@article {pmid32649987, year = {2020}, author = {Keskey, R and Cone, JT and DeFazio, JR and Alverdy, JC}, title = {The use of fecal microbiota transplant in sepsis.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.trsl.2020.07.002}, pmid = {32649987}, issn = {1878-1810}, abstract = {Sepsis is defined as a dysregulated inflammatory response, which ultimately results from a perturbed interaction of both an altered immune system and the biomass and virulence of involved pathogens. This response has been tied to the intestinal microbiota, as the microbiota and its associated metabolites play an essential role in regulating the host immune response to infection. In turn, critical illness as well as necessary healthcare treatments result in a collapse of the intestinal microbiota diversity and a subsequent loss of health-promoting short chain fatty acids, such as butyrate, leading to the development of a maladaptive pathobiome. These perturbations of the microbiota contribute to the dysregulated immune response and organ failure associated with sepsis. Several case series have reported the ability of fecal microbiota transplant (FMT) to restore the host immune response and aid in recovery of septic patients. Additionally, animal studies have revealed the mechanism of FMT rescue in sepsis is likely related to the ability of FMT to restore butyrate producing bacteria and alter the innate immune response aiding in pathogen clearance. However, several studies have reported lethal complications associated with FMT, including bacteremia. Therefore, FMT in the treatment of sepsis is and should remain investigational until a more detailed mechanism of how FMT restores the host immune response in sepsis is determined, allowing for the development of more fine-tuned microbiota therapies.}, }
@article {pmid32645991, year = {2020}, author = {Shin, YC and Shin, W and Koh, D and Wu, A and Ambrosini, YM and Min, S and Eckhardt, SG and Fleming, RYD and Kim, S and Park, S and Koh, H and Yoo, TK and Kim, HJ}, title = {Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip.}, journal = {Micromachines}, volume = {11}, number = {7}, pages = {}, doi = {10.3390/mi11070663}, pmid = {32645991}, issn = {2072-666X}, support = {F99CA245801//National Cancer Institute of the National Institutes of Health (NIH/NCI)/ ; BWF 1019990.01//Burroughs Wellcome Fund Collaborative Research Travel Grant/ ; 771066//American College of Veterinary Internal Medicine Advance Research Fellowships/ ; 2018M3A9H3025030//Ministry of Science and ICT, South Korea/ ; UTA18-000889/CRI/Cancer Research Institute/United States ; R21CA236690//National Cancer Institute of the National Institutes of Health/ ; 1912-03604//Leona M. and Harry B. Helmsley Charitable Trust/ ; RR160093//Cancer Prevention and Research Institute of Texas/ ; }, abstract = {The regeneration of the mucosal interface of the human intestine is critical in the host-gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed lumen and static culture condition substantially limit the utility of patient-derived organoids for microbiome-associated disease modeling. Here, we report a patient-specific three-dimensional (3D) physiodynamic mucosal interface-on-a-chip (PMI Chip) that provides a microphysiological intestinal milieu under defined biomechanics. The real-time imaging and computational simulation of the PMI Chip verified the recapitulation of non-linear luminal and microvascular flow that simulates the hydrodynamics in a living human gut. The multiaxial deformations in a convoluted microchannel not only induced dynamic cell strains but also enhanced particle mixing in the lumen microchannel. Under this physiodynamic condition, an organoid-derived epithelium obtained from the patients diagnosed with Crohn's disease, ulcerative colitis, or colorectal cancer independently formed 3D epithelial layers with disease-specific differentiations. Moreover, co-culture with the human fecal microbiome in an anoxic-oxic interface resulted in the formation of stochastic microcolonies without a loss of epithelial barrier function. We envision that the patient-specific PMI Chip that conveys genetic, epigenetic, and environmental factors of individual patients will potentially demonstrate the pathophysiological dynamics and complex host-microbiome crosstalk to target a patient-specific disease modeling.}, }
@article {pmid30994937, year = {2019}, author = {Nie, P and Li, Z and Wang, Y and Zhang, Y and Zhao, M and Luo, J and Du, S and Deng, Z and Chen, J and Wang, Y and Chen, S and Wang, L}, title = {Gut microbiome interventions in human health and diseases.}, journal = {Medicinal research reviews}, volume = {39}, number = {6}, pages = {2286-2313}, doi = {10.1002/med.21584}, pmid = {30994937}, issn = {1098-1128}, mesh = {*Disease ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Health ; Humans ; Molecular Targeted Therapy ; Signal Transduction ; }, abstract = {Ongoing studies have determined that the gut microbiota is a major factor influencing both health and disease. Host genetic factors and environmental factors contribute to differences in gut microbiota composition and function. Intestinal dysbiosis is a cause or a contributory cause for diseases in multiple body systems, ranging from the digestive system to the immune, cardiovascular, respiratory, and even nervous system. Investigation of pathogenesis has identified specific species or strains, bacterial genes, and metabolites that play roles in certain diseases and represent potential drug targets. As research progresses, gut microbiome-based diagnosis and therapy are proposed and applied, which might lead to considerable progress in precision medicine. We further discuss the limitations of current studies and potential solutions.}, }
@article {pmid32645451, year = {2020}, author = {Cheng, YW and Alhaffar, D and Saha, S and Khanna, S and Bohm, M and Phelps, E and Ghabril, M and Orman, E and Sashidhar, S and Rogers, N and Xu, H and Khoruts, A and Vaughn, B and Kao, D and Wong, K and Cammarota, G and Ianiro, G and Dhere, T and Kraft, CS and Mehta, N and Michael Woodworth, H and Allegretti, JR and Nativ, L and Marcus, J and El-Nachef, N and Fischer, M}, title = {Fecal Microbiota Transplantation is Safe and Effective in Patients with Clostridioides difficile Infection and Cirrhosis.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2020.06.051}, pmid = {32645451}, issn = {1542-7714}, abstract = {BACKGROUND &amp; AIMS: Clostridioides difficile infection (CDI) harms a large proportion of patients with cirrhosis. Fecal microbiota transplantation (FMT) is recommended for recurrent CDI, but its effects in patients with cirrhosis have not been established. We performed a multicenter, observational study to evaluate efficacy and safety of FMT for CDI in patients with cirrhosis.<br><br>METHODS: We performed a retrospective study of 63 adults with cirrhosis (median model for end-stage liver disease score, 14.5; 24 patients with decompensated cirrhosis) who underwent FMT for CDI from January 2012 through November 2018 at 8 academic centers in the United States, Canada, and Italy. We collected data on patient demographics and characteristics of cirrhosis, CDI, and FMT from medical records and compared differences among patients with different severities of cirrhosis, and FMT successes vs failures at 8 weeks follow up. We also obtained data on adverse events (AE) and severe AEs (SAE) within 12 weeks of FMT.<br><br>RESULTS: Patients underwent FMT for recurrent CDI (55/63; 87.3%), severe CDI (6/63; 9.5%), or fulminant CDI (2/63; 3.2%) primarily via colonoscopy (59/63; 93.7%) as outpatients (47/63; 76.8%). FMT success was achieved for 54 patients (85.7%). Among FMT failures, a higher proportion used non-CDI antibiotics at time of FMT (44.4% vs 5.6%; P<.001), had Child-Pugh scores of B or C (100% vs 37.7%; P<.001), used probiotics (77.8% vs 24.1%, P=.003), had pseudomembranes (22.2% vs 0; P=.018), and underwent FMT as inpatients (45.5% vs 19%; P=.039), compared with FMT successes. In multivariable analysis, use of non-CDI antibiotics at time of FMT (odds ratio, 17.43; 95% CI, 2.00-152.03; P=.01) and use of probiotics (odds ratio, 11.9; 95% CI, 1.81-78.3; P=.01) were associated with greater risk of FMT failure. FMT-related AEs occurred in 33.3% of patients (21/63)-most were self-limited abdominal cramps or diarrhea. There were only 5 SAEs that were possibly related to FMT; none involved infection or death.<br><br>CONCLUSIONS: In a retrospective study, we found FMT to be safe and effective for treatment of CDI in patients with cirrhosis.}, }
@article {pmid32641428, year = {2020}, author = {Seekatz, AM}, title = {mSphere of Influence: Translating Gut Microbiome Studies To Benefit Human Health.}, journal = {mSphere}, volume = {5}, number = {4}, pages = {}, doi = {10.1128/mSphere.00592-20}, pmid = {32641428}, issn = {2379-5042}, abstract = {Anna M. Seekatz works in the field of the gut microbiome as it related to infectious diseases. In this &quot;mSphere of Influence&quot; article, she reflects on how two studies, &quot;The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins&quot; (N. P. McNulty, T. Yatsunenko, A. Hsiao, et al., Sci Transl Med 3:106ra106, 2011) and &quot;High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria&quot; (M. J. Hamilton, A. R. Weingarden, T. Unno, A. Khoruts, and M. J. Sadowsky, Gut Microbes 4:125-135, 2013), shaped how she approaches interpreting microbiome studies.}, }
@article {pmid32639360, year = {2020}, author = {Van den Houte, K and Colomier, E and Schol, J and Carbone, F and Tack, J}, title = {Recent advances in diagnosis and management of irritable bowel syndrome.}, journal = {Current opinion in psychiatry}, volume = {}, number = {}, pages = {}, doi = {10.1097/YCO.0000000000000628}, pmid = {32639360}, issn = {1473-6578}, abstract = {PURPOSE OF REVIEW: This review summarizes recent progress in the diagnosis and management of irritable bowel syndrome, with a focus on dietary and microbiota aspects.<br><br>RECENT FINDINGS: From a pathophysiological point of view, IBS is a multifactorial condition with both peripheral (transit) as central (visceral hypersensitivity, anxiety, depression) contribution in a cumulative fashion to the symptom pattern and severity. More recently, the focus has shifted to diet and microbiota. The number of dietary options that can be used for IBS and the understanding of determinants of their efficacy is rapidly increasing. Several studies have confirmed the efficacy of the low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet. Sucrose-isomaltase deficiency has emerged as pathogenetic mechanisms in a subset of patients, who do not respond to low FODMAP diet but may respond to starch and sucrose elimination. Herbal remedies, probiotics and secretagogues have been the topic of additional treatment trials. The efficacy of fecal microbiota transplantation in IBS is variable across studies, but donor selection is emerging as a critical factor.<br><br>SUMMARY: Irritable bowel syndrome has evolved into a disorder of interaction between dietary factors and gut microbiota, with impact on bowel symptoms as well as extra-intestinal, central, symptoms. Dietary adjustments and treatments targeting the gut microbiota are areas of active research and clinical progress.}, }
