMT showed the potential to prevent necrotizing enterocolitis.}, }
@article {pmid30359194, year = {2018}, author = {Kiouptsi, K and Ruf, W and Reinhardt, C}, title = {Microbiota-Derived Trimethylamine.}, journal = {Circulation research}, volume = {123}, number = {10}, pages = {1112-1114}, doi = {10.1161/CIRCRESAHA.118.314039}, pmid = {30359194}, issn = {1524-4571}, }
@article {pmid30359185, year = {2018}, author = {Skye, SM and Zhu, W and Romano, KA and Guo, CJ and Wang, Z and Jia, X and Kirsop, J and Haag, B and Lang, JM and DiDonato, JA and Tang, WHW and Lusis, AJ and Rey, FE and Fischbach, MA and Hazen, SL}, title = {Microbial Transplantation With Human Gut Commensals Containing CutC Is Sufficient to Transmit Enhanced Platelet Reactivity and Thrombosis Potential.}, journal = {Circulation research}, volume = {123}, number = {10}, pages = {1164-1176}, pmid = {30359185}, issn = {1524-4571}, support = {R01 DK101674/DK/NIDDK NIH HHS/United States ; R01 DK106000/DK/NIDDK NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; R01 HL126827/HL/NHLBI NIH HHS/United States ; DP1 DK113598/DK/NIDDK NIH HHS/United States ; R01 DK108259/DK/NIDDK NIH HHS/United States ; T32 HL134622/HL/NHLBI NIH HHS/United States ; S10 OD016346/OD/NIH HHS/United States ; T32 DK007470/DK/NIDDK NIH HHS/United States ; P01 HL030568/HL/NHLBI NIH HHS/United States ; R01 DK110174/DK/NIDDK NIH HHS/United States ; }, abstract = {RATIONALE: Gut microbes influence cardiovascular disease and thrombosis risks through the production of trimethylamine N-oxide (TMAO). Microbiota-dependent generation of trimethylamine (TMA)-the precursor to TMAO-is rate limiting in the metaorganismal TMAO pathway in most humans and is catalyzed by several distinct microbial choline TMA-lyases, including the proteins encoded by the cutC/D (choline utilization C/D) genes in multiple human commensals.<br><br>OBJECTIVE: Direct demonstration that the gut microbial cutC gene is sufficient to transmit enhanced platelet reactivity and thrombosis potential in a host via TMA/TMAO generation has not yet been reported.<br><br>METHODS AND RESULTS: Herein, we use gnotobiotic mice and a series of microbial colonization studies to show that microbial cutC-dependent TMA/TMAO production is sufficient to transmit heightened platelet reactivity and thrombosis potential in a host. Specifically, we examine in vivo thrombosis potential employing germ-free mice colonized with either high TMA-producing stable human fecal polymcrobial communities or a defined CutC-deficient background microbial community coupled with a CutC-expressing human commensal±genetic disruption of its cutC gene (ie, Clostridium sporogenes Δ cutC).<br><br>CONCLUSIONS: Collectively, these studies point to the microbial choline TMA-lyase pathway as a rational molecular target for the treatment of atherothrombotic heart disease.}, }
@article {pmid30357440, year = {2019}, author = {Li, P and Zhang, T and Xiao, Y and Tian, L and Cui, B and Ji, G and Liu, YY and Zhang, F}, title = {Timing for the second fecal microbiota transplantation to maintain the long-term benefit from the first treatment for Crohn's disease.}, journal = {Applied microbiology and biotechnology}, volume = {103}, number = {1}, pages = {349-360}, doi = {10.1007/s00253-018-9447-x}, pmid = {30357440}, issn = {1432-0614}, support = {201502026//Special Scientific Research Fund of Public Welfare Profession of National Health and Family Planning Commission/ ; Zhang F//Jiangsu Province Creation Team and Leading Talents project/ ; 81670495//National Natural Science Foundation of China/ ; 81600417//National Natural Science Foundation of China/ ; 2015BAI13B07//National Clinical Research Center for Digestive Diseases/ ; BE2018751//Jiangsu Province Society Development project (CN)/ ; }, mesh = {Adult ; Crohn Disease/microbiology/*therapy ; Dysbiosis/microbiology ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/genetics ; Humans ; Male ; Middle Aged ; RNA, Ribosomal, 16S ; Time Factors ; Treatment Outcome ; Urinalysis/methods ; }, abstract = {Increasing evidence has shown that fecal microbiota transplantation (FMT) could be a promising treatment option for Crohn's disease (CD). However, the frequency of FMT for CD treatment remains unclear. This study aimed to evaluate the optimal timing for administering the second course of FMT to maintain the long-term clinical effects from the first FMT for patients with CD. Sixty-nine patients with active CD who underwent FMT twice and benefited from the first FMT were enrolled in this study. Clinical response, stool microbiota, and urine metabolome of patients were assessed during the follow-up. The median time of maintaining clinical response to the first FMT in total 69 patients was 125 days (IQR, 82.5-225.5). The time of maintaining clinical response to the second FMT in 56 of 69 patients was 176.5 days (IQR, 98.5-280). The fecal microbiota composition of each patient post the first FMT was closer to that of his/her donor. Compared to that of the baseline, patients prior to the second course of FMT showed significant differences in urinary metabolic profiles characterized by increased indoxyl sulfate, 4-hydroxyphenylacetate, creatinine, dimethylamine, glycylproline, hippurate, and trimethylamine oxide (TMAO). This study demonstrated that patients with CD could be administered the second course of FMT less than 4 months after the first FMT for maintaining the clinical benefits from the first FMT. This was supported by the host-microbial metabolism changes in patients with active CD. Trial registration: ClinicalTrials.gov , NCT01793831. Registered 18 February 2013. https://clinicaltrials.gov/ct2/show/NCT01793831?term=NCT01793831&amp;rank=1.}, }
@article {pmid30355801, year = {2018}, author = {Battaglioli, EJ and Hale, VL and Chen, J and Jeraldo, P and Ruiz-Mojica, C and Schmidt, BA and Rekdal, VM and Till, LM and Huq, L and Smits, SA and Moor, WJ and Jones-Hall, Y and Smyrk, T and Khanna, S and Pardi, DS and Grover, M and Patel, R and Chia, N and Nelson, H and Sonnenburg, JL and Farrugia, G and Kashyap, PC}, title = {Clostridioides difficile uses amino acids associated with gut microbial dysbiosis in a subset of patients with diarrhea.}, journal = {Science translational medicine}, volume = {10}, number = {464}, pages = {}, doi = {10.1126/scitranslmed.aam7019}, pmid = {30355801}, issn = {1946-6242}, support = {R03 DK111850/DK/NIDDK NIH HHS/United States ; K08 DK100638/DK/NIDDK NIH HHS/United States ; K23 DK103911/DK/NIDDK NIH HHS/United States ; R01 DK114007/DK/NIDDK NIH HHS/United States ; R01 CA179243/CA/NCI NIH HHS/United States ; P30 DK084567/DK/NIDDK NIH HHS/United States ; }, abstract = {The gut microbiota plays a critical role in pathogen defense. Studies using antibiotic-treated mice reveal mechanisms that increase susceptibility to Clostridioides difficile infection (CDI), but risk factors associated with CDI in humans extend beyond antibiotic use. Here, we studied the dysbiotic gut microbiota of a subset of patients with diarrhea and modeled the gut microbiota of these patients by fecal transplantation into germ-free mice. When challenged with C. difficile, the germ-free mice transplanted with fecal samples from patients with dysbiotic microbial communities showed increased gut amino acid concentrations and greater susceptibility to CDI. A C. difficile mutant that was unable to use proline as an energy source was unable to robustly infect germ-free mice transplanted with a dysbiotic or healthy human gut microbiota. Prophylactic dietary intervention using a low-proline or low-protein diet in germ-free mice colonized by a dysbiotic human gut microbiota resulted in decreased expansion of wild-type C. difficile after challenge, suggesting that amino acid availability might be important for CDI. Furthermore, a prophylactic fecal microbiota transplant in mice with dysbiosis reduced proline availability and protected the mice from CDI. Last, we identified clinical risk factors that could potentially predict gut microbial dysbiosis and thus greater susceptibility to CDI in a retrospective cohort of patients with diarrhea. Identifying at-risk individuals and reducing their susceptibility to CDI through gut microbiota-targeted therapies could be a new approach to preventing C. difficile infection in susceptible patients.}, }
@article {pmid30353027, year = {2018}, author = {Lai, ZL and Tseng, CH and Ho, HJ and Cheung, CKY and Lin, JY and Chen, YJ and Cheng, FC and Hsu, YC and Lin, JT and El-Omar, EM and Wu, CY}, title = {Fecal microbiota transplantation confers beneficial metabolic effects of diet and exercise on diet-induced obese mice.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {15625}, pmid = {30353027}, issn = {2045-2322}, abstract = {Diet and exercise are conventional methods for controlling body weight and are linked to alterations in gut microbiota. However, the associations of diet, exercise, and gut microbiota in the control of obesity remain largely unknown. In the present study, using 16S rRNA amplicon sequencing and fecal microbiota transplantation (FMT), normal fat diet (NFD), exercise and their combination resulted in improved metabolic profiles in comparison to sedentary lifestyle with high fat diet (HFD). Moreover, diet exerted more influence than exercise in shaping the gut microbiota. HFD-fed mice receiving FMT from NFD-exercised donors not only showed remarkably reduced food efficacy, but also mitigated metabolic profiles (p < 0.05). The transmissible beneficial effects of FMT were associated with bacterial genera Helicobacter, Odoribacter and AF12 and overrepresentation of oxidative phosphorylation and glycolysis genes. Our findings demonstrate that the beneficial effects of diet and exercise are transmissible via FMT, suggesting a potential therapeutic treatment for obesity.}, }
@article {pmid30345252, year = {2018}, author = {Yodoshi, T and Hurt, TL}, title = {Fecal Microbiota Transplantation to Patients with Refractory Very Early Onset Ulcerative Colitis.}, journal = {Pediatric gastroenterology, hepatology &amp; nutrition}, volume = {21}, number = {4}, pages = {355-360}, pmid = {30345252}, issn = {2234-8646}, abstract = {Recently, fecal microbiota transplantation (FMT) has been attracting attention as a possible medical treatment of ulcerative colitis (UC). A randomized controlled trial of FMT for children with UC is currently underway. Therapeutic effects of FMT for adults with UC remain controversial. We report two cases of early-onset UC in children. A patient was diagnosed with UC at age 1-year 9-month and underwent FMT at age 2-year 3-month. He attained clinical remission for three weeks after FMT, but then relapsed at four weeks, ultimately undergoing a total colectomy. Another child was diagnosed with UC at 2-year 10-month and she underwent FMT at age 5 years. She has remained in clinical remission following FMT for 24 months and her UC has been maintained without complications with tacrolimus and azathioprine. We report that FMT for early-onset UC appears to be safe and potentially effective.}, }
@article {pmid30342053, year = {2018}, author = {Vallianou, NG and Stratigou, T and Tsagarakis, S}, title = {Microbiome and diabetes: Where are we now?.}, journal = {Diabetes research and clinical practice}, volume = {146}, number = {}, pages = {111-118}, doi = {10.1016/j.diabres.2018.10.008}, pmid = {30342053}, issn = {1872-8227}, mesh = {Animals ; Diabetes Mellitus, Type 2/*microbiology ; Dysbiosis/*microbiology ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*genetics ; Humans ; Mice ; Prebiotics/*microbiology ; Probiotics/*metabolism ; }, abstract = {Alterations in the diversity or structure of gut microbiota known as dysbiosis, may affect metabolic activities, resulting in metabolic disorders, such as obesity and diabetes. The development of more sophisticated methods, such as metagenomics sequencing, PCR-denaturing gradient gel electrophoresis, microarrays and fluorescence in situ hybridization, has expanded our knowledge on gut microbiome. Dysbiosis has been related to increased plasma concentrations of gut microbiota-derived lipopolysaccharide (LPS), which triggers the production of a variety of cytokines and the recruitment of inflammatory cells. Metabolomics have demonstrated that butyrate and propionate suppress weight gain in mice with high fat diet-induced obesity, and acetate has been proven to reduce food intake in healthy mice. The role of prebiotics, probiotics, genetically modified bacteria and fecal microbiota transplantation, as potential therapeutic challenges for type 2 diabetes will be discussed in this review.}, }
@article {pmid30339501, year = {2019}, author = {Elkrief, A and Derosa, L and Zitvogel, L and Kroemer, G and Routy, B}, title = {The intimate relationship between gut microbiota and cancer immunotherapy.}, journal = {Gut microbes}, volume = {10}, number = {3}, pages = {424-428}, doi = {10.1080/19490976.2018.1527167}, pmid = {30339501}, issn = {1949-0984}, abstract = {Immunotherapy is widely used to treat a large variety of malignancies and has revolutionized the therapeutic approach to cancer. Major efforts are ongoing to identify biomarkers that predict response to immunotherapy as well as new strategies to improve ICI efficacy and clinical outcomes. Studies have shown that the gut microbiome determines the extent to which ICIs may invigorate the anticancer immune response. Here, the authors review recent studies that have described the effects of the gut microbiota on the efficacy of CTLA-4 and PD-1 inhibitors and outline potential future clinical directions of these findings.}, }
@article {pmid30338410, year = {2018}, author = {Chen, X and Devaraj, S}, title = {Gut Microbiome in Obesity, Metabolic Syndrome, and Diabetes.}, journal = {Current diabetes reports}, volume = {18}, number = {12}, pages = {129}, pmid = {30338410}, issn = {1539-0829}, abstract = {PURPOSE OF REVIEW: Obesity and diabetes are worldwide epidemics. There is also a growing body of evidence relating the gut microbiome composition to insulin resistance. The purpose of this review is to delineate the studies linking gut microbiota to obesity, metabolic syndrome, and diabetes.<br><br>RECENT FINDINGS: Animal studies as well as proof of concept studies using fecal transplantation demonstrate the pivotal role of the gut microbiota in regulating insulin resistance states and inflammation. While we still need to standardize methodologies to study the microbiome, there is an abundance of evidence pointing to the link between gut microbiome, inflammation, and insulin resistance, and future studies should be aimed at identifying unifying mechanisms.}, }
@article {pmid30337038, year = {2018}, author = {Pesce, M and Borrelli, O and Saliakellis, E and Thapar, N}, title = {Gastrointestinal Neuropathies: New Insights and Emerging Therapies.}, journal = {Gastroenterology clinics of North America}, volume = {47}, number = {4}, pages = {877-894}, doi = {10.1016/j.gtc.2018.07.011}, pmid = {30337038}, issn = {1558-1942}, mesh = {Enteric Nervous System/*pathology/*physiopathology ; Gastrointestinal Diseases/diagnosis/*etiology/*therapy ; Gastrointestinal Motility/*physiology ; Humans ; }, abstract = {The bewildering complexity of the enteric nervous system makes it susceptible to develop a wide array of motility disorders, collectively called enteric neuropathies. These gastrointestinal conditions are among the most challenging to manage, mainly given poor characterization of their etiopathophysiology and outcomes. Not surprisingly, therefore, targeted or curative therapies for enteric neuropathies are lacking and management is largely symptomatic. Nonetheless, recent advances in neurogastroenterology have witnessed improvements in established strategies, such as intestinal transplantation and the emergence of new treatments including novel drugs, electrical pacing, and manipulation of fecal microbiota, as well as stem cell and gene therapy.}, }
@article {pmid30328062, year = {2018}, author = {Wang, H and Cui, B and Li, Q and Ding, X and Li, P and Zhang, T and Yang, X and Ji, G and Zhang, F}, title = {The Safety of Fecal Microbiota Transplantation for Crohn's Disease: Findings from A Long-Term Study.}, journal = {Advances in therapy}, volume = {35}, number = {11}, pages = {1935-1944}, pmid = {30328062}, issn = {1865-8652}, support = {81670495//China National Science Foundation/ ; 81600417//China National Science Foundation/ ; 2015BAI13B07//National Clinical Research Center for Digestive Diseases/ ; }, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) has been used as a potential treatment option for Crohn's disease (CD). However, there is still lack of safety and efficacy evidence based on large samples of CD undergoing FMT. This study aimed to evaluate the risk factors of adverse event (AE) in the long term and the efficacy of FMT in the short term for patients with CD.<br><br>METHODS: FMT via mid-gut for mild to severe CD in a single center trial (NCT01793831) was performed from October 2012 to December 2016. The possible factors with AE and efficacy after FMT were prospectively recorded.<br><br>RESULTS: A total of 184 frequencies of FMT were performed for 139 patients who received FMT. During 1 month after FMT, 13.6% of mild AEs occurred, including increased frequency of defecation, fever, abdominal pain, flatulence, hematochezia, vomiturition, bloating and herpes zoster. No AE beyond 1 month was observed. Therefore, a 1 month cut-off could be suggested to define short-term and long-term AEs of FMT. Among the possible risk factors, only fecal microbiota purification methods were closely associated with the occurrence of AEs. The rate of AEs in patients undergoing manual methods for the preparation of fecal microbiota was 21.7%, which was significantly higher than the 8.7% in those experiencing an automatic method. The manual or automatic purification of fecal microbiota had no correlation with the efficacy of FMT.<br><br>CONCLUSION: This cohort study based on the largest size of cases demonstrated that improved fecal microbiota preparation reduced the rates of AEs, but did not affect the clinical efficacy in patients with CD.}, }
@article {pmid30323765, year = {2018}, author = {Li, J and Cui, H and Cai, Y and Lin, J and Song, X and Zhou, Z and Xiong, W and Zhou, H and Bian, Y and Wang, L}, title = {Tong-Xie-Yao-Fang Regulates 5-HT Level in Diarrhea Predominant Irritable Bowel Syndrome Through Gut Microbiota Modulation.}, journal = {Frontiers in pharmacology}, volume = {9}, number = {}, pages = {1110}, pmid = {30323765}, issn = {1663-9812}, abstract = {Tong-Xie-Yao-Fang (TXYF) has been widely used for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) in traditional Chinese medicine. However, its mechanism of action in the treatment of IBS-D remains to be fully understood. Recent reports have shown that Clostridium species in the gut can induce 5-HT production in the colon, which then contributes to IBS-D. Due to the wide use of TXYF in the clinical treatment of IBS-D and the close relationship between gut microbiota and IBS-D, we hypothesize that TXYF treats IBS-D by modulating gut microbiota and regulating colonic 5-HT levels. In this study, variation analysis of 16S rRNA was conducted to evaluate changes in the distribution of gut microbiota in IBS-D model rats after TXYF treatment. Moreover, we investigated whether TXYF could affect colonic 5-HT levels in IBS-D model rats. We then performed fecal transplantation experiments to confirm the effects of TXYF on gut microbiota and 5-HT levels. We found that TXYF treatment can ameliorate IBS-D and regulate 5-HT levels in colon tissue homogenates. TXYF treatment also affected the diversity of gut microbiota and altered the relative abundance of Akkermansia and Clostridium sensu stricto 1 in gut flora populations. Finally, we showed that fecal transplantation from TXYF-treated rats could relieve IBS-D and regulate 5-HT levels in colon tissue homogenates. In conclusion, the present study demonstrates that TXYF treatment diminishes colonic 5-HT levels and alleviates the symptoms of IBS-D by favorably affecting microbiota levels in gut flora communities.}, }
@article {pmid30320666, year = {2019}, author = {Cho, S and Spencer, E and Hirten, R and Grinspan, A and Dubinsky, MC}, title = {Fecal Microbiota Transplant for Recurrent Clostridium difficile Infection in Pediatric Inflammatory Bowel Disease.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {68}, number = {3}, pages = {343-347}, doi = {10.1097/MPG.0000000000002172}, pmid = {30320666}, issn = {1536-4801}, abstract = {OBJECTIVES: Recurrent Clostridium difficile infection (RCDI) increases morbidity and mortality in patients with inflammatory bowel disease (IBD). Fecal microbiota transplant (FMT) is known to be very effective for RCDI in non-IBD patients with cure rates up to 91%. The same success rates of FMT have not been reported in patients with IBD with RCDI, and the data in pediatrics are limited. We aimed to determine the effectiveness of FMT for RCDI in established pediatric patients with IBD.<br><br>METHODS: We performed a retrospective chart review of pediatric patients with IBD and RCDI (≥3 episodes) who underwent FMT via colonoscopy at a tertiary care IBD center. The primary outcome was the rate of RCDI within 60 days post-FMT. The secondary outcomes were recurrence rate by 6 months, rate of colectomy, and time to recurrence.<br><br>RESULTS: Of the 8 eligible patients, 6 had ulcerative colitis, 1 had IBD-unspecified, and 1 had Crohn disease. Median (interquartile range) age was 13 (11-14) years. All patients were on vancomycin at FMT. Two patients (25%) had RCDI by 60 days post-FMT and another 3 patients had RCDI between 60 days and 6 months. The median time to recurrence was 101 (40-139) days. Two patients (25%) who developed recurrence went to colectomy after FMT.<br><br>CONCLUSIONS: With a cure rate of 75% at 60 days, FMT administered for the treatment of RCDI may be an effective treatment option in pediatric IBD. However, there appears to be a significant rate of late recurrence of C difficile infection after 60 days in these patients.}, }
@article {pmid30320222, year = {2018}, author = {Cheng, S and Ma, X and Geng, S and Jiang, X and Li, Y and Hu, L and Li, J and Wang, Y and Han, X}, title = {Fecal Microbiota Transplantation Beneficially Regulates Intestinal Mucosal Autophagy and Alleviates Gut Barrier Injury.}, journal = {mSystems}, volume = {3}, number = {5}, pages = {}, pmid = {30320222}, issn = {2379-5077}, abstract = {Fecal microbiota transplantation (FMT) is one of the most effective ways to regulate the gut microbiota. Here, we investigated the effect of exogenous fecal microbiota on gut function from the perspective of analysis of the mucosal proteomes in a piglet model. A total of 289 differentially expressed proteins were annotated with 4,068 gene ontology (GO) function entries in the intestinal mucosa, and the levels of autophagy-related proteins in the forkhead box O (FoxO) signaling pathway were increased whereas the levels of proteins related to inflammation response were decreased in the recipient. Then, to assess the alleviation of epithelial injury in the Escherichia coli K88-infected piglets following FMT, intestinal microbiome-metabolome responses were determined. 16S rRNA gene sequencing showed that the abundances of beneficial bacteria, such as Lactobacillus and Succinivibrio, were increased whereas those of Enterobacteriaceae and Proteobacteria bacteria were decreased in the infected piglets following FMT. Metabolomic analysis revealed that levels of 58 metabolites, such as lactic acid and succinic acid, were enhanced in the intestinal lumen and that seven metabolic pathways, such as branched-chain amino acid metabolism pathways, were upregulated in the infected piglets following FMT. In concordance with the metabolome data, results of metagenomics prediction analysis also demonstrated that FMT modulated the metabolic functions of gut microbiota associated with linoleic acid metabolism. In addition, intestinal morphology was improved, a result that coincided with the decrease of intestinal permeability and the enhancement of mucins and mucosal expression of tight junction proteins in the recipient. Taken together, the results showed that FMT triggered intestinal mucosal protective autophagy and alleviated gut barrier injury through alteration of the gut microbial structure. IMPORTANCE The gut microbiota plays a crucial role in human and animal health, and its disorder causes multiple diseases. Over the past decade, FMT has gained increasing attention due to the success in treating Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). Although FMT appears to be effective, how FMT functions in the recipient remains unknown. Whether FMT exerts this beneficial effect through a series of changes in the host organism caused by alteration of gut microbial structure is also not known. In the present study, newborn piglets and E. coli K88-infected piglets were selected as models to explore the interplay between host and gut microbiota following FMT. Our results showed that FMT triggered intestinal mucosal autophagy and alleviated gut barrier injury caused by E. coli K88. This report provides a theoretical basis for the use of FMT as a viable therapeutic method for gut microbial regulation.}, }
@article {pmid30319644, year = {2018}, author = {Qi, X and Li, X and Zhao, Y and Wu, X and Chen, F and Ma, X and Zhang, F and Wu, D}, title = {Treating Steroid Refractory Intestinal Acute Graft-vs.-Host Disease With Fecal Microbiota Transplantation: A Pilot Study.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {2195}, pmid = {30319644}, issn = {1664-3224}, abstract = {Patients with steroid refractory gastrointestinal (GI) tract graft- vs.-host disease (GvHD) face a poor prognosis and limited therapeutic options. To accurately assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating steroid refractory GI tract GvHD, we conducted a pilot study involving eight patients. Having received FMTs, all patients' clinical symptoms relieved, bacteria enriched, and microbiota composition reconstructed. Compared to those who did not receive FMT, these eight patients achieved a higher progression-free survival. FMT can serve as a therapeutic option for GI tract aGVHD, but its effectiveness and safety need further evaluations. Clinical Trial Registration: NCT03148743.}, }
@article {pmid30319571, year = {2018}, author = {Zuo, T and Ng, SC}, title = {The Gut Microbiota in the Pathogenesis and Therapeutics of Inflammatory Bowel Disease.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2247}, pmid = {30319571}, issn = {1664-302X}, abstract = {In the twenty first century, the changing epidemiology of inflammatory bowel disease (IBD) globally with increasing disease incidence across many countries relates to the altered gut microbiota, due to a combinatorial effect of environmental factors, human immune responses and genetics. IBD is a gastrointestinal disease associated with a gut microbial dysbiosis, including an expansion of facultative anaerobic bacteria of the family Enterobacteriaceae. Advances in high-throughput sequencing enable us to entangle the gut microbiota in human health and IBD beyond the gut bacterial microbiota, expanding insights into the mycobiota, virobiota and helminthes. Caudovirales (viruses) and Basidiomycota, Ascomycota, and Candida albicans (fungi) are revealed to be increased in IBD. The deconvolution of the gut microbiota in IBD lays the basis for unveiling the roles of these various gut microbiota components in IBD pathogenesis and being conductive to instructing on future IBD diagnosis and therapeutics. Here we comprehensively elucidate the alterations in the gut microbiota in IBD, discuss the effect of diets in the gut microbiota in relation to IBD, and illustrate the potential of manipulation of gut microbiota for IBD therapeutics. The therapeutic strategy of antibiotics, prebiotics, probiotics and fecal microbiota transplantation will benefit the effective application of precision microbiome manipulation in IBD.}, }
@article {pmid30310254, year = {2018}, author = {Camara-Lemarroy, CR and Metz, LM and Yong, VW}, title = {Focus on the gut-brain axis: Multiple sclerosis, the intestinal barrier and the microbiome.}, journal = {World journal of gastroenterology}, volume = {24}, number = {37}, pages = {4217-4223}, pmid = {30310254}, issn = {2219-2840}, mesh = {Animals ; Bile Acids and Salts/chemistry ; Brain/physiopathology ; Central Nervous System/physiology ; Clinical Trials as Topic ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gastrointestinal Tract ; Humans ; Immune System ; Intestines/physiology ; Multiple Sclerosis/*microbiology/*physiopathology ; Probiotics ; }, abstract = {The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.}, }
@article {pmid30302341, year = {2018}, author = {Fang, H and Fu, L and Wang, J}, title = {Protocol for Fecal Microbiota Transplantation in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {8941340}, pmid = {30302341}, issn = {2314-6141}, mesh = {Adolescent ; Adult ; Child ; Cohort Studies ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Inflammatory Bowel Diseases/*therapy ; Middle Aged ; Publication Bias ; Randomized Controlled Trials as Topic ; Systematic Reviews as Topic ; Young Adult ; }, abstract = {Background: Fecal microbiota transplantation (FMT) is an emerging treatment approach for inflammatory bowel disease (IBD). The donor selection, the separation of fecal bacteria, the frequency of FMT, the way of infusion, the long-term safety, and efficacy are still uncertain.<br><br>Aim: To further study the efficacy and safety and protocol of FMT for IBD.<br><br>Methods: A systematic review and meta-analysis were conducted until February, 2018. Clinical remission was established as the primary outcome.<br><br>Results: A total of 596 paediatric and adult IBD patients were enrolled, and 459 patients received FMT therapy. 28.8% (132/459) patients achieved clinical remission during follow-up. 53% (241/459) patients achieved clinical response. The pooled estimated clinical remission for ulcerative colitis (UC) was 21% (95% CI: 8%-37%) and 30% (95% CI: 11%-52%) for Crohn's disease (CD), both with a risk of heterogeneity; 10% (95% CI: 0%-43%) for paediatric UC; 26% (95% CI: 10%-48%) for adult UC; 45% for paediatric CD (95% CI: 24%-66%); 22% (95% CI: 3%-52%) for adult CD. Meta-analysis of cohort studies showed that moderate-severe IBD patients could achieve more significant remission from FMT than mild-moderate patients (P=0.037). Delivery route has no impact on the efficacy of FMT in UC and CD. Based on current available evidence, a trend was observed towards higher clinical remission rate of frozen stool FMT than that of fresh stool for UC, while there was no significant difference between fresh and frozen FMT for CD. The optimal donor stool for FMT is still uncertain. Meta-analysis of RCTs showed that FMT treatment achieved significantly higher clinical remission rate than placebo for UC (28% versus 9%, P=0.0003).<br><br>Conclusion: FMT is an effective and safe therapy for both paediatric and adult IBD; fresh or frozen donor stool, delivery route, and antibiotic pretreatment or not have no impact on the efficacy of FMT in IBD. FMT might be a potential rescue therapy and even an initial standardized therapy for IBD. However, few data exist on long-term safety and efficacy and further validation is needed.}, }
@article {pmid30301167, year = {2018}, author = {Paule, A and Frezza, D and Edeas, M}, title = {Microbiota and Phage Therapy: Future Challenges in Medicine.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {6}, number = {4}, pages = {}, doi = {10.3390/medsci6040086}, pmid = {30301167}, issn = {2076-3271}, abstract = {An imbalance of bacterial quantity and quality of gut microbiota has been linked to several pathologies. New strategies of microbiota manipulation have been developed such as fecal microbiota transplantation (FMT); the use of pre/probiotics; an appropriate diet; and phage therapy. The presence of bacteriophages has been largely underestimated and their presence is a relevant component for the microbiome equilibrium. As a promising treatment, phage therapy has been extensively used in Eastern Europe to reduce pathogenic bacteria and has arisen as a new method to modulate microbiota diversity. Phages have been selected and &quot;trained&quot; to infect a wide spectrum of bacteria or tailored to infect specific antibiotic resistant bacteria present in patients. The new development of genetically modified phages may be an efficient tool to treat the gut microbiota dysbiosis associated with different pathologies and increased production of bacterial metabolites and subsequently decrease systemic low-grade chronic inflammation associated with chronic diseases. Microbiota quality and mitochondria dynamics can be remodulated and manipulated by phages to restore the equilibrium and homeostasis of the system. Our aim is to highlight the great interest for phages not only to eliminate and control pathogenic bacterial infection but also in the near future to modulate the microbiota by adding new functions to selected bacteria species and rebalance the dynamic among phages and bacteria. The challenge for the medicine of tomorrow is to re-think and redesign strategies differently and far from our traditional thinking.}, }
@article {pmid30300561, year = {2018}, author = {Paknikar, R and Pekow, J}, title = {Fecal Microbiota Transplantation for the Management of Clostridium difficile Infection.}, journal = {Surgical infections}, volume = {19}, number = {8}, pages = {785-791}, doi = {10.1089/sur.2018.221}, pmid = {30300561}, issn = {1557-8674}, abstract = {The clinical burden of Clostridium difficile infection (CDI) continues to grow. Despite the multitude of treatment options that have been developed and tested to combat the morbidity and death associated with CDI, recurrence remains common. As such, treatment modalities such as fecal microbiota transplantation (FMT) have become studied increasingly; FMT serves to transplant stool from carefully selected healthy subjects into C. difficile positive patients through a variety of delivery routes. In doing so, FMT is hypothesized to correct dysbiosis of the recipient gut microbiome addressing the root cause of the pathogenesis of C. difficile infection. A growing body of evidence shows FMT to be efficacious in this setting, and the study of FMT accordingly continues to evolve to identify novel indications for its utilization.}, }
@article {pmid30290648, year = {2018}, author = {Wen, W and Zhang, H and Shen, J and Wei, L and Shen, S}, title = {Fecal microbiota transplantation for patients with irritable bowel syndrome: A meta-analysis protocol.}, journal = {Medicine}, volume = {97}, number = {40}, pages = {e12661}, pmid = {30290648}, issn = {1536-5964}, mesh = {Fecal Microbiota Transplantation/*methods ; Humans ; Irritable Bowel Syndrome/*therapy ; Quality of Life ; Randomized Controlled Trials as Topic ; Research Design ; }, abstract = {Irritable bowel syndrome (IBS) is a common functional bowel disease characterized by chronic or recurrent abdominal pain, bloating, constipation, and diarrhea. Many patients with IBS have a poor quality of life due to abdominal discomfort, diarrhea, constipation, and the presence of other diseases. At present, intestinal motility inhibitors, adsorbents, astringents, intestinal mucosal protective agents, and antidepressants have been combined to treat IBS, but the treatment process is long, which results in a large economic burden to patients. Fecal microbiota transplantation (FMT) is a treatment involving the transplantation of functional bacteria from healthy human feces into the gastrointestinal tract of patients; thus, replacing the intestinal flora and modulating intestinal and extra-intestinal diseases. In recent years, the efficacy and economic benefits of FMT in the treatment of IBS have received increasing attention from researchers.A search for randomized controlled trials (RCTs) on treating IBS with FMT will be performed using 9 databases, including PubMed, the Cochrane Library, Embase, ClinicalTrails, China National Knowledge Infrastructure, Sino Med, ScienceDirect, VIP, and Wanfang Data. Two reviewers will independently screen data extraction studies and assess study quality and risk of bias. The risk of bias for each RCT will be assessed against the Cochrane Handbook standards to assess methodological quality. RevMan V.5.3 software will be used to calculate data synthesis when meta-analysis is allowed.This study will provide a high-quality synthesis of existing evidence on the effectiveness and safety of FMT in the treatment of IBS.This study will determine if FMT is an effective and safe intervention for IBS.PROSPERO registration number is PROSPERO CRD42018108080.}, }
@article {pmid30283047, year = {2019}, author = {Warner, BB}, title = {The contribution of the gut microbiome to neurodevelopment and neuropsychiatric disorders.}, journal = {Pediatric research}, volume = {85}, number = {2}, pages = {216-224}, doi = {10.1038/s41390-018-0191-9}, pmid = {30283047}, issn = {1530-0447}, abstract = {Bidirectional communication between the gut and brain is well recognized, with data now accruing for a specific role of the gut microbiota in that link, referred to as the microbiome-gut-brain axis. This review will discuss the emerging role of the gut microbiota in brain development and behavior. Animal studies have clearly demonstrated effects of the gut microbiota on gene expression and neurochemical metabolism impacting behavior and performance. Based on these changes, a modulating role of the gut microbiota has been demonstrated for a variety of neuropsychiatric disorders, including depression, anxiety, and movement including Parkinson's, and importantly for the pediatric population autism. Critical developmental windows that influence early behavioral outcomes have been identified that include both the prenatal environment and early postnatal colonization periods. The clearest data regarding the role of the gut microbiota on neurodevelopment and psychiatric disorders is from animal studies; however, human data have begun to emerge, including an association between early colonization patterns and cognition. The importance of understanding the contribution of the gut microbiota to the development and functioning of the nervous system lies in the potential to intervene using novel microbial-based approaches to treating neurologic conditions. While pathways of communication between the gut and brain are well established, the gut microbiome is a new component of this axis. The way in which organisms that live in the gut influence the central nervous system (CNS) and host behavior is likely to be multifactorial in origin. This includes immunologic, endocrine, and metabolic mechanisms, all of which are pathways used for other microbial-host interactions. Germ-free (GF) mice are an important model system for understanding the impact of gut microbes on development and function of the nervous system. Alternative animal model systems have further clarified the role of the gut microbiota, including antibiotic treatment, fecal transplantation, and selective gut colonization with specific microbial organisms. Recently, researchers have started to examine the human host as well. This review will examine the components of the CNS potentially influenced by the gut microbiota, and the mechanisms mediating these effects. Links between gut microbial colonization patterns and host behavior relevant to a pediatric population will be examined, highlighting important developmental windows in utero or early in development.}, }
@article {pmid30282817, year = {2018}, author = {Bromberg, JS and Hittle, L and Xiong, Y and Saxena, V and Smyth, EM and Li, L and Zhang, T and Wagner, C and Fricke, WF and Simon, T and Brinkman, CC and Mongodin, EF}, title = {Gut microbiota-dependent modulation of innate immunity and lymph node remodeling affects cardiac allograft outcomes.}, journal = {JCI insight}, volume = {3}, number = {19}, pages = {}, pmid = {30282817}, issn = {2379-3708}, support = {R01 AI114496/AI/NIAID NIH HHS/United States ; }, abstract = {We hypothesized that the gut microbiota influences survival of murine cardiac allografts through modulation of immunity. Antibiotic pretreated mice received vascularized cardiac allografts and fecal microbiota transfer (FMT), along with tacrolimus immunosuppression. FMT source samples were from normal, pregnant (immune suppressed), or spontaneously colitic (inflammation) mice. Bifidobacterium pseudolongum (B. pseudolongum) in pregnant FMT recipients was associated with prolonged allograft survival and lower inflammation and fibrosis, while normal or colitic FMT resulted in inferior survival and worse histology. Transfer of B. pseudolongum alone resulted in reduced inflammation and fibrosis. Stimulation of DC and macrophage lines with B. pseudolongum induced the antiinflammatory cytokine IL-10 and homeostatic chemokine CCL19 but induced lesser amounts of the proinflammatory cytokines TNFα and IL-6. In contrast, LPS and Desulfovibrio desulfuricans (D. desulfuricans), more abundant in colitic FMT, induced a more inflammatory cytokine response. Analysis of mesenteric and peripheral lymph node structure showed that B. pseudolongum gavage resulted in a higher laminin α4/α5 ratio in the lymph node cortical ridge, indicative of a suppressive environment, while D. desulfuricans resulted in a lower laminin α4/α5 ratio, supportive of inflammation. Discrete gut bacterial species alter immunity and may predict graft outcomes through stimulation of myeloid cells and shifts in lymph node structure and permissiveness.}, }
@article {pmid30280023, year = {2018}, author = {Li, X and Li, Z and Chang, Y and Hou, F and Huang, Z and Ni, H and Yang, R and Bi, Y}, title = {Successful transplantation of guinea pig gut microbiota in mice and its effect on pneumonic plague sensitivity.}, journal = {PeerJ}, volume = {6}, number = {}, pages = {e5637}, pmid = {30280023}, issn = {2167-8359}, abstract = {Microbiota-driven variations in the inflammatory response are predicted to regulate host responses to infection. Increasing evidence indicates that the gastrointestinal and respiratory tracts have an intimate relationship with each other. Gut microbiota can influence lung immunity whereby gut-derived injurious factors can reach the lungs and systemic circulation via the intestinal lymphatics. The intestinal microbiota's ability to resist colonization can be extended to systemic infections or to pathogens infecting distant sites such as the lungs. Unlike the situation with large mammals, the microtus Yersinia pestis 201 strain exhibits strong virulence in mice, but nearly no virulence to large mammals (such as guinea pigs). Hence, to assess whether the intestinal microbiota from guinea pigs was able to affect the sensitivity of mice to challenge infection with the Y. pestis 201 strain, we fed mice with guinea pig diets for two months, after which they were administered 0.5 ml of guinea pig fecal suspension for 30 days by oral gavage. The stools from each mouse were collected on days 0, 15, and 30, DNA was extracted from them, and 16S rRNA sequencing was performed to assess the diversity and composition of the gut microbiota. We found that the intestinal microbiota transplants from the guinea pigs were able to colonize the mouse intestines. The mice were then infected with Yersinia pestis 201 by lung invasion, but no statistical difference was found in the survival rates of the mice that were colonized with the guinea pig's gut microbiota and the control mice. This indicates that the intestinal microbiota transplantation from the guinea pigs did not affect the sensitivity of the mice to pneumonic plague.}, }
@article {pmid30271330, year = {2018}, author = {Liang, S and Wu, X and Jin, F}, title = {Gut-Brain Psychology: Rethinking Psychology From the Microbiota-Gut-Brain Axis.}, journal = {Frontiers in integrative neuroscience}, volume = {12}, number = {}, pages = {33}, pmid = {30271330}, issn = {1662-5145}, abstract = {Mental disorders and neurological diseases are becoming a rapidly increasing medical burden. Although extensive studies have been conducted, the progress in developing effective therapies for these diseases has still been slow. The current dilemma reminds us that the human being is a superorganism. Only when we take the human self and its partner microbiota into consideration at the same time, can we better understand these diseases. Over the last few centuries, the partner microbiota has experienced tremendous change, much more than human genes, because of the modern transformations in diet, lifestyle, medical care, and so on, parallel to the modern epidemiological transition. Existing research indicates that gut microbiota plays an important role in this transition. According to gut-brain psychology, the gut microbiota is a crucial part of the gut-brain network, and it communicates with the brain via the microbiota-gut-brain axis. The gut microbiota almost develops synchronously with the gut-brain, brain, and mind. The gut microbiota influences various normal mental processes and mental phenomena, and is involved in the pathophysiology of numerous mental and neurological diseases. Targeting the microbiota in therapy for these diseases is a promising approach that is supported by three theories: the gut microbiota hypothesis, the &quot;old friend&quot; hypothesis, and the leaky gut theory. The effects of gut microbiota on the brain and behavior are fulfilled by the microbiota-gut-brain axis, which is mainly composed of the nervous pathway, endocrine pathway, and immune pathway. Undoubtedly, gut-brain psychology will bring great enhancement to psychology, neuroscience, and psychiatry. Various microbiota-improving methods including fecal microbiota transplantation, probiotics, prebiotics, a healthy diet, and healthy lifestyle have shown the capability to promote the function of the gut-brain, microbiota-gut-brain axis, and brain. It will be possible to harness the gut microbiota to improve brain and mental health and prevent and treat related diseases in the future.}, }
@article {pmid30268564, year = {2019}, author = {Krajicek, E and Fischer, M and Allegretti, JR and Kelly, CR}, title = {Nuts and Bolts of Fecal Microbiota Transplantation.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {17}, number = {2}, pages = {345-352}, doi = {10.1016/j.cgh.2018.09.029}, pmid = {30268564}, issn = {1542-7714}, abstract = {Clostridium difficile infection (CDI) has become the leading cause of nosocomial infection in the United States with significant risk of both morbidity and mortality. While antimicrobial therapy forms the basis of treatment, there are several clinical scenarios in which antimicrobial therapy alone is insufficient. Evidence continues to show the safety and efficacy fecal microbiota transplantation (FMT) in recurrent and severe CDI. This review will outline FMT efficacy, safety, and indications and present practical advice for clinicians interested in best practices around delivery of FMT.}, }
@article {pmid30265170, year = {2018}, author = {Martinez, C and Edwards, J and Hassoun, A}, title = {Commercialized fecal microbiota transplantation provides efficacious treatment of Clostridium difficile infection.}, journal = {Infectious diseases (London, England)}, volume = {50}, number = {11-12}, pages = {864-867}, doi = {10.1080/23744235.2018.1500709}, pmid = {30265170}, issn = {2374-4243}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridium Infections/microbiology/*therapy ; Clostridium difficile/*physiology ; Cohort Studies ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Recurrence ; Self Report ; Treatment Outcome ; }, }
@article {pmid30257956, year = {2018}, author = {Taur, Y and Coyte, K and Schluter, J and Robilotti, E and Figueroa, C and Gjonbalaj, M and Littmann, ER and Ling, L and Miller, L and Gyaltshen, Y and Fontana, E and Morjaria, S and Gyurkocza, B and Perales, MA and Castro-Malaspina, H and Tamari, R and Ponce, D and Koehne, G and Barker, J and Jakubowski, A and Papadopoulos, E and Dahi, P and Sauter, C and Shaffer, B and Young, JW and Peled, J and Meagher, RC and Jenq, RR and van den Brink, MRM and Giralt, SA and Pamer, EG and Xavier, JB}, title = {Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant.}, journal = {Science translational medicine}, volume = {10}, number = {460}, pages = {}, doi = {10.1126/scitranslmed.aap9489}, pmid = {30257956}, issn = {1946-6242}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; }, abstract = {Antibiotic treatment can deplete the commensal bacteria of a patient's gut microbiota and, paradoxically, increase their risk of subsequent infections. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), antibiotic administration is essential for optimal clinical outcomes but significantly disrupts intestinal microbiota diversity, leading to loss of many beneficial microbes. Although gut microbiota diversity loss during allo-HSCT is associated with increased mortality, approaches to reestablish depleted commensal bacteria have yet to be developed. We have initiated a randomized, controlled clinical trial of autologous fecal microbiota transplantation (auto-FMT) versus no intervention and have analyzed the intestinal microbiota profiles of 25 allo-HSCT patients (14 who received auto-FMT treatment and 11 control patients who did not). Changes in gut microbiota diversity and composition revealed that the auto-FMT intervention boosted microbial diversity and reestablished the intestinal microbiota composition that the patient had before antibiotic treatment and allo-HSCT. These results demonstrate the potential for fecal sample banking and posttreatment remediation of a patient's gut microbiota after microbiota-depleting antibiotic treatment during allo-HSCT.}, }
@article {pmid30251184, year = {2018}, author = {Hughes, HK and Rose, D and Ashwood, P}, title = {The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders.}, journal = {Current neurology and neuroscience reports}, volume = {18}, number = {11}, pages = {81}, pmid = {30251184}, issn = {1534-6293}, support = {P01 ES011269/ES/NIEHS NIH HHS/United States ; R01 ES015359/ES/NIEHS NIH HHS/United States ; U54 HD079125/HD/NICHD NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: There is a growing body of evidence indicating the gut microbiota influence neurodevelopment and behavior. The purposes of this review are to provide an overview of studies analyzing the microbiota and their metabolites in autism spectrum disorders (ASD) and to discuss the possible mechanisms of action involved in microbial influence on the brain and behavior.<br><br>RECENT FINDINGS: The microbiota-gut-brain (MGB) axis has been extensively studied in animal models, and it is clear that alterations in the composition of microbiota alter neurological and behavioral outcomes. However, findings in human studies are less abundant. Although there are several studies so far showing altered microbiota (dysbiosis) in ASD, the results are heterogeneous and often contradictory. Intervention studies such as fecal microbiota transplant therapies show promise and lend credence to the involvement of the microbiota in ASD. A role for the microbiota in ASD is likely; however, further studies elucidating microbial or metabolomic signatures and mechanisms of action are needed. Future research should focus on intervention studies that can identify specific metabolites and immune mediators that improve with treatment to help identify etiologies and pathological mechanisms of ASD.}, }
@article {pmid30250472, year = {2018}, author = {Haak, BW and Prescott, HC and Wiersinga, WJ}, title = {Therapeutic Potential of the Gut Microbiota in the Prevention and Treatment of Sepsis.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {2042}, pmid = {30250472}, issn = {1664-3224}, support = {K08 GM115859/GM/NIGMS NIH HHS/United States ; }, abstract = {Alongside advances in understanding the pathophysiology of sepsis, there have been tremendous strides in understanding the pervasive role of the gut microbiota in systemic host resistance. In pre-clinical models, a diverse and balanced gut microbiota enhances host immunity to both enteric and systemic pathogens. Disturbance of this balance increases susceptibility to sepsis and sepsis-related organ dysfunction, while restoration of the gut microbiome is protective. Patients with sepsis have a profoundly distorted composition of the intestinal microbiota, but the impact and therapeutic potential of the microbiome is not well-established in human sepsis. Modulation of the microbiota consists of either resupplying the pool of beneficial microbes by administration of probiotics, improving the intestinal microenvironment to enhance the growth of beneficial species by dietary interventions and prebiotics, or by totally recolonizing the gut with a fecal microbiota transplantation (FMT). We propose that there are three potential opportunities to utilize these treatment modalities over the course of sepsis: to decrease sepsis incidence, to improve sepsis outcome, and to decrease late mortality after sepsis. Exploring these three avenues will provide insight into how disturbances of the microbiota can predispose to, or even perpetuate the dysregulated immune response associated with this syndrome, which in turn could be associated with improved sepsis management.}, }
@article {pmid30249750, year = {2018}, author = {Lee, KW and Kim, M and Lee, CH}, title = {Treatment of Dextran Sulfate Sodium-Induced Colitis with Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Inhibitor MI-2 Is Associated with Restoration of Gut Immune Function and the Microbiota.}, journal = {Infection and immunity}, volume = {86}, number = {12}, pages = {}, pmid = {30249750}, issn = {1098-5522}, mesh = {Acetanilides/*pharmacology ; Animals ; Cells, Cultured ; Colitis/chemically induced/*immunology/microbiology/*therapy ; Cytokines/immunology ; Dextran Sulfate ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Inflammation ; Intestines/drug effects/*immunology/microbiology ; Macrophages ; Mice ; Mice, Inbred C57BL ; Monocytes ; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein/*antagonists &amp; inhibitors/immunology ; Triazoles/*pharmacology ; }, abstract = {Disruption of the healthy intestinal microbiome and homeostasis of the intestinal immune system, which are closely interactive, are two key factors for ulcerative colitis. Here, we show that MI-2, a selective inhibitor of mucosa-associated lymphoid tissue lymphoma translocation-1 (MALT1), alleviated excessive inflammatory responses and was associated with restoration of healthy intestinal microbiome in mice suffering from dextran sulfate sodium (DSS)-induced colitis. We found that the diversity of intestinal microbiome of mice with DSS-induced colitis was significantly lower than that of healthy mice. However, MI-2 treatment in mice with DSS-induced colitis resulted in restored microbially diverse populations. To understand the possibility of the beneficial effect of the restored microbially diverse populations of MI-2-treated mice with DSS-induced colitis, we showed that inserting fecal microbiota from MI-2-treated mice with DSS-induced colitis and healthy control mice into mice with DSS-induced colitis could alleviate symptoms of colitis. The possibility of MI-2 treatment in DSS-induced colitis, associated with restoration of healthy microbially diverse populations in addition to reshaping host immune modulating capacity by reducing inflammatory cytokines (tumor necrosis factor alpha, interleukin-1β [IL-1β], IL-17α, and IL-22), may be considered therapeutic for ulcerative colitis.}, }
@article {pmid30249647, year = {2018}, author = {Plantamura, E and Dzutsev, A and Chamaillard, M and Djebali, S and Moudombi, L and Boucinha, L and Grau, M and Macari, C and Bauché, D and Dumitrescu, O and Rasigade, JP and Lippens, S and Plateroti, M and Kress, E and Cesaro, A and Bondu, C and Rothermel, U and Heikenwälder, M and Lina, G and Bentaher-Belaaouaj, A and Marie, JC and Caux, C and Trinchieri, G and Marvel, J and Michallet, MC}, title = {MAVS deficiency induces gut dysbiotic microbiota conferring a proallergic phenotype.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10404-10409}, pmid = {30249647}, issn = {1091-6490}, mesh = {Adaptor Proteins, Signal Transducing/*physiology ; Animals ; Disease Models, Animal ; Dysbiosis/*complications ; Female ; Gastrointestinal Microbiome/*immunology ; Homeodomain Proteins/genetics/metabolism ; Hypersensitivity/*etiology/metabolism/pathology ; Intestines/*immunology/microbiology/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phenotype ; Signal Transduction ; Skin Diseases, Bacterial/*etiology/metabolism/pathology ; }, abstract = {Prominent changes in the gut microbiota (referred to as &quot;dysbiosis&quot;) play a key role in the development of allergic disorders, but the underlying mechanisms remain unknown. Study of the delayed-type hypersensitivity (DTH) response in mice contributed to our knowledge of the pathophysiology of human allergic contact dermatitis. Here we report a negative regulatory role of the RIG-I-like receptor adaptor mitochondrial antiviral signaling (MAVS) on DTH by modulating gut bacterial ecology. Cohousing and fecal transplantation experiments revealed that the dysbiotic microbiota of Mavs-/- mice conferred a proallergic phenotype that is communicable to wild-type mice. DTH sensitization coincided with increased intestinal permeability and bacterial translocation within lymphoid organs that enhanced DTH severity. Collectively, we unveiled an unexpected impact of RIG-I-like signaling on the gut microbiota with consequences on allergic skin disease outcome. Primarily, these data indicate that manipulating the gut microbiota may help in the development of therapeutic strategies for the treatment of human allergic skin pathologies.}, }
@article {pmid30246002, year = {2018}, author = {Shogbesan, O and Poudel, DR and Victor, S and Jehangir, A and Fadahunsi, O and Shogbesan, G and Donato, A}, title = {A Systematic Review of the Efficacy and Safety of Fecal Microbiota Transplant for Clostridium difficile Infection in Immunocompromised Patients.}, journal = {Canadian journal of gastroenterology &amp; hepatology}, volume = {2018}, number = {}, pages = {1394379}, pmid = {30246002}, issn = {2291-2797}, mesh = {Clostridium Infections/diagnosis/microbiology/*therapy ; Clostridium difficile/*isolation &amp; purification ; Colonoscopy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Humans ; *Immunocompromised Host ; *Microbiota ; Treatment Outcome ; }, abstract = {Background: Fecal microbiota transplantation (FMT) has been shown to be effective in recurrent Clostridium difficile (CD) infection, with resolution in 80% to 90% of patients. However, immunosuppressed patients were often excluded from FMT trials, so safety and efficacy in this population are unknown.<br><br>Methods: We searched MEDLINE and EMBASE for English language articles published on FMT for treatment of CD infection in immunocompromised patients (including patients on immunosuppressant medications, patients with human immunodeficiency virus (HIV), inherited or primary immunodeficiency syndromes, cancer undergoing chemotherapy, or organ transplant, including-bone marrow transplant) of all ages. We excluded inflammatory bowel disease patients that were not on immunosuppressant medications. Resolution and adverse event rates (including secondary infection, rehospitalization, and death) were calculated.<br><br>Results: Forty-four studies were included, none of which were randomized designs. A total of 303 immunocompromised patients were studied. Mean patient age was 57.3 years. Immunosuppressant medication use was the reason for the immunocompromised state in the majority (77.2%), and 19.2% had greater than one immunocompromising condition. Seventy-six percent were given FMT via colonoscopy. Of the 234 patients with reported follow-up outcomes, 207/234 (87%) reported resolution after first treatment, with 93% noting success after multiple treatments. There were 2 reported deaths, 2 colectomies, 5 treatment-related infections, and 10 subsequent hospitalizations.<br><br>Conclusion: We found evidence that supports the use of FMT for treatment of CD infection in immunocompromised patients, with similar rates of serious adverse events to immunocompetent patients.}, }
@article {pmid30233520, year = {2018}, author = {Fortier, LC}, title = {Bacteriophages Contribute to Shaping Clostridioides (Clostridium) difficile Species.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2033}, pmid = {30233520}, issn = {1664-302X}, abstract = {Bacteriophages (phages) are bacterial viruses that parasitize bacteria. They are highly prevalent in nature, with an estimated 1031 viral particles in the whole biosphere, and they outnumber bacteria by at least 10-fold. Hence, phages represent important drivers of bacterial evolution, although our knowledge of the role played by phages in the mammalian gut is still embryonic. Several pathogens owe their virulence to the integrated phages (prophages) they harbor, which encode diverse virulence factors such as toxins. Clostridioides (Clostridium) difficile is an important opportunistic pathogen and several phages infecting this species have been described over the last decade. However, their exact contribution to the biology and virulence of this pathogen remains elusive. Current data have shown that C. difficile phages can alter virulence-associated phenotypes, in particular toxin production, by interfering with bacterial regulatory circuits through crosstalk with phage proteins for example. One phage has also been found to encode a complete binary toxin locus. Multiple regulatory genes have also been identified in phage genomes, suggesting that their impact on the host can be complex and often subtle. In this minireview, the current state of knowledge, major findings, and pending questions regarding C. difficile phages will be presented. In addition, with the apparent role played by phages in the success of fecal microbiota transplantation and the perspective of phage therapy for treatment of recurrent C. difficile infection, it has become even more crucial to understand what C. difficile phages do in the gut, how they impact their host, and how they influence the epidemiology and evolution of this clinically important pathogen.}, }
@article {pmid30232757, year = {2018}, author = {Lu, M and Wang, Z}, title = {Microbiota and Aging.}, journal = {Advances in experimental medicine and biology}, volume = {1086}, number = {}, pages = {141-156}, doi = {10.1007/978-981-13-1117-8_9}, pmid = {30232757}, issn = {0065-2598}, abstract = {The human gut microbiota is a huge ecosystem that provides lots of functions for host development, immune system, and metabolism. Gut microbiota is linked to lots of diseases, including human metabolic diseases such as obesity, type 2 diabetes (T2D), irritable bowel syndrome, and cardiovascular disease (CVD). Few studies, however, have noted the relationship between aging and microbiota; the connection between aging and microbiota remains largely to be researched. In this review, recent research findings are summarized on the role of gut microbiota in aging processes with emphasis on therapeutic potential of microbiome-targeted interventions in antiaging medicine.}, }
@article {pmid30227892, year = {2018}, author = {Staley, C and Kaiser, T and Vaughn, BP and Graiziger, CT and Hamilton, MJ and Rehman, TU and Song, K and Khoruts, A and Sadowsky, MJ}, title = {Predicting recurrence of Clostridium difficile infection following encapsulated fecal microbiota transplantation.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {166}, pmid = {30227892}, issn = {2049-2618}, support = {R21 AI114722/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacteria/classification/genetics/isolation &amp; purification ; Clostridium Infections/microbiology/*therapy ; Clostridium difficile/*physiology ; Cohort Studies ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). The use of freeze-dried, encapsulated donor material for FMT (cap-FMT) allows for an easy route of administration and remains clinically effective in the majority of rCDI patients. We hypothesized that specific shifts in the microbiota in response to cap-FMT could predict clinical outcome. We further evaluated the degree of donor microbiota engraftment to determine the extent that donor transfer contributed to recovery.<br><br>RESULTS: In total, 89 patients were treated with 100 separate cap-FMTs, with a success rate (no rCDI 60 days post cap-FMT) of 80%. Among responders, the lower alpha diversity (ANOVA P < 0.05) observed among patient's pre-FMT samples was restored following cap-FMT. At 1 week post-FMT, community composition varied by clinical outcome (ANOSIM P < 0.001), with similar abundances among families (Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae) in responder and donor samples. Families that showed differential abundances by outcome (response vs. recurrence) from samples collected 7 days following cap-FMT were used to construct a regression tree-based model to predict recurrence. Results showed a training accuracy of 100% to predict recurrence and the model was 97% accurate against a test data set of samples collected 8-20 days following cap-FMT. Evaluation of the extent of engraftment using the Bayesian algorithm SourceTracker revealed that approximately 50% of the post-FMT communities of responders were attributable to donor microbiota, while an additional 20-30% of the communities were similar to a composite healthy microbiota consisting of all donor samples.<br><br>CONCLUSIONS: Regression tree-based analyses of microbial communities identified taxa significantly related to clinical response after 7 days, which can be targeted to improve microbial therapeutics. Furthermore, reinstatement of a healthy assemblage following cap-FMT was only partially attributable to explicit donor engraftment and continued to develop towards an overall healthy assemblage, independent of donor.}, }
@article {pmid30223665, year = {Summ}, author = {Drastich, P and Bajer, L and Kverka, M}, title = {Possibilities of therapeutic manipulation of the gut microbiota.}, journal = {Vnitrni lekarstvi}, volume = {64}, number = {6}, pages = {665-671}, pmid = {30223665}, issn = {0042-773X}, mesh = {Clostridium Infections/therapy ; Clostridium difficile ; Dysbiosis ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Microbiota ; }, abstract = {Human gut microbiota, complex ecosystem of microbes associated with human gut, is essential for the development of the host's immune system and many other physiological functions. Recently, numerous diseases and syndromes were associated with disruption of this ecosystem thus stressing its importance in maintaining the host's health. Growing evidence suggests that by manipulating the gut microbiota, some of these diseases could be treated or even prevented. These manipulations include changes in diet, use of probiotics, prebiotics, antibiotics and fecal microbiota transplantation (FMT). The successes in FMT treatment of recurrent infection of Clostridium difficile led recently to a great interest in extending this treatment modality to other diseases with proven disruption of gut microbiota, such as ulcerative colitis or metabolic syndrome. Key words: Clostridium difficile - dysbiosis - fecal microbial transplantation - microbiota - prebiotics - probiotics.}, }
@article {pmid30221898, year = {2018}, author = {Reigadas, E and Olmedo, M and Valerio, M and Vázquez-Cuesta, S and Alcalá, L and Marín, M and Muñoz, P and Bouza, E}, title = {Fecal microbiota transplantation for recurrent Clostridium difficile infection: Experience, protocol, and results.}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {31}, number = {5}, pages = {411-418}, pmid = {30221898}, issn = {1988-9518}, mesh = {Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Bacteremia/etiology ; Capsules ; *Clostridium difficile ; Colonoscopy ; Enterocolitis, Pseudomembranous/*microbiology/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; Humans ; Intubation, Gastrointestinal ; Male ; *Microbiota ; Middle Aged ; Prospective Studies ; Recurrence ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (R-CDI). Despite its excellent efficacy, it is still not a routine procedure in most European centers. FMT has not been widely used in Spain to date. We describe our experience with FMT, including a novel approach based on oral fecal capsules.<br><br>METHODS: We analyzed a prospectively recorded case series of patients with R-CDI treated with FMT at a single center (June 2014-July 2017). Primary outcome was defined as resolution of CDI without recurrence in a two-month period. FMT was administered via colonoscopy, nasojejunal tube, or oral capsules. All stool donors were rigorously screened.<br><br>RESULTS: FMT was performed in 13 patients with R-CDI. Median age was 75.0 years and 76.9% were females. Six FMT were performed via nasojejunal tube, 5 via oral capsules, and 2 by colonoscopy. There were no procedure-related adverse events, except for bacteremia in one patient. During follow-up, R- CDI was observed in one patient at one month after FMT. The primary resolution rate was 83.3% and the overall resolution rate was 91.7%. FMT by capsules achieved a 100% resolution rate, colonoscopy 100%, and nasojejunal tube 80.0%.<br><br>CONCLUSIONS: In our cohort, FMT proved to be safe and effective, even in high risk patients. Oral administration in capsules also proved to be safe, well-tolerated, and highly effective for R-CDI. In our experience, the FMT capsule formulation seems feasible in the routine of a hospital. This administration method will allow FMT to be more widely used.}, }
@article {pmid30220230, year = {2018}, author = {Daniels, LM and Kufel, WD}, title = {Clinical review of Clostridium difficile infection: an update on treatment and prevention.}, journal = {Expert opinion on pharmacotherapy}, volume = {19}, number = {16}, pages = {1759-1769}, doi = {10.1080/14656566.2018.1524872}, pmid = {30220230}, issn = {1744-7666}, mesh = {Anti-Bacterial Agents/pharmacology/*therapeutic use ; Clostridium Infections/*drug therapy/pathology/*prevention &amp; control ; Clostridium difficile/*pathogenicity ; Humans ; Treatment Outcome ; }, abstract = {INTRODUCTION: Clostridium difficile infection (CDI) has become a significant healthcare-associated infection and is strongly associated with antibiotic use. Practice guidelines have recently been revised incorporating updated recommendations for diagnosis, treatment, and prevention.<br><br>AREAS COVERED: This review discusses updated aspects of CDI management. New and emerging pharmacologic options for treatment and prevention are reviewed.<br><br>EXPERT OPINION: Metronidazole is associated with lower rates of treatment success compared to vancomycin and should no longer be used as primary therapy for the first episode of CDI or recurrent disease. Vancomycin or fidaxomicin are now recommended for first-line therapy for most cases of CDI. Fecal microbiota transplant is effective and safe for the treatment of recurrent CDI. Evidence supports the use of fidaxomicin and bezlotoxumab for prevention of recurrent CDI; however, the costs associated with these therapies may limit their use. Validated risk prediction tools are needed to identify patients most likely to benefit from these treatments. Future advancements in microbiota targeting treatments will emerge as promising alternatives to standard CDI treatments. Antibiotic stewardship and infection control measures will remain essential components for CDI management.}, }
@article {pmid30218939, year = {2018}, author = {Schmulson, M and Bashashati, M}, title = {Fecal microbiota transfer for bowel disorders: efficacy or hype?.}, journal = {Current opinion in pharmacology}, volume = {43}, number = {}, pages = {72-80}, doi = {10.1016/j.coph.2018.08.012}, pmid = {30218939}, issn = {1471-4973}, abstract = {PURPOSE OF REVIEW: Dysbiosis has been related to the pathophysiology of disorders of - gut-brain interaction (DGBI) including irritable bowel syndrome (IBS) and functional constipation (FC). Accordingly, modulation of gut microbiota has been proposed as a potential treatment for these disorders. Gut microbiota modulation can be effected by probiotics, prebiotics, symbiotics, postbiotics, antibiotics and fecal transplantation (FMT) or bacteriotherapy. The latter is currently used for recurrent or severe Clostridium difficile colitis and has been the focus of recent research in IBS and FC.<br><br>RECENT FINDINGS: Several case series reported promising results for FMT in patients with IBS and FC, which prompted the conduction of randomized controlled trials (RCT) in these DGBI.<br><br>SUMMARY: Both case series and RCTs are herein discussed. To the best of our knowledge, as of yet, 5 RCTs have been published on IBS and one in FC with slow colonic transit. In IBS, the majority of studies have used the IBS severity scoring system (IBS-SSS) as an outcome measure; however, the selection criteria were different among the trials as well as the route and form of administration of the FMT. Therefore, the results are inconsistent and no conclusion can be drawn. Some studies suggest that the presence of post-infection (PI)-IBS and the baseline microbiota status in the donors could be predictor factors of successful FMT in IBS. In constipation with slow colonic transit, the FMT seems to be more effective, although the data is based on only one RCT. We believe that larger RCTs, controlled with true placebos and considering baseline intestinal microbiota of the study subjects as well as donors' microbiota are still needed before recommending FMT in IBS and/or FC. History of previous GI infection (e.g. PI-IBS) and IBS subtypes should also be taken into account.}, }
@article {pmid30216124, year = {2018}, author = {Diorio, C and Robinson, PD and Ammann, RA and Castagnola, E and Erickson, K and Esbenshade, A and Fisher, BT and Haeusler, GM and Kuczynski, S and Lehrnbecher, T and Phillips, R and Cabral, S and Dupuis, LL and Sung, L}, title = {Guideline for the Management of Clostridium Difficile Infection in Children and Adolescents With Cancer and Pediatric Hematopoietic Stem-Cell Transplantation Recipients.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {}, number = {}, pages = {JCO1800407}, pmid = {30216124}, issn = {1527-7755}, support = {G0800472//Medical Research Council/United Kingdom ; }, abstract = {Purpose The aim of this work was to develop a clinical practice guideline for the prevention and treatment of Clostridium difficile infection (CDI) in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation (HSCT) patients. Methods An international multidisciplinary panel of experts in pediatric oncology and infectious diseases with patient advocate representation was convened. We performed systematic reviews of randomized controlled trials for the prevention or treatment of CDI in any population and considered the directness of the evidence to children with cancer and pediatric HSCT patients. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to generate recommendations. Results The panel made strong recommendations to administer either oral metronidazole or oral vancomycin for the initial treatment of nonsevere CDI and oral vancomycin for the initial treatment of severe CDI. Fidaxomicin may be considered in the setting of recurrent CDI. The panel suggested that probiotics not be routinely used for the prevention of CDI, and that monoclonal antibodies and probiotics not be routinely used for the treatment of CDI. A strong recommendation to not use fecal microbiota transplantation was made in this population. We identified key knowledge gaps and suggested directions for future research. Conclusion We present a guideline for the prevention and treatment of CDI in children and adolescents with cancer and pediatric HSCT patients. Future research should include randomized controlled trials that involve children with cancer and pediatric HSCT patients to improve the management of CDI in this population.}, }
@article {pmid30214266, year = {2018}, author = {Sunkara, T and Rawla, P and Ofosu, A and Gaduputi, V}, title = {Fecal microbiota transplant - a new frontier in inflammatory bowel disease.}, journal = {Journal of inflammation research}, volume = {11}, number = {}, pages = {321-328}, pmid = {30214266}, issn = {1178-7031}, abstract = {Inflammatory bowel disease (IBD) is a chronic multifactorial disease that affects the gastrointestinal tract and results from an aberrant immune response toward luminal antigens in genetically susceptible people. Most of the current therapies for IBD focus on the management of the inflammation by using corticosteroids, immune modulators, and more recently, monoclonal antibodies (biological therapy). Although these therapies provide benefit in most cases, there are still a significant number of patients who do not respond or become refractory over time, suggesting the need for alternative therapeutic options. In the last decade, it has been recognized that &quot;dysbiosis,&quot; an imbalanced gut microbiota, is a key element in IBD suggesting microbiome-based therapies as an attractive approach. Recently, fecal microbiota transplant (FMT) has been successfully used for the treatment of Clostridium difficile infection, and it is now under investigation for the treatment of IBD. Clinical trials data are still poor but strongly support a future introduction of FMT in therapy to manage IBD microbiome. More studies are needed to assess the optimal route of administration and the frequency of FMT, the best matched donor for each patient as well as the risks associated with FMT in IBD.}, }
@article {pmid30212271, year = {2019}, author = {Ossorio, PN and Zhou, Y}, title = {Regulating stool for microbiota transplantation.}, journal = {Gut microbes}, volume = {10}, number = {2}, pages = {105-108}, doi = {10.1080/19490976.2018.1502537}, pmid = {30212271}, issn = {1949-0984}, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {In 2017 Gut Microbes published &quot;A proposed definition of microbiota transplantation for regulatory purposes,&quot; in which the authors suggest that regulators should draw a line between microbiota transplants and biologic drugs composed of microbial communities (or other products derived from the human microbiome). They develop a definition of microbiota transplantation (MT) to help regulators draw such a line, and suggest that MT need not be, and cannot be, regulated as a biologic drug (a live biotherapeutic product). However, an agency's regulatory scrutiny of a medical product should be commensurate with that product's degree of risk to patients. Products for MT, such as stool, are likely to be as or more dangerous than more highly manipulated microbial products that scientists and regulators agree should be regulated as biologic drugs. Therefore, we argue that MT, as defined by the authors, should receive the same regulatory oversight as any other biologic product intended to cure, mitigate, treat, or prevent disease. We also suggest that regulators might not be able to operationalize the proposed definition of MT.}, }
@article {pmid30210803, year = {2018}, author = {Wang, Z and Lou, H and Wang, Y and Shamir, R and Jiang, R and Chen, T}, title = {GePMI: A statistical model for personal intestinal microbiome identification.}, journal = {NPJ biofilms and microbiomes}, volume = {4}, number = {}, pages = {20}, pmid = {30210803}, issn = {2055-5008}, abstract = {Human gut microbiomes consist of a large number of microbial genomes, which vary by diet and health conditions and from individual to individual. In the present work, we asked whether such variation or similarity could be measured and, if so, whether the results could be used for personal microbiome identification (PMI). To address this question, we herein propose a method to estimate the significance of similarity among human gut metagenomic samples based on reference-free, long k-mer features. Using these features, we find that pairwise similarities between the metagenomes of any two individuals obey a beta distribution and that a p value derived accordingly well characterizes whether two samples are from the same individual or not. We develop a computational framework called GePMI (Generating inter-individual similarity distribution for Personal Microbiome Identification) and apply it to several human gut metagenomic datasets (>300 individuals and >600 samples in total). From the results of GePMI, most of the human gut microbiomes can be identified (auROC = 0.9470, auPRC = 0.8702). Even after antibiotic treatment or fecal microbiota transplantation, the individual k-mer signature still maintains a certain specificity.}, }