@article {pmid32636823, year = {2020}, author = {Moreno-Indias, I and Lundberg, R and Krych, L and Metzdorff, SB and Kot, W and Sørensen, DB and Nielsen, DS and Hansen, CHF and Hansen, AK}, title = {A Humanized Diet Profile May Facilitate Colonization and Immune Stimulation in Human Microbiota-Colonized Mice.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1336}, doi = {10.3389/fmicb.2020.01336}, pmid = {32636823}, issn = {1664-302X}, abstract = {Background: In spite of the importance of the use of gnotobiotic mice for human fecal transfer, colonization efficiency and immune stimulation after human microbiota inoculation in mice are poorly studied compared to mouse microbiota inoculation. We tested the colonization efficiency and immune responses in mice bred for one additional generation after inoculating the parent generation with either a human (HM) or a mouse microbiota (MM). Furthermore, we tested if colonization efficiency and immune stimulation could be improved in HM-colonized mice by dietary approaches: if these were fed a diet closer to the human diet either in its sources of animal fat and protein [the &quot;animal source&quot; (AS) diet] or in its proportions of macronutrients from the normal sources of a mouse diet [the &quot;human profile&quot; (HP) diet].<br><br>Results: Although significantly lower in mice with a human microbiota (30-40% vs. 61-70%) the colonization efficiency was significantly higher in HM mice fed the HP diet (40%), and in MM mice fed AS (70%). The microbiota of mice fed HP was comparable to the microbiota of mice fed a standard rodent chow, while the microbiota of mice fed the animal source diet (AS) clustered separately. Mice inoculated with mouse fecal matter had significantly more CD4+ T cells and Cd4 expression and significantly fewer regulatory T cells (Tregs) and FoxP3 expression than human microbiota inoculated mice, but cell proportions differences were mostly apparent between mice fed the AS diet. Mice fed the HP diet had significantly higher expression of Cd8a.<br><br>Conclusion: It is concluded that a diet with a humanized profile could support the establishment of a human microbiota in mice, which will, however, still elicit a lower colonization efficiency compared to mice inoculated with a mouse microbiota.}, }
@article {pmid32205337, year = {2020}, author = {Huang, Z and Chen, J and Li, B and Zeng, B and Chou, CH and Zheng, X and Xie, J and Li, H and Hao, Y and Chen, G and Pei, F and Shen, B and Kraus, VB and Wei, H and Zhou, X and Cheng, L}, title = {Faecal microbiota transplantation from metabolically compromised human donors accelerates osteoarthritis in mice.}, journal = {Annals of the rheumatic diseases}, volume = {79}, number = {5}, pages = {646-656}, doi = {10.1136/annrheumdis-2019-216471}, pmid = {32205337}, issn = {1468-2060}, mesh = {Animals ; Biomarkers/analysis ; Biopsy, Needle ; Disease Models, Animal ; Disease Progression ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Male ; Menisci, Tibial/pathology/surgery ; Metabolic Syndrome/*complications/pathology ; Mice, Inbred C57BL ; Multivariate Analysis ; Osteoarthritis, Knee/pathology/*therapy ; Random Allocation ; Reference Values ; Regression Analysis ; Risk Assessment ; }, abstract = {OBJECTIVES: Emerging evidence suggests that the microbiome plays an important role in the pathogenesis of osteoarthritis (OA). We aimed to test the two-hit model of OA pathogenesis and potentiation in which one 'hit' is provided by an adverse gut microbiome that activates innate immunity; the other 'hit' is underlying joint damage.<br><br>METHODS: Medical history, faecal and blood samples were collected from human healthy controls (OA-METS-, n=4), knee OA without metabolic syndrome (OA+METS-, n=7) and knee OA with metabolic syndrome (OA+METS+, n=9). Each group of human faecal samples, whose microbial composition was identified by 16S rRNA sequencing, was pooled and transplanted into germ-free mice 2 weeks prior to meniscal/ligamentous injury (MLI) (n≥6 per group). Eight weeks after MLI, mice were evaluated for histological OA severity and synovitis, systemic inflammation and gut permeability.<br><br>RESULTS: Histological OA severity following MLI was minimal in germ-free mice. Compared with the other groups, transplantation with the OA+METS+ microbiome was associated with higher mean systemic concentrations of inflammatory biomarkers (interleukin-1β, interleukin-6 and macrophage inflammatory protein-1α), higher gut permeability and worse OA severity. A greater abundance of Fusobacterium and Faecalibaterium and lesser abundance of Ruminococcaceae in transplanted mice were consistently correlated with OA severity and systemic biomarkers concentrations.<br><br>CONCLUSION: The study clearly establishes a direct gut microbiome-OA connection that sets the stage for a new means of exploring OA pathogenesis and potentially new OA therapeutics. Alterations of Fusobacterium, Faecalibaterium and Ruminococcaceae suggest a role of these particular microbes in exacerbating OA.}, }
@article {pmid32629118, year = {2020}, author = {Su, CW and Chen, CY and Jiao, L and Long, SR and Mao, T and Ji, Q and O'Donnell, S and Stanton, C and Zheng, S and Walker, WA and Cherayil, BJ and Shi, HN}, title = {Helminth-induced and Th2-dependent alterations of the gut microbiota attenuate obesity caused by high fat diet.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jcmgh.2020.06.010}, pmid = {32629118}, issn = {2352-345X}, abstract = {BACKGROUND &amp; AIMS: Epidemiological and animal studies have indicated an inverse correlation between the rising prevalence of obesity and metabolic syndrome and exposure to helminths. Whether helminth-induced immune response contributes to microbiota remodeling in obesity remains unknown. The aim of this study is to explore the immune-regulatory role of helminth in the prevention of HFD-induced obesity through remodeling gut microbiome.<br><br>METHODS: C57BL/6J WT and STAT6-/- mice were infected with Heligmosomoides polygyrus and followed by high fat diet (HFD) feeding for 6 weeks. The host immune response, body weight, and fecal microbiota composition were analyzed. We used adoptive transfer of M2 macrophages and microbiota transplantation approaches to determine the impact of these factors on HFD-obesity. We also examined stool microbiota composition and short chain fatty acids (SCFAs) concentration and determined the expression of SCFA-relevant receptors in the recipient mice.<br><br>RESULTS: Helminth infection of STAT6-/- (Th2-deficient) mice and adoptive transfer of helminth-induced alternatively activated (M2) macrophages demonstrated that the helminth-associated Th2 immune response plays an important role in the protection against obesity and induces changes in microbiota composition. Microbiota transplantation showed that helminth-induced, Th2-dependent alterations of the gut microbiota are sufficient to confer protection against obesity. Collectively, these results indicate that helminth infection protects against HFD-induced obesity by Th2-dependent, M2 macrophage-mediated alterations of the intestinal microbiota.<br><br>CONCLUSION: Our findings provide new mechanistic insights into the complex interplay between helminth infection, the immune system and the gut microbiota in a HFD-induced obesity model and holds promise for gut microbiome-targeted immunotherapy in obesity prevention.}, }
@article {pmid32620839, year = {2020}, author = {Xiao, Y and Angulo, MT and Lao, S and Weiss, ST and Liu, YY}, title = {An ecological framework to understand the efficacy of fecal microbiota transplantation.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {3329}, doi = {10.1038/s41467-020-17180-x}, pmid = {32620839}, issn = {2041-1723}, support = {61902418//National Natural Science Foundation of China (National Science Foundation of China)/ ; R01AI141529//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; R01HD093761//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; UH3OD023268//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; U19AI095219//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; U01HL089856//U.S. Department of Health &amp; Human Services | National Institutes of Health (NIH)/ ; }, abstract = {Human gut microbiota plays critical roles in physiology and disease. Our understanding of ecological principles that govern the dynamics and resilience of this highly complex ecosystem remains rudimentary. This knowledge gap becomes more problematic as new approaches to modifying this ecosystem, such as fecal microbiota transplantation (FMT), are being developed as therapeutic interventions. Here we present an ecological framework to understand the efficacy of FMT in treating conditions associated with a disrupted gut microbiota, using the recurrent Clostridioides difficile infection as a prototype disease. This framework predicts several key factors that determine the efficacy of FMT. Moreover, it offers an efficient algorithm for the rational design of personalized probiotic cocktails to decolonize pathogens. We analyze data from both preclinical mouse experiments and a clinical trial of FMT to validate our theoretical framework. The presented results significantly improve our understanding of the ecological principles of FMT and have a positive translational impact on the rational design of general microbiota-based therapeutics.}, }
@article {pmid32620549, year = {2020}, author = {Ianiro, G and Mullish, BH and Kelly, CR and Kassam, Z and Kuijper, EJ and Ng, SC and Iqbal, TH and Allegretti, JR and Bibbò, S and Sokol, H and Zhang, F and Fischer, M and Costello, SP and Keller, JJ and Masucci, L and van Prehn, J and Quaranta, G and Quraishi, MN and Segal, J and Kao, D and Satokari, R and Sanguinetti, M and Tilg, H and Gasbarrini, A and Cammarota, G}, title = {Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2020-321829}, pmid = {32620549}, issn = {1468-3288}, abstract = {The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.}, }