@article {pmid30202057, year = {2018}, author = {Zuo, T and Wong, SH and Cheung, CP and Lam, K and Lui, R and Cheung, K and Zhang, F and Tang, W and Ching, JYL and Wu, JCY and Chan, PKS and Sung, JJY and Yu, J and Chan, FKL and Ng, SC}, title = {Gut fungal dysbiosis correlates with reduced efficacy of fecal microbiota transplantation in Clostridium difficile infection.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {3663}, pmid = {30202057}, issn = {2041-1723}, mesh = {Adult ; Animals ; Anti-Bacterial Agents/therapeutic use ; Aspergillus ; Candida albicans ; Clostridium Infections/*therapy ; Clostridium difficile ; Dysbiosis/*complications ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Multivariate Analysis ; RNA, Ribosomal, 16S/genetics ; Recurrence ; Saccharomyces ; }, abstract = {Fecal microbiota transplantation (FMT) is effective in treating recurrent Clostridium difficile infection (CDI). Bacterial colonization in recipients after FMT has been studied, but little is known about the role of the gut fungal community, or mycobiota. Here, we show evidence of gut fungal dysbiosis in CDI, and that donor-derived fungal colonization in recipients is associated with FMT response. CDI is accompanied by over-representation of Candida albicans and decreased fungal diversity, richness, and evenness. Cure after FMT is associated with increased colonization of donor-derived fungal taxa in recipients. Recipients of successful FMT (&quot;responders&quot;) display, after FMT, a high relative abundance of Saccharomyces and Aspergillus, whereas &quot;nonresponders&quot; and individuals treated with antibiotics display a dominant presence of Candida. High abundance of C. albicans in donor stool also correlates with reduced FMT efficacy. Furthermore, C. albicans reduces FMT efficacy in a mouse model of CDI, while antifungal treatment reestablishes its efficacy, supporting a potential causal relationship between gut fungal dysbiosis and FMT outcome.}, }
@article {pmid30197631, year = {2018}, author = {Wei, YL and Chen, YQ and Gong, H and Li, N and Wu, KQ and Hu, W and Wang, B and Liu, KJ and Wen, LZ and Xiao, X and Chen, DF}, title = {Fecal Microbiota Transplantation Ameliorates Experimentally Induced Colitis in Mice by Upregulating AhR.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1921}, pmid = {30197631}, issn = {1664-302X}, abstract = {Ulcerative colitis (UC) is a chronic non-specific inflammatory disease that occurs in the colon and rectum. While fecal microbiota transplantation (FMT) is gaining attention as a clinical treatment of UC, the molecular mechanisms behind this effect have yet to be fully understood. A C57BL/6 mouse model was established to test whether FMT promotes the recovery of colon inflammation. Administration of 2% dextran sulfate sodium (DSS) for 7 days successfully induced acute colitis, as evidenced by diarrhea, hematochezia and colon shortening as well as a decrease in body weight. FMT alleviated the severity of colon mucosa injury and improved histological alterations compared with that of the DSS group. In addition, FMT promoted homeostasis of the intestinal microbiota. Furthermore, FMT upregulated the expression of aryl hydrocarbon receptor (AHR), interleukin-10 (IL-10), and transforming growth factor beta (TGF-β) in colon tissues. These results suggest that the significant anti-inflammatory effect of FMT may be attributed to its promotion of IL-10 and TGF-β production and AHR activation. Based on these results, FMT had a favorable therapeutic effect on DSS-induced colitis.}, }
@article {pmid30194287, year = {2018}, author = {Luo, Y and Zeng, B and Zeng, L and Du, X and Li, B and Huo, R and Liu, L and Wang, H and Dong, M and Pan, J and Zheng, P and Zhou, C and Wei, H and Xie, P}, title = {Gut microbiota regulates mouse behaviors through glucocorticoid receptor pathway genes in the hippocampus.}, journal = {Translational psychiatry}, volume = {8}, number = {1}, pages = {187}, pmid = {30194287}, issn = {2158-3188}, mesh = {Animals ; Anxiety/*microbiology ; *Behavior, Animal ; Depression/*microbiology ; Gastrointestinal Microbiome/*physiology ; Germ-Free Life ; Hippocampus/*metabolism ; Hydrocortisone/blood ; Hypothalamo-Hypophyseal System/microbiology/physiology ; Male ; Mice ; Mice, Inbred BALB C ; Pituitary-Adrenal System/microbiology/physiology ; Receptors, Glucocorticoid/*metabolism ; Stress, Psychological/microbiology ; }, abstract = {Gut microbiota has an important role in the immune system, metabolism, and digestion, and has a significant effect on the nervous system. Recent studies have revealed that abnormal gut microbiota induces abnormal behaviors, which may be associated with the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, we investigated the behavioral changes in germ-free (GF) mice by behavioral tests, quantified the basal serum cortisol levels, and examined glucocorticoid receptor pathway genes in hippocampus using microarray analysis followed by real-time PCR validation, to explore the molecular mechanisms by which the gut microbiota influences the host's behaviors and brain function. Moreover, we quantified the basal serum cortisol levels and validated the differential genes in an Escherichia coli-derived lipopolysaccharide (LPS) treatment mouse model and fecal &quot;depression microbiota&quot; transplantation mouse model by real-time PCR. We found that GF mice showed antianxiety- and antidepressant-like behaviors, whereas E. coli LPS-treated mice showed antidepressant-like behavior, but did not show antianxiety-like behavior. However, &quot;depression microbiota&quot; recipient mice exhibited anxiety- and depressive-like behaviors. In addition, six glucocorticoid receptor pathway genes (Slc22a5, Aqp1, Stat5a, Ampd3, Plekhf1, and Cyb561) were upregulated in GF mice, and of these only two (Stat5a and Ampd3) were upregulated in LPS-treated mice, whereas the shared gene, Stat5a, was downregulated in &quot;depression microbiota&quot; recipient mice. Furthermore, basal serum cortisol levels were decreased in E. coli LPS-treated mice but not in GF mice and &quot;depression microbiota&quot; recipient mice. These results indicated that the gut microbiota may lead to behavioral abnormalities in mice through the downstream pathway of the glucocorticoid receptor. Herein, we proposed a new insight into the molecular mechanisms by which gut microbiota influence depressive-like behavior.}, }
@article {pmid30193113, year = {2018}, author = {Suez, J and Zmora, N and Zilberman-Schapira, G and Mor, U and Dori-Bachash, M and Bashiardes, S and Zur, M and Regev-Lehavi, D and Ben-Zeev Brik, R and Federici, S and Horn, M and Cohen, Y and Moor, AE and Zeevi, D and Korem, T and Kotler, E and Harmelin, A and Itzkovitz, S and Maharshak, N and Shibolet, O and Pevsner-Fischer, M and Shapiro, H and Sharon, I and Halpern, Z and Segal, E and Elinav, E}, title = {Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT.}, journal = {Cell}, volume = {174}, number = {6}, pages = {1406-1423.e16}, doi = {10.1016/j.cell.2018.08.047}, pmid = {30193113}, issn = {1097-4172}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Animals ; Anti-Bacterial Agents/*pharmacology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Humans ; Intestinal Mucosa/drug effects/microbiology ; Lactobacillus/drug effects/genetics/isolation &amp; purification ; Lactococcus/genetics/isolation &amp; purification ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Probiotics/*administration &amp; dosage ; RNA, Ribosomal, 16S/analysis/genetics/metabolism ; Young Adult ; }, abstract = {Probiotics are widely prescribed for prevention of antibiotics-associated dysbiosis and related adverse effects. However, probiotic impact on post-antibiotic reconstitution of the gut mucosal host-microbiome niche remains elusive. We invasively examined the effects of multi-strain probiotics or autologous fecal microbiome transplantation (aFMT) on post-antibiotic reconstitution of the murine and human mucosal microbiome niche. Contrary to homeostasis, antibiotic perturbation enhanced probiotics colonization in the human mucosa but only mildly improved colonization in mice. Compared to spontaneous post-antibiotic recovery, probiotics induced a markedly delayed and persistently incomplete indigenous stool/mucosal microbiome reconstitution and host transcriptome recovery toward homeostatic configuration, while aFMT induced a rapid and near-complete recovery within days of administration. In vitro, Lactobacillus-secreted soluble factors contributed to probiotics-induced microbiome inhibition. Collectively, potential post-antibiotic probiotic benefits may be offset by a compromised gut mucosal recovery, highlighting a need of developing aFMT or personalized probiotic approaches achieving mucosal protection without compromising microbiome recolonization in the antibiotics-perturbed host.}, }
@article {pmid30189736, year = {Summ}, author = {Tutková, M and Rudá-Kučerová, J}, title = {Microbiome in connection with metabolic syndrome and the therapeutic potential of its influencing.}, journal = {Ceska a Slovenska farmacie : casopis Ceske farmaceuticke spolecnosti a Slovenske farmaceuticke spolecnosti}, volume = {67}, number = {2}, pages = {71-80}, pmid = {30189736}, issn = {1210-7816}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Metabolic Syndrome/*microbiology ; Prebiotics ; Probiotics ; }, abstract = {Several fields of medicine have been concerned with the role of the microbiome in maintaining the balance in the human body and its changes in the pathogenesis of diseases in recent years. The intestinal microbiome seems to play a key role in the regulation of metabolic pathways, inflammation and intestinal permeability. The aim of this review is to assess the importance of the intestinal microbiome in metabolic syndrome and the therapeutic or preventive potential of its manipulation. Key words: metabolic syndrome • microbiome • probiotics • prebiotics • fecal transplant.}, }
@article {pmid30188944, year = {2018}, author = {Sullender, ME and Baldridge, MT}, title = {Norovirus interactions with the commensal microbiota.}, journal = {PLoS pathogens}, volume = {14}, number = {9}, pages = {e1007183}, pmid = {30188944}, issn = {1553-7374}, support = {K22 AI127846/AI/NIAID NIH HHS/United States ; P30 DK052574/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Caliciviridae Infections/*etiology/immunology/*microbiology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Gastroenteritis/etiology/immunology/microbiology ; Gastrointestinal Microbiome/immunology/*physiology ; Host-Pathogen Interactions/immunology/physiology ; Humans ; Mice ; Norovirus/immunology/*pathogenicity ; }, }
@article {pmid30183484, year = {2019}, author = {Monaghan, T and Mullish, BH and Patterson, J and Wong, GK and Marchesi, JR and Xu, H and Jilani, T and Kao, D}, title = {Effective fecal microbiota transplantation for recurrent Clostridioides difficile infection in humans is associated with increased signalling in the bile acid-farnesoid X receptor-fibroblast growth factor pathway.}, journal = {Gut microbes}, volume = {10}, number = {2}, pages = {142-148}, doi = {10.1080/19490976.2018.1506667}, pmid = {30183484}, issn = {1949-0984}, support = {MR/R000875/1//Medical Research Council/United Kingdom ; }, abstract = {The mechanisms of efficacy for fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile infection (rCDI) remain poorly defined, with restored gut microbiota-bile acid interactions representing one possible explanation. Furthermore, the potential implications for host physiology of these FMT-related changes in gut bile acid metabolism are also not well explored. In this study, we investigated the impact of FMT for rCDI upon signalling through the farnesoid X receptor (FXR)-fibroblast growth factor (FGF) pathway. Herein, we identify that in addition to restoration of gut microbiota and bile acid profiles, FMT for rCDI is accompanied by a significant, sustained increase in circulating levels of FGF19 and reduction in FGF21. These FGF changes were associated with weight gain post-FMT, to a level not exceeding the pre-rCDI baseline. Collectively, these data support the hypothesis that the restoration of gut microbial communities by FMT for rCDI is associated with an upregulated FXR-FGF pathway, and highlight the potential systemic effect of FMT.}, }
@article {pmid30181015, year = {2019}, author = {Wang, JW and Kuo, CH and Kuo, FC and Wang, YK and Hsu, WH and Yu, FJ and Hu, HM and Hsu, PI and Wang, JY and Wu, DC}, title = {Fecal microbiota transplantation: Review and update.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {118 Suppl 1}, number = {}, pages = {S23-S31}, doi = {10.1016/j.jfma.2018.08.011}, pmid = {30181015}, issn = {0929-6646}, mesh = {Clostridium Infections/*therapy ; Clostridium difficile ; Fecal Microbiota Transplantation/*adverse effects/*methods/trends ; Gastrointestinal Diseases/*therapy ; Humans ; Practice Guidelines as Topic ; Randomized Controlled Trials as Topic ; Recurrence ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is a method to directly change the recipient's gut microbiota to normalize the composition and gain a therapeutic benefit. The history of FMT has been traced back to the 4th century and has been highly regarded since 2013, when the United States Food and Drug Administration approved FMT for treating recurrent and refractory Clostridium difficile infection. Since then, the range of FMT applications extended rapidly and broadly not only in gastrointestinal disorders, but also in extra-gastrointestinal diseases. Donor selection with questionnaire, interview, blood tests, and stool examinations should be strictly performed before FMT to reduce and prevent occurrence of any adverse events. Step-by-step cautious fecal and recipient preparation along with adequately choosing delivery methods based on individual clinical situations are key points of the FMT process. Although current evidence deems FMT as a generally safe therapeutic method with few adverse effects, the long-term outcomes of FMT have not been completely elucidated. Therefore, establishing periodicity and length of regular follow-up after FMT to monitor the clinical efficacy and long-term adverse events are other essential issues. In the future, we will look forward to personalized FMT for different patients and conditions according to varied hosts and diseases.}, }
@article {pmid30178233, year = {2018}, author = {Han, R and Ma, J and Li, H}, title = {Mechanistic and therapeutic advances in non-alcoholic fatty liver disease by targeting the gut microbiota.}, journal = {Frontiers of medicine}, volume = {12}, number = {6}, pages = {645-657}, doi = {10.1007/s11684-018-0645-9}, pmid = {30178233}, issn = {2095-0225}, mesh = {Animals ; Bile Acids and Salts/metabolism ; Choline/metabolism ; *Dietary Supplements ; Energy Metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Insulin Resistance ; Intestines/*microbiology ; Non-alcoholic Fatty Liver Disease/*microbiology/therapy ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic diseases currently in the context of obesity worldwide, which contains a spectrum of chronic liver diseases, including hepatic steatosis, non-alcoholic steatohepatitis and hepatic carcinoma. In addition to the classical &quot;Two-hit&quot; theory, NAFLD has been recognized as a typical gut microbiota-related disease because of the intricate role of gut microbiota in maintaining human health and disease formation. Moreover, gut microbiota is even regarded as a &quot;metabolic organ&quot; that play complementary roles to that of liver in many aspects. The mechanisms underlying gut microbiota-mediated development of NAFLD include modulation of host energy metabolism, insulin sensitivity, and bile acid and choline metabolism. As a result, gut microbiota have been emerging as a novel therapeutic target for NAFLD by manipulating it in various ways, including probiotics, prebiotics, synbiotics, antibiotics, fecal microbiota transplantation, and herbal components. In this review, we summarized the most recent advances in gut microbiota-mediated mechanisms, as well as gut microbiota-targeted therapies on NAFLD.}, }
@article {pmid30178042, year = {2018}, author = {Gupta, A and Cifu, AS and Khanna, S}, title = {Diagnosis and Treatment of Clostridium difficile Infection.}, journal = {JAMA}, volume = {320}, number = {10}, pages = {1031-1032}, doi = {10.1001/jama.2018.12194}, pmid = {30178042}, issn = {1538-3598}, mesh = {Adult ; Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; Child ; *Clostridium Infections/diagnosis/drug therapy/therapy ; Clostridium difficile/genetics ; *Fecal Microbiota Transplantation ; Fidaxomicin ; Humans ; Nucleic Acid Amplification Techniques ; *Practice Guidelines as Topic ; Recurrence ; Vancomycin/*therapeutic use ; }, }
@article {pmid30173572, year = {2018}, author = {Ruiz, L and López, P and Suárez, A and Sánchez, B and Margolles, A}, title = {The role of gut microbiota in lupus: what we know in 2018?.}, journal = {Expert review of clinical immunology}, volume = {14}, number = {10}, pages = {787-792}, doi = {10.1080/1744666X.2018.1519395}, pmid = {30173572}, issn = {1744-8409}, mesh = {Dysbiosis/*immunology ; Gastrointestinal Microbiome/*immunology/physiology ; Humans ; Lupus Erythematosus, Systemic/*immunology/*microbiology ; }, abstract = {INTRODUCTION: The role of the human intestinal microbiota in the maintenance of a healthy physiological condition, as well as its relation to the development of disease, remains to be clarified. Current evidence suggests that intestinal microbes could be involved in the initiation and amplification of autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus (SLE). Despite recent progress in understanding how these microbes influence the pathophysiology of lupus, studies are still limited. Areas covered: In this review, we have tried to summarize the most relevant findings that have contributed to our understanding of the links between the human intestinal microbiota and the development of lupus. We also describe the potential role of individual microbial players in the physiology of lupus, and how they can shape relevant immune responses. Expert commentary: Culture-independent techniques based on massive sequencing represent a powerful tool to unravel the biological activity of gut microbes. Current data demonstrates that, depending on the pattern of intestinal microorganisms or the presence of specific bacteria, different responses related to lupus physiology can be triggered. Fecal microbiota transplantation, live biotherapeutics, or dietary interventions targeting the microbiota will likely become a treatment for SLE.}, }
@article {pmid30173562, year = {2018}, author = {Delaune, V and Orci, LA and Lacotte, S and Peloso, A and Schrenzel, J and Lazarevic, V and Toso, C}, title = {Fecal microbiota transplantation: a promising strategy in preventing the progression of non-alcoholic steatohepatitis and improving the anti-cancer immune response.}, journal = {Expert opinion on biological therapy}, volume = {18}, number = {10}, pages = {1061-1071}, doi = {10.1080/14712598.2018.1518424}, pmid = {30173562}, issn = {1744-7682}, mesh = {Carcinoma, Hepatocellular/*immunology/microbiology/pathology/*prevention &amp; control ; Disease Progression ; Dysbiosis/complications/immunology/therapy ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/physiology ; Humans ; Immunity, Cellular/physiology ; Liver Neoplasms/*immunology/microbiology/pathology/*prevention &amp; control ; Non-alcoholic Fatty Liver Disease/complications/immunology/pathology/*therapy ; }, abstract = {INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has the potential to progress to hepatocellular carcinoma (HCC). However, limited therapies are currently available for the treatment of advanced HCC, and one must strive to search for novel strategies.<br><br>AREAS COVERED: We provide insight on current knowledge related to gut microbiota and NAFLD, summarize the sequence linking obesity to HCC and highlight gut dysbiosis in obesity and its consequences on the liver. We detail the impact of the gut microbiota on immune checkpoint inhibitors, and speculate on the role of fecal microbiota transplantation (FMT) in NAFLD and in improving anti-neoplastic immune response.<br><br>EXPERT OPINION: Manipulation of the gut microbiota seems promising in the secondary prevention of NAFLD/NASH and/or in potentiating anti-cancer immune response, notably by a global 'resetting' using FMT. However, the composition of a 'harmful' gut microbiome in HCC still needs to be characterized, and the impact of FMT on HCC growth needs to be assessed.}, }
@article {pmid30172346, year = {2018}, author = {Hum, RM and Deambrosis, D and Lum, SH and Davies, E and Bonney, D and Guiver, M and Turner, A and Wynn, RF and Hiwarkar, P}, title = {Molecular monitoring of adenovirus reactivation in faeces after haematopoietic stem-cell transplantation to predict systemic infection: a retrospective cohort study.}, journal = {The Lancet. Haematology}, volume = {5}, number = {9}, pages = {e422-e429}, doi = {10.1016/S2352-3026(18)30130-3}, pmid = {30172346}, issn = {2352-3026}, mesh = {Adenoviridae/*physiology ; Adenoviridae Infections/*diagnosis ; Child ; Child, Preschool ; Cohort Studies ; Feces/*virology ; Female ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Infant ; Male ; Prognosis ; Retrospective Studies ; *Virus Activation ; }, abstract = {BACKGROUND: Faecal shedding of adenovirus following allogeneic haematopoietic stem-cell transplantation (HSCT) is an early sign of loss of immune control over adenovirus, but there is no consensus on the role of monitoring of faecal adenoviral load by serial testing. We investigated whether serial faecal PCR monitoring could predict the risk of adenoviraemia and survival outcomes after HSCT.<br><br>METHODS: We did a retrospective cohort study at the Royal Manchester Children's Hospital, Manchester, UK, of patients who had received their first allogeneic HSCT between Feb 1, 2003, and Sept 1, 2016, and adenovirus infection recorded in their medical records. We excluded patients who had received second or third transplants or autologous HSCT transplants. We obtained characteristics of patients and transplants, including mortality and adenoviral reactivation, from medical records and the hospital database. All patients had blood samples tested weekly for adenovirus by PCR until immunosuppression was stopped and CD3 T-cell count recovered to greater than 0·3 × 109/L. Faecal PCR was done before transplantation in all patients, and after transplantation in patients who had diarrhoea, at the onset of symptoms and weekly thereafter until diarrhoea resolved. We analysed all samples available before and after HSCT. We did subgroup analyses for patients undergoing HSCT for cancer versus non-malignant conditions. We also assessed whether 5 log10 copies per g faeces was a suitable predictive threshold for adenoviraemia.<br><br>FINDINGS: We included 341 patients who had undergone a first allogeneic HSCT (median age 4·6 years, IQR 1·5-8·0, range 0-20·0). After HSCT, PCR was done in 4116 faecal samples from 293 (86%) patients who had diarrhoea and in 10 649 blood samples from 341 patients. Follow-up ended on July 14, 2017. 173 (59%) of 293 patients had adenovirus in faecal samples and 63 (18%) of 341 had adenovirus in blood samples. Maximum faecal viral load before adenoviraemia correlated significantly with maximum blood viral load (r=0·51, 95% CI 0·38-0·61, p<0·0001). Faecal adenoviral viral load greater than 5 log10 copies per g faeces was predictive of adenoviraemia (odds ratio 10·2, 95% CI 4·9-21·6, p<0·0001) with sensitivity 75·9% and specificity 74·8%. These values were increased further in patients with cancer, to 86·4% and 87·5%, respectively. Among the 28 patients who had positive faecal and blood samples and who had undergone serial faecal PCR monitoring after HSCT, the median time between reaching the faecal viral load threshold and onset of adenoviraemia was 8·0 days (IQR 2·3-21·8, 95% CI 4·0-16·0). Non-relapse mortality was not associated with adenovirus reactivation in faeces alone (9·2%, 95% CI 5·4-14·3 in patients without reactivation vs 7·8%, 3·8-13·7 in those with positive faeces only), but was significantly increased in patients who developed adenoviraemia (27·0%, 95% CI 16·7-38·4, p<0·0001).<br><br>INTERPRETATION: We identified a threshold faecal viral load that can predict the risk of adenoviraemia. Our findings support proliferation of adenovirus in the gastrointestinal tract before viraemia develops. Faecal PCR is suitable for early detection of children and young adults at risk of adenoviraemia, and its use might help reduce non-relapse mortality in allogeneic HSCT recipients.<br><br>FUNDING: None.}, }
@article {pmid30158649, year = {2018}, author = {Wang, S and Huang, M and You, X and Zhao, J and Chen, L and Wang, L and Luo, Y and Chen, Y}, title = {Gut microbiota mediates the anti-obesity effect of calorie restriction in mice.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {13037}, pmid = {30158649}, issn = {2045-2322}, support = {2016YFA0500103//Ministry of Science and Technology of the People&amp;apos;s Republic of China (Chinese Ministry of Science and Technology)/ ; }, abstract = {Calorie restriction (CR) extends lifespan and elicits numerous effects beneficial to health and metabolism in various model organisms, but the underlying mechanisms are not completely understood. Gut microbiota has been reported to be associated with the beneficial effects of CR; however, it is unknown whether these effects of CR are causally mediated by gut microbiota. In this study, we employed an antibiotic-induced microbiota-depleted mouse model to investigate the functional role of gut microbiota in CR. Depletion of gut microbiota rendered mice resistant to CR-induced loss of body weight, accompanied by the increase in fat mass, the reduction in lean mass and the decline in metabolic rate. Depletion of gut microbiota led to increases in fasting blood glucose and cholesterol levels independent of CR. A few metabolism-modulating hormones including leptin and insulin were altered by CR and/or gut microbiota depletion. In addition, CR altered the composition of gut microbiota with significant increases in major probiotic genera such as Lactobacillus and Bifidobacterium, together with the decrease of Helicobacter. In addition, we performed fecal microbiota transplantation in mice fed with high-fat diet. Mice with transferred microbiota from calorie-restricted mice resisted high fat diet-induced obesity and exhibited metabolic improvement such as alleviated hepatic lipid accumulation. Collectively, these data indicate that CR-induced metabolic improvement especially in body weight reduction is mediated by intestinal microbiota to a certain extent.}, }
@article {pmid30158252, year = {2018}, author = {Enck, P}, title = {Primum non nocere: is faecal microbiota transplantation doing harm to patients with IBS?.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2018-317277}, pmid = {30158252}, issn = {1468-3288}, }
@article {pmid30155958, year = {2018}, author = {Barfuss, S and Knackstedt, ED and Jensen, K and Molina, K and Lal, A}, title = {Cardiac allograft vasculopathy following fecal microbiota transplantation for recurrent C. difficile infection.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {20}, number = {6}, pages = {e12983}, doi = {10.1111/tid.12983}, pmid = {30155958}, issn = {1399-3062}, mesh = {Allografts/*blood supply/immunology ; Anti-Bacterial Agents/therapeutic use ; Child, Preschool ; Clostridium Infections/microbiology/*therapy ; Clostridium difficile/isolation &amp; purification ; Coronary Vessels/immunology ; Fecal Microbiota Transplantation/*adverse effects ; Graft Rejection/*immunology/surgery ; Heart Transplantation/*adverse effects ; Humans ; Male ; Myocardium/immunology ; Recurrence ; Reoperation ; Vascular Diseases/*immunology/surgery ; }, abstract = {We report the case of a 3-year-old male who developed recurrent Clostridium difficile infection after receiving an orthotopic heart transplant. Despite multiple courses of antibiotics, C. difficile infection was persistent and he underwent a fecal microbiota transplant. The patient responded with resolution of his diarrhea. However, within 2 months he developed severe mixed rejection with high circulating donor-specific antibodies and significant coronary vasculopathy. Organ dysfunction led to the need for re-transplantation. The patient's postoperative course has since been complicated by pneumatosis intestinalis and recurrent C. difficile infection.}, }
@article {pmid30154767, year = {2018}, author = {Kho, ZY and Lal, SK}, title = {The Human Gut Microbiome - A Potential Controller of Wellness and Disease.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1835}, pmid = {30154767}, issn = {1664-302X}, abstract = {Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.}, }
@article {pmid30154172, year = {2018}, author = {Mullish, BH and Quraishi, MN and Segal, JP and McCune, VL and Baxter, M and Marsden, GL and Moore, DJ and Colville, A and Bhala, N and Iqbal, TH and Settle, C and Kontkowski, G and Hart, AL and Hawkey, PM and Goldenberg, SD and Williams, HRT}, title = {The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.}, journal = {Gut}, volume = {67}, number = {11}, pages = {1920-1941}, doi = {10.1136/gutjnl-2018-316818}, pmid = {30154172}, issn = {1468-3288}, support = {MR/R000875/1//Medical Research Council/United Kingdom ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/*therapy ; Clostridium difficile/drug effects ; Fecal Microbiota Transplantation/*methods ; Gastroenterology/organization &amp; administration ; Gastrointestinal Tract/*microbiology ; Humans ; Recurrence ; Societies, Medical ; Tissue Donors ; United Kingdom ; }, abstract = {Interest in the therapeutic potential of faecal microbiota transplant (FMT) has been increasing globally in recent years, particularly as a result of randomised studies in which it has been used as an intervention. The main focus of these studies has been the treatment of recurrent or refractory Clostridium difficile infection (CDI), but there is also an emerging evidence base regarding potential applications in non-CDI settings. The key clinical stakeholders for the provision and governance of FMT services in the UK have tended to be in two major specialty areas: gastroenterology and microbiology/infectious diseases. While the National Institute for Health and Care Excellence (NICE) guidance (2014) for use of FMT for recurrent or refractory CDI has become accepted in the UK, clear evidence-based UK guidelines for FMT have been lacking. This resulted in discussions between the British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS), and a joint BSG/HIS FMT working group was established. This guideline document is the culmination of that joint dialogue.}, }
@article {pmid30153805, year = {2018}, author = {Brown, JR and Flemer, B and Joyce, SA and Zulquernain, A and Sheehan, D and Shanahan, F and O'Toole, PW}, title = {Changes in microbiota composition, bile and fatty acid metabolism, in successful faecal microbiota transplantation for Clostridioides difficile infection.}, journal = {BMC gastroenterology}, volume = {18}, number = {1}, pages = {131}, pmid = {30153805}, issn = {1471-230X}, support = {(SFI/12/RC/2273)//Science Foundation Ireland/Ireland ; SFI/12/RC/2273//Science Foundation Ireland/Ireland ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bile Acids and Salts/metabolism ; Clostridium Infections/metabolism/*microbiology/*therapy ; *Clostridium difficile ; Fatty Acids, Volatile/metabolism ; *Fecal Microbiota Transplantation ; Feces/chemistry ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Recurrence ; Young Adult ; }, abstract = {BACKGROUND: Alteration of the gut microbiota by repeated antibiotic treatment increases susceptibility to Clostridioides difficile infection. Faecal microbiota transplantation from donors with a normal microbiota effectively treats C. difficile infection.<br><br>METHODS: The study involved 10 patients with recurrent C. difficile infection, nine of whom received transplants from individual donors and one who received a donor unit from a stool bank (OpenBiome).<br><br>RESULTS: All individuals demonstrated enduring post-transplant resolution of C. difficile- associated diarrhoea. Faecal microbiota diversity of recipients significantly increased, and the composition of the microbiota resembled that of the donor. Patients with C. difficile infection exhibited significantly lower faecal levels of secondary/ bile acids and higher levels of primary bile acids. Levels of secondary bile acids were restored in all transplant recipients, but to a lower degree with the OpenBiome transplant. The abundance increased of bacterial genera known from previous studies to confer resistance to growth and germination of C. difficile. These were significantly negatively associated with primary bile acid levels and positively related with secondary bile acid levels. Although reduced levels of the short chain fatty acids, butyrate, propionate and acetate, have been previously reported, here we report elevations in SCFA, pyruvic and lactic fatty acids, saturated, ω-6, monounsaturated, ω-3 and ω-6 polyunsaturated fatty acids (PUFA) in C. difficile infection. This potentially indicates one or a combination of increased dietary FA intake, microbial modification of FAs or epithelial cell damage and inflammatory cell recruitment. No reversion to donor FA profile occurred post-FMT but ω-3 to ω-6 PUFA ratios were altered in the direction of the donor. Archaeal metabolism genes were found in some samples post FMT.<br><br>CONCLUSION: A consistent metabolic signature was identified in the post-transplant microbiota, with reduced primary bile acids and substantial restoration of secondary bile acid production capacity. Total FA levels were unchanged but the ratio of inflammatory to non-inflammatory FAs decreased.}, }
@article {pmid30150145, year = {2018}, author = {Zhang, X and Zhao, S and Song, X and Jia, J and Zhang, Z and Zhou, H and Fu, H and Cui, H and Hu, S and Fang, M and Liu, X and Bian, Y}, title = {Inhibition effect of glycyrrhiza polysaccharide (GCP) on tumor growth through regulation of the gut microbiota composition.}, journal = {Journal of pharmacological sciences}, volume = {137}, number = {4}, pages = {324-332}, doi = {10.1016/j.jphs.2018.03.006}, pmid = {30150145}, issn = {1347-8648}, mesh = {Animals ; *Antineoplastic Agents, Phytogenic ; Cell Line, Tumor ; Cell Transformation, Neoplastic/*drug effects ; Colonic Neoplasms/*drug therapy/*pathology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects/*physiology ; Glycyrrhiza uralensis/*chemistry ; Male ; Mice, Inbred BALB C ; *Phytotherapy ; Polysaccharides/*isolation &amp; purification/*pharmacology ; }, abstract = {Glycyrrhiza Uralensis Polysaccharide (GCP), as a macromolecular polysaccharide extracted from the Traditional Chinese Medicine (TCM) - Licorice has been proved to inhibit tumor growth in vitro and in vivo; however, the specific anti-tumor mechanism of GCP needs to be further investigated. In this study, we explore the anti-tumor mechanism of GCP from the angle of gut microbiota. Colon carcinoma cells (CT-26) were used to set up a tumor-bearing mouse model. After 14 days of GCP treatment, the weights of tumors were significantly reduced. In addition, HE staining of tissue sections reflected that GCP could effectively inhibit tumor metastasis. 16SrRNA high-throughput sequencing of fecal samples showed a significant change between the model group and GCP group in the composition of gut microbiota. Subsequently, gut microbiota depletion and fecal transplantation experiments further confirmed the relationship between the anti-tumor effects of GCP and gut microbiota. Following depletion of gut microbiota, GCP cannot inhibit tumor growth. Fecal transplantation experiments found that transplanting the feces of GCP-treated mice, to a certain extent, could inhibit tumor growth and metastasis. These results indicate that Glycyrrhiza Polysaccharides exert anti-tumor effects by affecting gut microbiota composition.}, }
@article {pmid30148975, year = {2018}, author = {Tampaki, EC and Tampakis, A and Posabella, A and Patsouris, E and Kontzoglou, K and Kouraklis, G}, title = {Current clostridium difficile treatments: Lessons that need to be learned from the clinical trials.}, journal = {Human vaccines &amp; immunotherapeutics}, volume = {14}, number = {12}, pages = {2874-2875}, doi = {10.1080/21645515.2018.1493327}, pmid = {30148975}, issn = {2164-554X}, abstract = {Clostridium difficile infection (CDI) is the most common infectious disease cause of nosocomial diarrhea in adults in developed countries. Judging from the clinical trials on drugs used in CDIs, no approved treatment for recurrences exists, possibly indicating that a combination of treatment approaches are mandatory especially in severe infections, with current studies not being fully representative. Among the new strategies researched intensively fidaxomicin is presented, which demonstrates reduced CDI recurrences. Moreover, biotherapeutic strategies, mainly fecal microbiota transplantation but also competitive inhibition with non-toxigenic strains of C. difficile, and finally monoclonal antibodies against C. difficile toxins which offer protection against recurrences. Careful interpretation of the results based on lessons learned from previous trials conducted seems crucial. Questions are raised regarding how the results of future studies regarding new strategies researched will be managed and interpreted especially with regard to recurrence management as relevant data must be monitored for at least 30 days after end of treatment.}, }
@article {pmid30146910, year = {2018}, author = {Balakrishnan, B and Taneja, V}, title = {Microbial modulation of the gut microbiome for treating autoimmune diseases.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {12}, number = {10}, pages = {985-996}, doi = {10.1080/17474124.2018.1517044}, pmid = {30146910}, issn = {1747-4132}, mesh = {Anti-Bacterial Agents/therapeutic use ; Autoimmune Diseases/microbiology/*therapy ; Bacteroides fragilis ; Bacteroides thetaiotaomicron ; Diet ; Faecalibacterium prausnitzii ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/immunology ; Humans ; Microorganisms, Genetically-Modified ; Prevotella ; Probiotics/pharmacology/*therapeutic use ; Verrucomicrobia ; }, abstract = {INTRODUCTION: Many studies have shown the relationship between autoimmune diseases and the gut microbiome in humans: those with autoimmune conditions display gut microbiome dysbiosis. The big question that needs to be addressed is if restoring eubiosis of the gut microbiota can help suppress the autoimmune condition by activating various immune regulatory mechanisms. Inducing these self-healing mechanisms should prolong good health in affected individuals. Area covered: Here, we review the available clinical and preclinical studies that have used selective bacteria for modulating gut microbiota for treating autoimmune diseases. The potential bacterial candidates and their mechanism of action in treating autoimmune diseases will be discussed. We searched for genetically modified and potential probiotics for diseases and discuss the most likely candidates. Expert commentary: To achieve eubiosis, manipulation of the gut microbiota must occur in some form. Several approaches for modulating gut microbiota include prebiotic diets, antimicrobial interventions, fecal microbiota transplants, and selective probiotics. One novel approach showing promising results is the use of selective bacterial candidates to modulate microbial composition. Use of single microbe for treatment has an advantage as compared to multi-species as microbes grow at different rates and if needed, a single microbe is easy to target.}, }