@article {pmid32618725, year = {2020}, author = {Claytor, JD and El-Nachef, N}, title = {Fecal microbial transplant for inflammatory bowel disease.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCO.0000000000000676}, pmid = {32618725}, issn = {1473-6519}, abstract = {PURPOSE OF REVIEW: The purpose of this brief review is to investigate the current utility of fecal microbial transplantation (FMT) to ameliorate dysbiosis contributing to inflammatory bowel disease pathogenesis.<br><br>RECENT FINDINGS: Increasing data from randomized, controlled trials support a role for multiple FMT administrations in the induction of remission and even as a maintenance therapy in mild-to-moderate Ulcerative Colitis. Small series and one small randomized controlled trial among patients with Crohn's Disease and with pouchitis continue to produce conflicting clinical results and microbial profile data on the host and donor levels. It is not clear whether patients with Crohn's disease are more susceptible to disease flare after FMT. Novel FMT delivery systems, including oral, and early-intensity colonoscopic devices, are under investigation.<br><br>SUMMARY: The allure of minimizing the risks and cost of long-term immunosuppression via modulation of patient microbiota remains enticing, and the most recent randomized controlled data in ulcerative colitis reveals acceptable clinical remission rates. However, prior to wide adoption of FMT within the inflammatory bowel disease treatment armamentarium, large clinical trials identifying biomarkers of treatment success, ensuring safety across all indications, and cultivating optimized donor and host selection are needed.}, }
@article {pmid32618656, year = {2020}, author = {Craven, L and Rahman, A and Nair Parvathy, S and Beaton, M and Silverman, J and Qumosani, K and Hramiak, I and Hegele, R and Joy, T and Meddings, J and Urquhart, B and Harvie, R and McKenzie, C and Summers, K and Reid, G and Burton, JP and Silverman, M}, title = {Allogenic Fecal Microbiota Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial.}, journal = {The American journal of gastroenterology}, volume = {115}, number = {7}, pages = {1055-1065}, doi = {10.14309/ajg.0000000000000661}, pmid = {32618656}, issn = {1572-0241}, abstract = {INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability.<br><br>METHODS: Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT.<br><br>RESULTS: There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT.<br><br>DISCUSSION: FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.}, }
@article {pmid32618640, year = {2020}, author = {Khanna, S and Pardi, D}, title = {Fecal Microbiota Transplantation for Recurrent Clostridioides difficile infection: The COVID-19 Era.}, journal = {The American journal of gastroenterology}, volume = {115}, number = {7}, pages = {971-974}, doi = {10.14309/ajg.0000000000000689}, pmid = {32618640}, issn = {1572-0241}, }
@article {pmid32617914, year = {2020}, author = {Floyd, JL and Grant, MB}, title = {The Gut-Eye Axis: Lessons Learned from Murine Models.}, journal = {Ophthalmology and therapy}, volume = {}, number = {}, pages = {}, doi = {10.1007/s40123-020-00278-2}, pmid = {32617914}, issn = {2193-8245}, support = {R01EY025383/NH/NIH HHS/United States ; R01EY012601/NH/NIH HHS/United States ; R01EY028858/NH/NIH HHS/United States ; R01EY028037/NH/NIH HHS/United States ; }, abstract = {A healthy gut microbiota is essential in maintaining the human body in a homeostatic state by its functions in digestion and immune tolerance. Under states of aberrant microbial composition or function (dysbiosis), the gut microbiota induces systemic inflammation that can lead to the onset of many diseases. In this review, we describe some evidence, largely from rodent studies, that supports the possible role of a dysbiotic gut microbiota in the onset and exacerbation of ocular diseases, primarily diabetic retinopathy, age-related macular degeneration, choroidal neovascularization, and uveitis. Furthermore, we examine several potential therapeutic measures that show promise in restoring the gut microbiota to a eubiotic state, preventing the aforementioned disease pathologies.}, }
@article {pmid32611702, year = {2020}, author = {Woodworth, MH}, title = {mSphere of Influence: Microbiome-Associated Phenotypes Are Modifiable.}, journal = {mSphere}, volume = {5}, number = {4}, pages = {}, doi = {10.1128/mSphere.00508-20}, pmid = {32611702}, issn = {2379-5042}, abstract = {Michael Woodworth focuses on translational microbiome therapeutic research. In this mSphere of Influence article, he reflects on how &quot;Gut microbiomes of Malawian twin pairs discordant for kwashiorkor&quot; by Michelle Smith et al. (M. I. Smith, T. Yatsunenko, M. J. Manary, I. Trehan, et al., Science 339:548-554, 2013, https://doi.org/10.1126/science.1229000) made an impact on him by revealing the causal influence of microbial communities in the development of severe malnutrition.}, }
@article {pmid32610522, year = {2020}, author = {Bilinski, J and Dziurzynski, M and Grzesiowski, P and Podsiadly, E and Stelmaszczyk-Emmel, A and Dzieciatkowski, T and Dziewit, L and Basak, GW}, title = {Multimodal Approach to Assessment of Fecal Microbiota Donors based on Three Complementary Methods.}, journal = {Journal of clinical medicine}, volume = {9}, number = {7}, pages = {}, doi = {10.3390/jcm9072036}, pmid = {32610522}, issn = {2077-0383}, support = {1WP/FS200/ZW2/17//Ministerstwo Nauki i Szkolnictwa Wyższego/ ; }, abstract = {Methods of stool assessment are mostly focused on next-generation sequencing (NGS) or classical culturing, but only rarely both. We conducted a series of experiments using a multi-method approach to trace the stability of gut microbiota in various donors over time, to find the best method for the proper selection of fecal donors and to find &quot;super-donor&quot; indicators. Ten consecutive stools donated by each of three donors were used for the experiments (30 stools in total). The experiments assessed bacterial viability measured by flow cytometry, stool culturing on different media and in various conditions, and NGS (90 samples in total). There were no statistically significant differences between live and dead cell numbers; however, we found a group of cells classified as not-dead-not-alive, which may be possibly important in selection of &quot;good&quot; donors. Donor C, being a regular stool donor, was characterized by the largest number of cultivable species (64). Cultivable core microbiota (shared by all donors) was composed of only 16 species. ANCOM analysis of NGS data highlighted particular genera to be more abundant in one donor vs. the others. There was a correlation between the not-dead-not-alive group found in flow cytometry and Anaeroplasma found by NGS, and we could distinguish a regular stool donor from the others. In this work, we showed that combining various methods of microbiota assessment gives more information than each method separately.}, }
@article {pmid31524867, year = {2019}, author = {Daharsh, L and Zhang, J and Ramer-Tait, A and Li, Q}, title = {A Double Humanized BLT-mice Model Featuring a Stable Human-Like Gut Microbiome and Human Immune System.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {150}, pages = {}, pmid = {31524867}, issn = {1940-087X}, support = {R21 AI122377/AI/NIAID NIH HHS/United States ; P20 GM103427/GM/NIGMS NIH HHS/United States ; R01 AI124804/AI/NIAID NIH HHS/United States ; P30 CA036727/CA/NCI NIH HHS/United States ; R21 AI143405/AI/NIAID NIH HHS/United States ; R01 AI111862/AI/NIAID NIH HHS/United States ; P30 GM110768/GM/NIGMS NIH HHS/United States ; P30 MH062261/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Immune System ; Mice ; Mice, Inbred NOD ; *Models, Animal ; RNA, Ribosomal, 16S ; }, abstract = {Humanized mice (hu-mice) that feature a functional human immune system have fundamentally changed the study of human pathogens and disease. They can be used to model diseases that are otherwise difficult or impossible to study in humans or other animal models. The gut microbiome can have a profound impact on human health and disease. However, the murine gut microbiome is very different than the one found in humans. There is a need for improved pre-clinical hu-mice models that have an engrafted human gut microbiome. Therefore, we created double hu-mice that feature both a human immune system and stable human-like gut microbiome. NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice are one of the best animals for humanization due to their high level of immunodeficiency. However, germ-free NSG mice, and various other important germ-free mice models are not currently commercially available. Further, many research settings do not have access to gnotobiotic facilities, and working under gnotobiotic conditions can often be expensive and time consuming. Importantly, germ-free mice have several immune deficiencies that exist even after the engraftment of microbes. Therefore, we developed a protocol that does not require germ-free animals or gnotobiotic facilities. To generate double hu-mice, NSG mice were treated with radiation prior to surgery to create bone-marrow, liver, thymus-humanized (hu-BLT) mice. The mice were then treated with broad spectrum antibiotics to deplete the pre-existing murine gut microbiome. After antibiotic treatment, the mice were given fecal transplants with healthy human donor samples via oral gavage. Double hu-BLT mice had unique 16S rRNA gene profiles based on the individual human donor sample that was transplanted. Importantly, the transplanted human-like microbiome was stable in the double hu-BLT mice for the duration of the study up to 14.5 weeks post-transplant.}, }
@article {pmid31038755, year = {2019}, author = {Bajaj, JS and Salzman, NH and Acharya, C and Sterling, RK and White, MB and Gavis, EA and Fagan, A and Hayward, M and Holtz, ML and Matherly, S and Lee, H and Osman, M and Siddiqui, MS and Fuchs, M and Puri, P and Sikaroodi, M and Gillevet, PM}, title = {Fecal Microbial Transplant Capsules Are Safe in Hepatic Encephalopathy: A Phase 1, Randomized, Placebo-Controlled Trial.}, journal = {Hepatology (Baltimore, Md.)}, volume = {70}, number = {5}, pages = {1690-1703}, pmid = {31038755}, issn = {1527-3350}, support = {UL1 TR002649/TR/NCATS NIH HHS/United States ; I0CX001076//Office of Research and Development/International ; I01 CX001076/CX/CSRD VA/United States ; R21 TR002024/TR/NCATS NIH HHS/United States ; }, mesh = {Administration, Oral ; Capsules ; *Fecal Microbiota Transplantation/methods ; Female ; Hepatic Encephalopathy/complications/*therapy ; Humans ; Liver Cirrhosis/complications ; Male ; Middle Aged ; Single-Blind Method ; }, abstract = {Hepatic encephalopathy (HE) can cause major morbidity despite standard of care (SOC; rifaximin/lactulose). Fecal microbial transplant (FMT) enemas postantibiotics are safe, but the effect of FMT without antibiotics using the capsular route requires investigation. The aim of this work was to determine the safety, tolerability, and impact on mucosal/stool microbiota and brain function in HE after capsular FMT in a randomized, single-blind, placebo-controlled clinical trial in Virginia. Patients with cirrhosis with recurrent HE with MELD (Model for End-Stage Liver Disease) <17 on SOC were randomized 1:1 into receiving 15 FMT capsules versus placebo from a single donor enriched in Lachnospiraceae and Ruminococcaceae. Endoscopies with duodenal and sigmoid biopsies, stool analysis, cognition, serum lipopolysaccharide-binding protein (LBP), and duodenal antimicrobial peptide (AMP) expression at baseline were used. Clinical follow-up with SOC maintenance was performed until 5 months. FMT-assigned patients underwent repeat endoscopies 4 weeks postenrollment. Twenty subjects on lactulose/rifaximin were randomized 1:1. MELD score was similar at baseline (9.6 vs. 10.2) and study end (10.2 vs. 10.5). Six patients in the placebo group required hospitalizations compared to 1 in FMT, which was deemed unrelated to FMT. Infection/HE episodes were similar between groups. Baseline microbial diversity was similar in all tissues between groups. Post-FMT, duodenal mucosal diversity (P = 0.01) increased with higher Ruminococcaceae and Bifidobacteriaceae and lower Streptococcaceae and Veillonellaceae. Reduction in Veillonellaceae were noted post-FMT in sigmoid (P = 0.04) and stool (P = 0.05). Duodenal E-cadherin (P = 0.03) and defensin alpha 5 (P = 0.03) increased whereas interleukin-6 (P = 0.02) and serum LBP (P = 0.009) reduced post-FMT. EncephalApp performance improved post-FMT only (P = 0.02). Conclusion: In this phase 1 study, oral FMT capsules are safe and well tolerated in patients with cirrhosis and recurrent HE. FMT was associated with improved duodenal mucosal diversity, dysbiosis, and AMP expression, reduced LBP, and improved EncephalApp performance. Further studies are needed to prove efficacy.}, }