@article {pmid30146033, year = {2018}, author = {Pouch, SM and Friedman-Moraco, RJ}, title = {Prevention and Treatment of Clostridium difficile-Associated Diarrhea in Solid Organ Transplant Recipients.}, journal = {Infectious disease clinics of North America}, volume = {32}, number = {3}, pages = {733-748}, doi = {10.1016/j.idc.2018.05.001}, pmid = {30146033}, issn = {1557-9824}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/*complications/drug therapy/microbiology ; Diarrhea/complications/*microbiology ; Fecal Microbiota Transplantation ; Humans ; Organ Transplantation/*adverse effects ; Postoperative Complications/drug therapy/*microbiology ; }, abstract = {Clostridium difficile infection is a significant cause of morbidity and mortality in solid organ transplant recipients. Risk factors in this population include frequent hospitalizations, receipt of immunosuppressive agents, and intestinal dysbiosis triggered by several factors, including exposure to broad-spectrum antimicrobials. The incidence and potential for significant adverse outcomes among solid organ transplant recipients with C difficile infection highlight the evolving need for strategic C difficile infection risk factor modification and novel approaches to disease management in this patient population. This review focuses on current concepts related to the prevention and treatment of C difficile infection in solid organ transplant recipients.}, }
@article {pmid30140609, year = {2018}, author = {Dias, C and Pipa, S and Duarte-Ribeiro, F and Mota, M}, title = {Fecal microbiota transplantation as a potential way to eradicate multiresistant microorganisms.}, journal = {IDCases}, volume = {13}, number = {}, pages = {e00432}, pmid = {30140609}, issn = {2214-2509}, abstract = {Multiresistant microorganism infection often can produce a life-threatening situation. We report two cases in which fecal microbiota transplantation used for the treatment of recurrent Clostridium difficile infection were effective in eradicating colonization by carbapenemase-producing Enterobacteriaceae. The presented cases illustrate the potential benefit of fecal microbiota transplantation in resolution of asymptomatic carrier states of multiresistant microorganisms, suggesting the need for further investigations with a view to their applicability in this area.}, }
@article {pmid30138161, year = {2018}, author = {Khan, MY and Dirweesh, A and Khurshid, T and Siddiqui, WJ}, title = {Comparing fecal microbiota transplantation to standard-of-care treatment for recurrent Clostridium difficile infection: a systematic review and meta-analysis.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {30}, number = {11}, pages = {1309-1317}, doi = {10.1097/MEG.0000000000001243}, pmid = {30138161}, issn = {1473-5687}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridium Infections/diagnosis/microbiology/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: The use of fecal microbiota transplantation (FMT) as a treatment option for recurrent Clostridium difficile infection (rCDI) is well established. Various studies have used different forms and administration routes for FMT. We performed a systemic review and meta-analysis to update the clinical knowledge about different FMT modalities for curing rCDI compared with medical treatment (MT).<br><br>PATIENTS AND METHODS: We searched PubMed and Medline from inception through 10 May 2018 for randomized control trials (RCTs) comparing FMT (fresh or frozen) versus MT. We used Cochrane Collaboration's Risk of Bias tool to assess bias in the RCTs. We estimated odds ratio (OR) with 95% confidence interval (CI) for each outcome using a random effects model. P values of less than 0.05 were considered significant.<br><br>RESULTS: We included seven RCTs comprising a total of 543 patients with recurrent CDI. There was a nonsignificant trend toward resolution of diarrhea following a single fresh FMT infusion compared with frozen FMT and MT (OR=2.45, 95% CI=0.78-7.71, P=0.12, I=69%). Subgroup analysis of fresh FMT vs. frozen FMT showed no difference between the two groups (OR=2.13, 95% CI=0.22-20.41, P=0.51, I=61%). Frozen FMT infusion through upper route versus lower route showed no difference (OR=0.62, 95% CI=0.15-2.54, P=0.51, I=0%). There was a nonsignificant trend favoring multiple treatments with FMT versus multiple courses of MT (OR=3.68, 95% CI=0.74-18.22, P=0.11, I=0%).<br><br>CONCLUSION: FMT is a promising treatment modality for rCDI compared with MT alone. Different forms and routes of FMT administration seem to be equally efficacious. In future, more well-designed RCTs directed at homogenous FMT preparation and delivery methods are required to validate these findings.}, }
@article {pmid30124831, year = {2018}, author = {Ishikawa, D and Sasaki, T and Takahashi, M and Kuwahara-Arai, K and Haga, K and Ito, S and Okahara, K and Nakajima, A and Shibuya, T and Osada, T and Hiramatsu, K and Watanabe, S and Nagahara, A}, title = {The Microbial Composition of Bacteroidetes Species in Ulcerative Colitis Is Effectively Improved by Combination Therapy With Fecal Microbiota Transplantation and Antibiotics.}, journal = {Inflammatory bowel diseases}, volume = {24}, number = {12}, pages = {2590-2598}, doi = {10.1093/ibd/izy266}, pmid = {30124831}, issn = {1536-4844}, abstract = {Background: We previously reported that fresh fecal microbiota transplantation (FMT) after triple-antibiotic therapy (amoxicillin, fosfomycin, and metronidazole [AFM]; A-FMT) synergistically contributed to the recovery of phylum Bacteroidetes composition associated with the endoscopic severity and treatment efficacy of ulcerative colitis (UC). Here, we performed further microbial analyses using a higher-resolution method to identify the key bacterial species in UC and determine whether viable Bacteroidetes species from donor feces were successfully colonized by A-FMT.<br><br>Methods: The taxonomic composition of Bacteroidetes in 25 healthy donors and 27 UC patients at baseline was compared at the species level using a heat-shock protein (hsp) 60-based microbiome method. Microbiota alterations before and after treatment of UC patients were also analyzed in 24 cases (n = 17 A-FMT; n = 3 mono-AFM; n = 4 mono-FMT).<br><br>Results: We found species-level dysbiosis within the phylum Bacteroidetes in UC samples, which was associated with reduced species diversity, resulting from hyperproliferation and hypoproliferation of particular species. Moreover, in responders treated with A-FMT, diversity was significantly recovered at 4 weeks after a fresh round of FMT, after which high degrees of similarity in Bacteroidetes species composition among recipients and donors were observed.<br><br>Conclusions: A-FMT alleviated intestinal dysbiosis, which is caused by the loss of Bacteroidetes species diversity in patients with UC. Eradication of dysbiotic indigenous Bacteroidetes species by AFM pretreatment might promote the colonization of viable Bacteroidetes cells, thereby improving the intestinal microbiota dysbiosis induced by UC. Our findings serve as a basis for further investigations into the mechanisms of FMT.}, }
@article {pmid30123820, year = {2018}, author = {Williamson, IA and Arnold, JW and Samsa, LA and Gaynor, L and DiSalvo, M and Cocchiaro, JL and Carroll, I and Azcarate-Peril, MA and Rawls, JF and Allbritton, NL and Magness, ST}, title = {A High-Throughput Organoid Microinjection Platform to Study Gastrointestinal Microbiota and Luminal Physiology.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {6}, number = {3}, pages = {301-319}, pmid = {30123820}, issn = {2352-345X}, support = {UL1 TR001111/TR/NCATS NIH HHS/United States ; R01 DK091427/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; R01 DK081426/DK/NIDDK NIH HHS/United States ; R01 DK109559/DK/NIDDK NIH HHS/United States ; UL1 TR001117/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Bifidobacterium adolescentis/genetics/growth &amp; development/isolation &amp; purification ; Colon/anatomy &amp; histology/*cytology ; Escherichia coli/genetics/growth &amp; development ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*physiology ; Humans ; Male ; Mice ; Microinjections/*methods ; Organoids/anatomy &amp; histology/*cytology ; Single-Cell Analysis ; Video Recording ; Yersinia pseudotuberculosis/genetics/growth &amp; development ; }, abstract = {Background &amp; Aims: The human gut microbiota is becoming increasingly recognized as a key factor in homeostasis and disease. The lack of physiologically relevant in vitro models to investigate host-microbe interactions is considered a substantial bottleneck for microbiota research. Organoids represent an attractive model system because they are derived from primary tissues and embody key properties of the native gut lumen; however, access to the organoid lumen for experimental perturbation is challenging. Here, we report the development and validation of a high-throughput organoid microinjection system for cargo delivery to the organoid lumen and high-content sampling.<br><br>Methods: A microinjection platform was engineered using off-the-shelf and 3-dimensional printed components. Microinjection needles were modified for vertical trajectories and reproducible injection volumes. Computer vision (CVis) and microfabricated CellRaft Arrays (Cell Microsystems, Research Triangle Park, NC) were used to increase throughput and enable high-content sampling of mock bacterial communities. Modeling preformed using the COMSOL Multiphysics platform predicted a hypoxic luminal environment that was functionally validated by transplantation of fecal-derived microbial communities and monocultures of a nonsporulating anaerobe.<br><br>Results: CVis identified and logged locations of organoids suitable for injection. Reproducible loads of 0.2 nL could be microinjected into the organoid lumen at approximately 90 organoids/h. CVis analyzed and confirmed retention of injected cargos in approximately 500 organoids over 18 hours and showed the requirement to normalize for organoid growth for accurate assessment of barrier function. CVis analyzed growth dynamics of a mock community of green fluorescent protein- or Discosoma sp. red fluorescent protein-expressing bacteria, which grew within the organoid lumen even in the presence of antibiotics to control media contamination. Complex microbiota communities from fecal samples survived and grew in the colonoid lumen without appreciable changes in complexity.<br><br>Conclusions: High-throughput microinjection into organoids represents a next-generation in vitro approach to investigate gastrointestinal luminal physiology and the gastrointestinal microbiota.}, }
@article {pmid30118620, year = {2019}, author = {Farowski, F and Els, G and Tsakmaklis, A and Higgins, PG and Kahlert, CR and Stein-Thoeringer, CK and Bobardt, JS and Dettmer-Wilde, K and Oefner, PJ and Vehreschild, JJ and Vehreschild, MJGT}, title = {Assessment of urinary 3-indoxyl sulfate as a marker for gut microbiota diversity and abundance of Clostridiales.}, journal = {Gut microbes}, volume = {10}, number = {2}, pages = {133-141}, doi = {10.1080/19490976.2018.1502536}, pmid = {30118620}, issn = {1949-0984}, abstract = {OBJECTIVES: After allogeneic hematopoietic stem cell transplantation (allo-HCT), urinary levels of 3-indoxyl sulfate (3-IS) correlate with the relative abundance of bacteria from the class Clostridia (RAC), and antibiotic treatment is considered the major determinant of this outcome. A high RAC has been associated with favorable outcome after allo-HCT and protection from Clostridium difficile infection (CDI). We assessed correlations between alpha diversity, RAC and urinary 3-IS levels in a non-allo-HCT clinical cohort of antibiotic treated patients to further explore 3-IS as a biomarker of reduced diversity and predisposition to CDI.<br><br>METHODS: Fecal and urinary specimens were analyzed from 40 non-allo-HCT hospitalized patients before and 9 ± 2 days after initiation of intravenous antibiotic treatment. Fecal microbiota were analyzed by 16s RNA sequencing and urinary 3-IS was analyzed by liquid chromatography-tandem mass spectrometry. Receiver operating characteristic (ROC) analysis was performed to assess the predictive value of 3-IS.<br><br>RESULTS: At a RAC cutoff of <30%, the binary logarithm of 3-IS (medium 3-IS: ≤2.5; high 3-IS: >2.5) was predictive with an accuracy of 82% (negative predictive value: 87%, positive predictive value 67%). Accuracy was improved by combing antibiotic history with 3-IS levels (accuracy 89%, npv 88%, ppv 92%).<br><br>CONCLUSION: In conjunction with patient antibiotic history, 3-IS is a candidate marker to predict RAC.}, }
@article {pmid30109576, year = {2018}, author = {Biehl, LM and Cruz Aguilar, R and Farowski, F and Hahn, W and Nowag, A and Wisplinghoff, H and Vehreschild, MJGT}, title = {Fecal microbiota transplantation in a kidney transplant recipient with recurrent urinary tract infection.}, journal = {Infection}, volume = {46}, number = {6}, pages = {871-874}, pmid = {30109576}, issn = {1439-0973}, support = {BI 1899/1-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {*Fecal Microbiota Transplantation ; Female ; Germany ; Humans ; *Kidney Transplantation ; Middle Aged ; Recurrence ; *Transplant Recipients ; Treatment Outcome ; Urinary Tract Infections/*therapy ; }, abstract = {PURPOSE: We report on a kidney transplant recipient treated with fecal microbiota transplantation (FMT) for recurrent urinary tract infections.<br><br>METHODS: FMT was administered via frozen capsulized microbiota. Before and after FMT, urinary, fecal and vaginal microbiota compositions were analyzed.<br><br>RESULTS: The patient remained without symptoms after FMT.<br><br>CONCLUSIONS: Underlying mechanisms of action need to be addressed in depth by future research.}, }
@article {pmid30099108, year = {2019}, author = {Colombel, JF and Shin, A and Gibson, PR}, title = {AGA Clinical Practice Update on Functional Gastrointestinal Symptoms in Patients With Inflammatory Bowel Disease: Expert Review.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {17}, number = {3}, pages = {380-390.e1}, doi = {10.1016/j.cgh.2018.08.001}, pmid = {30099108}, issn = {1542-7714}, support = {KL2 TR001106/TR/NCATS NIH HHS/United States ; UL1 TR001108/TR/NCATS NIH HHS/United States ; }, abstract = {DESCRIPTION: The purpose of this clinical practice update review is to describe key principles in the diagnosis and management of functional gastrointestinal (GI) symptoms in patients with inflammatory bowel disease (IBD).<br><br>METHODS: The evidence and best practices summarized in this manuscript are based on relevant scientific publications, systematic reviews, and expert opinion where applicable. Best practice advice 1: A stepwise approach to rule-out ongoing inflammatory activity should be followed in IBD patients with persistent GI symptoms (measurement of fecal calprotectin, endoscopy with biopsy, cross-sectional imaging). Best practice advice 2: In those patients with indeterminate fecal calprotectin levels and mild symptoms, clinicians may consider serial calprotectin monitoring to facilitate anticipatory management. Best practice advice 3: Anatomic abnormalities or structural complications should be considered in patients with obstructive symptoms including abdominal distention, pain, nausea and vomiting, obstipation or constipation. Best practice advice 4: Alternative pathophysiologic mechanisms should be considered and evaluated (small intestinal bacterial overgrowth, bile acid diarrhea, carbohydrate intolerance, chronic pancreatitis) based on predominant symptom patterns. Best practice advice 5: A low FODMAP diet may be offered for management of functional GI symptoms in IBD with careful attention to nutritional adequacy. Best practice advice 6: Psychological therapies (cognitive behavioural therapy, hypnotherapy, mindfulness therapy) should be considered in IBD patients with functional symptoms. Best practice advice 7: Osmotic and stimulant laxative should be offered to IBD patients with chronic constipation. Best practice advice 8: Hypomotility agents or bile-acid sequestrants may be used for chronic diarrhea in quiescent IBD. Best practice advice 9: Antispasmodics, neuropathic-directed agents, and anti-depressants should be used for functional pain in IBD while use of opiates should be avoided. Best practice advice 10: Probiotics may be considered for treatment of functional symptoms in IBD. Best practice advice 11: Pelvic floor therapy should be offered to IBD patients with evidence of an underlying defecatory disorder. Best practice advice 12: Until further evidence is available, fecal microbiota transplant should not be offered for treatment of functional GI symptoms in IBD. Best practice advice 13: Physical exercise should be encourage in IBD patients with functional GI symptoms. Best practice advice 14: Until further evidence is available, complementary and alternative therapies should not be routinely offered for functional symptoms in IBD. This Clinical Practice Update was produced by the AGA Institute.}, }
@article {pmid30093802, year = {2018}, author = {Filip, M and Tzaneva, V and Dumitrascu, DL}, title = {Fecal transplantation: digestive and extradigestive clinical applications.}, journal = {Clujul medical (1957)}, volume = {91}, number = {3}, pages = {259-265}, pmid = {30093802}, issn = {1222-2119}, abstract = {Background and aim: Fecal transplantation or fecal material transplantation (FMT) became a hot topic in gastroenterology in recent years. Therefore it is important to disseminate the up-to-date information on FMT. The aim of the paper is to review the knowledge on FMT and its clinical applications.<br><br>Methods: An extensive review of the literature was carried out. Titles from Pubmed were searched and analyzed. A narrative review has been written with emphasis on indications of FMT in different conditions.<br><br>Results: The guidelines recommend FMT in relapsing infection with Clostridium difficile. Several attempts to use FMT in other conditions have been analyzed. Attempts were recorded in other bowel disorders like IBD, IBS, chronic constipation and even colorectal cancer. The attempt to change the microbiota by FMT in diabetes and obesity represent challenges for the future.<br><br>Conclusions: Fecal transplantation represents an important therapeutic method, intensively investigated these years. Beside the indication for persistent and recurrent Clostridium difficile infection, several attempts were undertaken in other intestinal diseases and in metabolic conditions. The efficiency of these applications has to be demonstrated.}, }
@article {pmid30090049, year = {2018}, author = {Micic, D and Hirsch, A and Setia, N and Rubin, DT}, title = {Enteric infections complicating ulcerative colitis.}, journal = {Intestinal research}, volume = {16}, number = {3}, pages = {489-493}, pmid = {30090049}, issn = {1598-9100}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; }, abstract = {Enteric infections have previously been postulated to play a role in the pathogenesis of inflammatory bowel disease (IBD), however, little evidence exists in the etiologic role of specific enteric infections in the development of IBD. When encountered in the setting of IBD, enteric infections pose a clinical challenge in management given the competing treatment strategies for infectious conditions and autoimmune disorders. Here we present the case of a young male with enteric infections complicating a new diagnosis of IBD. Our patient's initial clinical presentation included diagnoses of Klebsiella oxytoca isolation and Clostridium difficile infection. Directed therapies to include withdrawal of antibiotics and fecal microbiota transplantation were performed without resolution of clinical symptoms. Given persistence of symptoms and active colitis, the patient was diagnosed with ulcerative colitis (UC), requiring treatments directed at severe UC to include cyclosporine therapy. The finding of multiple enteric infections in a newly presenting patient with IBD is an unexpected finding that has treatment implications.}, }
@article {pmid30090033, year = {2018}, author = {Yu, LC and Wei, SC and Ni, YH}, title = {Impact of microbiota in colorectal carcinogenesis: lessons from experimental models.}, journal = {Intestinal research}, volume = {16}, number = {3}, pages = {346-357}, pmid = {30090033}, issn = {1598-9100}, abstract = {A role of gut microbiota in colorectal cancer (CRC) growth was first suggested in germ-free rats almost 50 years ago, and the existence of disease-associated bacteria (termed pathobionts) had becoming increasingly evident from experimental data of fecal transplantation, and microbial gavage or monoassociation. Altered bacterial compositions in fecal and mucosal specimens were observed in CRC patients compared to healthy subjects. Microbial fluctuations were found at various cancer stages; an increase of bacterial diversity was noted in the adenoma specimens, while a reduction of bacterial richness was documented in CRC samples. The bacterial species enriched in the human cancerous tissues included Escherichia coli, Fusobacterium nucleatum, and enterotoxigenic Bacteroides fragilis. The causal relationship of gut bacteria in tumorigenesis was established by introducing particular bacterial strains in in situ mouse CRC models. Detailed experimental protocols of bacterial gavage and the advantages and caveats of different experimental models are summarized in this review. The microbial genotoxins, enterotoxins, and virulence factors implicated in the mechanisms of bacteria-driven tumorigenesis are described. In conclusion, intestinal microbiota is involved in colon tumorigenesis. Bacteria-targeting intervention would be the next challenge for CRC.}, }
@article {pmid30087270, year = {2018}, author = {Gagliardi, A and Totino, V and Cacciotti, F and Iebba, V and Neroni, B and Bonfiglio, G and Trancassini, M and Passariello, C and Pantanella, F and Schippa, S}, title = {Rebuilding the Gut Microbiota Ecosystem.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {8}, pages = {}, pmid = {30087270}, issn = {1660-4601}, mesh = {Dysbiosis/microbiology/*prevention &amp; control ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Microbial Consortia ; Phage Therapy ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage/therapeutic use ; Synbiotics/administration &amp; dosage ; }, abstract = {A microbial ecosystem in which bacteria no longer live in a mutualistic association is called dysbiotic. Gut microbiota dysbiosis is a condition related with the pathogenesis of intestinal illnesses (irritable bowel syndrome, celiac disease, and inflammatory bowel disease) and extra-intestinal illnesses (obesity, metabolic disorder, cardiovascular syndrome, allergy, and asthma). Dysbiosis status has been related to various important pathologies, and many therapeutic strategies aimed at restoring the balance of the intestinal ecosystem have been implemented. These strategies include the administration of probiotics, prebiotics, and synbiotics; phage therapy; fecal transplantation; bacterial consortium transplantation; and a still poorly investigated approach based on predatory bacteria. This review discusses the various aspects of these strategies to counteract intestinal dysbiosis.}, }
@article {pmid30085388, year = {2019}, author = {Cheng, YW and Phelps, E and Ganapini, V and Khan, N and Ouyang, F and Xu, H and Khanna, S and Tariq, R and Friedman-Moraco, RJ and Woodworth, MH and Dhere, T and Kraft, CS and Kao, D and Smith, J and Le, L and El-Nachef, N and Kaur, N and Kowsika, S and Ehrlich, A and Smith, M and Safdar, N and Misch, EA and Allegretti, JR and Flynn, A and Kassam, Z and Sharfuddin, A and Vuppalanchi, R and Fischer, M}, title = {Fecal microbiota transplantation for the treatment of recurrent and severe Clostridium difficile infection in solid organ transplant recipients: A multicenter experience.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {19}, number = {2}, pages = {501-511}, doi = {10.1111/ajt.15058}, pmid = {30085388}, issn = {1600-6143}, support = {UM1 AI104681/AI/NIAID NIH HHS/United States ; TL1 TR002382/TR/NCATS NIH HHS/United States ; //IU GI Divisional Research Grant/ ; UL1TR000454//National Center of Advancing Translational Sciences of the National Institutes of Health/ ; UL1 TR000454/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; UM1Al104681//National Institute of Allergy and Infectious Diseases of the National Institutes of Health/ ; }, abstract = {Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti-CDI antibiotics, respectively. Ninety-four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT-related adverse events (AE) occurred in 22.3% of cases, mainly comprising self-limiting conditions including nausea, abdominal pain, and FMT-related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT-related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus-seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non-CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.}, }
@article {pmid30083142, year = {2018}, author = {Niederwerder, MC and Constance, LA and Rowland, RRR and Abbas, W and Fernando, SC and Potter, ML and Sheahan, MA and Burkey, TE and Hesse, RA and Cino-Ozuna, AG}, title = {Fecal Microbiota Transplantation Is Associated With Reduced Morbidity and Mortality in Porcine Circovirus Associated Disease.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1631}, pmid = {30083142}, issn = {1664-302X}, abstract = {Porcine circovirus associated disease (PCVAD) is a term used to describe the multi-factorial disease syndromes caused by porcine circovirus type 2 (PCV-2), which can be reproduced in an experimental setting through the co-infection of pigs with PCV-2 and porcine reproductive and respiratory syndrome virus (PRRSV). The resulting PCVAD-affected pigs represent a subpopulation within the co-infected group. In co-infection studies, the presence of increased microbiome diversity is linked to a reduction in clinical signs. In this study, fecal microbiota transplantation (FMT) was investigated as a means to prevent PCVAD in pigs co-infected with PRRSV and PCV-2d. The sources of the FMT material were high-parity sows with a documented history of high health status and robust litter characteristics. The analysis of the donated FMT material showed the absence of common pathogens along with the presence of diverse microbial phyla and families. One group of pigs (n = 10) was administered the FMT while a control group (n = 10) was administered a sterile mock-transplant. Over the 42-day post-infection period, the FMT group showed fewer PCVAD-affected pigs, as evidenced by a significant reduction in morbidity and mortality in transplanted pigs, along with increased antibody levels. Overall, this study provides evidence that FMT decreases the severity of clinical signs following co-infection with PRRSV and PCV-2 by reducing the prevalence of PCVAD.}, }
@article {pmid30081949, year = {2018}, author = {Montassier, E and Al-Ghalith, GA and Hillmann, B and Viskocil, K and Kabage, AJ and McKinlay, CE and Sadowsky, MJ and Khoruts, A and Knights, D}, title = {CLOUD: a non-parametric detection test for microbiome outliers.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {137}, pmid = {30081949}, issn = {2049-2618}, mesh = {Bacteria/*classification ; Clostridium Infections/microbiology/*therapy ; Clostridium difficile/pathogenicity ; Computational Biology/*methods ; Dysbiosis/*diagnosis ; Enterocolitis/microbiology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; }, abstract = {BACKGROUND: Dysbiosis of the human gut microbiome is defined as a maladaptive or clinically relevant deviation of the community profile from the healthy or normal state. Dysbiosis has been implicated in an extensive set of metabolic, auto-immune, and infectious diseases, and yet there is substantial inter-individual variation in microbiome composition even within body sites of healthy humans. An individual's microbiome varies over time in a high-dimensional space to form their personal microbiome cloud. This cloud may or may not be similar to that of other people, both in terms of the average microbiome profile (conformity) and the diameter of the cloud (stability). However, there is currently no robust non-parametric test that determines whether a patient's microbiome cloud is an outlier with respect to a reference group of healthy individuals with widely varying microbiome profiles.<br><br>METHODS: Here, we propose a test for outliers' detection in the human gut microbiome that accounts for the wide range of microbiome phenotypes observed in a typical set of healthy individuals and for intra-individual temporal variation. Our robust nonparametric outlier detection test, the CLOUD test, performs two assessments of a patient's microbiome health: conformity, the extent to which the patient's microbiome cloud is ecologically similar to a subset of healthy subjects; and stability, which compares the cloud diameter of a patient to those of healthy subjects. The CLOUD test is based on locally linear embedded ecological distances, allowing it to account for widely varying microbiome compositions among reference individuals. It also leverages temporal variability within patients and reference individuals to increase the robustness of the test.<br><br>RESULTS: We describe the CLOUD test, and we apply it to one novel and two previously published cohorts of patients receiving fecal microbiota transplantation for recurrent Clostridium difficile colitis, as well as to two known healthy cohorts, demonstrating high concordance of the CLOUD conformity and stability indices with clinical outcomes.<br><br>CONCLUSIONS: Although the CLOUD test is not, on its own, a test for clinical dysbiosis, it nonetheless provides a framework for outlier testing that could be incorporated into evaluation of suspected dysbiosis, which may play a role in diagnosis and prognosis of numerous pediatric and adult diseases.}, }
@article {pmid30078058, year = {2018}, author = {Singh, S}, title = {Evolution of Clinical Trials in Inflammatory Bowel Diseases.}, journal = {Current gastroenterology reports}, volume = {20}, number = {9}, pages = {41}, pmid = {30078058}, issn = {1534-312X}, mesh = {Clinical Trials as Topic/*standards ; Endoscopy, Gastrointestinal/standards ; Fecal Microbiota Transplantation ; Humans ; Inflammatory Bowel Diseases/*diagnosis/*therapy ; Patient Reported Outcome Measures ; }, abstract = {PURPOSE OF REVIEW: Since the first clinical trial of cortisone in ulcerative colitis in 1955, remarkable progress has been made in the design and conduct of clinical trials in inflammatory bowel diseases (IBD). In this review article, we will discuss evolution of clinical trials in IBD over the last 3-5 years.<br><br>RECENT FINDINGS: Recognizing limitations intrinsic to clinical disease activity indices in IBD, regulatory authorities have recommended evaluating co-primary endpoints of patient-reported outcomes and endoscopic disease activity in clinical trials. Biomarker-enriched trial enrolment and central endoscopy reading have emerged as critical events in trial recruitment and outcome assessment and have driven placebo response rates down. While trials of novel biologic therapies and advanced small molecules continue at an accelerated pace, pragmatic comparative efficacy trials of treatment strategy aimed at optimizing current therapies (such as early combined immunosuppression [REACT], tight disease control [CALM], therapeutic drug monitoring [TAXIT, TAILORIX]) have directly informed clinical practice. With emphasis on value-based care and population health management, multi-pronged remote monitoring, self-management, and telemedicine approaches in the era of smartphones have re-emerged with promise. Non-conventional therapies such as fecal microbiota transplantation, though still experimental, have provided insight into disease pathogenesis and offered hope for microbial manipulation strategies for treating these complex diseases. Clinical trials have rapidly evolved over the last 5 years not only focusing on novel therapies but also optimizing existing treatment approaches and population health management. Over the next decade, these trials will continue to advance the field, and be readily translatable into clinical practice.}, }
@article {pmid30077182, year = {2018}, author = {Ye, Z and Zhang, N and Wu, C and Zhang, X and Wang, Q and Huang, X and Du, L and Cao, Q and Tang, J and Zhou, C and Hou, S and He, Y and Xu, Q and Xiong, X and Kijlstra, A and Qin, N and Yang, P}, title = {A metagenomic study of the gut microbiome in Behcet's disease.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {135}, pmid = {30077182}, issn = {2049-2618}, mesh = {Animals ; Bacteria/*classification/genetics/isolation &amp; purification ; Bacterial Capsules/genetics ; Behcet Syndrome/*microbiology ; Case-Control Studies ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Gene Expression Regulation, Bacterial ; Humans ; Male ; Metagenomics/*methods ; Mice ; Phylogeny ; RNA, Ribosomal, 16S/*genetics ; Saliva/microbiology ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Behcet's disease (BD) is a recalcitrant, multisystemic inflammatory disease that can lead to irreversible blindness. Microbial agents have been considered to contribute to the pathogenesis of this disease, but the underlying mechanisms remain unclear. In this study, we investigated the association of gut microbiome composition with BD as well as its possible roles in the development of this disease.<br><br>METHODS: Fecal and saliva samples were collected from 32 active BD patients and 74 healthy controls. DNA extracted from fecal samples was subjected to metagenomic analysis, whereas DNA extracted from saliva samples was subjected to 16S rRNA gene sequencing analysis. The results were used to compare the composition and biological function of the microbiome between patients and healthy controls. Lastly, transplantation of pooled fecal samples from active BD patients into B10RIII mice undergoing experimental autoimmune uveitis (EAU) was performed to determine the causal relationship between the gut microbiome and BD.<br><br>RESULTS: Fecal samples from active BD patients were shown to be enriched in Bilophila spp., a sulfate-reducing bacteria (SRB) and several opportunistic pathogens (e.g., Parabacteroides spp. and Paraprevotella spp.) along with a lower level of butyrate-producing bacteria (BPB) Clostridium spp. and methanogens (Methanoculleus spp. Methanomethylophilus spp.). Analysis of microbial functions revealed that capsular polysaccharide transport system, oxidation-reduction process, type III, and type IV secretion systems were also increased in active BD patients. Network analysis showed that the BD-enriched SRB and opportunistic pathogens were positively correlated with each other, but they were negatively associated with the BPB and methanogens. Animal experiments revealed that fecal microbiota transplantation with feces from BD patients significantly exacerbated EAU activity and increased the production of inflammatory cytokines including IL-17 and IFN-γ.<br><br>CONCLUSIONS: Our findings revealed that BD is associated with considerable gut microbiome changes, which is corroborated by a mouse study of fecal microbiota transplants. A model explaining the association of the gut microbiome composition with BD pathogenesis is proposed.}, }
@article {pmid30075573, year = {2018}, author = {Chehri, M and Christensen, AH and Halkjær, SI and Günther, S and Petersen, AM and Helms, M}, title = {Case series of successful treatment with fecal microbiota transplant (FMT) oral capsules mixed from multiple donors even in patients previously treated with FMT enemas for recurrent Clostridium difficile infection.}, journal = {Medicine}, volume = {97}, number = {31}, pages = {e11706}, pmid = {30075573}, issn = {1536-5964}, mesh = {Adult ; Aged ; Aged, 80 and over ; Capsules ; Clostridium Infections/*therapy ; Denmark ; Drug Administration Routes ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; }, abstract = {RATIONALE: Studies have shown that fecal microbiota transplantation (FMT) is a safe and highly efficient treatment for recurrent Clostridium difficile infection (rCDI). However, it is still unknown if one versus multiple donors or enemas versus capsule FMT are most efficient.<br><br>PATIENT CONCERNS: 10 patients with at least 3 previous episodes of CDI were offered treatment with FMT capsules. 9 patients decided to participate.<br><br>DIAGNOSES: In this study, we treated 9 patients (25-86 years) with rCDI.<br><br>INTERVENTIONS: From October to November 2016, a total of 9 patients with recurrent CDI were treated with oral fecal microbiota capsules, with mixed donor feces from 4 donors with high microbiota diversity. All patients received treatment with vancomycin prior to the capsule regime.<br><br>OUTCOME: Patients had previous recurrences ranging from 2 to 10 recurrences. All 9 patients were successfully treated without recurrence after 180 days follow-up, even 2 patients previously treated with FMT enemas.<br><br>LESSONS: FMT capsules based on multiple donors are highly efficient in patients with rCDI.}, }
@article {pmid30057174, year = {2018}, author = {Jacobson, A and Lam, L and Rajendram, M and Tamburini, F and Honeycutt, J and Pham, T and Van Treuren, W and Pruss, K and Stabler, SR and Lugo, K and Bouley, DM and Vilches-Moure, JG and Smith, M and Sonnenburg, JL and Bhatt, AS and Huang, KC and Monack, D}, title = {A Gut Commensal-Produced Metabolite Mediates Colonization Resistance to Salmonella Infection.}, journal = {Cell host &amp; microbe}, volume = {24}, number = {2}, pages = {296-307.e7}, pmid = {30057174}, issn = {1934-6069}, support = {R01 AI116059/AI/NIAID NIH HHS/United States ; T32 AI007290/AI/NIAID NIH HHS/United States ; R01 AI089722/AI/NIAID NIH HHS/United States ; F32 AI133917/AI/NIAID NIH HHS/United States ; R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 GM007276/GM/NIGMS NIH HHS/United States ; P50 GM107615/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacterial Shedding/physiology ; Bacteroides/physiology ; Cation Transport Proteins/genetics/metabolism ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Host-Pathogen Interactions/*physiology ; Intestinal Diseases/microbiology ; Male ; Mice, Inbred C57BL ; Propionates/*metabolism ; Salmonella Infections/*etiology ; Salmonella typhimurium/*pathogenicity ; }, abstract = {The intestinal microbiota provides colonization resistance against pathogens, limiting pathogen expansion and transmission. These microbiota-mediated mechanisms were previously identified by observing loss of colonization resistance after antibiotic treatment or dietary changes, which severely disrupt microbiota communities. We identify a microbiota-mediated mechanism of colonization resistance against Salmonella enterica serovar Typhimurium (S. Typhimurium) by comparing high-complexity commensal communities with different levels of colonization resistance. Using inbred mouse strains with different infection dynamics and S. Typhimurium intestinal burdens, we demonstrate that Bacteroides species mediate colonization resistance against S. Typhimurium by producing the short-chain fatty acid propionate. Propionate directly inhibits pathogen growth in vitro by disrupting intracellular pH homeostasis, and chemically increasing intestinal propionate levels protects mice from S. Typhimurium. In addition, administering susceptible mice Bacteroides, but not a propionate-production mutant, confers resistance to S. Typhimurium. This work provides mechanistic understanding into the role of individualized microbial communities in host-to-host variability of pathogen transmission.}, }