@article {pmid32607098, year = {2020}, author = {Park, R and Umar, S and Kasi, A}, title = {Immunotherapy in Colorectal Cancer: Potential of Fecal Transplant and Microbiota-augmented Clinical Trials.}, journal = {Current colorectal cancer reports}, volume = {16}, number = {4}, pages = {81-88}, doi = {10.1007/s11888-020-00456-1}, pmid = {32607098}, issn = {1556-3790}, abstract = {Purpose of review: This review summarizes the role of the microbiome in colorectal cancer (CRC) in the setting of immunotherapy and emphasizes the potential of microbiota-influencing strategies with a focus on the use of fecal microbiota transplant (FMT).<br><br>Recent findings: Observations from preclinical and clinical studies suggest that the human gut microbiome is implicated in the CRC carcinogenesis and is integral in determining the clinical response and toxicity to immunotherapy. Among the therapeutic methods devised to exploit the microbiome, FMT is the most direct method and is backed by the highest level of evidence of efficacy in nonneoplastic disease settings. Furthermore, a favorable microbiome has the potential to overcome immunotherapy resistance and ameliorate immune-related adverse events (irAEs). To this end, clinical trials are underway to evaluate the potential of FMT and microbiota-augmented methods in the setting of immunotherapy in CRC.<br><br>Summary: Evidence from animal studies, retrospective studies, and smaller-scale prospective human studies have led to initiation of a number of microbiota-augmented clinical trials in CRC. Given the intimate relationship between the gut microbiota and the immune system as well as antitumor immune responses, potentiating immunotherapy and managing its toxicity are major areas of research in microbiota-augmented therapies in cancer. Therefore, evaluation of the patient microbiome as a routine part of clinical outcome analysis is warranted in future clinical trials.}, }
@article {pmid32605650, year = {2020}, author = {Benech, N and Sokol, H}, title = {Fecal microbiota transplantation in gastrointestinal disorders: time for precision medicine.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {58}, doi = {10.1186/s13073-020-00757-y}, pmid = {32605650}, issn = {1756-994X}, abstract = {Fecal microbiota transplantation (FMT) has demonstrated efficacy in treating inflammatory bowel diseases and irritable bowel syndrome in an increasing number of randomized controlled trials. Recently published data gives striking insights into the factors associated with FMT success paving the road for the use of precision medicine in gastrointestinal disorders.}, }
@article {pmid32601752, year = {2020}, author = {Meyer, DC and Hill, SS and Bebinger, DM and McDade, JA and Davids, JS and Alavi, K and Maykel, JA}, title = {Resolution of multiply recurrent and multifocal diverticulitis after fecal microbiota transplantation.}, journal = {Techniques in coloproctology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10151-020-02275-w}, pmid = {32601752}, issn = {1128-045X}, abstract = {BACKGROUND: The exact pathophysiology of diverticulitis is not well understood and may be multifactorial. Recent studies highlight dysbiosis as a plausible mechanism. FMT is a safe strategy to restore commensal colon microbiota and has proven to be an effective treatment for gastrointestinal dysbiosis such as Clostridium difficile infection (CDI). There have been no studies reporting the treatment of diverticulitis with FMT. Our aim was to describe the novel application of fecal microbiota transplantation (FMT) for the treatment of recurrent diverticulitis.<br><br>CASE: We report a case of a 63-year-old woman who had a 13-year history of multiply recurrent and multifocal diverticulitis previously treated with numerous short courses of intravenous and oral antibiotics for acute flares, two segmental colon resections, and suppressive antibiotic therapy for recurrent disease. Secondary to multiple courses of antibiotics , the patient developed CDI. She was treated with a single round of FMT and subsequently stopped all antibiotics at the time of FMT.<br><br>RESULTS: In 20 months of follow-up, the patient has had no further recurrence of diverticulitis or CDI.<br><br>CONCLUSIONS: FMT could prove to be a novel therapy for refractory diverticulitis but requires further investigation.}, }
@article {pmid32600151, year = {2020}, author = {Hazan, S}, title = {Rapid improvement in Alzheimer's disease symptoms following fecal microbiota transplantation: a case report.}, journal = {The Journal of international medical research}, volume = {48}, number = {6}, pages = {300060520925930}, doi = {10.1177/0300060520925930}, pmid = {32600151}, issn = {1473-2300}, abstract = {Alzheimer's disease (AD), the most common form of dementia, is a leading cause of death and a major cause of morbidity in older people. The disease is characterized by progressive memory loss, cognitive impairment, and the cerebral accumulation of amyloid-β peptide. Given the health and economic impacts of AD, treatments that target the underlying etiology of AD or modify the course of the disease are of significant interest. The gut microbiome has been increasingly implicated in the pathogenesis of several neurological diseases, including multiple sclerosis and Parkinson's disease. Furthermore, emerging evidence has demonstrated that there are alterations in gut microbiome composition in patients with AD, suggesting involvement of the microbiome-gut-brain axis. We present symptom improvement in a patient with AD following fecal microbiota transplantation for a Clostridioides difficile infection.}, }
@article {pmid32594732, year = {2020}, author = {Chen, QY and Tian, HL and Yang, B and Qin, HL and Li, N}, title = {[A case report of refractory methemoglobinemia after nitrite poisoning treated by fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {90-92}, doi = {10.3760/cma.j.cn.441530-20200416-00218}, pmid = {32594732}, issn = {1671-0274}, }
@article {pmid32594731, year = {2020}, author = {Yang, B and Chen, QY and Tian, HL and Lin, ZL and Zhao, D and Ye, C and Zhang, XY and Qin, HL and Li, N}, title = {[Application of modified blind nasojejunal tube technique in fecal microbiota transplantation - report of 2267 cases].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {86-89}, doi = {10.3760/cma.j.cn.441530-20200414-00209}, pmid = {32594731}, issn = {1671-0274}, }
@article {pmid32594729, year = {2020}, author = {Chen, QY and Yang, B and Tian, HL and Lin, ZL and Zhao, D and Ye, C and Zhang, XY and Qin, HL and Li, N}, title = {[Association between the clinical efficacy of fecal microbiota transplantation in recipients and the choice of donor].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {69-76}, doi = {10.3760/cma.j.cn.441530-20200417-00222}, pmid = {32594729}, issn = {1671-0274}, support = {81670493//National Natural Science Fundation of China/ ; }, abstract = {Objective: To examine the association between the clinical efficacy of fecal microbiota transplantation (FMT) in recipients and the choice of donor, and to observe the characteristics of intestinal flora and metabolites among different donors. Methods: A retrospective case-control study was conducted. Donor whose feces was administrated for more than 30 recipients was enrolled. Data of 20 FMT donors and corresponding recipients at Intestinal Microecology Diagnosis and Treatment Center of the Tenth People's Hospital from October 2018 to December 2019 were collected retrospectively. During follow-up, the efficacy of each recipient 8-week after FMT treatment was recorded and analyzed. Based on the efficacy of each donor, the donors were divided into three groups: high efficacy group (effective rate >60%, 10 donors), moderate efficacy group (effective rate 30%-60%, 6 donors) and low efficacy group (effective rate <30%, 4 donors). The structure of the bacterial flora and the content of fecal short-chain fatty acids in each group of donors were detected and compared among groups. Association of the efficacy of each donor group with the morbidity of complications, and association of efficacy of recipients with donors were analyzed. The evaluation indicators of FMT efficacy included objective clinical effectiveness and/or subjective effectiveness. Objective effectiveness indicated clinical cure plus clinical improvement, and subjective effectiveness indicated marked effectiveness plus medium effectiveness through questionnaire during follow-up. Results: A total of 1387 recipients were treated by 20 donors, including 749 cases of chronic constipation, 141 cases of chronic diarrhea, 107 cases of inflammatory bowel disease (IBD), 121 cases of irritable bowel syndrome (IBS), 83 cases of autism, and 186 cases of other diseases, such as radiation bowel injury, intestinal pseudo-obstruction, paralytic intestinal obstruction, functional bloating and allergic diseases. There were 829 cases, 403 cases, and 155 cases in high efficacy group, moderate efficacy group and low efficacy group respectively. Baseline data among 3 groups were not significantly different (all P> 0.05). In comparison of bacterial abundance (operational taxonomic unit, OTU) among different effective donor groups, the high efficacy group was the highest (330.68±57.28), the moderate efficacy group was the second (237.79±41.89), and the low efficacy group was the lowest (160.60±49.61), whose difference was statistically significant (F=16.910, P<0.001). In comparison of bacterial diversity (Shannon index), the high efficacy group and the moderate efficacy group were higher (2.96±0.36 and 2.67±0.54, respectively), and the low