@article {pmid30055267, year = {2019}, author = {Vaughn, BP and Rank, KM and Khoruts, A}, title = {Fecal Microbiota Transplantation: Current Status in Treatment of GI and Liver Disease.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {17}, number = {2}, pages = {353-361}, doi = {10.1016/j.cgh.2018.07.026}, pmid = {30055267}, issn = {1542-7714}, abstract = {Fecal microbiota transplantation was originally introduced as a method to repair intestinal microbiota following failure of multiple treatments of recurrent Clostridiumdifficile infection with antibiotics. However, it is hypothesized that intestinal dysbiosis may contribute to the pathogenesis of many diseases, especially those involving the gastrointestinal tract. Therefore, fecal microbiota transplantation is increasingly being explored as a potential treatment that aims to optimize microbiota composition and functionality. Here, we review the current state of fecal microbiota transplantation development and applications in conditions of greatest interest to a gastroenterologist.}, }
@article {pmid30054112, year = {2019}, author = {Su, HJ and Chiu, YT and Chiu, CT and Lin, YC and Wang, CY and Hsieh, JY and Wei, SC}, title = {Inflammatory bowel disease and its treatment in 2018: Global and Taiwanese status updates.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {118}, number = {7}, pages = {1083-1092}, doi = {10.1016/j.jfma.2018.07.005}, pmid = {30054112}, issn = {0929-6646}, abstract = {The global incidence and prevalence of inflammatory bowel disease (IBD) has increased over the last 2-4 decades, likely because of the adoption of a more &quot;western&quot; lifestyle as well as improved detection and awareness, and Taiwan is no exception. To characterize the increasing burden of IBD, we conducted a comprehensive review of IBD in the existing literature. The following parameters were reviewed: background knowledge and current standard care for IBD, including natural history, epidemiology, pathogenesis, diagnosis, monitoring, and treatment. In addition, new imaging modalities and treatment options such as combined positron emission tomography and magnetic resonance enterography, new biologic agents, small-molecule therapy, biosimilar therapeutics, mesenchymal stem cell transplantation, and fecal microbiota transplantation, all of which have been introduced for IBD management, were reviewed. We also used the hospital-based as well as population-based Taiwan National Health Insurance Research Database to assess Taiwan-specific trends for comparison with global trends.}, }
@article {pmid30052094, year = {2018}, author = {Laing, B and Barnett, MPG and Marlow, G and Nasef, NA and Ferguson, LR}, title = {An update on the role of gut microbiota in chronic inflammatory diseases, and potential therapeutic targets.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {12}, number = {10}, pages = {969-983}, doi = {10.1080/17474124.2018.1505497}, pmid = {30052094}, issn = {1747-4132}, mesh = {Age Factors ; Diet ; Dysbiosis/*complications/*therapy ; Environment ; Exercise ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/genetics/immunology/*physiology ; Humans ; Inflammation/*microbiology ; Intestinal Mucosa/immunology/*physiology ; Probiotics/therapeutic use ; }, abstract = {INTRODUCTION: The human microbiome plays a critical role in human health, having metabolic, protective, and trophic functions, depending upon its' exact composition. This composition is affected by a number of factors, including the genetic background of the individual, early life factors (including method of birth, length of breastfeeding) and nature of the diet and other environmental exposures (including cigarette smoking) and general life habits. It plays a key role in the control of inflammation, and in turn, its' composition is significantly influenced by inflammation. Areas covered: We consider metabolic, protective, and trophic functions of the microbiome and influences through the lifespan from post-partum effects, to diet later in life in healthy older adults, the effects of aging on both its' composition, and influence on health and potential therapeutic targets that may have anti-inflammatory effects. Expert commentary: The future will see the growth of more effective therapies targeting the microbiome particularly with respect to the use of specific nutrients and diets personalized to the individual.}, }
@article {pmid30048534, year = {2018}, author = {Jiang, M and Leung, NH and Ip, M and You, JHS}, title = {Cost-effectiveness analysis of ribotype-guided fecal microbiota transplantation in Chinese patients with severe Clostridium difficile infection.}, journal = {PloS one}, volume = {13}, number = {7}, pages = {e0201539}, pmid = {30048534}, issn = {1932-6203}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Asian Continental Ancestry Group ; China/epidemiology ; Clostridium Infections/economics/epidemiology/*therapy ; Clostridium difficile/classification/*genetics ; Cost-Benefit Analysis ; Decision Support Techniques ; Enterocolitis, Pseudomembranous/economics/epidemiology/*therapy ; Fecal Microbiota Transplantation/*economics/*methods/statistics &amp; numerical data ; Female ; Gene Frequency ; Humans ; Male ; Middle Aged ; *Ribotyping/economics/methods ; Severity of Illness Index ; Survival Rate ; Treatment Outcome ; Vancomycin/therapeutic use ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) caused by ribotype 002 strain is associated with poor outcomes in Chinese patients. Fecal microbiota transplantation (FMT) is an effective but costly treatment for CDI. We aimed to examine potential cost-effectiveness of ribotype-guided FMT in Chinese patients with severe CDI.<br><br>METHODS: A decision-analytic model was designed to simulate outcomes of ribotype 002-guided FMT versus vancomycin treatment in Chinese patients with severe CDI in the hospital setting. Outcome measures included mortality rate; direct medical cost; and quality-adjusted life year (QALY) loss for CDI. Sensitivity analysis was performed to examine robustness of base-case results.<br><br>RESULTS: Comparing to vancomycin treatment, ribotype-guided FMT group reduced mortality (11.6% versus 17.1%), cost (USD8,807 versus USD9,790), and saved 0.472 QALYs in base-case analysis. One-way sensitivity analysis found the ribotype-guided FMT group to remain cost-effective when patient acceptance rate of FMT was >0.6% and ribotype 002 prevalence was >0.07%. In probabilistic sensitivity analysis, ribotype-guided FMT gained higher QALYs at 100% of simulations with mean QALY gain of 0.405 QALYs (95%CI: 0.400-0.410; p<0.001). The ribotype-guided group was less costly in 97.9% of time, and mean cost-saving was USA679 (95%CI: 670-688; p<0.001).<br><br>CONCLUSIONS: In the present model, ribotype-guided FMT appears to be a potential option to save QALYs and cost when comparing with vancomycin. The cost-effectiveness of ribotype-guided FMT is subject to the patient acceptance to FMT and prevalence of ribotype 002.}, }
@article {pmid30047327, year = {2019}, author = {Mogilnicka, I and Ufnal, M}, title = {Gut Mycobiota and Fungal Metabolites in Human Homeostasis.}, journal = {Current drug targets}, volume = {20}, number = {2}, pages = {232-240}, doi = {10.2174/1389450119666180724125020}, pmid = {30047327}, issn = {1873-5592}, abstract = {BACKGROUND: Accumulating evidence suggests that microbiota play an important role in host's homeostasis. Thus far, researchers have mostly focused on the role of bacterial microbiota. However, human gut is a habitat for several fungal species, which produce numerous metabolites. Furthermore, various types of food and beverages are rich in a wide spectrum of fungi and their metabolites.<br><br>METHODS: We searched PUBMED and Google Scholar databases to identify clinical and pre-clinical studies on fungal metabolites, composition of human mycobiota and fungal dysbiosis.<br><br>RESULTS: Fungal metabolites may serve as signaling molecules and exert significant biological effects including trophic, anti-inflammatory or antibacterial actions. Finally, research suggests an association between shifts in gut fungi composition and human health. Changes in mycobiota composition have been found in obesity, hepatitis and inflammatory bowel diseases.<br><br>CONCLUSION: The influence of mycobiota and dietary fungi on homeostasis in mammals suggests a pharmacotherapeutic potential of modulating the mycobiota which may include treatment with probiotics and fecal transplantation. Furthermore, antibacterial action of fungi-derived molecules may be considered as a substitution for currently used antibacterial agents and preservatives in food industry.}, }
@article {pmid30031625, year = {2019}, author = {Leclercq, S and Stärkel, P and Delzenne, NM and de Timary, P}, title = {The gut microbiota: A new target in the management of alcohol dependence?.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {74}, number = {}, pages = {105-111}, doi = {10.1016/j.alcohol.2018.03.005}, pmid = {30031625}, issn = {1873-6823}, abstract = {The gastrointestinal tract is the natural habitat for a huge community of microorganisms, comprising bacteria, viruses, fungi and yeast. This microbial ecosystem codevelops with the host throughout life and is subject to a complex interplay that depends on multiple factors including host genetics, nutrition, life-style, stress, diseases and antibiotics use. The gut microbiota, that refers to intestinal bacteria, has profound influence on the host immune system, metabolism and nervous system. Indeed, intestinal bacteria supply the host with essential nutrients such as vitamins, metabolize bile acids and undigested compounds, defend against pathogen invasion, participate to the development of the intestinal architecture and the intestinal immune system and play an important role in the maintenance of the gut barrier function. More recently, the gut microbiota has been shown to influence brain functions, such as myelin synthesis, the blood-brain barrier permeability and neuroinflammatory responses but also mood and behavior. The cross-talk between microbes and the host implicates a vast array of signaling pathways that involve many different classes of molecules like metabolites produced by the bacteria from dietary or endogenous sources of carbohydrates and proteins (i.e. short-chain fatty acids (SCFAs), indole), neurotransmitters and inflammatory cytokines. This review will focus on the involvement of the gut microbiota in the pathophysiological aspects of alcohol dependence related to the gut barrier function, liver damage and psychological disturbances. We will also discuss the possibility to create new and realistic humanized animal models of alcohol dependence by the use of fecal transplantation.}, }
@article {pmid30025704, year = {2018}, author = {McDonald, JAK and Mullish, BH and Pechlivanis, A and Liu, Z and Brignardello, J and Kao, D and Holmes, E and Li, JV and Clarke, TB and Thursz, MR and Marchesi, JR}, title = {Inhibiting Growth of Clostridioides difficile by Restoring Valerate, Produced by the Intestinal Microbiota.}, journal = {Gastroenterology}, volume = {155}, number = {5}, pages = {1495-1507.e15}, doi = {10.1053/j.gastro.2018.07.014}, pmid = {30025704}, issn = {1528-0012}, support = {P62104//Medical Research Council/United Kingdom ; 107660/Z/15Z//Wellcome Trust/United Kingdom ; MR/R000875/1//Medical Research Council/United Kingdom ; MR/L009226/1//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Bile Acids and Salts/analysis ; Chromatography, High Pressure Liquid ; Clindamycin/pharmacology ; Clostridium Infections/*therapy ; Clostridium difficile/*drug effects/growth &amp; development ; Feces/chemistry ; Female ; Gas Chromatography-Mass Spectrometry ; *Gastrointestinal Microbiome ; Magnetic Resonance Spectroscopy ; Mice, Inbred C57BL ; Spores, Bacterial ; Triglycerides/therapeutic use ; Valerates/metabolism/*pharmacology ; }, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) is effective for treating recurrent Clostridioides difficile infection (CDI), but there are concerns about its long-term safety. Understanding the mechanisms of the effects of FMT could help us design safer, targeted therapies. We aimed to identify microbial metabolites that are important for C difficile growth.<br><br>METHODS: We used a CDI chemostat model as a tool to study the effects of FMT in vitro. The following analyses were performed: C difficile plate counts, 16S rRNA gene sequencing, proton nuclear magnetic resonance spectroscopy, and ultra-performance liquid chromatography and mass spectrometry bile acid profiling. FMT mixtures were prepared using fresh fecal samples provided by donors enrolled in an FMT program in the United Kingdom. Results from chemostat experiments were validated using human stool samples, C difficile batch cultures, and C57BL/6 mice with CDI. Human stool samples were collected from 16 patients with recurrent CDI and healthy donors (n = 5) participating in an FMT trial in Canada.<br><br>RESULTS: In the CDI chemostat model, clindamycin decreased valerate and deoxycholic acid concentrations and increased C difficile total viable counts and valerate precursors, taurocholic acid, and succinate concentrations. After we stopped adding clindamycin, levels of bile acids and succinate recovered, whereas levels of valerate and valerate precursors did not. In the CDI chemostat model, FMT increased valerate concentrations and decreased C difficile total viable counts (94% decrease), spore counts (86% decrease), and valerate precursor concentrations; concentrations of bile acids were unchanged. In stool samples from patients with CDI, valerate was depleted before FMT but restored after FMT. Clostridioides difficile batch cultures confirmed that valerate decreased vegetative growth, and that taurocholic acid was required for germination but had no effect on vegetative growth. Clostridioides difficile total viable counts were decreased by 95% in mice with CDI given glycerol trivalerate compared with phosphate buffered saline.<br><br>CONCLUSIONS: We identified valerate as a metabolite that is depleted with clindamycin and only recovered with FMT. Valerate is a target for a rationally designed recurrent CDI therapy.}, }
@article {pmid30011107, year = {2018}, author = {Lin, SC and Alonso, CD and Moss, AC}, title = {Fecal microbiota transplantation for recurrent Clostridium difficile infection in patients with solid organ transplants: an institutional experience and review of the literature.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {20}, number = {6}, pages = {e12967}, doi = {10.1111/tid.12967}, pmid = {30011107}, issn = {1399-3062}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Bacterial Toxins/isolation &amp; purification ; Clostridium Infections/diagnosis/microbiology/*therapy ; Clostridium difficile/*isolation &amp; purification ; Colonoscopy/methods ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Humans ; Kidney Transplantation/*adverse effects ; Male ; Middle Aged ; Pancreas Transplantation/*adverse effects ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridium difficile, an anaerobic gram-positive, spore-forming bacillus, has become the most common cause of nosocomial infectious diarrhea, and is associated with increased mortality in all populations. Patients who have received solid organ transplants (SOT) are at increased risk of Clostridium difficile infection (CDI) and CDI recurrence (rCDI). This may be related to chronic immunosuppression, frequent antibiotic exposure, and increased or prolonged hospitalizations. Increased morbidity and mortality from CDI is well-described in SOT patients. Conventional treatments for index and recurrent CDI include vancomycin and fidaxomicin. Fecal microbiota transplantation has emerged as an effective and safe alternative for treating rCDI in the general population. Reports of its safety in certain immunocompromised populations, such as those with inflammatory bowel disease, appear reassuring, but outcomes among SOT patients are less well known. Here, we summarize the experiences published to date on the treatment of rCDI with FMT in SOT patient, and also describe our detailed FMT protocol and experience in treating a series of SOT patients with rCDI. In addition to reporting the safety and efficacy of our FMT experience, we also discuss the diagnostic challenges and considerations in this population of solid organ transplant recipients.}, }
@article {pmid30010747, year = {2018}, author = {Nusbaum, DJ and Sun, F and Ren, J and Zhu, Z and Ramsy, N and Pervolarakis, N and Kunde, S and England, W and Gao, B and Fiehn, O and Michail, S and Whiteson, K}, title = {Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitis patients.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, doi = {10.1093/femsec/fiy133}, pmid = {30010747}, issn = {1574-6941}, support = {R01 GM120624/GM/NIGMS NIH HHS/United States ; R01 HD081197/HD/NICHD NIH HHS/United States ; T32 EB009418/EB/NIBIB NIH HHS/United States ; R56 HL126754/HL/NHLBI NIH HHS/United States ; }, mesh = {Child ; Clostridiaceae/classification/genetics/*isolation &amp; purification ; Colitis, Ulcerative/*microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Metabolomics ; Metagenomics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Ulcerative colitis is a chronic inflammatory disease of the colon that carries a significant disease burden in children. Therefore, new therapeutic approaches are being explored to help children living with this disease. Fecal microbiota transplantation (FMT) has been successful in some children with ulcerative colitis. However, the mechanism of its therapeutic effect in this patient population is not well understood. To characterize changes in gut microbial and metabolomic profiles after FMT, we performed 16S rRNA gene sequencing, shotgun metagenomic sequencing, virome analysis and untargeted metabolomics by gas chromatography-time of flight-mass spectrometry on stool samples collected before and after FMT from four children with ulcerative colitis who responded to this treatment. Alpha diversity of the gut microbiota increased after intervention, with species richness rising from 251 (S.D. 125) to 358 (S.D. 27). In responders, the mean relative abundance of bacteria in the class Clostridia shifted toward donor levels, increasing from 33% (S.D. 11%) to 54% (S.D. 16%). Patient metabolomic and viromic profiles exhibited a similar but less pronounced shift toward donor profiles after FMT. The fecal concentrations of several metabolites were altered after FMT, correlating with clinical improvement. Larger studies using a similar multi-omics approach may suggest novel strategies for the treatment of pediatric ulcerative colitis.}, }
@article {pmid30010734, year = {2018}, author = {Geng, S and Cheng, S and Li, Y and Wen, Z and Ma, X and Jiang, X and Wang, Y and Han, X}, title = {Faecal Microbiota Transplantation Reduces Susceptibility to Epithelial Injury and Modulates Tryptophan Metabolism of the Microbial Community in a Piglet Model.}, journal = {Journal of Crohn's &amp; colitis}, volume = {12}, number = {11}, pages = {1359-1374}, doi = {10.1093/ecco-jcc/jjy103}, pmid = {30010734}, issn = {1876-4479}, mesh = {Animals ; Colitis/chemically induced/pathology/*prevention &amp; control ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Homeostasis ; Indoleacetic Acids/metabolism ; Interleukins/metabolism ; Intestinal Mucosa/metabolism/*pathology ; Lipopolysaccharides ; Mass Spectrometry ; Metabolome ; RNA, Ribosomal, 16S/analysis ; Receptors, Aryl Hydrocarbon/metabolism ; Swine ; Tryptophan/*metabolism ; }, abstract = {Background and Aims: Faecal microbiota transplantation [FMT] has shown promise as a treatment for inflammatory bowel disease [IBD]. Using a piglet model, our previous study indicated that exogenous faecal microbiota can increase the expressions of tight junction proteins, mucin and antimicrobial peptide in the intestinal mucosa, suggesting a beneficial effect of FMT on gut barrier and gastrointestinal health. However, specific connections between FMT-induced microbial changes and modulation of the intestinal barrier remain to be fully illustrated. Here, we aimed to determine the potential role of metabolic function of gut microbiota in the beneficial effects of FMT.<br><br>Methods: The influence of FMT on the maintenance of intestinal homeostasis was assessed by early-life gut microbiota intervention on newborn piglets and subsequent lipopolysaccharide [LPS] challenge. Analysis of the gut microbiome and metabolome was carried out by 16S rRNA gene sequencing and multiple mass spectrometry platforms.<br><br>Results: FMT modulated the diversity and composition of colonic microbiota and reduced the susceptibility to LPS-induced destruction of epithelial integrity and severe inflammatory response. Metabolomic analysis revealed functional changes of the gut metabolome along with a significant increase of the typical microbiota-derived tryptophan catabolite indole-3-acetic acid in the colonic lumen. In concordance with the metabolome data, metagenomics prediction analysis based on 16S rRNA gene sequencing also demonstrated that FMT modulated the metabolic functions of gut microbiota associated with indole alkaloid biosynthesis, cytochrome P450 and intestinal homeostasis, which coincided with up-regulation of cytokine interleukin-22 and enhanced activation of aryl hydrocarbon receptor in the recipient colon.<br><br>Conclusions: Our data reveal a regulatory effect of FMT on tryptophan metabolism of gut microbiota in the recipient colon, which may play a potential role in maintenance of the intestinal barrier.}, }
@article {pmid30009869, year = {2018}, author = {Cheminet, G and Kapel, N and Bleibtreu, A and Sadou-Yaye, H and Bellanger, A and Duval, X and Joly, F and Fantin, B and de Lastours, V and , }, title = {Faecal microbiota transplantation with frozen capsules for relapsing Clostridium difficile infections: the first experience from 15 consecutive patients in France.}, journal = {The Journal of hospital infection}, volume = {100}, number = {2}, pages = {148-151}, doi = {10.1016/j.jhin.2018.07.005}, pmid = {30009869}, issn = {1532-2939}, }
@article {pmid30007918, year = {2019}, author = {Wu, TR and Lin, CS and Chang, CJ and Lin, TL and Martel, J and Ko, YF and Ojcius, DM and Lu, CC and Young, JD and Lai, HC}, title = {Gut commensal Parabacteroides goldsteinii plays a predominant role in the anti-obesity effects of polysaccharides isolated from Hirsutella sinensis.}, journal = {Gut}, volume = {68}, number = {2}, pages = {248-262}, doi = {10.1136/gutjnl-2017-315458}, pmid = {30007918}, issn = {1468-3288}, mesh = {Animals ; *Ascomycota ; Bacteroidetes/*drug effects/*physiology ; Diabetes Mellitus, Type 2/*prevention &amp; control ; Diet, High-Fat ; Fecal Microbiota Transplantation ; Fungal Polysaccharides/*pharmacology ; Gastrointestinal Microbiome/*drug effects ; Insulin Resistance ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Weight ; Obesity/*prevention &amp; control ; Prebiotics ; Symbiosis ; }, abstract = {OBJECTIVE: The medicinal fungus Ophiocordyceps sinensis and its anamorph Hirsutella sinensis have a long history of use in traditional Chinese medicine for their immunomodulatory properties. Alterations of the gut microbiota have been described in obesity and type 2 diabetes. We examined the possibility that H. sinensis mycelium (HSM) and isolated fractions containing polysaccharides may prevent diet-induced obesity and type 2 diabetes by modulating the composition of the gut microbiota.<br><br>DESIGN: High-fat diet (HFD)-fed mice were treated with HSM or fractions containing polysaccharides of different molecular weights. The effects of HSM and polysaccharides on the gut microbiota were assessed by horizontal faecal microbiota transplantation (FMT), antibiotic treatment and 16S rDNA-based microbiota analysis.<br><br>RESULTS: Fraction H1 containing high-molecular weight polysaccharides (>300 kDa) considerably reduced body weight gain (∼50% reduction) and metabolic disorders in HFD-fed mice. These effects were associated with increased expression of thermogenesis protein markers in adipose tissues, enhanced gut integrity, reduced intestinal and systemic inflammation and improved insulin sensitivity and lipid metabolism. Gut microbiota analysis revealed that H1 polysaccharides selectively promoted the growth of Parabacteroides goldsteinii, a commensal bacterium whose level was reduced in HFD-fed mice. FMT combined with antibiotic treatment showed that neomycin-sensitive gut bacteria negatively correlated with obesity traits and were required for H1's anti-obesogenic effects. Notably, oral treatment of HFD-fed mice with live P. goldsteinii reduced obesity and was associated with increased adipose tissue thermogenesis, enhanced intestinal integrity and reduced levels of inflammation and insulin resistance.<br><br>CONCLUSIONS: HSM polysaccharides and the gut bacterium P. goldsteinii represent novel prebiotics and probiotics that may be used to treat obesity and type 2 diabetes.}, }
@article {pmid30004130, year = {2018}, author = {Inserra, A and Rogers, GB and Licinio, J and Wong, ML}, title = {The Microbiota-Inflammasome Hypothesis of Major Depression.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {40}, number = {9}, pages = {e1800027}, doi = {10.1002/bies.201800027}, pmid = {30004130}, issn = {1521-1878}, mesh = {Animals ; Depressive Disorder, Major/*metabolism/*pathology ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammasomes/*metabolism ; Inflammation/metabolism/microbiology ; Metabolic Networks and Pathways/physiology ; Signal Transduction/physiology ; }, abstract = {We propose the &quot;microbiota-inflammasome&quot; hypothesis of major depressive disorder (MDD, a mental illness affecting the way a person feels and thinks, characterized by long-lasting feelings of sadness). We hypothesize that pathological shifts in gut microbiota composition (dysbiosis) caused by stress and gut conditions result in the upregulation of pro-inflammatory pathways mediated by the Nod-like receptors family pyrin domain containing 3 (NLRP3) inflammasome (an intracellular platform involved in the activation of inflammatory processes). This upregulation exacerbates depressive symptomatology and further compounds gut dysbiosis. In this review we describe MDD/chronic stress-induced changes in: 1) NLRP3 inflammasome; 2) gut microbiota; and 3) metabolic pathways; and how inflammasome signaling may affect depressive-like behavior and gut microbiota composition. The implication is that novel therapeutic strategies could emerge for MDD and co-morbid conditions. A number of testable predictions surface from this microbiota-gut-inflammasome-brain hypothesis of MDD, using approaches that modulate gut microbiota composition via inflammasome modulation, fecal microbiota transplantation, psychobiotics supplementation, or dietary change.}, }
@article {pmid30003334, year = {2018}, author = {Adachi, K and Tamada, K}, title = {Microbial biomarkers for immune checkpoint blockade therapy against cancer.}, journal = {Journal of gastroenterology}, volume = {53}, number = {9}, pages = {999-1005}, pmid = {30003334}, issn = {1435-5922}, mesh = {Animals ; Antibodies, Monoclonal/therapeutic use ; Biomarkers, Tumor/*immunology ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunologic Factors/therapeutic use ; Immunotherapy/*methods ; Mice ; Molecular Targeted Therapy/*methods ; Neoplasms/*immunology/*therapy ; Programmed Cell Death 1 Receptor/immunology ; Treatment Outcome ; }, abstract = {Three major standard treatments, i.e., surgery, chemotherapy, and radiotherapy, were traditionally applied to the treatment of cancer and saved many patients. Meanwhile, clinical studies as well as basic research of immunotherapy are being actively conducted for intractable or advanced malignancies that cannot be cured by the conventional standard treatments. Remarkable therapeutic efficacies have been recently reported in clinical trials on some cancer types, and immunotherapy is now being recognized as the &quot;fourth&quot; standard therapy against cancer. In particular, immune checkpoint inhibitor therapy (ICI) has demonstrated the effectiveness of immunotherapy through large-scale randomized clinical trials, leading to the paradigm-shift in cancer treatment. Immune checkpoint molecules transduce co-inhibitory signals to immunocompetent cells including T cells, and crucially contribute to the formation of an immunosuppressive microenvironment in tumor tissues, which intrinsically confers the treatment resistance. Programmed death-1 (PD-1, CD279) is one of the typical immune checkpoint molecules. Anti-tumor therapies targeting PD-1 and its ligands had been developed and approved in many countries, and various studies utilizing clinical specimens are currently progressing. In this review, we provide an overview of the biomarkers based on the analysis of enteric microbiota that correlate with the clinical efficacy/inefficacy of PD-1-based therapy.}, }
@article {pmid29997912, year = {2018}, author = {Heimesaat, MM and Escher, U and Grunau, A and Fiebiger, U and Bereswill, S}, title = {Peroral Low-Dose Toxoplasma gondii Infection of Human Microbiota-Associated Mice - A Subacute Ileitis Model to Unravel Pathogen-Host Interactions.}, journal = {European journal of microbiology &amp; immunology}, volume = {8}, number = {2}, pages = {53-61}, pmid = {29997912}, issn = {2062-509X}, abstract = {Within 1 week following high-dose Toxoplasma gondii infection, mice develop lethal necrotizing ileitis. However, data from a subacute T. gondii-induced ileitis model are scarce. Therefore, mice harboring a human gut microbiota were perorally infected with one cyst of T. gondii. Within 9 days post-infection, the intestinal microbiota composition shifted towards higher loads of commensal enterobacteria and enterococci. Following T. gondii infection, mice were clinically only mildly affected, whereas ≈60% of mice displayed fecal blood and mild-to-moderate ileal histopathological changes. Intestinal inflammation was further characterized by increased apoptotic intestinal epithelial cells, which were accompanied by elevated proliferating gut epithelial cell numbers. As compared to naive controls, infected mice displayed elevated numbers of intestinal T lymphocytes and regulatory T-cells and increased pro-inflammatory mediator secretion. Remarkably, T. gondii-induced apoptotic and pro-inflammatory immune responses were not restricted to the gut, but could also be observed in extra-intestinal compartments including kidney, liver, and lung. Strikingly, low-dose T. gondii infection resulted in increased serum levels of pro- and anti-inflammatory cytokines. In conclusion, the here presented subacute ileitis model following peroral low-dose T. gondii infection of humanized mice allows for detailed investigations of the molecular mechanism underlying the &quot;ménage à trois&quot; of pathogens, human gut microbiota, and immunity.}, }
@article {pmid29997909, year = {2018}, author = {Escher, U and Giladi, E and Dunay, IR and Bereswill, S and Gozes, I and Heimesaat, MM}, title = {Anti-inflammatory Effects of the Octapeptide NAP in Human Microbiota-Associated Mice Suffering from Subacute Ileitis.}, journal = {European journal of microbiology &amp; immunology}, volume = {8}, number = {2}, pages = {34-40}, pmid = {29997909}, issn = {2062-509X}, abstract = {The octapeptide NAP is well known for its neuroprotective properties. We here investigated whether NAP treatment could alleviate pro-inflammatory immune responses during experimental subacute ileitis. To address this, mice with a human gut microbiota were perorally infected with one cyst of Toxoplasma gondii (day 0) and subjected to intraperitoneal synthetic NAP treatment from day 1 until day 8 postinfection (p.i.). Whereas placebo (PLC) control animals displayed subacute ileitis at day 9 p.i., NAP-treated mice exhibited less pronounced pro-inflammatory immune responses as indicated by lower numbers of intestinal mucosal T and B lymphocytes and lower interferon (IFN)-γ concentrations in mesenteric lymph nodes. The NAP-induced anti-inflammatory effects were not restricted to the intestinal tract but could also be observed in extra-intestinal including systemic compartments, given that pro-inflammatory cytokines were lower in liver, kidney, and lung following NAP as compared to PLC application, whereas at day 9 p.i., colonic and serum interleukin (IL)-10 concentrations were higher in the former as compared to the latter. Remarkably, probiotic commensal bifidobacterial loads were higher in the ileal lumen of NAP as compared to PLC-treated mice with ileitis. Our findings thus further support that NAP might be regarded as future treatment option directed against intestinal inflammation.}, }
@article {pmid29992140, year = {2018}, author = {Bai, T and Zhang, L and Wang, H and Qian, W and Song, J and Hou, X}, title = {Fecal Microbiota Transplantation Is Effective in Relieving Visceral Hypersensitivity in a Postinfectious Model.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {3860743}, pmid = {29992140}, issn = {2314-6141}, mesh = {Animals ; *Bifidobacterium ; *Fecal Microbiota Transplantation ; Feces ; Male ; Mice ; Microbiota ; Trichinella spiralis ; }, abstract = {Aim: To investigate the effect of fecal microbiota transplantation on visceral hypersensitivity compared with Bifidobacterium longum.<br><br>Methods: Mice visceral hypersensitivity was induced by Trichinella spiralis. After 8 weeks, they were divided into three groups (controls, Bifidobacterium longum, and fecal microbiota transplantation) and were daily treated by gavage with 0.2 ml PBS, Bifidobacterium longum HB55020, or fecal microbiota for 7 days. Visceral hypersensitivity was tested with abdominal withdrawal reflex. Permeability of colon epithelium was assessed with Ussing chamber.<br><br>Results: After administration of Bifidobacterium longum, compared with mice in postinfectious group, mice had higher pain threshold (p < 0.05). After administration of fecal microbiota, compared with mice in postinfectious group, mice had higher pain threshold (p < 0.05). Fecal microbiota transplantation was as effective as Bifidobacterium in relieving visceral hypersensitivity. Administration of Bifidobacterium longum or fecal microbiota transplantation improved colon epithelium permeability. Expression of occluding-1 was increased.<br><br>Conclusion: Manipulation of microbiota is effective in relieving visceral hypersensitivity. Fecal microbiota transplantation is as effective as Bifidobacterium longum administration.}, }
@article {pmid29991941, year = {2018}, author = {Moayyedi, P}, title = {Update on Fecal Microbiota Transplantation in Patients With Inflammatory Bowel Disease.}, journal = {Gastroenterology &amp; hepatology}, volume = {14}, number = {5}, pages = {319-322}, pmid = {29991941}, issn = {1554-7914}, }
@article {pmid29983136, year = {2019}, author = {Cheng, CS and Wei, HK and Wang, P and Yu, HC and Zhang, XM and Jiang, SW and Peng, J}, title = {Early intervention with faecal microbiota transplantation: an effective means to improve growth performance and the intestinal development of suckling piglets.}, journal = {Animal : an international journal of animal bioscience}, volume = {13}, number = {3}, pages = {533-541}, doi = {10.1017/S1751731118001611}, pmid = {29983136}, issn = {1751-732X}, mesh = {Animals ; Fecal Microbiota Transplantation/*veterinary ; *Gastrointestinal Microbiome ; Intestines/immunology/*physiology ; Random Allocation ; Sus scrofa/growth &amp; development/immunology/*microbiology/*physiology ; }, abstract = {Recent studies indicate that early postnatal period is a critical window for gut microbiota manipulation to optimise the immunity and body growth. This study investigated the effects of maternal faecal microbiota orally administered to neonatal piglets after birth on growth performance, selected microbial populations, intestinal permeability and the development of intestinal mucosal immune system. In total, 12 litters of crossbred newborn piglets were selected in this study. Litter size was standardised to 10 piglets. On day 1, 10 piglets in each litter were randomly allotted to the faecal microbiota transplantation (FMT) and control groups. Piglets in the FMT group were orally administrated with 2ml faecal suspension of their nursing sow per day from the age of 1 to 3 days; piglets in the control group were treated with the same dose of a placebo (0.1M potassium phosphate buffer containing 10% glycerol (vol/vol)) inoculant. The experiment lasted 21 days. On days 7, 14 and 21, plasma and faecal samples were collected for the analysis of growth-related hormones and cytokines in plasma and lipocalin-2, secretory immunoglobulin A (sIgA), selected microbiota and short-chain fatty acids (SCFAs) in faeces. Faecal microbiota transplantation increased the average daily gain of piglets during week 3 and the whole experiment period. Compared with the control group, the FMT group had increased concentrations of plasma growth hormone and IGF-1 on days 14 and 21. Faecal microbiota transplantation also reduced the incidence of diarrhoea during weeks 1 and 3 and plasma concentrations of zonulin, endotoxin and diamine oxidase activities in piglets on days 7 and 14. The populations of Lactobacillus spp. and Faecalibacterium prausnitzii and the concentrations of faecal and plasma acetate, butyrate and total SCFAs in FMT group were higher than those in the control group on day 21. Moreover, the FMT piglets have higher concentrations of plasma transforming growth factor-β and immunoglobulin G, and faecal sIgA than the control piglets on day 21. These findings indicate that early intervention with maternal faecal microbiota improves growth performance, decreases intestinal permeability, stimulates sIgA secretion, and modulates gut microbiota composition and metabolism in suckling piglets.}, }
@article {pmid29981382, year = {2018}, author = {Imangaliyev, S and Prodan, A and Nieuwdorp, M and Groen, AK and van Riel, NAW and Levin, E}, title = {Domain intelligible models.}, journal = {Methods (San Diego, Calif.)}, volume = {149}, number = {}, pages = {69-73}, doi = {10.1016/j.ymeth.2018.06.011}, pmid = {29981382}, issn = {1095-9130}, mesh = {*Algorithms ; Gastrointestinal Microbiome/*physiology ; Humans ; Metagenome/*physiology ; *Models, Biological ; *Phylogeny ; }, abstract = {Mining biological information from rich &quot;-omics&quot; datasets is facilitated by organizing features into groups that are related to a biological phenomenon or clinical outcome. For example, microorganisms can be grouped based on a phylogenetic tree that depicts their similarities regarding genetic or physical characteristics. Here, we describe algorithms that incorporate auxiliary information in terms of groups of predictors and the relationships between them into the metagenome learning task to build intelligible models. In particular, our cost function guides the feature selection process using auxiliary information by requiring related groups of predictors to provide similar contributions to the final response. We apply the developed algorithms to a recently published dataset analyzing the effects of fecal microbiota transplantation (FMT) in order to identify factors that are associated with improved peripheral insulin sensitivity, leading to accurate predictions of the response to the FMT.}, }
@article {pmid29980607, year = {2018}, author = {Halkjær, SI and Christensen, AH and Lo, BZS and Browne, PD and Günther, S and Hansen, LH and Petersen, AM}, title = {Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study.}, journal = {Gut}, volume = {67}, number = {12}, pages = {2107-2115}, doi = {10.1136/gutjnl-2018-316434}, pmid = {29980607}, issn = {1468-3288}, mesh = {Adolescent ; Adult ; Double-Blind Method ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/microbiology/*therapy ; Male ; Middle Aged ; Psychometrics ; Quality of Life ; Severity of Illness Index ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: IBS is associated with an intestinal dysbiosis and faecal microbiota transplantation (FMT) has been hypothesised to have a positive effect in patients with IBS. We performed a randomised, double-blind placebo-controlled trial to investigate if FMT resulted in an altered gut microbiota and improvement in clinical outcome in patients with IBS.<br><br>DESIGN: We performed this study in 52 adult patients with moderate-to-severe IBS. At the screening visit, clinical history and symptoms were assessed and faecal samples were collected. Patients were randomised to FMT or placebo capsules for 12 days and followed for 6 months. Study visits were performed at baseline, 1, 3 and 6 months, where patients were asked to register their symptoms using the IBS-severity scoring system (IBS-SSS) and IBS-specific quality of life (IBS-QoL). Prior to each visit, faecal samples were collected.<br><br>RESULTS: A significant difference in improvement in IBS-SSS score was observed 3 months after treatment (p=0.012) favouring placebo. This was similar for IBS-QoL data after 3 months (p=0.003) favouring placebo. Patients receiving FMT capsules had an increase in faecal microbial biodiversity while placebos did not.<br><br>CONCLUSION: In this randomised double-blinded placebo-controlled study, we found that FMT changed gut microbiota in patients with IBS. But patients in the placebo group experienced greater symptom relief compared with the FMT group after 3 months. Altering the gut microbiota is not enough to obtain clinical improvement in IBS. However, different study designs and larger studies are required to examine the role of FMT in IBS.<br><br>TRIAL REGISTRATION NUMBER: NCT02788071.}, }