efficacy group was lower (2.09±0.55), whose difference was statistically significant (F=5.255, P=0.017). In comparison of butyric acid content among three groups, the high efficacy group had the highest [(59.20±9.00) μmol/g], followed by middle efficacy group [(46.92±9.48) μmol/g], and the low efficacy group had the lowest [(37.23±5.03) μmol/g], whose difference was statistically significant (F=10.383, P=0.001). The differences of acetic acid and propionic acid among three groups were not statistically significant (all P>0.05). A total of 418 cases developed complications (30.1%). Morbidity of complication in low efficacy group, moderate efficacy group and high efficacy group was 40.6% (63/155), 30.0% (121/403) and 28.2% (243/829) respectively, and the difference was statistically significant (χ(2)=9.568, P=0.008). The incidence of diarrhea in low efficacy group, moderate efficacy group and high efficacy group was 7.1% (11/155), 4.0% (16/403) and 2.8% (23/829) respectively, and the difference was statistically significant (χ(2)=7.239, P=0.027). Comparing the incidences of other types of complications, no statistically significant differences were found (all P>0.05). Follow up began 8 weeks after the FMT treatment. The total follow-up rate was 83.6% (1160/1387). The overall effective rate 58.3% (676/1160). Effective rates of various diseases were as follows: chronic constipation 54.3% (328/604), chronic diarrhea 88.5% (115/130), IBD 56.1% (55/98), IBS 55.1% (59/107), autism 61.6% (45/73), and other diseases 50.0% (74/148). Comparing the effective rate of three groups of donors for different diseases, there was no statistically significant difference in chronic diarrhea (P>0.05); there was a positive correlation trend in IBD, IBS and autism, but the differences were not statistically significant (all P>0.05). For chronic constipation and other diseases, high efficacy group had the highest effective rate [65.0% (243/374) and 63.2% (55/87)], followed by moderate efficacy group [49.4% (86/174) and 38.1% (16/42)], and low efficacy group had the lowest [16.1% (9/56) and 15.8% (3/19)], whose differences were significant (all P<0.05). Conclusions: Different donors have different efficacy in different diseases. Chronic constipation, radiation bowel injury, etc. need to choose donors with high efficacy. IBD, IBS and autism may also be related to the effectiveness of donors, while chronic diarrhea is not associated to the donor. The efficiency of the donor is negatively correlated to the morbidity of complications. The abundance and diversity of intestinal flora and the content of butyric acid may affect the efficacy of the donor.}, }
@article {pmid32594728, year = {2020}, author = {Tian, HL and Chen, QY and Yang, B and Ma, CL and Lin, ZL and Zhang, XY and Zhou, SL and Qin, HL and Li, N}, title = {[Effects of fecal microbiota transplantation in different routes on the clinical efficacy of slow transit constipation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {63-68}, doi = {10.3760/cma.j.cn.441530-20200415-00212}, pmid = {32594728}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; 04.99.18001//Special fund for the construction of the clinical center of Tenth People's Hospital of Tongji University/ ; }, abstract = {Objective: To evaluate the efficacy and safety of the fecal microbiota transplantation (FMT) in the different route administration for slow transit constipation (STC). Methods: A retrospective cohort study was conducted. The clinical data of 270 STC patients who voluntarily received FMT treatment in the Tenth People's Hospital of Tongji University from May 2018 to May 2019 were collected. Non-relative healthy adult standard donors were applied. The treatment routes of bacterial flora transplantation included nasojejunal tube (nasal enteral tube group, 120 cases), oral enterobacterial capsule treatment (oral capsule group, 120 cases), and colonoscopy infusion (colonoscopy group, 30 cases). The efficacy and safety of treatment among the three groups were compared. Results: Transplanted bacteria of three groups were extracted from 100 g of fresh feces. All the patients successfully completed the transplantation. The waiting time for the nasal enteral tube group, oral capsule group and colonoscopy group was (1.5±0.5) d, (0.4±0.3) d and (3.6±0.8) d respectively; the cost of establishing the transplantation path was (495±20) yuan, (25±10) yuan and (1420±45) yuan respectively, whose differences were statistically significant (F=9.210, P=0.03; F=10.600,P=0.01). The clinical improvement rates at 1 month after FMT treatment in the nasojejunal tube group, oral capsule group and colonoscopy group were 74.2% (89/120), 60.0% (72/120) and 53.3% (16/30) respectively, whose difference was statistically significant (χ(2)=5.990, P<0.05). The clinical improvement rates at 3 months after treatment were 71.1% (69/97), 53.6% (45/84), and 44.0% (11/25) respectively, whose difference was statistically significant (χ(2)=7.620, P<0.05). The incidence of adverse reactions in the colonoscopy group was 76.7% (23/30), which was higher than that in the nasal nasojejunal group (39.2%, 47/120) and oral capsule group (21.7%, 26/120). The most common adverse reactions in the nasojejunal tube group, oral capsule group and colonoscopy group were respiratory discomfort (17.5%, 21/120), nausea and vomiting (10.0%, 12/120), and diarrhea (36.7%, 11/30). During the 3-month follow-up after treatment, no FMT-related adverse reactions were reported. Conclusions: The nasojejunal tube route has stable clinical efficacy and operability, while the oral capsule route has shorter waiting time and less cost. However, the adverse reactions caused by different transplantation methods are different, thus personalized transplantation method should be recommended.}, }
@article {pmid32594727, year = {2020}, author = {Lin, ZL and Chen, QY and Tian, HL and Yang, B and Zhao, D and Ye, C and Zhang, XY and Ma, CL and Qin, HL and Li, N}, title = {[Effect of fecal bacterial preservation time on the outcomes of fecal microbiota transplantation for slow transit constipation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {56-62}, doi = {10.3760/cma.j.cn.441530-20200414-00207}, pmid = {32594727}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; 04.99.18001//Special Fund for the Construction of the Clinical Center of Tenth People's Hospital of Tongji University/ ; }, abstract = {Objective: To investigate the effect of different fecal bacterial preservation time on the efficacy and complications of FMT. Methods: A retrospective cohort study was carried out. Clinical data of 483 patients with slow transit constipation undergoing voluntary FMT at Intestinal Microecology Diagnosis and Treatment Center from August 2017 to October 2019 were retrospectively collected. According to the storage time of fecal bacterial samples used in FMT treatment, the cases were divided into fresh bacterial solution (n=29), bacterial solution stored at -80℃ for 1 week (n=187), 1 month (n=121), 3 months (n=89), 6 months (n=38), and 12 months (n=19). The total number of complete bowel movement, Wexner constipation score, gastrointestinal quality of life index (GIQLI), FMT satisfaction score and related adverse reactions were summarized and compared among groups 1 week and 1 month after FMT treatment. Results: There were no statistically significant differences in the baseline data of patients among different bacterial solution storage time (all P>0.05). After 1 month of treatment, the overall frequency of defecation of all the patients was (3.83 ± 1.22) times/week, Wexner constipation score was (6.74 ± 3.56) points, GIQLI score was (108.76 ± 15.38) points, clinical cure rate was 57.8% (279/483). The improvement rate was 66.3% (320/483), and the treatment satisfaction was (3.85 ± 0.93) points. No severe FMT-associated complication and death were observed during treatment and follow-up period. FMT-related adverse events occurred in 115 cases (23.8%), including nausea in 25 cases (5.2%), vomiting in 13 (2.7%), diarrhea in 21 (4.3%), abdominal pain in 16 (3.3%), abdominal distension in 33 (6.8%), sore throat in 56 (11.6%) and fever in 16(3.3%), all of which relieved after symptomatic treatment. There were no statistically significant differences in the number of defecations, Wexner constipation scores, and GIQLI scores before FMT, 1 week and 1 month after FMT treatment among different bacterial solution storage groups (all P>0.05). Differences of clinical cure rate, clinical improvement rate, and treatment satisfaction of patients 1 week and 1 month after treatment were not statistically significant (all P>0.05). Among the groups, differences in the overall complications and types of complications after FMT treatment were not statistically significant (all P>0.05). Conclusions: FMT is safe and effective in the treatment of slow transit constipation. Fresh fecal bacterial samples or fecal bacterial samples frozen at -80℃ for 1 year can be safely applied to FMT for the treatment of slow transit constipation, with stable short-term efficacy and without serious adverse reactions.}, }
@article {pmid32594726, year = {2020}, author = {Chen, QY and Tian, HL and Yang, B and Lin, ZL and Zhao, D and Ye, C and Zhang, XY and Qin, HL and Li, N}, title = {[Effect of intestinal preparation on the efficacy and safety of fecal microbiota transplantation treatment].