@article {pmid29976114, year = {2018}, author = {Wang, J and Wang, P and Tian, H and Tian, F and Zhang, Y and Zhang, L and Gao, X and Wang, X}, title = {Aryl hydrocarbon receptor/IL-22/Stat3 signaling pathway is involved in the modulation of intestinal mucosa antimicrobial molecules by commensal microbiota in mice.}, journal = {Innate immunity}, volume = {24}, number = {5}, pages = {297-306}, doi = {10.1177/1753425918785016}, pmid = {29976114}, issn = {1753-4267}, mesh = {Animals ; Anti-Bacterial Agents ; Basic Helix-Loop-Helix Transcription Factors/antagonists &amp; inhibitors/*metabolism ; Carbazoles/administration &amp; dosage/pharmacology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Interleukins/*metabolism ; Intestinal Mucosa/*immunology ; Male ; Mice ; Mice, Inbred C57BL ; Pancreatitis-Associated Proteins/metabolism ; Protein Precursors/metabolism ; Receptors, Aryl Hydrocarbon/antagonists &amp; inhibitors/*metabolism ; STAT3 Transcription Factor/*metabolism ; Signal Transduction ; }, abstract = {Compelling evidence demonstrates the crucial role of the commensal microbiota in host physiology and the detrimental effects of its perturbations following antibiotic treatment. However, the effects of commensal microbiota on intestinal mucosa antimicrobial molecules have not been elucidated systematically. Here, we investigate the impacts of antibiotic-induced depletion and subsequent restoration of the intestinal microbiota on the murine antimicrobial molecules in intestinal mucosa. Our results demonstrate that depletion of commensal microbiota leads to intestinal mucosa atrophy and reduction of antimicrobial molecules, including lysozyme, regenerating islet-derived protein 3 gamma (RegIIIγ), and cryptdin 5 mRNA, whereas subsequent reconstitution of intestinal microbiota by fecal microbiota transplantation (FMT) rescues mucosa morphology and antimicrobials. Importantly, our study shows that down-regulation of aryl hydrocarbon receptor (AhR), interleukin-22 (IL-22), and phosphorylated Stat3 (p-Stat3) is associated with decreased antimicrobials, which might mediate the antibiotic-associated intestinal mucosa injury. Last, exogenous activation of the AhR/IL-22/Stat3 signaling pathway with the AhR agonist 6-formylindolo(3,2-b)carbazole (Ficz) rescued antimicrobial molecule levels markedly after antibiotic treatment to levels similar to those following reconstitution of intestinal microbiota by FMT. Together, our results demonstrate that the AhR/IL-22/Stat3 signaling pathway is involved in the modulation of intestinal mucosa antimicrobial molecules by commensal microbiota and suggest this pathway as a promising target in the treatment of antibiotic-associated gut barrier damage.}, }
@article {pmid29972839, year = {2018}, author = {Klag, T and Wehkamp, J}, title = {[Crohn's Disease - New Therapies].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {113}, number = {13}, pages = {953-959}, doi = {10.1055/a-0538-3671}, pmid = {29972839}, issn = {1439-4413}, mesh = {Anti-Bacterial Agents/therapeutic use ; Antibodies, Monoclonal/adverse effects/therapeutic use ; Antibodies, Monoclonal, Humanized/adverse effects/therapeutic use ; Clinical Trials as Topic ; Colitis, Ulcerative/immunology/*therapy ; Crohn Disease/immunology/*therapy ; Defensins/adverse effects/therapeutic use ; Fecal Microbiota Transplantation ; Humans ; Immunosuppressive Agents/adverse effects/therapeutic use ; Integrins/antagonists &amp; inhibitors ; Lecithins/therapeutic use ; Probiotics/adverse effects/therapeutic use ; Ustekinumab/therapeutic use ; }, abstract = {New promising treatment options for chronic inflammatory bowel diseases, confirm the expanded pathophysiological understanding in terms of the interactions of the gastrointestinal microbiome with the adaptive and innate immune response and barrier protection. Therefore, these interrelations are focus of research and therapeutic strategies. The following review will give insights into the pathomechanisms, current treatment options and future developments.}, }
@article {pmid29971061, year = {2018}, author = {Hu, J and Chen, L and Tang, Y and Xie, C and Xu, B and Shi, M and Zheng, W and Zhou, S and Wang, X and Liu, L and Yan, Y and Yang, T and Niu, Y and Hou, Q and Xu, X and Yan, X}, title = {Standardized Preparation for Fecal Microbiota Transplantation in Pigs.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1328}, pmid = {29971061}, issn = {1664-302X}, abstract = {The intestine of pigs harbors a mass of microorganisms which are essential for intestinal homeostasis and host health. Intestinal microbial disorders induce enteric inflammation and metabolic dysfunction, thereby causing adverse effects on the growth and health of pigs. In the human medicine, fecal microbiota transplantation (FMT), which engrafts the fecal microbiota from a healthy donor into a patient recipient, has shown efficacy in intestinal microbiota restoration. In addition, it has been used widely in therapy for human gastrointestinal diseases, including Clostridium difficile infection, inflammatory bowel diseases, and irritable bowel syndrome. Given that pigs share many similarities with humans, in terms of anatomy, nutritional physiology, and intestinal microbial compositions, FMT may also be used to restore the normal intestinal microbiota of pigs. However, feasible procedures for performing FMT in pigs remains unclear. Here, we summarize a standardized preparation for FMT in pigs by combining the standard methodology for human FMT with pig production. The key issues include the donor selection, fecal material preparation, fecal material transfer, stool bank establishment, and the safety for porcine FMT. Optimal donors should be selected to ensure the efficacy of porcine FMT and reduce the risks of transmitting infectious diseases to recipients during FMT. Preparing for fresh fecal material is highly recommended. Alternatively, frozen fecal suspension can also be prepared as an optimal choice because it is convenient and has similar efficacy. Oral administration of fecal suspension could be an optimal method for porcine fecal material transfer. Furthermore, the dilution ratio of fecal materials and the frequency of fecal material transfer could be adjusted according to practical situations in the pig industry. To meet the potential large-scale requirement in the pig industry, it is important to establish a stool bank to make porcine FMT readily available. Future studies should also focus on providing more robust safety data on FMT to improve the safety and tolerability of the recipient pigs. This standardized preparation for porcine FMT can facilitate the development of microbial targeted therapies and improve the intestinal health of pigs.}, }
@article {pmid29966323, year = {2018}, author = {Chai, J and Lee, CH}, title = {Management of Primary and Recurrent Clostridium difficile Infection: An Update.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {7}, number = {3}, pages = {}, pmid = {29966323}, issn = {2079-6382}, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections (HAI) in the United States and Canada, and incidence rates have increased worldwide in recent decades. Currently, antibiotics are the mainstay treatments for both primary and recurrent CDI, but their efficacy is limited, prompting further therapies to be developed. Aim: This review summarizes current and emerging therapies in CDI management including antibiotics, fecal microbiota transplantation, monoclonal antibodies, spore-based therapies, and vaccinations.}, }
@article {pmid29953876, year = {2018}, author = {van der Beek, CM and Canfora, EE and Kip, AM and Gorissen, SHM and Olde Damink, SWM and van Eijk, HM and Holst, JJ and Blaak, EE and Dejong, CHC and Lenaerts, K}, title = {The prebiotic inulin improves substrate metabolism and promotes short-chain fatty acid production in overweight to obese men.}, journal = {Metabolism: clinical and experimental}, volume = {87}, number = {}, pages = {25-35}, doi = {10.1016/j.metabol.2018.06.009}, pmid = {29953876}, issn = {1532-8600}, mesh = {Adult ; Appetite/drug effects ; Blood Glucose/analysis ; Cross-Over Studies ; Dietary Carbohydrates/metabolism ; Double-Blind Method ; Energy Metabolism/drug effects ; Fatty Acids, Volatile/*biosynthesis ; Feces/chemistry ; Humans ; Insulin/blood ; Inulin/pharmacology/*therapeutic use ; Lipids/blood ; Male ; Middle Aged ; Obesity/*drug therapy/*metabolism ; Overweight/*drug therapy/*metabolism ; Oxidation-Reduction ; *Prebiotics ; Satiety Response/drug effects ; Young Adult ; }, abstract = {BACKGROUND AND AIMS: Human gut microbiota play an important role in maintaining human health. Dietary fibers, i.e. prebiotics, are fermented by human gut microbiota into the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate. SCFAs promote fat oxidation and improve metabolic health. Therefore, the prebiotic inulin might be an effective dietary strategy to improve human metabolism. We aimed to investigate the acute metabolic effects of ingesting inulin compared with digestible carbohydrates and to trace inulin-derived SCFAs using stable isotope tracer methodology.<br><br>METHODS: In a double-blind, randomized, placebo-controlled crossover design, 14 healthy, overweight to obese men consumed a high-fat milkshake containing A) 24 g inulin of which 0.5 g was U-13C-inulin (INU) or B) 24 g maltodextrin placebo (PLA), with a wash-out period of at least five days. Fat oxidation was measured via an open-circuit ventilated hood and blood samples were collected up to 7 h after ingestion. Plasma, breath, and fecal samples were collected, and appetite and satiety scores were assessed.<br><br>RESULTS: Fat oxidation increased in the early postprandial phase (0-3 h), and both plasma glucose and insulin were lower after INU ingestion compared with PLA (all P < 0.05). Plasma free fatty acids were higher in the early, and lower in the late postprandial period after INU ingestion. Inulin was fermented into SCFAs as indicated by higher plasma acetate concentrations after INU compared with PLA (P < 0.05). In addition, we found continuous increases in plasma 13C-SCFA enrichments (P < 0.05 from t = 120 onwards) and breath 13CO2 enrichments after INU intake. There were no effects on plasma triglycerides, free glycerol, satiety hormones GLP-1 and PYY, and appetite and satiety scores.<br><br>CONCLUSIONS: Ingestion of the prebiotic inulin improves fat oxidation and promotes SCFA production in overweight to obese men. Overall, replacing digestible carbohydrates with the fermentable inulin may favor human substrate metabolism.<br><br>CLINICAL TRIAL REGISTRY: The trial was registered at clinicaltrials.gov under number NCT02009670.}, }
@article {pmid29946308, year = {2018}, author = {Baktash, A and Terveer, EM and Zwittink, RD and Hornung, BVH and Corver, J and Kuijper, EJ and Smits, WK}, title = {Mechanistic Insights in the Success of Fecal Microbiota Transplants for the Treatment of Clostridium difficile Infections.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1242}, pmid = {29946308}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation has proven to be an effective treatment for infections with the gram-positive enteropathogen Clostridium difficile. Despite its effectiveness, the exact mechanisms that underlie its success are largely unclear. In this review, we highlight the pleiotropic effectors that are transferred during fecal microbiota transfer and relate this to the C. difficile lifecycle. In doing so, we show that it is likely that multiple factors contribute to the elimination of symptoms of C. difficile infections after fecal microbiota transplantation.}, }
@article {pmid29943234, year = {2018}, author = {Bellocchi, C and Volkmann, ER}, title = {Update on the Gastrointestinal Microbiome in Systemic Sclerosis.}, journal = {Current rheumatology reports}, volume = {20}, number = {8}, pages = {49}, pmid = {29943234}, issn = {1534-6307}, abstract = {PURPOSE OF REVIEW: Accumulating evidence suggests that gut microbiota affect the development and function of the immune system and may play a role in the pathogenesis of autoimmune diseases. The purpose of this review is to summarize recent studies reporting gastrointestinal microbiota aberrations associated with the systemic sclerosis disease state.<br><br>RECENT FINDINGS: The studies described herein have identified common changes in gut microbial composition. Specifically, patients with SSc have decreased abundance of beneficial commensal genera (e.g., Faecalibacterium, Clostridium, and Bacteroides) and increased abundance of pathobiont genera (e.g., Fusobacterium, Prevotella, Erwinia). In addition, some studies have linked specific genera with the severity of gastrointestinal symptoms in systemic sclerosis. More research is needed to further characterize the gastrointestinal microbiota in systemic sclerosis and understand how microbiota perturbations can affect inflammation, fibrosis, and clinical outcomes. Interventional studies aimed at addressing/correcting these perturbations, either through dietary modification, pro/pre-biotic supplementation, or fecal transplantation, may lead to improved outcomes for patients with systemic sclerosis.}, }
@article {pmid29942096, year = {2018}, author = {Hoyles, L and Fernández-Real, JM and Federici, M and Serino, M and Abbott, J and Charpentier, J and Heymes, C and Luque, JL and Anthony, E and Barton, RH and Chilloux, J and Myridakis, A and Martinez-Gili, L and Moreno-Navarrete, JM and Benhamed, F and Azalbert, V and Blasco-Baque, V and Puig, J and Xifra, G and Ricart, W and Tomlinson, C and Woodbridge, M and Cardellini, M and Davato, F and Cardolini, I and Porzio, O and Gentileschi, P and Lopez, F and Foufelle, F and Butcher, SA and Holmes, E and Nicholson, JK and Postic, C and Burcelin, R and Dumas, ME}, title = {Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women.}, journal = {Nature medicine}, volume = {24}, number = {7}, pages = {1070-1080}, pmid = {29942096}, issn = {1546-170X}, support = {MR/L01632X/1//Medical Research Council/United Kingdom ; MR/M501797/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Cells, Cultured ; Cohort Studies ; Confounding Factors (Epidemiology) ; Diabetes Mellitus/*genetics ; Fecal Microbiota Transplantation ; Female ; Hepatocytes/metabolism ; Humans ; Metabolome ; Metabolomics ; *Metagenomics ; Mice ; Microbiota ; Non-alcoholic Fatty Liver Disease/*genetics ; Obesity/*genetics ; Phenotype ; Transcriptome/genetics ; }, abstract = {Hepatic steatosis is a multifactorial condition that is often observed in obese patients and is a prelude to non-alcoholic fatty liver disease. Here, we combine shotgun sequencing of fecal metagenomes with molecular phenomics (hepatic transcriptome and plasma and urine metabolomes) in two well-characterized cohorts of morbidly obese women recruited to the FLORINASH study. We reveal molecular networks linking the gut microbiome and the host phenome to hepatic steatosis. Patients with steatosis have low microbial gene richness and increased genetic potential for the processing of dietary lipids and endotoxin biosynthesis (notably from Proteobacteria), hepatic inflammation and dysregulation of aromatic and branched-chain amino acid metabolism. We demonstrated that fecal microbiota transplants and chronic treatment with phenylacetic acid, a microbial product of aromatic amino acid metabolism, successfully trigger steatosis and branched-chain amino acid metabolism. Molecular phenomic signatures were predictive (area under the curve = 87%) and consistent with the gut microbiome having an effect on the steatosis phenome (>75% shared variation) and, therefore, actionable via microbiome-based therapies.}, }
@article {pmid29941542, year = {2018}, author = {Zhao, M and Xiong, X and Ren, K and Xu, B and Cheng, M and Sahu, C and Wu, K and Nie, Y and Huang, Z and Blumberg, RS and Han, X and Ruan, HB}, title = {Deficiency in intestinal epithelial O-GlcNAcylation predisposes to gut inflammation.}, journal = {EMBO molecular medicine}, volume = {10}, number = {8}, pages = {}, pmid = {29941542}, issn = {1757-4684}, support = {P30 DK078392/DK/NIDDK NIH HHS/United States ; R01 DK088199/DK/NIDDK NIH HHS/United States ; R21 AI103388/AI/NIAID NIH HHS/United States ; }, mesh = {Acetylglucosamine/*metabolism ; Animals ; Colitis/pathology/therapy ; Dysbiosis/physiopathology ; Epithelial Cells/*metabolism ; Fecal Microbiota Transplantation ; Female ; Homeostasis ; Humans ; Inflammatory Bowel Diseases/*metabolism/therapy ; Intestinal Mucosa/*metabolism/physiopathology ; Male ; Mice ; N-Acetylglucosaminyltransferases/*metabolism ; Paneth Cells/metabolism/pathology ; Protein Processing, Post-Translational/physiology ; Pyrans/pharmacology/therapeutic use ; STAT Transcription Factors/metabolism ; Thiazoles/pharmacology/therapeutic use ; beta-N-Acetylhexosaminidases/antagonists &amp; inhibitors/*metabolism ; }, abstract = {Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease. The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored. Here, we found that levels of protein O-GlcNAcylation and the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety, were reduced in IECs in human IBD patients. Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice. Using fecal microbiota transplantation in mice, we demonstrated that microbial dysbiosis although was insufficient to induce spontaneous inflammation but exacerbated chemical-induced colitis. Paneth cell-specific deletion of OGT led to Paneth cell dysfunction, which might predispose mice to chemical-induced colitis. On the other hand, the augmentation of O-GlcNAc signaling by inhibiting O-GlcNAcase, the enzyme removing O-GlcNAcylation, alleviated chemical-induced colitis. Our data reveal that protein O-GlcNAcylation in IECs controls key regulatory mechanisms to maintain mucosal homeostasis.}, }
@article {pmid29939968, year = {2018}, author = {Bouri, S and Hart, A}, title = {Fecal microbial transplantation: an update.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {21}, number = {5}, pages = {405-410}, doi = {10.1097/MCO.0000000000000488}, pmid = {29939968}, issn = {1473-6519}, mesh = {Clostridium Infections/therapy ; Colitis, Ulcerative/microbiology/therapy ; Donor Selection ; Dysbiosis/therapy ; *Fecal Microbiota Transplantation/adverse effects/methods/trends ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology/therapy ; }, abstract = {PURPOSE OF REVIEW: The purpose of this article is to provide an update on recent developments in fecal microbiota transplantation (FMT) in the last year.<br><br>RECENT FINDINGS: Although FMT is an accepted treatment for recurrent Clostridium difficile infection (CDI), recently it is also gaining acceptance for the treatment of refractory CDI. FMT is showing promise in ulcerative colitis and is experimental in many other conditions. The optimal practical aspects to enhance the success of FMT are still being established.<br><br>SUMMARY: The implication of current research is that the indications of FMT may be extended to other conditions in the future.}, }
@article {pmid29933742, year = {2018}, author = {Cui, B and Su, D and Li, W and She, X and Zhang, M and Wang, R and Zhai, Q}, title = {Effects of chronic noise exposure on the microbiome-gut-brain axis in senescence-accelerated prone mice: implications for Alzheimer's disease.}, journal = {Journal of neuroinflammation}, volume = {15}, number = {1}, pages = {190}, pmid = {29933742}, issn = {1742-2094}, mesh = {Aging/blood/*genetics ; Animals ; Avoidance Learning/physiology ; Brain/*metabolism ; Claudins/genetics/metabolism ; Cognition Disorders/etiology ; Corticosterone/blood ; Cytokines/genetics/*metabolism ; Disease Models, Animal ; Endotoxins/blood ; Gastrointestinal Microbiome/*physiology ; Inflammation/etiology/metabolism ; Mice ; Microbiota/physiology ; Noise/*adverse effects ; Occludin/genetics/metabolism ; RNA, Ribosomal, 16S/metabolism ; Serotonin/blood ; Tight Junctions/pathology ; Zonula Occludens-1 Protein/genetics/metabolism ; Zonula Occludens-2 Protein/genetics/metabolism ; gamma-Aminobutyric Acid/blood ; }, abstract = {BACKGROUND: Chronic noise exposure is associated with neuroinflammation and gut microbiota dysregulation and increases the risk of Alzheimer's disease (AD). Environmental hazards are also thought to be associated with genetic susceptibility factors that increase AD pathogenesis. However, there is limited experimental evidence regarding the link between chronic noise stress and microbiome-gut-brain axis alterations, which may be closely related to AD development.<br><br>METHODS: The aim of the present study was to systematically investigate the effects of chronic noise exposure on the microbiome-gut-brain axis in the senescence-accelerated mouse prone 8 (SAMP8) strain. We established SAMP8 mouse models to examine the consequences of noise exposure on the microbiome-gut-brain axis. Hippocampal amyloid-β (Aβ) assessment and the Morris water maze were used to evaluate AD-like changes, 16S ribosomal RNA sequencing analyses were used for intestinal flora measurements, and assessment of endothelial tight junctions and serum neurotransmitter and inflammatory mediator levels, as well as fecal microbiota transplant, was conducted to explore the underlying pathological mechanisms.<br><br>RESULTS: Chronic noise exposure led to cognitive impairment and Aβ accumulation in young SAMP8 mice, similar to that observed in aging SAMP8 mice. Noise exposure was also associated with decreased gut microbiota diversity and compositional alterations. Axis-series studies showed that endothelial tight junction proteins were decreased in both the intestine and brain, whereas serum neurotransmitter and inflammatory mediator levels were elevated in young SAMP8 mice exposed to chronic noise, similar to the observations made in the aging group. The importance of intestinal bacteria in noise exposure-induced epithelial integrity impairment and Aβ accumulation was further confirmed through microbiota transplantation experiments. Moreover, the effects of chronic noise were generally intensity-dependent.<br><br>CONCLUSION: Chronic noise exposure altered the gut microbiota, accelerated age-related neurochemical and inflammatory dysregulation, and facilitated AD-like changes in the brain of SAMP8 mice.}, }
@article {pmid29931479, year = {2018}, author = {Philips, CA and Phadke, N and Ganesan, K and Ranade, S and Augustine, P}, title = {Corticosteroids, nutrition, pentoxifylline, or fecal microbiota transplantation for severe alcoholic hepatitis.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {37}, number = {3}, pages = {215-225}, pmid = {29931479}, issn = {0975-0711}, mesh = {Administration, Oral ; Adult ; Aged ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Hepatitis, Alcoholic/microbiology/*therapy ; Humans ; Male ; Middle Aged ; *Nutrition Therapy ; Pentoxifylline/*therapeutic use ; Prednisolone/*administration &amp; dosage ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {INTRODUCTION: Alcohol-induced intestinal dysbiosis is central to the development of the severe alcoholic liver disease. We present the first study to compare outcomes in patients of severe alcoholic hepatitis (SAH) on nutritional therapy, corticosteroids, pentoxifylline, and healthy donor fecal transplantation (FMT) and discuss distinct microbial community and microbiome metabolic functional changes after FMT.<br><br>METHODS: Out of 1271 liver disease patients, 809 (63.7%) were diagnosed to have the alcoholic liver disease, of which 51 patients (8 treated with corticosteroids, 17 with nutritional support only, 10 with pentoxifylline, 16 receiving FMT) were included. Clinical, biochemical parameters, liver disease, and alcoholic hepatitis severity scores at baseline and mortality at the end of 1 and 3 months were analyzed between groups. Stool microbiota (SM) analysis was performed for healthy controls (HC) and respective recipients after FMT.<br><br>RESULTS: All the patients were male. The proportions of patients surviving at the end of 1 and 3 months in the steroids, nutrition, pentoxifylline, and FMT group were 63%, 47%, 40% and 75% [p = 0.179] and 38%, 29%, 30%, and 75% [p = 0.036], respectively. When compared with FMT, relative risk and hazard ratios for death were higher in all the other groups. Following FMT, distinct and beneficial modulation of SM and pathways of dysregulated metabolism, infections, inflammation, and oxidative stress in SAH patients were noted in tandem with improved clinical outcomes.<br><br>CONCLUSIONS: Healthy donor FMT for SAH improves survival beyond what is offered by current therapies and can function as a cost-effective bridge to liver transplant (LT) or for improving transplant-free survival. Larger studies and randomized trials are unmet needs.}, }
@article {pmid29929472, year = {2018}, author = {Kumar, A and Vlasova, AN and Deblais, L and Huang, HC and Wijeratne, A and Kandasamy, S and Fischer, DD and Langel, SN and Paim, FC and Alhamo, MA and Shao, L and Saif, LJ and Rajashekara, G}, title = {Impact of nutrition and rotavirus infection on the infant gut microbiota in a humanized pig model.}, journal = {BMC gastroenterology}, volume = {18}, number = {1}, pages = {93}, pmid = {29929472}, issn = {1471-230X}, support = {R01 AI099451/AI/NIAID NIH HHS/United States ; AI099451//National Institutes of Health/ ; }, mesh = {Animals ; Diarrhea/microbiology/virology ; Disease Susceptibility ; Feces/microbiology ; Gastroenteritis/*complications/*microbiology/virology ; *Gastrointestinal Microbiome ; Humans ; Infant ; Intestines/microbiology ; Malnutrition/*complications/*microbiology/virology ; RNA, Ribosomal, 16S ; Rotavirus Infections/*complications/*microbiology/virology ; Sequence Analysis, RNA ; Swine ; Virus Shedding ; Weight Gain ; }, abstract = {BACKGROUND: Human rotavirus (HRV) is a major cause of viral gastroenteritis in infants; particularly in developing countries where malnutrition is prevalent. Malnutrition perturbs the infant gut microbiota leading to sub-optimal functioning of the immune system and further predisposing infants to enteric infections. Therefore, we hypothesized that malnutrition exacerbates rotavirus disease severity in infants.<br><br>METHODS: In the present study, we used a neonatal germ free (GF) piglets transplanted with a two-month-old human infant's fecal microbiota (HIFM) on protein deficient and sufficient diets. We report the effects of malnourishment on the HRV infection and the HIFM pig microbiota in feces, intestinal and systemic tissues, using MiSeq 16S gene sequencing (V4-V5 region).<br><br>RESULTS: Microbiota analysis indicated that the HIFM transplantation resulted in a microbial composition in pigs similar to that of the original infant feces. This model was then used to understand the interconnections between microbiota diversity, diet, and HRV infection. Post HRV infection, HIFM pigs on the deficient diet had lower body weights, developed more severe diarrhea and increased virus shedding compared to HIFM pigs on sufficient diet. However, HRV induced diarrhea and shedding was more pronounced in non-colonized GF pigs compared to HIFM pigs on either sufficient or deficient diet, suggesting that the microbiota alone moderated HRV infection. HRV infected pigs on sufficient diet showed increased microbiota diversity in intestinal tissues; whereas, greater diversity was observed in systemic tissues of HRV infected pigs fed with deficient diet.<br><br>CONCLUSIONS: These results suggest that proper nourishment improves the microbiota quality in the intestines, alleviates HRV disease and lower probability of systemic translocation of potential opportunistic pathogens/pathobionts. In conclusion, our findings further support the role for microbiota and proper nutrition in limiting enteric diseases.}, }
@article {pmid29920927, year = {2019}, author = {Lee, JR and Magruder, M and Zhang, L and Westblade, LF and Satlin, MJ and Robertson, A and Edusei, E and Crawford, C and Ling, L and Taur, Y and Schluter, J and Lubetzky, M and Dadhania, D and Pamer, E and Suthanthiran, M}, title = {Gut microbiota dysbiosis and diarrhea in kidney transplant recipients.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {19}, number = {2}, pages = {488-500}, doi = {10.1111/ajt.14974}, pmid = {29920927}, issn = {1600-6143}, support = {//Chinese American Medical Society/ ; K23 AI 124464//National Institute of Allergy and Infectious Diseases/ ; R37 AI 051652//National Institute of Allergy and Infectious Diseases/ ; K23 AI124464/AI/NIAID NIH HHS/United States ; R37 AI051652/AI/NIAID NIH HHS/United States ; }, abstract = {Posttransplant diarrhea is associated with kidney allograft failure and death, but its etiology remains unknown in the majority of cases. Because altered gut microbial ecology is a potential basis for diarrhea, we investigated whether posttransplant diarrhea is associated with gut dysbiosis. We enrolled 71 kidney allograft recipients for serial fecal specimen collections in the first 3 months of transplantation and profiled the gut microbiota using 16S ribosomal RNA (rRNA) gene V4-V5 deep sequencing. The Shannon diversity index was significantly lower in 28 diarrheal fecal specimens from 25 recipients with posttransplant diarrhea than in 112 fecal specimens from 46 recipients without posttransplant diarrhea. We found a lower relative abundance of 13 commensal genera (Benjamini-Hochberg adjusted P ≤ .15) in the diarrheal fecal specimens including the same 4 genera identified in our prior study. The 28 diarrheal fecal specimens were also evaluated by a multiplexed polymerase chain reaction (PCR) assay for 22 bacterial, viral, and protozoan gastrointestinal pathogens, and 26 specimens were negative for infectious etiologies. Using PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) to predict metagenomic functions, we found that diarrheal fecal specimens had a lower abundance of metabolic genes. Our findings suggest that posttransplant diarrhea is not associated with common infectious diarrheal pathogens but with a gut dysbiosis.}, }
@article {pmid29914912, year = {2018}, author = {Hota, SS and Poutanen, SM}, title = {Fecal microbiota transplantation for recurrent Clostridium difficile infection.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {190}, number = {24}, pages = {E746}, pmid = {29914912}, issn = {1488-2329}, }
@article {pmid29912755, year = {2018}, author = {Rizzatti, G and Ianiro, G and Gasbarrini, A}, title = {Antibiotic and Modulation of Microbiota: A New Paradigm?.}, journal = {Journal of clinical gastroenterology}, volume = {52 Suppl 1, Proceedings from the 9th Probiotics, Prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition &amp; Human and Microbiota Health Meeting, held in Rome, Italy from September 10 to 12, 2017}, number = {}, pages = {S74-S77}, doi = {10.1097/MCG.0000000000001069}, pmid = {29912755}, issn = {1539-2031}, abstract = {Recently new insights on gut microbiota have revolutionized many concepts of the modern medicine. The alteration of microbiota, which is called dysbiosis, has been associated with an expanding list of diseases and conditions. The development of next-generation sequencing techniques allowed comprehensive analysis of gut microbiota composition without the limitations of classic culture methods. Furthermore, introduction of functional techniques such as metabolomics and proteomics allowed for integrated analysis thus obtaining more robust insights on microbiota functions in health and disease. These tools allow to address the role of factors able to modify the gut microbiota, the so called &quot;microbiota influencers.&quot; These data are useful to explain the physiopathology of several disease and thus to identify new potential therapeutic targets. Among microbiota influencers, many studies focused on the impact of antibiotic administration on the gut microbiota, because of their widespread use. Notably, beside the known beneficial effect of antibiotic in treating infectious diseases, these drugs have shown detrimental effects on gut microbiota which, in turn, might have long-term consequences on the host. Finally, therapeutic modulation of gut microbiota, by means of selected antibiotics with eubiotic effects, probiotics and with fecal microbiota transplantation seems of great interest as it might be able to prevent or even revert antibiotic-induced dysbiosis.}, }
@article {pmid29910564, year = {2018}, author = {Duarte-Chavez, R and Wojda, TR and Zanders, TB and Geme, B and Fioravanti, G and Stawicki, SP}, title = {Early Results of Fecal Microbial Transplantation Protocol Implementation at a Community-based University Hospital.}, journal = {Journal of global infectious diseases}, volume = {10}, number = {2}, pages = {47-57}, pmid = {29910564}, issn = {0974-777X}, abstract = {Introduction: Clostridium difficile (CD) is a serious and increasingly prevalent healthcare-associated infection. The pathogenesis of CD infection (CDI) involves the acquisition of CD with a concurrent disruption of the native gut flora. Antibiotics are a major risk although other contributing factors have also been identified. Clinical management combines discontinuation of the offending antibiotic, initiation of CD-specific antibiotic therapy, probiotic agent use, fecal microbiota transplantation (FMT), and surgery as the &quot;last resort&quot; option. The aim of this study is to review short-term clinical results following the implementation of FMT protocol (FMTP) at our community-based university hospital.<br><br>Methods: After obtaining Institutional Review Board and Infection Control Committee approvals, we implemented an institution-wide FMTP for patients diagnosed with CDI. Prospective tracking of all patients receiving FMT between July 1, 2015, and February 1, 2017, was conducted using REDCap™ electronic data capture system. According to the FMTP, indications for FMT included (a) three or more CDI recurrences, (b) two or more hospital admissions with severe CDI, or (c) first episode of complicated CDI (CCDI). Risk factors for initial infection and for treatment failure were assessed. Patients were followed for at least 3 months to monitor for cure/failure, relapse, and side effects. Frozen 250 mL FMT samples were acquired from OpenBiome (Somerville, MA, USA). After 4 h of thawing, the liquid suspension was applied using colonoscopy, beginning with terminal ileum and proceeding distally toward mid-transverse colon. Monitored clinical parameters included disease severity (Hines VA CDI Severity Score or HVCSS), concomitant medications, number of FMT treatments, non-FMT therapies, cure rates, and mortality. Descriptive statistics were utilized to outline the study results.<br><br>Results: A total of 35 patients (mean age 58.5 years, 69% female) were analyzed, with FMT-attributable primary cure achieved in 30/35 (86%) cases. Within this subgroup, 2/30 (6.7%) patients recurred and were subsequently cured with long-term oral vancomycin. Among five primary FMT failures (14% total sample), 3 (60%) achieved medical cure with long-term oral vancomycin therapy and 2 (40%) required colectomy. For the seven patients who either failed FMT or recurred, long-term vancomycin therapy was curative in all but two cases. For patients with severe CDI (HVCSS ≥3), primary and overall cure rates were 6/10 (60%) and 8/10 (80%), respectively. Patients with CCDI (n = 4) had higher HVCSS (4 vs. 3) and a mortality of 25%. Characteristics of patients who failed initial FMT included older age (70 vs. 57 years), female sex (80% vs. 67%), severe CDI (80% vs. 13%), and active opioid use during the initial infection (60% vs. 37%) and at the time of FMT (60% vs. 27%). The most commonly reported side effect of FMT was loose stools.<br><br>Conclusions: This pilot study supports the efficacy and safety of FMT administration for CDI in the setting of a community-based university hospital. Following FMTP implementation, primary (86%) and overall (94%) nonsurgical cure rates were similar to those reported in other studies. The potential role of opioids as a modulator of CDI warrants further clinical investigation.}, }
@article {pmid29904348, year = {2018}, author = {Cui, H and Cai, Y and Wang, L and Jia, B and Li, J and Zhao, S and Chu, X and Lin, J and Zhang, X and Bian, Y and Zhuang, P}, title = {Berberine Regulates Treg/Th17 Balance to Treat Ulcerative Colitis Through Modulating the Gut Microbiota in the Colon.}, journal = {Frontiers in pharmacology}, volume = {9}, number = {}, pages = {571}, pmid = {29904348}, issn = {1663-9812}, abstract = {Berberine (BBR), an alkaloid isolated from Rhizoma Coptidis, Cortex Phellode, and Berberis, has been widely used in the treatment of ulcerative colitis (UC). However, the mechanism of BBR on UC is unknown. In this study, we investigated the activities of T regulatory cell (Treg) and T helper 17 cell (Th17) in a dextran sulfate sodium (DSS)-induced UC mouse model after BBR administration. We also investigated the changes of gut microbiota composition using 16S rRNA analysis. We also examined whether BBR could regulate the Treg/Th17 balance by modifying gut microbiota. The mechanism was further confirmed by depleting gut microbiota through a combination of antibiotic treatment and fecal transplantations. Results showed that BBR treatment could improve the Treg/Th17 balance in the DSS-induced UC model. BBR also reduced diversity of the gut microbiota and interfered with the relative abundance of Desulfovibrio, Eubacterium, and Bacteroides. Moreover, BBR treatment did not influence the Treg/Th17 balance after the depletion of gut microbiota. Our results also revealed that fecal transplantation from BBR-treated mice could relieve UC and regulate the Treg/Th17 balance. In conclusion, our study provides evidence that BBR prevents UC by modifying gut microbiota and regulating the balance of Treg/Th17.}, }