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {48-55}, doi = {10.3760/cma.j.cn.441530-20200418-00225}, pmid = {32594726}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; }, abstract = {Objective: To investigate the effect of intestinal preparation on the efficacy and complications of fecal microbiota transplantation (FMT). Methods: A retrospective cohort study was performed. Clinical and follow-up data of 1501 patients who received FMT in the department of Colorectal Disease Specialty, Intestinal Microecology Diagnosis and Treatment Center, the Tenth People's Hospital, Tongji University from February 2018 to June 2019 were collected retrospectively. According to the intestinal preparation before FMT treatment, patients were divided into non-intestinal preparation group (n=216), antibiotic pretreatment group (n=383), intestinal cleansing group (n=267), and antibiotic combined with intestinal cleansing group (n=635). The adverse reactions after FMT treatment and the effective rates at 4-week and 8-week after treatment among the groups were compared. Patients, who repeated FMT treatment in the 3rd month and the 6th month due to reduced efficacy or ineffectiveness were divided into two subgroups: without intestinal preparation group and with intestinal preparation group. The effective rates of the two subgroups were compared. Results: Of the 1501 cases, 588 were male and 913 were female with mean age of (43.3±13.7) years and body mass index of (20.2±2.1) kg/m(2). Transplantation course was (3.3±1.7) weeks. The underlying diseases mainly included constipation (n=564), Crohn's disease (n=157), ulcerative colitis (n=142), irritable bowel syndrome (n=158), recurrent C. difficile infection (CDI) (n=106), autism (n=84), radiation intestinal injury (n=133), radiation enteritis (n=133), and non-CDI chronic diarrhea (n=60); the remaining cases (n=155). Baseline data among the 4 groups were not significantly different (all P>0.05). The overall morbidity of complication was 31.1% (467/1501), including 41 cases of vomiting (2.7%), 91 of nausea (6.1%), 49 of diarrhea (3.3%), 41 of abdominal pain (2.7%), 79 of bloating (5.3%), 72 of throat pain (4.8%), 38 of dizziness (2.5%), 51 of fever (3.4%), 3 of pulmonary infection (0.2%) and 2 of intestinal infection (0.1%). The above symptoms disappeared after symptomatic treatment. There was no statistically significant difference in the incidence of adverse reactions among the 4 groups (P>0.05). After 4-week of FMT treatment, the overall effective rate was 63.5% (902/1420); the effective rate of non-intestinal preparation group, antibiotic pretreatment group, intestinal cleaning group, and antibiotic combined with intestinal cleansing groupwas 57.6% (114/198), 64.2% (231/360), 60.2% (154/265) and 66.5% (403/606), respectively, with no statistically significant difference (χ(2)=6.659, P=0.084). After 8-week of FMT treatment, the overall effective rate was 61.3% (729/1293); the effective rate of non-intestinal preparation group, antibiotic pretreatment group, intestinal cleaning group, and antibiotic combined with intestinal cleansing group was 54.0% (88/163), 62.2% (202/325), 57.4% (132/230) and 64.4% (370/575), respectively, with no statistically significant difference (χ(2)=13.620, P=0.003). The effective rates of antibiotic combined with intestinal cleansing group and antibiotic pretreatment group were obviously higher than that of non-intestinal preparation group (χ(2)=5.789, P=0.016; χ(2)=10.117, P=0.001). Subgroup analysis showed that in the third month, the effective rate at 4-week after treatment was 60.1% (184/306) in the without intestinal preparation group and 61.5% (115/187) in the with intestinal preparation group, whose difference was not significant (χ(2)=0.091, P=0.763); however, in the sixth month, the effective rate at 4-week after treatment was 51.4% (89/173) in the without intestinal preparation group and 61.2% (161/263) in the with intestinal preparationgroup, whose difference was significant (χ(2)=4.229, P=0.040). Conclusions: FMT treatment is safe and effective. The combination of antibiotics and intestinal cleaning can improve overall efficacy of FMT. For patients who need repeated FMT treatment, the combination of antibiotics and intestinal cleaning program within 3 months has no significant effect on the effective rate, but in the sixth month, combinedpreparation is necessary.}, }
@article {pmid32594725, year = {2020}, author = {Zhang, FM and Liu, YF}, title = {[Evidence and decision of the choice of delivery way in washed microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {45-47}, doi = {10.3760/cma.j.cn.441530-20200507-00259}, pmid = {32594725}, issn = {1671-0274}, abstract = {Washed microbiota transplantation (WMT) is a new concept and technique of fecal microbiota transplantation. The delivery routes of WMT include oral capsule, nasogastric tube, nasojejunal tube, gastroscopy, colonic transendoscopic enteral tubing, and anal enema. The research results among different indications or different designs based on the same indication are quite different, partially because of the influence of WMT delivery route. In the process of clinical research design and clinical practice, there are four aspects that affect the decision-making of WMT delivery route: safety, efficacy, cost-effectiveness, and patients' willingness. This article focuses on how to integrate the four aspects mentioned above in the decision-making process of choosing proper delivery of WMT for the final goal of mutual satisfaction between doctors and patients.}, }
@article {pmid32594720, year = {2020}, author = {,  and ,  and ,  and , }, title = {[Chinese experts consensus on clinical practice of the selection and establishment of fecal microbiota transplantation delivery routes].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {14-20}, doi = {10.3760/cma.j.cn.441530-20200420-00228}, pmid = {32594720}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; }, abstract = {Fecal microbiota transplantation (FMT) has gradually shown application prospects in the treatment of intestinal and extraintestinal diseases. In order to standardized FMT operation, based on the clinical experience of the Tenth People's Hospital Affiliated to Tongji University, combined with domestic and foreign literature, Parenteral and Enteral Nutrition Branch of Chinese Medical Association, Enhanced Recovery after Surgery Branch of China International Health Care Promotion Exchange Association, China Microecological Treatment Innovation Alliance, and Microecology Committee of Shanghai Preventive Medicine Association to formulated the&quot; Chinese experts consensus on clinical practice of the selection and establishment of fecal microbiota transplantation delivery routes&quot;. It includes four parts: the selection of delivery route, the methodology of transplantation path establishment, the clinical application, and the monitoring of adverse events.}, }
@article {pmid32594719, year = {2020}, author = {,  and ,  and ,  and , }, title = {[Chinese experts consensus on standardized methodology and clinical application of fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {5-13}, doi = {10.3760/cma.j.cn.441530-20200420-00231}, pmid = {32594719}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; }, abstract = {Fecal microbiota transplantation (FMT) is to transplant the functional bacteria in the feces of healthy people into the patients' intestines, rebuild the new balance of intestinal flora, and achieve the treatment goals of intestinal and extraintestinal diseases. In the past 10 years, FMT has made a breakthrough in the treatment of intestinal and extraintestinal diseases, which is highly expected to treat difficult diseases. However, due to the complexity of FMT methodology and the lack of a unified standard, there is a high heterogeneity in FMT efficacy among various researches, greatly affected its clinical application. Under the initiative of Parenteral and Enteral Nutrition Branch of Chinese Medical Association, Enhanced Recovery after Surgery Branch of China International Health Care Promotion Exchange Association, China Microecological Treatment Innovation Alliance, and Microecology Committee of Shanghai Preventive Medicine Association, the first expert consensus on standardized methodology and clinical application of FMT was established in China, with a view to improving the efficacy of FMT, reducing the incidence of adverse reactions and promoting the clinical application of FMT.}, }
@article {pmid32594718, year = {2020}, author = {Li, N}, title = {[Practice and consideration of fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {1-4}, doi = {10.3760/cma.j.cn.441530-20200420-00230}, pmid = {32594718}, issn = {1671-0274}, abstract = {As an innovative therapy, FMT has made a breakthrough in the treatment of recurrent Clostridium difficile infection (CDI). With the rapid development of biotechnology, the relationship between intestinal microflora and diseases has been gradually eluciated. Great hope has also been given to FMT in other intestinal and extraintestinal diseases with ineffective traditional treatment. However, as a new therapy method, FMT still has many unknown fields, such as the selection of clinical donors, the preparation of standardized bacterial solution and capsule, the selection of indications, the matching of donor and receptor, and the prevention and treatment of complications. Since 2012, our center has carried out treatment research and practice of FMT, so far with more than 60 000 FMTs for more than 3500 cases. Based on large sample data and experience, this special issue reports and discusses the above topics, and focuses on the establishment and clinical application of standardized methodology of FMT, which will undoubtedly play a positive role in promoting the healthy development of FMT treatment in China.}, }
@article {pmid31784367, year = {2020}, author = {Mikail, M and O'Doherty, KC and Poutanen, SM and Hota, SS}, title = {Ethical implications of recruiting universal stool donors for faecal microbiota transplantation.}, journal = {The Lancet. Infectious diseases}, volume = {20}, number = {3}, pages = {e44-e49}, doi = {10.1016/S1473-3099(19)30569-9}, pmid = {31784367}, issn = {1474-4457}, mesh = {Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*ethics/*methods ; Humans ; Tissue Donors/*ethics ; }, abstract = {Faecal microbiota transplantation is an effective therapy for recurrent Clostridioides difficile infection, with potential therapeutic applications in other health conditions. As research uncovers potential associations between the intestinal microbiome and various disease states, stool donor screening has become increasingly stringent, leading to low donor acceptance. Many stool banks have opted to recruit universal stool donors, who are encouraged to donate frequently over a prolonged period and whose stool is used to treat multiple patients. However, various ethical concerns arise when recruiting universal stool donors, which need to be addressed to mitigate harm to donors. In this Personal View, we describe the major ethical issues with universal stool banks across six domains: informed consent, privacy, the imposing of restrictions on autonomy, stewardship of microbiome information, financial incentives, and preventing a sense of obligation. We also suggest several priorities for future research that should be pursued to address these crucial issues and develop more donor-centric stool banks.}, }
@article {pmid31610731, year = {2019}, author = {Duan, Y and Prasad, R and Feng, D and Beli, E and Li Calzi, S and Longhini, ALF and Lamendella, R and Floyd, JL and Dupont, M and Noothi, SK and Sreejit, G and Athmanathan, B and Wright, J and Jensen, AR and Oudit, GY and Markel, TA and Nagareddy, PR and Obukhov, AG and Grant, MB}, title = {Bone Marrow-Derived Cells Restore Functional Integrity of the Gut Epithelial and Vascular Barriers in a Model of Diabetes and ACE2 Deficiency.}, journal = {Circulation research}, volume = {125}, number = {11}, pages = {969-988}, pmid = {31610731}, issn = {1524-4571}, support = {R01 HL137799/HL/NHLBI NIH HHS/United States ; R01 EY012601/EY/NEI NIH HHS/United States ; R01 HL115140/HL/NHLBI NIH HHS/United States ; P30 DK079626/DK/NIDDK NIH HHS/United States ; T32 HL134640/HL/NHLBI NIH HHS/United States ; P30 EY003039/EY/NEI NIH HHS/United States ; R01 EY025383/EY/NEI NIH HHS/United States ; K99 HL122505/HL/NHLBI NIH HHS/United States ; R01 EY028037/EY/NEI NIH HHS/United States ; R01 EY028858/EY/NEI NIH HHS/United States ; R00 HL122505/HL/NHLBI NIH HHS/United States ; T32 HL105349/HL/NHLBI NIH HHS/United States ; }, mesh = {Adherens Junctions/metabolism ; Animals ; Bacteria/*metabolism ; *Bone Marrow Transplantation ; *Capillary Permeability ; Cells, Cultured ; Diabetes Mellitus, Type 2/enzymology/microbiology/physiopathology/*surgery ; Disease Models, Animal ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; Inflammation Mediators/metabolism ; Intestinal Mucosa/*blood supply/metabolism/*microbiology/pathology ; Intestine, Small/*blood supply/enzymology/*microbiology/pathology ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; *Neovascularization, Physiologic ; Peptidoglycan/metabolism ; Peptidyl-Dipeptidase A/*deficiency/genetics ; Recovery of Function ; }, abstract = {RATIONALE: There is incomplete knowledge of the impact of bone marrow cells on the gut microbiome and gut barrier function.<br><br>OBJECTIVE: We postulated that diabetes mellitus and systemic ACE2 (angiotensin-converting enzyme 2) deficiency would synergize to adversely impact both the microbiome and gut barrier function.<br><br>METHODS AND RESULTS: Bacterial 16S rRNA sequencing and metatranscriptomic analysis were performed on fecal samples from wild-type, ACE2-/y, Akita (type 1 diabetes mellitus), and ACE2-/y-Akita mice. Gut barrier integrity was assessed by immunofluorescence, and bone marrow cell extravasation into the small intestine was evaluated by flow cytometry. In the ACE2-/y-Akita or Akita mice, the disrupted barrier was associated with reduced levels of myeloid angiogenic cells, but no increase in inflammatory monocytes was observed within the gut parenchyma. Genomic and metatranscriptomic analysis of the microbiome of ACE2-/y-Akita mice demonstrated a marked increase in peptidoglycan-producing bacteria. When compared with control cohorts treated with saline, intraperitoneal administration of myeloid angiogenic cells significantly decreased the microbiome gene expression associated with peptidoglycan biosynthesis and restored epithelial and endothelial gut barrier integrity. Also indicative of diabetic gut barrier dysfunction, increased levels of peptidoglycan and FABP-2 (intestinal fatty acid-binding protein 2) were observed in plasma of human subjects with type 1 diabetes mellitus (n=21) and type 2 diabetes mellitus (n=23) compared with nondiabetic controls (n=23). Using human retinal endothelial cells, we determined that peptidoglycan activates a noncanonical TLR-2 (Toll-like receptor 2) associated MyD88 (myeloid differentiation primary response protein 88)-ARNO (ADP-ribosylation factor nucleotide-binding site opener)-ARF6 (ADP-ribosylation factor 6) signaling cascade, resulting in destabilization of p120-catenin and internalization of VE-cadherin as a mechanism of deleterious impact of peptidoglycan on the endothelium.<br><br>CONCLUSIONS: We demonstrate for the first time that the defect in gut barrier function and dysbiosis in ACE2-/y-Akita mice can be favorably impacted by exogenous administration of myeloid angiogenic cells.}, }
@article {pmid32592577, year = {2020}, author = {Jiang, S and Wang, B and Sha, T and Li, X}, title = {Changes in the Intestinal Microbiota in Patients with Stage 5 Chronic Kidney Disease on a Low-Protein Diet and the Effects of Human to Rat Fecal Microbiota Transplantation.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {26}, number = {}, pages = {e921557}, doi = {10.12659/MSM.921557}, pmid = {32592577}, issn = {1643-3750}, abstract = {BACKGROUND Dietary protein restriction is recommended for patients with stage 5 chronic kidney disease (CKD), or end-stage renal disease (ESRD). This study aimed to investigate the changes in the intestinal microbiota due to different dietary regimens in patients with stage 5 CKD and the effects of human to rat fecal microbiota transplantation. MATERIAL AND METHODS Second-generation high-throughput sequencing was used to analyze the amplifiers in the 16S rRNA V4 region in the intestinal microbiota of patients with stage 5 CKD and healthy individuals. The intestinal microbiota of patients with stage 5 CKD in the low-protein group and the healthy individual group was transferred by human to rat fecal microbiota transplantation using Sprague-Dawley rats. Data underwent meta-analysis using Meta-Stat. RESULTS Patients with CKD on a very low-protein diet showed an increase in intestinal Escherichia, Shigella, and Klebsiella, a decrease in Blautia, heat map analysis showed that Christensenellaceae R-7 group rs1 were significantly increased, and MetaStat analysis showed that Bacteroides, Prevotella, and Mitsuokella were significantly increased. Following human to rat fecal microbiota transplantation from patients with stage 5 CKD, the profile of the rat intestinal microbiota became similar to the human donors. The weight of the rats fed a very low-protein diet after fecal microbiota transplantation significantly decreased after six weeks compared with normal rats and rats that received normal fecal microbiota transplantation. CONCLUSIONS Patients with stage 5 CKD on a very low-protein diet showed changes in the intestinal microbiota that could be transferred from humans to rats by fecal microbiota transplantation.}, }
@article {pmid32588829, year = {2020}, author = {Zhgun, ES and Kislun, YV and Kalachniuk, TN and Veselovsky, VA and Urban, AS and Tikhonova, PO and Pavlenko, AV and Ilchenko, GN and Ilina, EN}, title = {[Evaluation of metabolites levels in feces of patients with inflammatory bowel diseases].}, journal = {Biomeditsinskaia khimiia}, volume = {66}, number = {3}, pages = {233-240}, doi = {10.18097/PBMC20206603233}, pmid = {32588829}, issn = {2310-6972}, abstract = {Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn's disease (CD), are chronic intestinal inflammatory disorders with an unknown etiology. They are characterized by chronic recurrent inflammation of the intestinal mucosa and lead to a significant decrease in the quality of life and death of patients. IBD are associated with suppression of normal intestinal microflora, including a decrease in bacteria, producers of short chain fatty acids (SCFAs), exhibiting anti-inflammatory and protective properties. Among the various methods of intestinal microflora correction, fecal microbiota transplantation (FMT), which engrafts the fecal microbiota from a healthy donor into a patient recipient, is of a particular interest. As a result, a positive therapeutic effect is observed, accompanied by the restoration of the normal intestinal microflora of the patient. A significant drawback of the method is the lack of standardization. Metabolites produced by intestinal microflora, namely SCFAs, allow objective assessment of the functional state of the intestinal microbiota and, consequently, the success of the FMT procedure. Using gas chromatography and nuclear magnetic resonance spectroscopy techniques, we have analyzed concentrations and molar ratios of SCFAs in fecal samples of 60 healthy donors. Results were in good accord when comparing two methods as well as with published data. Analysis of SCFAs in feces of patients with UC (19 patients) and CD (17 patients) revealed a general decrease in the concentration of fatty acids in the experimental groups with significant fluctuations in the values in experimental groups compared to control group of healthy donors. On the limited group of IBD patients (6 patients with UC and 5 patients with CD) concentration of SCFAs before and within 30 days of observation after FMT was determined. It was shown that FMT had a significant impact on the SCFAs levels within 1 month term; tendency to reach characteristics of healthy donors is unambiguously traced for both diseases.}, }
@article {pmid32587239, year = {2020}, author = {Li, H and Xu, H and Li, Y and Jiang, Y and Hu, Y and Liu, T and Tian, X and Zhao, X and Zhu, Y and Wang, S and Zhang, C and Ge, J and Wang, X and Wen, H and Bai, C and Sun, Y and Song, L and Zhang, Y and Hui, R and Cai, J and Chen, J}, title = {Alterations of gut microbiota contribute to the progression of unruptured intracranial aneurysms.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {3218}, doi = {10.1038/s41467-020-16990-3}, pmid = {32587239}, issn = {2041-1723}, abstract = {Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Whether changes in gut microbial composition participate in the development of UIAs remains largely unknown. We perform a case-control metagenome-wide association study in two cohorts of Chinese UIA patients and control individuals and mice that receive fecal transplants from human donors. After fecal transplantation, the UIA microbiota is sufficient to induce UIAs in mice. We identify UIA-associated gut microbial species link to changes in circulating taurine. Specifically, the abundance of Hungatella hathewayi is markedly decreased and positively correlated with the circulating taurine concentration in both humans and mice. Consistently, gavage with H. hathewayi normalizes the taurine levels in serum and protects mice against the formation and rupture of intracranial aneurysms. Taurine supplementation also reverses the progression of intracranial aneurysms. Our findings provide insights into a potential role of H. hathewayi-associated taurine depletion as a key factor in the pathogenesis of UIAs.}, }
@article {pmid32585945, year = {2020}, author = {Leo, S and Lazarevic, V and Girard, M and Gaïa, N and Schrenzel, J and de Lastours, V and Fantin, B and Bonten, M and Carmeli, Y and Rondinaud, E and Harbarth, S and Huttner, BD}, title = {Metagenomic Characterization of Gut Microbiota of Carriers of Extended-Spectrum Beta-Lactamase or Carbapenemase-Producing Enterobacteriaceae Following Treatment with Oral Antibiotics and Fecal Microbiota Transplantation: Results from a Multicenter Randomized Trial.}, journal = {Microorganisms}, volume = {8}, number = {6}, pages = {}, doi = {10.3390/microorganisms8060941}, pmid = {32585945}, issn = {2076-2607}, support = {282512//European Commission under the Seventh Framework Programme (FP7/2007) for Research and technology/ ; }, abstract = {Background: The R-GNOSIS (Resistance in Gram-Negative Organisms: Studying Intervention Strategies) WP3 study was the first multicenter randomized clinical trial systematically investigating fecal microbiota transplantation (FMT) for intestinal decolonization of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Here, we characterized the temporal dynamics of fecal microbiota changes in a sub-cohort of the R-GNOSIS WP3 participants before and after antibiotics/FMT using whole metagenome shotgun sequencing. Methods: We sequenced fecal DNA obtained from 16 ESBL-E/CPE carriers having received oral colistin/neomycin followed by FMT and their corresponding seven donors. Ten treatment-naïve controls from the same trial were included. Fecal samples were collected at baseline (V0), after antibiotics but before FMT (V2) and three times after FMT (V3, V4 and V5). Results: Antibiotic treatment transiently decreased species richness and diversity and increased the abundance of antibiotic resistance determinants (ARDs). Bifidobacterium species, together with butyrate- and propionate-producing species from Lachnospiraceae and Ruminococcaceae families were significantly enriched in post-FMT microbiota of treated carriers. After FMT, the proportion of Enterobacteriaceae was lower compared to baseline but without statistical significance. Conclusions: Combined antibiotic and FMT treatment resulted in enrichment of species that are likely to limit the gut colonization by ESBL-E/CPE.}, }