@article {pmid29903041, year = {2018}, author = {Zhao, L and Huang, Y and Lu, L and Yang, W and Huang, T and Lin, Z and Lin, C and Kwan, H and Wong, HLX and Chen, Y and Sun, S and Xie, X and Fang, X and Yang, H and Wang, J and Zhu, L and Bian, Z}, title = {Saturated long-chain fatty acid-producing bacteria contribute to enhanced colonic motility in rats.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {107}, pmid = {29903041}, issn = {2049-2618}, support = {FRG2/15-16/001, FRG2/16-17/003//Faculty Research Grant of Hong Kong Baptist University/International ; C2012-15G//The Research Grants Council of Hong Kong Collaborative Research Fund/International ; 2016A050503039//Guangdong-Hong Kong Technology Cooperation Funding Scheme/International ; }, mesh = {Animals ; Bacteroidetes/*metabolism ; Biodiversity ; Colon/microbiology/physiology ; Disease Models, Animal ; Dysbiosis/microbiology ; Fatty Acids/*analysis ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Gastrointestinal Motility/*physiology ; Gastrointestinal Tract/microbiology ; Germ-Free Life ; Lactobacillus/*metabolism ; Maternal Deprivation ; Muscle Contraction/physiology ; Prevotella/*metabolism ; Rats ; Rats, Sprague-Dawley ; }, abstract = {BACKGROUND: The gut microbiota is closely associated with gastrointestinal (GI) motility disorder, but the mechanism(s) by which bacteria interact with and affect host GI motility remains unclear. In this study, through using metabolomic and metagenomic analyses, an animal model of neonatal maternal separation (NMS) characterized by accelerated colonic motility and gut dysbiosis was used to investigate the mechanism underlying microbiota-driven motility dysfunction.<br><br>RESULTS: An excess of intracolonic saturated long-chain fatty acids (SLCFAs) was associated with enhanced bowel motility in NMS rats. Heptadecanoic acid (C17:0) and stearic acid (C18:0), as the most abundant odd- and even-numbered carbon SLCFAs in the colon lumen, can promote rat colonic muscle contraction and increase stool frequency. Increase of SLCFAs was positively correlated with elevated abundances of Prevotella, Lactobacillus, and Alistipes. Functional annotation found that the level of bacterial LCFA biosynthesis was highly enriched in NMS group. Essential synthetic genes Fabs were largely identified from the genera Prevotella, Lactobacillus, and Alistipes. Pseudo germ-free (GF) rats receiving fecal microbiota from NMS donors exhibited increased defecation frequency and upregulated bacterial production of intracolonic SLCFAs. Modulation of gut dysbiosis by neomycin effectively attenuated GI motility and reduced bacterial SLCFA generation in the colon lumen of NMS rats.<br><br>CONCLUSIONS: These findings reveal a previously unknown relationship between gut bacteria, intracolonic SLCFAs, and host GI motility, suggesting the importance of SLCFA-producing bacteria in GI motility disorders. Further exploration of this relationship could lead to a precise medication targeting the gut microbiota for treating GI motility disorders.}, }
@article {pmid29901551, year = {2018}, author = {Bulik-Sullivan, EC and Roy, S and Elliott, RJ and Kassam, Z and Lichtman, SN and Carroll, IM and Gulati, AS}, title = {Intestinal Microbial and Metabolic Alterations Following Successful Fecal Microbiota Transplant for D-Lactic Acidosis.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {67}, number = {4}, pages = {483-487}, doi = {10.1097/MPG.0000000000002043}, pmid = {29901551}, issn = {1536-4801}, abstract = {Fecal microbiota transplantation (FMT) involves the transfer of stool from a healthy individual into the intestinal tract of a diseased recipient. Although used primarily for recurrent Clostridium difficile infection, FMT is increasingly being attempted as an experimental therapy for other illnesses, including metabolic disorders. D-lactic acidosis (D-LA) is a metabolic disorder that may occur in individuals with short bowel syndrome when lactate-producing bacteria in the colon overproduce D-lactate. This results in elevated systemic levels of D-lactate, metabolic acidosis, and encephalopathy. In this study, we report the successful use of FMT for the treatment of recurrent D-LA in a child who was unresponsive to conventional therapies. Importantly, we also present profiles of the enteric microbiota, as well as fecal D-/L-lactic acid metabolites, before and longitudinally after FMT. These data provide valuable insight into the putative mechanisms of D-LA pathogenesis and its treatment.}, }
@article {pmid29896165, year = {2018}, author = {Valenzuela, MJ and Caruffo, M and Herrera, Y and Medina, DA and Coronado, M and Feijóo, CG and Muñoz, S and Garrido, D and Troncoso, M and Figueroa, G and Toro, M and Reyes-Jara, A and Magne, F and Navarrete, P}, title = {Evaluating the Capacity of Human Gut Microorganisms to Colonize the Zebrafish Larvae (Danio rerio).}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1032}, pmid = {29896165}, issn = {1664-302X}, support = {T37 MD001425/MD/NIMHD NIH HHS/United States ; }, abstract = {In this study we evaluated if zebrafish larvae can be colonized by human gut microorganisms. We tested two strategies: (1) through transplantation of a human fecal microbiota and (2) by successively transplanting aerotolerant anaerobic microorganisms, similar to the colonization in the human intestine during early life. We used conventionally raised zebrafish larvae harboring their own aerobic microbiota to improve the colonization of anaerobic microorganisms. The results showed with the fecal transplant, that some members of the human gut microbiota were transferred to larvae. Bacillus, Roseburia, Prevotella, Oscillospira, one unclassified genus of the family Ruminococcaceae and Enterobacteriaceae were detected in 3 days post fertilization (dpf) larvae; however only Bacillus persisted to 7 dpf. Successive inoculation of Lactobacillus, Bifidobacterium and Clostridioides did not improve their colonization, compared to individual inoculation of each bacterial species. Interestingly, the sporulating bacteria Bacillus clausii and Clostridioides difficile were the most persistent microorganisms. Their endospores persisted at least 5 days after inoculating 3 dpf larvae. However, when 5 dpf larvae were inoculated, the proportion of vegetative cells in larvae increased, revealing proliferation of the inoculated bacteria and better colonization of the host. In conclusion, these results suggest that it is feasible to colonize zebrafish larvae with some human bacteria, such as C. difficile and Bacillus and open an interesting area to study interactions between these microorganisms and the host.}, }
@article {pmid29895922, year = {2018}, author = {Reardon, S}, title = {Faecal transplants could help preserve vulnerable species.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {173-174}, doi = {10.1038/d41586-018-05352-1}, pmid = {29895922}, issn = {1476-4687}, mesh = {Animals ; Animals, Wild/microbiology ; Animals, Zoo/microbiology ; Anura/microbiology ; Conservation of Natural Resources/*methods ; Diet/*veterinary ; *Endangered Species ; Eucalyptus ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Food Preferences ; Gastrointestinal Microbiome/*physiology ; Male ; Mycoses/microbiology/prevention &amp; control/veterinary ; Perissodactyla/*microbiology/physiology ; Phascolarctidae/*microbiology/physiology ; Survival Rate ; }, }
@article {pmid29895255, year = {2019}, author = {Katsi, V and Didagelos, M and Skevofilax, S and Armenis, I and Kartalis, A and Vlachopoulos, C and Karvounis, H and Tousoulis, D}, title = {GUT Microbiome-GUT Dysbiosis-Arterial Hypertension: New Horizons.}, journal = {Current hypertension reviews}, volume = {15}, number = {1}, pages = {40-46}, doi = {10.2174/1573402114666180613080439}, pmid = {29895255}, issn = {1875-6506}, abstract = {Arterial hypertension is a progressive cardiovascular syndrome arising from complex and interrelated etiologies. The human microbiome refers to the community of microorganisms that live in or on the human body. They influence human physiology by interfering in several processes such as providing nutrients and vitamins in Phase I and Phase II drug metabolism. The human gut microbiota is represented mainly by Firmicutes and Bacteroidetes and to a lesser degree by Actinobacteria and Proteobacteria, with each individual harbouring at least 160 such species. Gut microbiota contributes to blood pressure homeostasis and the pathogenesis of arterial hypertension through production, modification, and degradation of a variety of microbial-derived bioactive metabolites. Animal studies and to a lesser degree human research has unmasked relative mechanisms, mainly through the effect of certain microbiome metabolites and their receptors, outlining this relationship. Interventions to utilize these pathways, with probiotics, prebiotics, antibiotics and fecal microbiome transplantation have shown promising results. Personalized microbiome-based disease prediction and treatment responsiveness seem futuristic. Undoubtedly, a long way of experimental and clinical research should be pursued to elucidate this novel, intriguing and very promising horizon.}, }
@article {pmid29890556, year = {2018}, author = {Bruensing, J and Buendgens, L and Jochum, C and Herbers, U and Canbay, A and Braun, G and Trautwein, C and Huber, W and Koch, A and Tacke, F}, title = {[Management of Clostridium difficile infections at German intensive care units - results from a survey among intensivists].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {56}, number = {6}, pages = {551-560}, doi = {10.1055/s-0044-102103}, pmid = {29890556}, issn = {1439-7803}, abstract = {BACKGROUND: Clostridium difficile associated colitis is a frequent cause of nosocomial diarrhea at the intensive care unit (ICU) and is associated with poor prognosis in critically ill patients. Few studies have evaluated the efficacy of treatment options or adherence to guideline recommendations of Clostridium difficile infections at the ICU.<br><br>METHODS: Therefore, on behalf of the Gastroenterology Intensive Care Medicine working group of the DGVS, we have conducted an online-based survey among leading intensivists in Germany.<br><br>RESULTS: Out of the 351 invited, 85 (24.2 %), primarily leading executive physicians at primary to tertiary care hospitals, completed the survey. They reported standardized diagnostic algorithms of 79.3 %, in line with current guideline recommendations (i. e., toxin testing in stool, possibly GDH screening, and endoscopy). First-line therapy of Clostridium difficile infections at the ICU was reported to be oral vancomycin in 48.3 % and oral metronidazole in 34.5 %. The success of first-line therapy was estimated at 67 % for clinical cure, 15 % persisting colitis, 5 % sepsis or megacolon, 10 % recurrence, and 3 % death. Hospitals of primary/secondary care more often used metronidazole compared to university hospitals. Standard treatments for recurrent infection were vancomycin orally (40 % alone, 29.1 % combined with metronidazole) or, more rarely, fidaxomicin (25.5 %). Fidaxomicin has been used at least once at the ICU in 79 % of the respondents. Eleven percent have used fecal microbiota transplant (FMT) in selected cases at the ICU.<br><br>CONCLUSION: Our survey indicated a high awareness of German intensivists for Clostridium difficile infections, but also marked differences in local therapeutic algorithms, especially in first-line treatment.}, }
@article {pmid29886561, year = {2018}, author = {Bhutiani, N and Schucht, JE and Miller, KR and McClave, SA}, title = {Technical Aspects of Fecal Microbial Transplantation (FMT).}, journal = {Current gastroenterology reports}, volume = {20}, number = {7}, pages = {30}, pmid = {29886561}, issn = {1534-312X}, mesh = {Donor Selection ; Enterocolitis, Pseudomembranous/therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Patient Selection ; }, abstract = {PURPOSE OF REVIEW: Fecal microbial transplantation (FMT) has become established as an effective therapeutic modality in the treatment of antibiotic-refractory recurrent Clostridium difficile colitis. A number of formulations and methods of delivery of FMT are currently available, each with distinct advantages. This review aims to review donor and patient selection for FMT as well as procedural aspects of FMT to help guide clinical practice.<br><br>RECENT FINDINGS: FMT can be obtained in fresh, frozen, lyophilized, and capsule-based formulations for delivery by oral ingestion, nasoenteric tube, colonoscopy, or enema (depending on the formulation used). Choosing the optimal method relies heavily on patient-related factors, including underlying pathology and severity of illness. As potential applications for FMT expand, careful donor screening and patient selection are critical to minimizing risk to patients and physicians. FMT represents an excellent therapeutic option for treatment of recurrent Clostridium difficile colitis and holds promise as a possible treatment modality in a variety of other conditions. The wide array of delivery methods allows for its application in various disease states in both the inpatient and outpatient setting.}, }
@article {pmid29884929, year = {2018}, author = {Panchal, P and Budree, S and Scheeler, A and Medina, G and Seng, M and Wong, WF and Elliott, R and Mitchell, T and Kassam, Z and Allegretti, JR and Osman, M}, title = {Correction to: Scaling Safe Access to Fecal Microbiota Transplantation: Past, Present, and Future.}, journal = {Current gastroenterology reports}, volume = {20}, number = {7}, pages = {28}, doi = {10.1007/s11894-018-0634-9}, pmid = {29884929}, issn = {1534-312X}, abstract = {In the original version of this article, author Ryan Elliott's name was misspelled as Ryan Eliott. The correct spelling of the name is Ryan Elliott.}, }
@article {pmid29880966, year = {2018}, author = {Golfeyz, S}, title = {Celiac Disease and Fecal Microbiota Transplantation: A New Beginning?.}, journal = {The American journal of gastroenterology}, volume = {113}, number = {8}, pages = {1256}, doi = {10.1038/s41395-018-0094-8}, pmid = {29880966}, issn = {1572-0241}, }
@article {pmid29880353, year = {2018}, author = {Gu, B and Bo, GZ and Ke, C}, title = {Exploration of Fecal Microbiota Transplantation in the Treatment of Refractory Diarrhea After Renal Transplantation.}, journal = {Transplantation proceedings}, volume = {50}, number = {5}, pages = {1326-1331}, doi = {10.1016/j.transproceed.2018.03.013}, pmid = {29880353}, issn = {1873-2623}, mesh = {Adult ; Aged ; Diarrhea/etiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Immunosuppressive Agents/therapeutic use ; Kidney Transplantation/*adverse effects ; Male ; Middle Aged ; Postoperative Complications/etiology/*therapy ; Prognosis ; Tacrolimus/therapeutic use ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: Exploration of fecal microbiota transplantation in the treatment of refractory diarrhea after renal transplantation.<br><br>METHODS: Summarize the etiology of 120 cases with diarrhea after renal transplantation from 2014 to 2017 in our hospital. There were 4 recipients of refractory diarrhea who accepted fecal microbiota transplantation with informed consent, and we collected clinical data of stool and bacterial culture, gut microbiota analysis, graft function, electrolytes, immunosuppressant concentrations of prognostic evaluation of patients with fecal transplantation.<br><br>RESULTS: The absorption of electrolyte is slightly higher and concentration of tacrolimus and creatinine were not significantly changed compared with before.<br><br>CONCLUSION: Fecal microbiota transplantation provides a new choice to refractory diarrhea after renal transplantation as an innovative treatment, but the effectiveness of fecal microbiota transplantation needs long-term observation and further evaluation through large sample data.}, }
@article {pmid29879241, year = {2018}, author = {Meyers, S and Shih, J and Neher, JO and Safranek, S}, title = {Clinical Inquiries: How effective and safe is fecal microbial transplant in preventing C difficile recurrence?.}, journal = {The Journal of family practice}, volume = {67}, number = {6}, pages = {386-388}, pmid = {29879241}, issn = {1533-7294}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; Clostridium Infections/*drug therapy/*prevention &amp; control ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; Secondary Prevention/*methods ; Treatment Outcome ; }, abstract = {Fecal microbial transplant (fmt) is reasonably safe and effective. In patients who have had multiple Clostridium difficile infections (CDIs), fecal microbial transplant (FMT) results in a 65% to 80% cure rate with one treatment and 90% to 95% cure rate with repeated treatments compared with a 25% to 27% cure rate for antibiotics (strength of recommendation [SOR]: B, small open-label randomized controlled trials [RCTs]). Fresh and frozen donor feces, administered by either nasogastric tube or colonoscope, produce equal results (SOR B, RCTs). FMT has an overall adverse event rate of 30%, primarily involving abdominal discomfort, but also, rarely, severe infections (0.7%) and death (0.1%) (SOR: B, systematic review not limited to RCTs).}, }
@article {pmid29877649, year = {2018}, author = {Mareschal, J and Schrenzel, J and Lazarevic, V and Genton, L}, title = {[Microbiota and malnutrition: an overview].}, journal = {Revue medicale suisse}, volume = {14}, number = {610}, pages = {1194-1199}, pmid = {29877649}, issn = {1660-9379}, abstract = {Currently, there is an increased interest in the role of gut microbiota in health issues. Evidence shows that an imbalance of gut microbiota or dysbiosis is involved in the mechanisms of weight changes. This review aims at summarizing the present knowledge between gut microbiota and malnutrition. Intestinal bacterial diversity and richness are altered in malnourished people compared to healthy people. The first studies on the modulation of the gut microbiota by probiotics, prebiotics, symbiotics, fecal transplantation and antibiotics for weight gain are encouraging. However, further studies are needed to develop and implement effective treatment for malnutrition.}, }
@article {pmid29877092, year = {2019}, author = {Kang, Y and Cai, Y}, title = {Altered Gut Microbiota in HIV Infection: Future Perspective of Fecal Microbiota Transplantation Therapy.}, journal = {AIDS research and human retroviruses}, volume = {35}, number = {3}, pages = {229-235}, doi = {10.1089/AID.2017.0268}, pmid = {29877092}, issn = {1931-8405}, abstract = {HIV infection progressively destroys CD4+ mononuclear cells, leading to profound cellular immune deficiency that manifests as life-threatening opportunistic infections and malignancies (i.e., AIDS). Gut microbiota plays key roles in the modulation of host metabolism and gene expression, maintenance of epithelial integrity, and mediation of inflammatory and immunity. Hence, the normal intestinal microbiota plays a major role in the maintenance of health and disease prevention. In fact, a large number of studies have shown that the alteration of the gut microbiota contributes to the pathogenesis of several diseases, such as inflammatory bowel diseases, irritable bowel syndrome, metabolic diseases, anorexia nervosa, autoimmune diseases, multiple sclerosis, cancer, neuropsychiatric disorders, and cardiovascular diseases. Recently, accumulating evidence has shed light on the association of dysbiosis of gut microbiota with HIV infection. Hence, the modification of gut microbiota may be a potential therapeutic tool. Fecal microbiota transplantation may improve the conditions of patients with HIV infection by manipulating the human intestinal bacteria. However, the relevant research is very limited, and a large amount of scientific research work needs to be done in the near future.}, }
@article {pmid29874567, year = {2018}, author = {Cignarella, F and Cantoni, C and Ghezzi, L and Salter, A and Dorsett, Y and Chen, L and Phillips, D and Weinstock, GM and Fontana, L and Cross, AH and Zhou, Y and Piccio, L}, title = {Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota.}, journal = {Cell metabolism}, volume = {27}, number = {6}, pages = {1222-1235.e6}, doi = {10.1016/j.cmet.2018.05.006}, pmid = {29874567}, issn = {1932-7420}, support = {P30 DK056341/DK/NIDDK NIH HHS/United States ; R01 NS102633/NS/NINDS NIH HHS/United States ; C06 RR014513/RR/NCRR NIH HHS/United States ; }, abstract = {Multiple sclerosis (MS) is more common in western countries with diet being a potential contributing factor. Here we show that intermittent fasting (IF) ameliorated clinical course and pathology of the MS model, experimental autoimmune encephalomyelitis (EAE). IF led to increased gut bacteria richness, enrichment of the Lactobacillaceae, Bacteroidaceae, and Prevotellaceae families and enhanced antioxidative microbial metabolic pathways. IF altered T cells in the gut with a reduction of IL-17 producing T cells and an increase in regulatory T cells. Fecal microbiome transplantation from mice on IF ameliorated EAE in immunized recipient mice on a normal diet, suggesting that IF effects are at least partially mediated by the gut flora. In a pilot clinical trial in MS patients, intermittent energy restriction altered blood adipokines and the gut flora resembling protective changes observed in mice. In conclusion, IF has potent immunomodulatory effects that are at least partially mediated by the gut microbiome.}, }
@article {pmid29870851, year = {2018}, author = {Ruppé, E and Martin-Loeches, I and Rouzé, A and Levast, B and Ferry, T and Timsit, JF}, title = {What's new in restoring the gut microbiota in ICU patients? Potential role of faecal microbiota transplantation.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {24}, number = {8}, pages = {803-805}, doi = {10.1016/j.cmi.2018.05.020}, pmid = {29870851}, issn = {1469-0691}, mesh = {Critical Care/methods ; Critical Illness/*therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Intensive Care Units ; }, }
@article {pmid29870270, year = {2018}, author = {Larroya-García, A and Navas-Carrillo, D and Orenes-Piñero, E}, title = {Impact of gut microbiota on neurological diseases: Diet composition and novel treatments.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/10408398.2018.1484340}, pmid = {29870270}, issn = {1549-7852}, abstract = {Gut microbiota has significant effects on the structure and function of the enteric and central nervous system including human behaviour and brain regulation. Herein, we analyze the role of this intestinal ecosystem, the effects of dietary changes and the administration of nutritional supplements, such as probiotics, prebiotics, or fecal transplantation in neuropsychiatric disorders. Numerous factors have been highlighted to influence gut microbiota composition, including genetics, health status, mode of birth delivery and environment. However, diet composition and nutritional status has been repeatedly shown to be one of the most critical modifiable factors of this ecosystem. A comprehensively analysis of the microbiome-intestine-brain axis has been performed, including the impact of intestinal bacteria in alterations in the nervous, immune and endocrine systems and their metabolites. Finally, we discuss the latest literature examining the effects of diet composition, nutritional status and microbiota alterations in several neuropsychiatric disorders, such as autism, anxiety, depression, Alzheimer's disease and anorexia nervosa.}, }
@article {pmid29868248, year = {2018}, author = {Fareed, S and Sarode, N and Stewart, FJ and Malik, A and Laghaie, E and Khizer, S and Yan, F and Pratte, Z and Lewis, J and Immergluck, LC}, title = {Applying fecal microbiota transplantation (FMT) to treat recurrent Clostridium difficile infections (rCDI) in children.}, journal = {PeerJ}, volume = {6}, number = {}, pages = {e4663}, pmid = {29868248}, issn = {2167-8359}, abstract = {Background: Fecal Microbiota Transplantation (FMT) is an innovative means of treating recurrent Clostridium difficile infection (rCDI), through restoration of gut floral balance. However, there is a lack of data concerning the efficacy of FMT and its impact on the gut microbiome among pediatric patients. This study analyzes clinical outcomes and microbial community composition among 15 pediatric patients treated for rCDI via FMT.<br><br>Methods: This is a prospective, observational, pilot study of 15 children ≤18 years, who presented for rCDI and who met inclusion criteria for FMT at a pediatric hospital and pediatric gastroenterology clinic. Past medical history and demographics were recorded at enrollment and subsequent follow-up. Specimens of the donors' and the patients' pre-FMT and post-FMT fecal specimen were collected and used to assess microbiome composition via 16S rRNA gene sequencing.<br><br>Results: FMT successfully prevented rCDI episodes for minimum of 3 months post-FMT in all patients, with no major adverse effects. Three patients reported continued GI bleeding; however, all three also had underlying Inflammatory Bowel Disease (IBD). Our analyses confirm a significant difference between pre-and post-FMT gut microbiome profiles (Shannon diversity index), whereas no significant difference was observed between post-FMT and donor microbiome profiles. At the phyla level, post-FMT profiles showed significantly increased levels of Bacteroidetes and significantly decreased levels of Proteobacteria. Subjects with underlying IBD showed no difference in their pre-and post-FMT profiles.<br><br>Conclusion: The low rate of recurrence or re-infection by C. difficile, coupled with minimal adverse effects post-FMT, suggests that FMT is a viable therapeutic means to treat pediatric rCDI. Post-FMT microbiomes are different from pre-FMT microbiomes, and similar to those of healthy donors, suggesting successful establishment of a healthier microbiome.}, }
@article {pmid29860912, year = {2018}, author = {Juul, FE and Garborg, K and Bretthauer, M and Skudal, H and Øines, MN and Wiig, H and Rose, Ø and Seip, B and Lamont, JT and Midtvedt, T and Valeur, J and Kalager, M and Holme, Ø and Helsingen, L and Løberg, M and Adami, HO}, title = {Fecal Microbiota Transplantation for Primary Clostridium difficile Infection.}, journal = {The New England journal of medicine}, volume = {378}, number = {26}, pages = {2535-2536}, doi = {10.1056/NEJMc1803103}, pmid = {29860912}, issn = {1533-4406}, mesh = {Anti-Infective Agents/*therapeutic use ; Clostridium Infections/drug therapy/*therapy ; Clostridium difficile ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Metronidazole/*therapeutic use ; Recurrence ; Treatment Outcome ; }, }
@article {pmid29858434, year = {2018}, author = {Mullish, BH and Williams, HR}, title = {Clostridium difficile infection and antibiotic-associated diarrhoea.}, journal = {Clinical medicine (London, England)}, volume = {18}, number = {3}, pages = {237-241}, doi = {10.7861/clinmedicine.18-3-237}, pmid = {29858434}, issn = {1473-4893}, support = {MR/R000875/1//Medical Research Council/United Kingdom ; }, mesh = {Anti-Bacterial Agents/adverse effects/*therapeutic use ; Clostridium Infections/chemically induced/diagnosis/therapy ; Clostridium difficile ; Diarrhea/chemically induced/diagnosis/*therapy ; Enterocolitis, Pseudomembranous/chemically induced/diagnosis/*therapy ; *Fecal Microbiota Transplantation ; Fidaxomicin/therapeutic use ; Humans ; Metronidazole/therapeutic use ; Probiotics/*therapeutic use ; Vancomycin/therapeutic use ; }, abstract = {Antibiotic-associated diarrhoea is among the most common adverse events related to antibiotic use. Most cases are mild, but Clostridium difficile infection causes a spectrum of disease, ranging from occasional diarrhoea to colitis, toxic megacolon, and potentially death. Recent developments in our understanding of the biology of the gut microbiota have provided new insights into the pathogenesis of these conditions, and have revealed a role for manipulation of the gut microbiota as a novel therapeutic approach. This review will give an overview of the assessment of these conditions, before focusing on the rapidly developing area of their treatment.}, }
@article {pmid29851248, year = {2018}, author = {Toral, M and Romero, M and Rodríguez-Nogales, A and Jiménez, R and Robles-Vera, I and Algieri, F and Chueca-Porcuna, N and Sánchez, M and de la Visitación, N and Olivares, M and García, F and Pérez-Vizcaíno, F and Gálvez, J and Duarte, J}, title = {Lactobacillus fermentum Improves Tacrolimus-Induced Hypertension by Restoring Vascular Redox State and Improving eNOS Coupling.}, journal = {Molecular nutrition &amp; food research}, volume = {}, number = {}, pages = {e1800033}, doi = {10.1002/mnfr.201800033}, pmid = {29851248}, issn = {1613-4133}, abstract = {SCOPE: The aim is to analyze whether the probiotic Lactobacillus fermentum CECT5716 (LC40) can prevent endothelial dysfunction and hypertension induced by tacrolimus in mice.<br><br>METHODS AND RESULTS: Tacrolimus increases systolic blood pressure (SBP) and impairs endothelium-dependent relaxation to acetylcholine and these effects are partially prevented by LC40. Endothelial dysfunction induced by tacrolimus is related to both increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) and uncoupled endothelial nitric oxide synthase (eNOS)-driven superoxide production and Rho-kinase-mediated eNOS inhibition. LC40 treatment prevents all the aortic changes induced by tacrolimus. LC40 restores the imbalance between T-helper 17 (Th17)/regulatory T (Treg) cells induced by tacrolimus in mesenteric lymph nodes and the spleen. Tacrolimus-induced gut dysbiosis, that is, it decreases microbial diversity, increases the Firmicutes/Bacteroidetes (F/B) ratio and decreases acetate- and butyrate-producing bacteria, and these effects are prevented by LC40. Fecal microbiota transplantation (FMT) from LC40-treated mice to control mice prevents the increase in SBP and the impaired relaxation to acetylcholine induced by tacrolimus.<br><br>CONCLUSION: LC40 treatment prevents hypertension and endothelial dysfunction induced by tacrolimus by inhibiting gut dysbiosis. These effects are associated with a reduction in vascular oxidative stress, mainly through NOX2 downregulation and prevention of eNOS uncoupling, and inflammation possibly because of decreased Th17 and increased Treg cells polarization in mesenteric lymph nodes.}, }
@article {pmid29849592, year = {2018}, author = {Cao, Y and Zhang, B and Wu, Y and Wang, Q and Wang, J and Shen, F}, title = {The Value of Fecal Microbiota Transplantation in the Treatment of Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis.}, journal = {Gastroenterology research and practice}, volume = {2018}, number = {}, pages = {5480961}, pmid = {29849592}, issn = {1687-6121}, abstract = {Background and Aims: Fecal microbiota transplantation (FMT) has challenged the traditional management of ulcerative colitis (UC) in recent years, while it remained controversial. We aimed to provide a systematic protocol of FMT treatment on UC.<br><br>Methods: Studies reporting on FMT treatment in UC patients were performed. A fixed-effect model was used to assess the efficacy of FMT.<br><br>Results: Eighteen studies were enrolled (n = 446). A pooled proportion of patients who received FMT had a significant efficacy compared to the placebo group (odds ratio (OR): 2.73, P = 0.002) with a low risk of heterogeneity (P = 0.59, I2 = 0%). The Mayo score decreased to 5 points in a state of mild-moderate activity after FMT treatment, and the optimal range of the Mayo score baseline was 6-9 for FMT administration. Then, the baseline of the Shannon diversity index (SDI) had a negative correlation with the clinical response rate (R = -0.992, P = 0.08) or remission rate (R = -0.998, P = 0.036), and the optimal diversity of bacteria was at 7 days to one month. Moreover, the colonoscopy delivery and unrelated fecal donor had slight superiorities of FMT treatment.<br><br>Conclusion: FMT treatment had a higher efficacy and shorter time-point of early assessment of effectiveness on UC patients compared to traditional therapies. And the optimal FMT delivery and donor were colonoscopy delivery and unrelated donor in clinical practice.}, }
@article {pmid29846464, year = {2018}, author = {Messias, BA and Franchi, BF and Pontes, PH and Barbosa, DÁAM and Viana, CAS}, title = {Fecal microbiota transplantation in the treatment of Clostridium difficile infection: state of the art and literature review.}, journal = {Revista do Colegio Brasileiro de Cirurgioes}, volume = {45}, number = {2}, pages = {e1609}, doi = {10.1590/0100-6991e-20181609}, pmid = {29846464}, issn = {1809-4546}, mesh = {*Clostridium difficile ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Humans ; }, abstract = {Clostridium difficile infection is a common complication following intestinal dysbiosis caused by abusive antibiotic use. It presents medical importance due to the high rates of recurrence and morbidity. Fecal microbiota transplantation is an effective alternative for the treatment of recurrent and refractory C. difficile infection and consists of introducing the intestinal microbiota from a healthy donor into a patient with this infection. The exact physiological mechanism by which fecal microbiota transplantation alters the intestinal microbiota is not well established, but it is clear that it restores the diversity and structure of the microbiota by promoting increased resistance to colonization by C. difficile. Several routes of transplant administration are being studied and used according to the advantages presented. All forms of application had a high cure rate, and the colonoscopic route was the most used. No relevant complications and adverse events have been documented, and the cost-effectiveness over conventional treatment has proven advantageous. Despite its efficacy, it is not commonly used as initial therapy, and more studies are needed to establish this therapy as the first option in case of refractory and recurrent Clostridium difficileinfection.}, }
@article {pmid29843959, year = {2018}, author = {Adolph, TE and Grander, C and Moschen, AR and Tilg, H}, title = {Liver-Microbiome Axis in Health and Disease.}, journal = {Trends in immunology}, volume = {39}, number = {9}, pages = {712-723}, doi = {10.1016/j.it.2018.05.002}, pmid = {29843959}, issn = {1471-4981}, mesh = {Animals ; *Disease Susceptibility ; Gastrointestinal Microbiome/immunology ; *Homeostasis ; Host-Pathogen Interactions/immunology ; Humans ; Liver/*physiology ; Liver Diseases/etiology/metabolism/pathology ; Liver Regeneration ; *Microbiota/immunology ; }, abstract = {The intestinal and hepatobiliary tract exhibits host-specific commensal colonization. The resident microbiota has emerged as a key player in intestinal and hepatic diseases. Alcoholic and nonalcoholic fatty liver diseases (ALD/NAFLD), primary sclerosing cholangitis (PSC), liver cirrhosis, and some of their clinical complications, such as hepatic encephalopathy (HE), have been linked to a microbial signature, as also observed for severe liver inflammation in alcoholic hepatitis. In turn, the liver impacts, and communicates with, the microbiota through hepatic mediators, such as bile acids or inflammatory signals. Therefore, a liver-microbiome bidirectional crosstalk appears to be critical in health and various liver diseases and could be therapeutically targeted, such as by fecal microbiota transplantation.}, }
@article {pmid29843854, year = {2018}, author = {Lee, S and Drennan, K and Simons, G and Hepple, A and Karlsson, K and Lowman, W and Gaylard, PC and McNamara, L and Fabian, J}, title = {The 'ins and outs' of faecal microbiota transplant for recurrent Clostridium difficile diarrhoea at Wits Donald Gordon Medical Centre, Johannesburg, South Africa.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {108}, number = {5}, pages = {403-407}, doi = {10.7196/SAMJ.2018.v108i5.12367}, pmid = {29843854}, issn = {0256-9574}, mesh = {Adult ; Aged ; Anti-Bacterial Agents/administration &amp; dosage/adverse effects ; Clostridium Infections/complications/diagnosis/epidemiology/*therapy ; Clostridium difficile/*isolation &amp; purification ; *Cross Infection/epidemiology/microbiology/therapy ; Diarrhea/epidemiology/microbiology/*therapy ; Drug Resistance, Bacterial ; *Fecal Microbiota Transplantation/adverse effects/methods/statistics &amp; numerical data ; Female ; Humans ; Intubation, Gastrointestinal/adverse effects/methods ; Male ; *Metronidazole/administration &amp; dosage/adverse effects ; Middle Aged ; Outcome and Process Assessment (Health Care) ; Recurrence ; South Africa/epidemiology ; *Vancomycin/administration &amp; dosage/adverse effects ; }, abstract = {BACKGROUND: Clostridium difficile-associated diarrhoea (CDAD) is a potentially life-threatening condition that is becoming increasingly common. A persistent burden of this infectious illness has been demonstrated over the past 4 years at Wits Donald Gordon Medical Centre (WDGMC), Johannesburg, South Africa, through implementation of active surveillance of hospital-acquired infections as part of the infection prevention and control programme. Oral treatment with metronidazole or vancomycin is recommended, but there is a major problem with symptomatic recurrence after treatment. Replacement of normal flora by the administration of donor stool through colonoscopy or nasogastric/duodenal routes is becoming increasingly popular.<br><br>OBJECTIVES: To identify risk factors for the development of CDAD in patients referred for faecal microbiota transplant (FMT) and evaluate the safety of administration of donor stool as an outpatient procedure, including via the nasogastric route.<br><br>METHODS: A retrospective record review of patients with recurrent CDAD referred for FMT at WDGMC between 1 January 2012 and 31 December 2016 was conducted.<br><br>RESULTS: Twenty-seven patients were identified, all of whom fulfilled the criteria for recurrent CDAD. One-third were aged >65 years, and the majority were female. The most common risk factors were prior exposure to antibiotics or proton-pump inhibitors and underlying inflammatory bowel disease. Three procedures were carried out as inpatients and 24 in the outpatient gastroenterology unit. At 4-week follow-up, all patients reported clinical resolution of their diarrhoea after a single treatment and there were no recurrences. The FMT procedure was associated with no morbidity (with particular reference to the risk of aspiration when administered via the nasogastric route) or mortality.<br><br>CONCLUSIONS: This case series confirms that FMT is a safe and effective therapy for recurrent CDAD. In most cases it can be administered via the nasogastric route in the outpatient department. We propose that the recently published South African Gastroenterology Society guidelines be reviewed with regard to recommendations for the route of administration of FMT and hospital admission. Meticulous prescription practice by clinicians practising in hospitals and outpatient settings, with particular attention to antimicrobials and chronic medication, is urgently required to prevent this debilitating and potentially life-threatening condition.}, }
@article {pmid29807377, year = {2018}, author = {Lübbert, C and Lippmann, N and von Braun, A}, title = {[New Guidelines and Data to Clostridium difficile - What's New?].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {143}, number = {11}, pages = {787-792}, doi = {10.1055/a-0585-9595}, pmid = {29807377}, issn = {1439-4413}, mesh = {Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/epidemiology/therapy ; *Clostridium difficile ; Fecal Microbiota Transplantation ; Fidaxomicin ; Germany ; Humans ; Practice Guidelines as Topic ; }, abstract = {The incidence of Clostridium difficile infections (CDI) remains on a high level globally. In Germany, the burden of disease and especially the number of severe or even lethal cases continue to increase. The main risk factor for the development of CDI is the exposure to broad-spectrum antibiotics, which disturb the intestinal microbiota and therefore enable the colonization with C. difficile. According to IDSA's and SHEA's updated US guidelines, vancomycin is the treatment of choice. Fidaxomicin is as effective as vancomycin, but its advantage is the lower rate of recurrence. For the treatment of multiple relapsing CDI, there are assured treatment successes of ≥ 90 % through a fecal microbiome transfer (FMT), whereby FMT in Germany currently only has the status of an individual therapeutic attempt. Thus, an evidence-based general recommendation for clinical practice is not possible. Currently, new antibiotics with narrow-spectrum activity and low intestinal resorption have been developed for the treatment of CDI, including surotomycin, cadazolid, and ridinilazol. Furthermore, recent clinical studies demonstrated that significantly fewer recurrences occurred in patients who additionally received the monoclonal antibody bezlotoxumab. Novel toxoid vaccines are expected to become an efficacious tool in the prevention of CDI. However, pivotal clinical trials have so far not been completed.}, }
@article {pmid29804272, year = {2018}, author = {Jeon, SR and Chai, J and Kim, C and Lee, CH}, title = {Current Evidence for the Management of Inflammatory Bowel Diseases Using Fecal Microbiota Transplantation.}, journal = {Current infectious disease reports}, volume = {20}, number = {8}, pages = {21}, pmid = {29804272}, issn = {1523-3847}, abstract = {PURPOSE OF REVIEW: Fecal microbiota transplantation (FMT) has been investigated as a potential treatment for inflammatory bowel disease (IBD). This review examines current evidence around the efficacy and safety of FMT for patients with IBD.<br><br>RECENT FINDINGS: Randomized controlled trials (RCTs) and meta-analyses have suggested that FMT may facilitate clinical and endoscopic remission in patients with active ulcerative colitis (UC). Although the evidence for FMT in Crohn's disease (CD) is more limited, positive outcomes have been observed in small cohort studies. Most adverse events (AEs) were mild and included transient gastrointestinal symptoms. Serious adverse events (SAEs) did not differ significantly between the FMT and control groups, and a marginal increased rate of IBD flares following FMT was observed. Microbiota analysis following FMT showed increased intestinal bacterial diversity and a shift towards the donor microbial profile in recipients' stools. FMT for patients with IBD is promising as RCTs have shown the benefit of FMT for UC, although the efficacy of FMT for CD is less clear. Further large and well-designed trials are necessary to resolve critical issues such as the donor selection, the ideal route of administration, duration, frequency of FMT, and the long-term sustained efficacy and safety.}, }
@article {pmid29794015, year = {2018}, author = {Kamdar, K and Johnson, AMF and Chac, D and Myers, K and Kulur, V and Truevillian, K and DePaolo, RW}, title = {Innate Recognition of the Microbiota by TLR1 Promotes Epithelial Homeostasis and Prevents Chronic Inflammation.}, journal = {Journal of immunology (Baltimore, Md. : 1950)}, volume = {201}, number = {1}, pages = {230-242}, doi = {10.4049/jimmunol.1701216}, pmid = {29794015}, issn = {1550-6606}, support = {R01 DK104908/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/isolation &amp; purification/*metabolism ; Bacterial Adhesion/physiology ; Colon/cytology/immunology/pathology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Inflammation/pathology/*prevention &amp; control ; Intestinal Mucosa/*immunology/microbiology/pathology ; Intestine, Small/microbiology/pathology ; Mice ; Mice, Knockout ; Paneth Cells/*pathology ; Signal Transduction/immunology ; Toll-Like Receptor 1/*immunology ; }, abstract = {There is cross-talk between the intestinal epithelium and the microbiota that functions to maintain a tightly regulated microenvironment and prevent chronic inflammation. This communication is partly mediated through the recognition of bacterial proteins by host-encoded innate receptors, such as TLRs. However, studies examining the role of TLR signaling on colonic homeostasis have given variable and conflicting results. Despite its critical role in mediating immunity during enteric infection of the small intestine, TLR1-mediated recognition of microbiota-derived ligands and their influence on colonic homeostasis has not been well studied. In this study, we demonstrate that defective TLR1 recognition of the microbiome by epithelial cells results in disruption of crypt homeostasis specifically within the secretory cell compartment, including a defect in the mucus layer, ectopic Paneth cells in the colon, and an increase in the number of rapidly dividing cells at the base of the crypt. As a consequence of the perturbed epithelial barrier, we found an increase in mucosal-associated and translocated commensal bacteria and chronic low-grade inflammation characterized by an increase in lineage-negative Sca1+Thy1hi innate lymphoid-like cells that exacerbate inflammation and worsen outcomes in a model of colonic injury and repair. Our findings demonstrate that sensing of the microbiota by TLR1 may provide key signals that regulate the colonic epithelium, thereby limiting inflammation through the prevention of bacterial attachment to the mucosa and exposure to the underlying immune system.}, }
@article {pmid29793999, year = {2018}, author = {Bidu, C and Escoula, Q and Bellenger, S and Spor, A and Galan, M and Geissler, A and Bouchot, A and Dardevet, D and Morio, B and Cani, PD and Lagrost, L and Narce, M and Bellenger, J}, title = {The Transplantation of ω3 PUFA-Altered Gut Microbiota of fat-1 Mice to Wild-Type Littermates Prevents Obesity and Associated Metabolic Disorders.}, journal = {Diabetes}, volume = {67}, number = {8}, pages = {1512-1523}, doi = {10.2337/db17-1488}, pmid = {29793999}, issn = {1939-327X}, mesh = {Animals ; Cadherins/genetics/metabolism ; Diet, Carbohydrate Loading/adverse effects ; Diet, High-Fat/adverse effects ; Dietary Sucrose/adverse effects ; Dysbiosis/microbiology/physiopathology/therapy ; Endotoxemia/etiology/prevention &amp; control ; Fatty Acids, Omega-3/*metabolism ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Glucose Intolerance/microbiology/pathology/physiopathology/*prevention &amp; control ; *Insulin Resistance ; Intestinal Mucosa/metabolism/microbiology/pathology/physiopathology ; Intestines/microbiology/pathology/physiopathology ; Liver/metabolism/pathology ; Male ; Mice, Transgenic ; Muscle, Skeletal/metabolism ; Non-alcoholic Fatty Liver Disease/microbiology/pathology/physiopathology/*prevention &amp; control ; Obesity/microbiology/pathology/physiopathology/*prevention &amp; control ; Permeability ; Phylogeny ; }, abstract = {Altering the gut microbiome may be beneficial to the host and recently arose as a promising strategy to manage obesity. Here, we investigated the relative contribution of ω3 polyunsaturated fatty acid (PUFA)-mediated alterations in the microbiota to metabolic parameter changes in mice. Four groups were compared: male fat-1 transgenic mice (with constitutive production of ω3 PUFAs) and male wild-type (WT) littermates fed an obesogenic (high fat/high sucrose [HFHS]) or a control diet. Unlike WT mice, HFHS-fed fat-1 mice were protected against obesity, glucose intolerance, and hepatic steatosis. Unlike WT mice, fat-1 mice maintained a normal barrier function, resulting in a significantly lower metabolic endotoxemia. The fat-1 mice displayed greater phylogenic diversity in the cecum, and fecal microbiota transplantation from fat-1 to WT mice was able to reverse weight gain and to normalize glucose tolerance and intestinal permeability. We concluded that the ω3 PUFA-mediated alteration of gut microbiota contributed to the prevention of metabolic syndrome in fat-1 mice. It occurred independently of changes in the PUFA content of host tissues and may represent a promising strategy to prevent metabolic disease and preserve a lean phenotype.}, }
@article {pmid29793539, year = {2018}, author = {McIntosh, CM and Chen, L and Shaiber, A and Eren, AM and Alegre, ML}, title = {Gut microbes contribute to variation in solid organ transplant outcomes in mice.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {96}, pmid = {29793539}, issn = {2049-2618}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 AI115716/AI/NIAID NIH HHS/United States ; T32 HD007009/HD/NICHD NIH HHS/United States ; R01 AI115716//National Institute of Allergy and Infectious Diseases/International ; }, mesh = {Animals ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Graft Rejection/*microbiology ; Graft Survival/*physiology ; Mice ; Mice, Inbred C57BL ; *Organ Transplantation ; Skin/microbiology ; *Skin Transplantation ; Treatment Outcome ; }, abstract = {BACKGROUND: Solid organ transplant recipients show heterogeneity in the occurrence and timing of acute rejection episodes. Understanding the factors responsible for such variability in patient outcomes may lead to improved diagnostic and therapeutic approaches. Rejection kinetics of transplanted organs mainly depends on the extent of genetic disparities between donor and recipient, but a role for environmental factors is emerging. We have recently shown that major alterations of the microbiota following broad-spectrum antibiotics, or use of germ-free animals, promoted longer skin graft survival in mice. Here, we tested whether spontaneous differences in microbial colonization between genetically similar individuals can contribute to variability in graft rejection kinetics.<br><br>RESULTS: We compared rejection kinetics of minor mismatched skin grafts in C57BL/6 mice from Jackson Laboratory (Jax) and Taconic Farms (Tac), genetically similar animals colonized by different commensal microbes. Female Tac mice rejected skin grafts from vendor-matched males more quickly than Jax mice. We observed prolonged graft survival in Tac mice when they were exposed to Jax mice microbiome through co-housing or fecal microbiota transplantation (FMT) by gastric gavage. In contrast, exposure to Tac mice did not change graft rejection kinetics in Jax mice, suggesting a dominant suppressive effect of Jax microbiota. High-throughput sequencing of 16S rRNA gene amplicons from Jax and Tac mice fecal samples confirmed a convergence of microbiota composition after cohousing or fecal transfer. Our analysis of amplicon data associated members of a single bacterial genus, Alistipes, with prolonged graft survival. Consistent with this finding, members of the genus Alistipes were absent in a separate Tac cohort, in which fecal transfer from Jax mice failed to prolong graft survival.<br><br>CONCLUSIONS: These results demonstrate that differences in resident microbiome in healthy individuals may translate into distinct kinetics of graft rejection, and contribute to interpersonal variability in graft outcomes. The association between Alistipes and prolonged skin graft survival in mice suggests that members of this genus might affect host physiology, including at sites distal to the gastrointestinal tract. Overall, these findings allude to a potential therapeutic role for specific gut microbes to promote graft survival through the administration of probiotics, or FMT.}, }
@article {pmid29781761, year = {2019}, author = {Eliakim-Raz, N and Bishara, J}, title = {Prevention and treatment of Clostridium difficile associated diarrhea by reconstitution of the microbiota.}, journal = {Human vaccines &amp; immunotherapeutics}, volume = {15}, number = {6}, pages = {1453-1456}, doi = {10.1080/21645515.2018.1472184}, pmid = {29781761}, issn = {2164-554X}, abstract = {This review summarizes the latest advances in treating and preventing Clostridium difficile infection (CDI), the most common infectious disease cause of nosocomial diarrhea in adults in developed countries. As customary antibiotic therapies against C. difficile, metronidazole and vancomycin, are broad spectrum, they affect greatly the gut microbiota, which result in very high recurrence rates. Therefore, new strategies are researched intensively. New therapies focus on limiting further destruction of the gut microbiota or restoring the microbiota to its pre-destructed state. These include new antibiotics, such as fidaxomicin, which demonstrates reduced CDI recurrences, among other new drugs, biotherapeutic strategies, mainly fecal microbiota transplantation but also competitive inhibition with non-toxigenic strains of C. difficile, and finally, monoclonal antibodies against C. difficile toxins which offer protection against recurrences.}, }
@article {pmid29780597, year = {2018}, author = {Ding, C and Fan, W and Gu, L and Tian, H and Ge, X and Gong, J and Nie, Y and Li, N}, title = {Outcomes and prognostic factors of fecal microbiota transplantation in patients with slow transit constipation: results from a prospective study with long-term follow-up.}, journal = {Gastroenterology report}, volume = {6}, number = {2}, pages = {101-107}, pmid = {29780597}, issn = {2052-0034}, abstract = {Background and aim: Gut microbiota may contribute to regulate colonic motility, which is involved in the etiology of constipation. Fecal microbiota transplantation (FMT) has been demonstrated to restore intestinal homeostasis. The aim of this study was to evaluate the clinical outcomes and prognostic factors of FMT for the treatment of slow transit constipation (STC).<br><br>Methods: Fifty-two patients with STC received standardized FMT and were followed up for 6 months. Bowel habit, colonic transit time, constipation-related symptoms (PAC-SYM score), quality of life (PAC-QOL score), treatment satisfaction scores and adverse events were monitored. The primary efficacy endpoint was the proportion of patients having on average three or more complete spontaneous bowel movements (CSBMs) per week.<br><br>Results: The primary efficacy endpoint was achieved in 50.0%, 38.5% and 32.7% of patients over week intervals 3-4, 9-12 and 21-24, respectively (P < 0.01 for all comparisons). Significant improvements were also observed in other bowel movement assessments, colonic transit time, constipation-related symptoms and quality of life; but all improvements diminished at weeks 12 and 24. Incompleteness of evacuation served as the only factor associated with efficacy. No serious treatment-related adverse events were observed.<br><br>Conclusion: This study suggested FMT was effective and safe for STC, while a late loss of efficacy was also observed. A lower degree of sensation of incompleteness predicted a better outcome.}, }
@article {pmid29779619, year = {2018}, author = {Hochman, J}, title = {Immunoassay helps limit overdiagnosis of Clostridium difficile infection.}, journal = {The Journal of pediatrics}, volume = {199}, number = {}, pages = {283}, doi = {10.1016/j.jpeds.2018.04.030}, pmid = {29779619}, issn = {1097-6833}, mesh = {Child ; *Clostridium Infections ; *Clostridium difficile ; Fecal Microbiota Transplantation ; Humans ; Immunoassay ; Medical Overuse ; }, }
@article {pmid29774575, year = {2018}, author = {Bajaj, JS and Savidge, T and Kassam, ZA and Hylemon, PB and Gillevet, PM}, title = {Reply.}, journal = {Hepatology (Baltimore, Md.)}, volume = {68}, number = {3}, pages = {1206}, doi = {10.1002/hep.30092}, pmid = {29774575}, issn = {1527-3350}, mesh = {*Anti-Bacterial Agents ; *Fecal Microbiota Transplantation ; Humans ; Liver Cirrhosis ; Microbiota ; }, }
@article {pmid29774567, year = {2018}, author = {Mullish, BH and McDonald, JAK and Thursz, MR and Marchesi, JR}, title = {Antibiotic-Associated Disruption of Microbiota Composition and Function in Cirrhosis Is Restored by Fecal Transplant.}, journal = {Hepatology (Baltimore, Md.)}, volume = {68}, number = {3}, pages = {1205}, doi = {10.1002/hep.30090}, pmid = {29774567}, issn = {1527-3350}, support = {MR/R000875/1//Medical Research Council/United Kingdom ; }, mesh = {*Anti-Bacterial Agents ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Liver Cirrhosis ; Microbiota ; }, }
@article {pmid29773467, year = {2018}, author = {Daliri, EB and Tango, CN and Lee, BH and Oh, DH}, title = {Human microbiome restoration and safety.}, journal = {International journal of medical microbiology : IJMM}, volume = {308}, number = {5}, pages = {487-497}, doi = {10.1016/j.ijmm.2018.05.002}, pmid = {29773467}, issn = {1618-0607}, mesh = {Anti-Bacterial Agents ; Bacteria/classification/isolation &amp; purification ; Diet ; Dysbiosis/*therapy ; Fecal Microbiota Transplantation/*adverse effects/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Probiotics/*administration &amp; dosage ; }, abstract = {The human gut microbiome consists of many bacteria which are in symbiotic relationship with human beings. The gut microbial metabolism, as well as the microbial-host co-metabolism, has been found to greatly influence health and disease. Factors such as diet, antibiotic use and lifestyle have been associated with alterations in the gut microbial community and may result in several pathological conditions. For this reason, several strategies including fecal microbiota transplant and probiotic administration have been applied and proven to be feasible and effective in restoring the gut microbiota in humans. Yet, safety concerns such as potential health risks that may arise from such interventions and how these strategies are regulated need to be addressed. Also, it will be important to know if these microbiome restoration strategies can have a profound impact on health. This review provides an overview of our current knowledge of the microbiome restoration strategies and safety issues on how these strategies are regulated.}, }
@article {pmid29770137, year = {2018}, author = {Stanisavljević, S and Dinić, M and Jevtić, B and Đedović, N and Momčilović, M and Đokić, J and Golić, N and Mostarica Stojković, M and Miljković, Đ}, title = {Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {942}, pmid = {29770137}, issn = {1664-3224}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Cytokines/metabolism ; Disease Models, Animal ; *Disease Resistance/immunology ; Encephalomyelitis, Autoimmune, Experimental/*etiology/metabolism/therapy ; Fecal Microbiota Transplantation/methods ; Female ; *Gastrointestinal Microbiome/drug effects/immunology ; Lymph Nodes/immunology/metabolism ; Metagenome ; Metagenomics/methods ; Peyer's Patches/immunology/metabolism ; Rats ; }, abstract = {Albino Oxford (AO) rats are extremely resistant to induction of experimental autoimmune encephalomyelitis (EAE). EAE is an animal model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS), with established autoimmune pathogenesis. The autoimmune response against the antigens of the CNS is initiated in the peripheral lymphoid tissues after immunization of AO rats with CNS antigens. Subsequently, limited infiltration of the CNS occurs, yet without clinical sequels. It has recently become increasingly appreciated that gut-associated lymphoid tissues (GALT) and gut microbiota play an important role in regulation and propagation of encephalitogenic immune response. Therefore, modulation of AO gut microbiota by antibiotics was performed in this study. The treatment altered composition of gut microbiota in AO rats and led to a reduction in the proportion of regulatory T cells in Peyer's patches, mesenteric lymph nodes, and in lymph nodes draining the site of immunization. Upregulation of interferon-γ and interleukin (IL)-17 production was observed in the draining lymph nodes. The treatment led to clinically manifested EAE in AO rats with more numerous infiltrates and higher production of IL-17 observed in the CNS. Importantly, transfer of AO gut microbiota into EAE-prone Dark Agouti rats ameliorated the disease. These results clearly imply that gut microbiota is an important factor in AO rat resistance to EAE and that gut microbiota transfer is an efficacious way to treat CNS autoimmunity. These findings also support the idea that gut microbiota modulation has a potential as a future treatment of multiple sclerosis.}, }
@article {pmid29750050, year = {2018}, author = {Segal, JP and Abbasi, F and Kanagasundaram, C and Hart, A}, title = {Does the Internet promote the unregulated use of fecal microbiota transplantation: a potential public health issue?.}, journal = {Clinical and experimental gastroenterology}, volume = {11}, number = {}, pages = {179-183}, pmid = {29750050}, issn = {1178-7023}, abstract = {Introduction: The Internet has become an increasingly popular resource for medical information. Fecal microbiota transplantation (FMT) has changed the treatment of Clostridium difficile with cure rates of 81% following one infusion of FMT, further studies have since validated these findings. The Medicines and Health care Products Regulatory Agency has classified FMT as a medicine and hence should be only utilized in strict clinical settings.<br><br>Methods: We searched Facebook, Twitter, Google, and YouTube using the words &quot;Faecal Microbiota Transplantation&quot; and &quot;FMT&quot;. We utilized the first 50 hits on each site. We analyzed the percentage of articles that fell outside regulated medical practice. We searched how many clinics in the UK advertised practice that falls outside suggested guidelines.<br><br>Results: Google, YouTube, and Facebook had a variety of information regarding FMT available. Nine out of 50 (18%) of the top 50 google searches can be considered articles that fall outside regulated practice. YouTube highlighted four videos describing how to self-administer FMT, one of these was for ulcerative colitis. Fourteen percent of the top 50 YouTube videos fall outside regulated practice and 8% of the top 50 Facebook searches fall outside regulated clinical practice. There were two clinics in the UK advertising FMT for uses that fall outside regulated practice.<br><br>Conclusion: Clinicians and patients need to be aware of the resources available through social media and the Internet. It should be appreciated that some websites fall outside regulated clinical practice. Private clinics offering FMT need to ensure that they are offering FMT within a regulated framework.}, }
@article {pmid29748817, year = {2018}, author = {Mohajeri, MH and Brummer, RJM and Rastall, RA and Weersma, RK and Harmsen, HJM and Faas, M and Eggersdorfer, M}, title = {The role of the microbiome for human health: from basic science to clinical applications.}, journal = {European journal of nutrition}, volume = {57}, number = {Suppl 1}, pages = {1-14}, doi = {10.1007/s00394-018-1703-4}, pmid = {29748817}, issn = {1436-6215}, mesh = {Brain/physiology ; Clostridium Infections ; Diet ; Fatty Acids, Volatile ; Female ; Fermentation ; Gastrointestinal Microbiome/drug effects/physiology ; *Health Status ; Humans ; Hypersensitivity ; Immunity ; Inflammatory Bowel Diseases ; Intestines/growth &amp; development/microbiology ; Microbiota/*physiology ; Netherlands ; Prebiotics/administration &amp; dosage ; Pregnancy ; Probiotics/administration &amp; dosage ; Signal Transduction ; Vitamins/administration &amp; dosage ; }, abstract = {The 2017 annual symposium organized by the University Medical Center Groningen in The Netherlands focused on the role of the gut microbiome in human health and disease. Experts from academia and industry examined interactions of prebiotics, probiotics, or vitamins with the gut microbiome in health and disease, the development of the microbiome in early-life and the role of the microbiome on the gut-brain axis. The gut microbiota changes dramatically during pregnancy and intrinsic factors (such as stress), in addition to extrinsic factors (such as diet, and drugs) influence the composition and activity of the gut microbiome throughout life. Microbial metabolites, e.g. short-chain fatty acids affect gut-brain signaling and the immune response. The gut microbiota has a regulatory role on anxiety, mood, cognition and pain which is exerted via the gut-brain axis. Ingestion of prebiotics or probiotics has been used to treat a range of conditions including constipation, allergic reactions and infections in infancy, and IBS. Fecal microbiota transplantation (FMT) highly effective for treating recurrent Clostridium difficile infections. The gut microbiome affects virtually all aspects of human health, but the degree of scientific evidence, the models and technologies and the understanding of mechanisms of action vary considerably from one benefit area to the other. For a clinical practice to be broadly accepted, the mode of action, the therapeutic window, and potential side effects need to thoroughly be investigated. This calls for further coordinated state-of-the art research to better understand and document the human gut microbiome's effects on human health.}, }
@article {pmid29745777, year = {2018}, author = {Hvas, CL and Bendix, M and Dige, A and Dahlerup, JF and Agnholt, J}, title = {Current, experimental, and future treatments in inflammatory bowel disease: a clinical review.}, journal = {Immunopharmacology and immunotoxicology}, volume = {40}, number = {6}, pages = {446-460}, doi = {10.1080/08923973.2018.1469144}, pmid = {29745777}, issn = {1532-2513}, abstract = {Inflammatory bowel diseases (IBDs) may result from dysregulated mucosal immune responses directed toward the resident intestinal microbiota. This review describes the hallmark immunobiology of Crohn's disease and ulcerative colitis as well as therapeutic targets and mechanisms of action for current, experimental, and future treatments in IBD. Conventional therapies include 5-aminosalicylic acid, glucocorticosteroids, thiopurines, and methotrexate. Since 1997, monoclonal antibodies have gained widespread use. These consist of antibodies directed against pro-inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-12, and IL-23, or anti-homing antibodies directed against α4β7 integrin. Emerging oral therapies include modulators of intracellular signal transduction such as Janus kinase inhibitors. Vitamin D may help to regulate innate and adaptive immune responses. Modulation of the intestinal microbiota, using live microorganisms (probiotics), substrates for the colonic microbiota (prebiotics), or fecal microbiota transplantation (FMT), is in development. Dietary supplements are in widespread use, but providing evidence for their benefit is challenging. Stem cell treatment and nervous stimulation are promising future treatments.}, }
@article {pmid29744928, year = {2018}, author = {Chen, YJ and Wu, H and Wu, SD and Lu, N and Wang, YT and Liu, HN and Dong, L and Liu, TT and Shen, XZ}, title = {Parasutterella, in association with irritable bowel syndrome and intestinal chronic inflammation.}, journal = {Journal of gastroenterology and hepatology}, volume = {33}, number = {11}, pages = {1844-1852}, doi = {10.1111/jgh.14281}, pmid = {29744928}, issn = {1440-1746}, support = {81272388//National Natural Science Foundation of China/ ; 81172273//National Natural Science Foundation of China/ ; 81101637//National Natural Science Foundation of China/ ; 81101540//National Natural Science Foundation of China/ ; //Foundation of Shanghai Institute of Liver Diseases/ ; 16YF1401500//Shanghai Sailing Program/ ; 2015ZSQN08//Youth Foundation of Zhongshan Hospital/ ; }, mesh = {Adolescent ; Adult ; Aged ; Animals ; Betaproteobacteria/genetics/isolation &amp; purification/*pathogenicity ; DNA, Bacterial/isolation &amp; purification ; Disease Models, Animal ; Disease Progression ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; High-Throughput Nucleotide Sequencing ; Humans ; Irritable Bowel Syndrome/*etiology/*microbiology ; Male ; Mice, Inbred C57BL ; Middle Aged ; Real-Time Polymerase Chain Reaction ; Young Adult ; }, abstract = {BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is a highly prevalent chronic functional gastrointestinal disorder. Recent studies have showed increasing important role of gut microbiota in the pathophysiological changes of IBS. Our study aims to elaborate the association between intestinal flora with the genesis and the development of IBS.<br><br>METHODS: Illumina high-throughput sequencing technology was applied to investigate microbial communities of IBS patients and healthy donors. Stool specimens from the IBS-D patients were equally premixed and implanted into germ free C57B/6 mice to construct IBS animal model, and the normal group was also transplanted with normal premixed feces. The post-transplant defecation and intra-epithelial lymphocyte counts were evaluated. Microbial communities were also checked by the illumina high-throughput sequencing technology.<br><br>RESULTS: Fifteen genuses significantly different were found expressed in the gut flora of IBS patients, and six genuses showed significantly different abundances between the stool specimens of mice of IBS group and normal group. Among these differences, Parasutterella expression was remarkably different in both screening and validation experiments and also related to chronic intestinal inflammation; therefore, Parasutterella expression is considered in association with the development and progression of IBS.<br><br>CONCLUSION: Parasutterella may be related with the genesis and development of IBS and also associated with chronic intestinal inflammation in IBS patients.}, }
@article {pmid29743833, year = {2018}, author = {Fairhurst, NG and Travis, SPL}, title = {Why is it so difficult to evaluate faecal microbiota transplantation as a treatment for ulcerative colitis?.}, journal = {Intestinal research}, volume = {16}, number = {2}, pages = {209-215}, pmid = {29743833}, issn = {1598-9100}, abstract = {Faecal microbiota transplantation (FMT) has recently re-emerged as a viable therapeutic option for colonic disorders. Its efficacy has been proved in the treatment of Clostridium difficile infection which has encouraged research into the use of FMT for other disorders involving gut dysbiosis, such as ulcerative colitis (UC), a chronic inflammatory disease characterized by relapsing and remitting colonic inflammation. Although the FMT protocol for C. difficile treatment is well established, there are numerous additional factors to consider when applying FMT to treat inflammatory diseases. Various studies have attempted to address these factors but technical inconsistency between reports has resulted in a failure to achieve clinically significant findings. Case reports of FMT in UC have shown favorable outcomes yet demonstrating these effects on a larger scale has proved difficult. The following review aims to explore these issues and to analyze why they may be hindering the progression of FMT therapy in UC.}, }
@article {pmid29743671, year = {2018}, author = {Shepherd, ES and DeLoache, WC and Pruss, KM and Whitaker, WR and Sonnenburg, JL}, title = {An exclusive metabolic niche enables strain engraftment in the gut microbiota.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {434-438}, pmid = {29743671}, issn = {1476-4687}, support = {R01 DK085025/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteroides/growth &amp; development/isolation &amp; purification/physiology ; Colon/*microbiology ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Mice ; Sepharose/analogs &amp; derivatives/metabolism ; }, abstract = {The dense microbial ecosystem in the gut is intimately connected to numerous facets of human biology, and manipulation of the gut microbiota has broad implications for human health. In the absence of profound perturbation, the bacterial strains that reside within an individual are mostly stable over time 1 . By contrast, the fate of exogenous commensal and probiotic strains applied to an established microbiota is variable, generally unpredictable and greatly influenced by the background microbiota2,3. Therefore, analysis of the factors that govern strain engraftment and abundance is of critical importance to the emerging field of microbiome reprogramming. Here we generate an exclusive metabolic niche in mice via administration of a marine polysaccharide, porphyran, and an exogenous Bacteroides strain harbouring a rare gene cluster for porphyran utilization. Privileged nutrient access enables reliable engraftment of the exogenous strain at predictable abundances in mice harbouring diverse communities of gut microbes. This targeted dietary support is sufficient to overcome priority exclusion by an isogenic strain 4 , and enables strain replacement. We demonstrate transfer of the 60-kb porphyran utilization locus into a naive strain of Bacteroides, and show finely tuned control of strain abundance in the mouse gut across multiple orders of magnitude by varying porphyran dosage. Finally, we show that this system enables the introduction of a new strain into the colonic crypt ecosystem. These data highlight the influence of nutrient availability in shaping microbiota membership, expand the ability to perform a broad spectrum of investigations in the context of a complex microbiota, and have implications for cell-based therapeutic strategies in the gut.}, }
@article {pmid29743453, year = {2018}, author = {Mizuno, S and Nanki, K and Kanai, T}, title = {[Future perspectives on fecal microbiota transplantation].}, journal = {Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology}, volume = {115}, number = {5}, pages = {449-459}, doi = {10.11405/nisshoshi.115.449}, pmid = {29743453}, issn = {0446-6586}, mesh = {Clostridium difficile ; *Fecal Microbiota Transplantation ; Feces ; }, }
@article {pmid29742710, year = {2018}, author = {Wang, HG and Liu, SP and Ma, TH and Yan, W and Zhou, JF and Shi, YT and Shen, P and Yang, XZ and Wu, SN}, title = {Fecal microbiota transplantation treatment for refractory ulcerative colitis with allergy to 5-aminosalicylic acid: A case report.}, journal = {Medicine}, volume = {97}, number = {19}, pages = {e0675}, pmid = {29742710}, issn = {1536-5964}, mesh = {*Anti-Inflammatory Agents, Non-Steroidal ; Colitis, Ulcerative/*therapy ; *Drug Hypersensitivity ; *Fecal Microbiota Transplantation ; Humans ; Male ; *Mesalamine ; Middle Aged ; Remission Induction ; }, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) is currently being explored as a potential therapy for ulcerative colitis (UC). Here, we report the first case of a UC patient with allergy to 5-aminosalicylic acid (5-ASA) who underwent FMT and achieved clinical remission.<br><br>CASE PRESENTATION: This patient had a 9-year history of UC and was allergic to 5-ASA. He suffered from gradually aggravated abdominal pain and frequent bloody diarrhea. There was a continuous distribution of superficial erosion and ulceration by colonoscopy. After steroid therapy failed, he underwent FMT. The donated fecal microbes were purified in laboratory and then transplanted into the terminal ileum and right colon of the patient by colonoscopy. During the 9 months' follow-up, FMT has proved its efficacy in inducing and maintaining clinical and endoscopic remission of the patient.<br><br>CONCLUSION: The choice of treatment for refractory UC patients who are allergic to 5-ASA is relatively limited. In our case, we highlight the specific role of FMT for refractory UC with absence of 5-ASA through intestinal microbiota reconstruction.}, }
@article {pmid29738579, year = {2018}, author = {Solbach, P and Chhatwal, P and Woltemate, S and Tacconelli, E and Buhl, M and Gerhard, M and Thoeringer, CK and Vehreschild, MJGT and Jazmati, N and Rupp, J and Manns, MP and Bachmann, O and Suerbaum, S}, title = {BaiCD gene cluster abundance is negatively correlated with Clostridium difficile infection.}, journal = {PloS one}, volume = {13}, number = {5}, pages = {e0196977}, pmid = {29738579}, issn = {1932-6203}, mesh = {Anti-Bacterial Agents/therapeutic use ; Bacterial Proteins/*genetics ; Bacterial Toxins ; Bile/microbiology ; Bile Acids and Salts/biosynthesis/*genetics ; Clostridium Infections/*genetics/microbiology/transmission ; Clostridium difficile/*genetics/pathogenicity ; Diarrhea/*genetics/microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; Male ; Microbiota/genetics ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is a major cause of hospital-acquired diarrhea. Secondary bile acids were shown to confer resistance to colonization by C. difficile. 7α-dehydroxylation is a key step in transformation of primary to secondary bile acids and required genes have been located in a single bile acid-inducible (bai) operon in C. scindens as well as in C. hiranonis, two Clostridium sp. recently reported to protect against C. difficile colonization.<br><br>AIM: To analyze baiCD gene abundance in C. difficile positive and negative fecal samples.<br><br>MATERIAL &amp; METHODS: A species-specific qPCR for detecting baiCD genes was established. Fecal samples of patients with CDI, asymptomatic toxigenic C. difficile colonization (TCD), non-toxigenic C. difficile colonization (NTCD), of C. difficile negative (NC) patients, and of two patients before and after fecal microbiota transplantation (FMT) for recurrent CDI (rCDI) were tested for the presence of the baiCD genes.<br><br>RESULTS: The prevalence of the baiCD gene cluster was significantly higher in C. difficile negative fecal samples than in samples of patients diagnosed with CDI (72.5% (100/138) vs. 35.9% (23/64; p<0.0001). No differences in baiCD gene cluster prevalence were seen between NC and NTCD or NC and TCD samples. Both rCDI patients were baiCD-negative at baseline, but one of the two patients turned positive after successful FMT from a baiCD-positive donor.<br><br>CONCLUSION: Fecal samples of CDI patients are less frequently baiCD-positive than samples from asymptomatic carriers or C. difficile-negative individuals. Furthermore, we present a case of baiCD positivity observed after successful FMT for rCDI.}, }
@article {pmid29736607, year = {2018}, author = {Hwang, IY and Lee, HL and Huang, JG and Lim, YY and Yew, WS and Lee, YS and Chang, MW}, title = {Engineering microbes for targeted strikes against human pathogens.}, journal = {Cellular and molecular life sciences : CMLS}, volume = {75}, number = {15}, pages = {2719-2733}, pmid = {29736607}, issn = {1420-9071}, support = {NUHSRO/2016/053/SRP/05//National University Health System/ ; DPRT/943/09/14//National University of Singapore (SG)/ ; HDTRA1-13-0037//Defense Threat Reduction Agency (US)/ ; MINDEF//Ministry of Defense of Singapore/ ; RE2016-074//Ministry of Defense of Singapore/ ; }, mesh = {Anti-Infective Agents/metabolism/therapeutic use ; Bacteria/*genetics/metabolism ; Bacteriophages/*genetics/metabolism ; Communicable Diseases/diagnosis/therapy ; Fecal Microbiota Transplantation ; *Genetic Engineering ; Humans ; Microbiota ; Phage Therapy ; Probiotics/therapeutic use ; }, abstract = {Lack of pathogen specificity in antimicrobial therapy causes non-discriminant microbial cell killing that disrupts the microflora present. As a result, potentially helpful microbial cells are killed along with the pathogen, altering the biodiversity and dynamic interactions within the population. Moreover, the unwarranted exposure of antibiotics to microbes increases the likelihood of developing resistance and perpetuates the emergence of multidrug resistance. Synthetic biology offers an alternative solution where specificity can be conferred to reduce the non-specific, non-targeted activity of currently available antibiotics, and instead provides targeted therapy against specific pathogens and minimising collateral damage to the host's inherent microbiota. With a greater understanding of the microbiome and the available genetic engineering tools for microbial cells, it is possible to devise antimicrobial strategies for novel antimicrobial therapy that are able to precisely and selectively remove infectious pathogens. Herein, we review the strategies developed by unlocking some of the natural mechanisms used by the microbes and how these may be utilised in targeted antimicrobial therapy, with the promise of reducing the current global bane of multidrug antimicrobial resistance.}, }
@article {pmid29728643, year = {2018}, author = {Couturier-Maillard, A and Froux, N and Piotet-Morin, J and Michaudel, C and Brault, L and Le Bérichel, J and Sénéchal, A and Robinet, P and Chenuet, P and Jejou, S and Dumoutier, L and Renauld, JC and Iovanna, J and Huber, S and Chamaillard, M and Quesniaux, V and Sokol, H and Chamaillard, M and Ryffel, B}, title = {Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation.}, journal = {Mucosal immunology}, volume = {11}, number = {4}, pages = {1181-1190}, doi = {10.1038/s41385-018-0005-8}, pmid = {29728643}, issn = {1935-3456}, mesh = {Animals ; Cells, Cultured ; Disease Progression ; Gastrointestinal Microbiome/*immunology ; Inflammation/*immunology ; Interleukins/genetics/*metabolism ; Intestines/*immunology/parasitology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pancreatitis-Associated Proteins/genetics/metabolism ; Parasite Load ; Receptors, Interleukin/genetics/metabolism ; Toxoplasma/*physiology ; Toxoplasmosis/*immunology ; }, abstract = {Upon oral infection with Toxoplasma gondii cysts (76 K strain) tachyzoites are released into the intestinal lumen and cross the epithelial barrier causing damage and acute intestinal inflammation in C57BL/6 (B6) mice. Here we investigated the role of microbiota and IL-22 in T.gondii-induced small intestinal inflammation. Oral T.gondii infection in B6 mice causes inflammation with IFNγ and IL-22 production. In IL-22-deficient mice, T.gondii infection augments the Th1 driven inflammation. Deficiency in either IL-22bp, the soluble IL-22 receptor or Reg3γ, an IL-22-dependent antimicrobial lectin/peptide, did not reduce inflammation. Under germ-free conditions, T.gondii-induced inflammation was reduced in correlation with parasite load. But intestinal inflammation is still present in germ-free mice, at low level, in the lamina propria, independently of IL-22 expression. Exacerbated intestinal inflammation driven by absence of IL-22 appears to be independent of IL-22 deficiency associated-dysbiosis as similar inflammation was observed after fecal transplantation of IL-22-/- or WT microbiota to germ-free-WT mice. Our result