@article {pmid32585148, year = {2020}, author = {Basson, AR and Zhou, Y and Seo, B and Rodriguez-Palacios, A and Cominelli, F}, title = {Autologous fecal microbiota transplantation for the treatment of inflammatory bowel disease.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.trsl.2020.05.008}, pmid = {32585148}, issn = {1878-1810}, abstract = {The term autologous fecal microbiota transplantation (a-FMT) refers herein to the use of one's feces during a healthy state for later use to restore gut microbial communities after perturbations. Generally, heterologous fecal microbiota transplantation (h-FMT), where feces from a ``healthy&quot; donor is transplanted into a person with illness, has been used to treat infectious diseases such as recurrent Clostridioides difficile infection (CDI), with cure rates of up to 90%. In humans, due to limited response to medicines, h-FMT has become a hallmark intervention to treat CDI. Extrapolating the benefits from CDI, h-FMT has been attempted in various diseases, including inflammatory bowel disease (IBD), but clinical response has been variable and less effective (ranging between 24% and 50%). Differences in h-FMT clinical response could be because CDI is caused by a Clostridial infection, whereas IBD is a complex, microbiome-driven immunological inflammatory disorder that presents predominantly within the gut wall of genetically-susceptible hosts. FMT response variability could also be due to differences in microbiome composition between donors, recipients, and within individuals, which vary with diet, and environments, across regions. While donor selection has emerged as a key factor in FMT success, the use of heterologous donor stool still places the recipient at risk of exposure to infectious/pathogenic microorganisms. As an implementable solution, herein we review the available literature on a-FMT, and list some considerations on the benefits of a-FMT for IBD.}, }
@article {pmid32584703, year = {2020}, author = {Gong, Z and Wang, Y}, title = {Immune Checkpoint Inhibitor-Mediated Diarrhea and Colitis: A Clinical Review.}, journal = {JCO oncology practice}, volume = {}, number = {}, pages = {OP2000002}, doi = {10.1200/OP.20.00002}, pmid = {32584703}, issn = {2688-1535}, abstract = {Immune-mediated diarrhea and colitis (IMDC) is among the most common immune-related adverse events in patients with cancer treated with immune checkpoint inhibitors (ICIs). Many factors will affect the risk of IMDC, including the type of ICI used, the type of underlying cancer, and patient characteristics. A recent study showed that preexisting inflammatory bowel disease significantly increases the risk of diarrhea and colitis with ICI treatment. In terms of management, early endoscopic evaluation improves clinical outcome by identifying high-risk patients who will benefit from early add-on immunosuppressants. Inflammatory markers, including fecal lactoferrin and calprotectin, are good screening tools to predict which patients are at risk for colitis. Calprotectin especially is associated with colitis outcome and can be used as a surrogate marker to follow treatment response. Corticosteroids remain the first-line medical treatment of IMDC management, and add-on therapy with vedolizumab or infliximab should be considered in selected patients. Fecal microbiota transplantation may be considered in refractory cases. The decision to resume ICI should be decided by balancing the risk of recurrent IMDC and the likelihood of benefiting from further ICI treatment. There is no clear evidence about whether the use of immunosuppressants will result in a worse cancer outcome. With emerging evidence, our understanding and management strategies are likely to evolve in the future.}, }
@article {pmid32582202, year = {2020}, author = {Yan, Y and Zhou, X and Guo, K and Zhou, F and Yang, H}, title = {Chlorogenic Acid Protects Against Indomethacin-Induced Inflammation and Mucosa Damage by Decreasing Bacteroides-Derived LPS.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {1125}, doi = {10.3389/fimmu.2020.01125}, pmid = {32582202}, issn = {1664-3224}, abstract = {Background: Chlorogenic acid (CGA), a natural bioactive polyphenol, exerts anti-inflammatory, antioxidant, and antibacterial effects that support the maintenance of intestinal health. However, the influence of CGA on gut microbiota and their metabolites, as well as its potential effects and mechanism of action in inflammatory bowel disease, remain to be elucidated. Methods: First, an oral gavage was used to administer CGA to indomethacin-treated mice. Then, fecal microbiota transplantation was performed to explore the role of intestinal microbiota in indomethacin-induced inflammation. Results: CGA treatment protected against body weight loss, damage to intestinal morphology and integrity, inflammation, and alteration of microbiota composition in indomethacin-treated mice. Interestingly, CGA failed to inhibit inflammation or protect intestine integrity in mice treated with antibiotics. Notably, mice who had been colonized with intestinal microbiota from CGA-treated or CGA-and-indomethacin-treated mice, through the fecal microbiota transplantation program, were protected from indomethacin-induced inflammation, growth of Bacteroides, and the accumulation of Bacteroides-derived LPS, in congruence with those who had been treated with CGA. Conclusion: The results suggest that CGA may protect intestine integrity and alleviate inflammatory responses, primarily by inhibiting the growth of Bacteroides and the accumulation of Bacteroides-derived LPS, in indomethacin-induced colitis. This newly identified mechanism broadens our knowledge of how CGA exerts protective effects on intestinal inflammation and provides strategies for the prevention of gastrointestinal mucosal damage in patients treated with indomethacin.}, }
@article {pmid32582121, year = {2020}, author = {Liang, W and Zhao, L and Zhang, J and Fang, X and Zhong, Q and Liao, Z and Wang, J and Guo, Y and Liang, H and Wang, L}, title = {Colonization Potential to Reconstitute a Microbe Community in Pseudo Germ-Free Mice After Fecal Microbe Transplant From Equol Producer.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1221}, doi = {10.3389/fmicb.2020.01221}, pmid = {32582121}, issn = {1664-302X}, abstract = {Human intestinal microbiota plays a crucial role in the conversion of isoflavones into equol. Usually, human microbiota-associated (HMA) animal models are used, since it is difficult to establish the mechanism and causal relationship between equol and microbiota in human studies. Currently, several groups have successfully established HMA animal models that produce equol through germ-free mice or rats; however, the HMA model of producing equol through pseudo germ-free mice has not been established. The objective of this study is to establish an HMA mice model for equol production through pseudo germ-free mice, mimicking the gut microbiota of an adult human equol producer. First, a higher female equol producer was screened as a donor from 15 volunteers. Then, mice were exposed to vancomycin, neomycin sulfate, metronidazole, and ampicillin for 3 weeks to obtain pseudo germ-free mice. Finally, pseudo germ-free mice were inoculated with fecal microbiota of the equol producer for 3 weeks to establish HMA mice of producing equol. The results showed that (i) the ability to produce equol was partially transferred from the donor to the HMA mice. (ii) Most of the original intestinal microbiota of mice were eliminated after broad-spectrum antibiotic administration. (iii) The taxonomy data from HMA mice revealed similar taxa to the donor sample, and the species richness returned to the level close to the donor. (iv) The family Coriobacteriaceae and genera Collinsella were successfully transferred from the donor to HMA mice. In conclusion, the HMA mice model for equol production, based on pseudo germ-free mice, can replace the model established by germ-free mice. The model also provides a basis for studying microbiota during the conversion from isoflavones into equol.}, }
@article {pmid32580023, year = {2020}, author = {Inamura, K}, title = {Gut microbiota contributes towards immunomodulation against cancer: New frontiers in precision cancer therapeutics.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2020.06.006}, pmid = {32580023}, issn = {1096-3650}, abstract = {The microbiota influences human health and the development of diverse diseases, including cancer. Microbes can influence tumor initiation and development in either a positive or negative manner. In addition, the composition of the gut microbiota affects the efficacy and toxicity of cancer therapeutics as well as therapeutic resistance. The striking impact of microbiota on oncogenesis and cancer therapy provides compelling evidence to support the notion that manipulating microbial networks represents a promising strategy for treating and preventing cancer. Specific microbes or the microbial ecosystem can be modified via a multiplicity of processes, and therapeutic methods and approaches have been evolving. Microbial manipulation can be applied as an adjunct to traditional cancer therapies such as chemotherapy and immunotherapy. Furthermore, this approach displays great promise as a stand-alone therapy following the failure of standard therapy. Moreover, such strategies may also benefit patients by avoiding the emergence of toxic side effects that result in treatment discontinuation. A better understanding of the host-microbial ecosystem in patients with cancer, together with the development of methodologies for manipulating the microbiome, will help expand the frontiers of precision cancer therapeutics, thereby improving patient care. This review discusses the roles of the microbiota in oncogenesis and cancer therapy, with a focus on efforts to harness the microbiota to fight cancer.}, }
@article {pmid32577835, year = {2020}, author = {McQuade, JL and Ologun, GO and Arora, R and Wargo, JA}, title = {Gut Microbiome Modulation Via Fecal Microbiota Transplant to Augment Immunotherapy in Patients with Melanoma or Other Cancers.}, journal = {Current oncology reports}, volume = {22}, number = {7}, pages = {74}, doi = {10.1007/s11912-020-00913-y}, pmid = {32577835}, issn = {1534-6269}, abstract = {PURPOSE OF REVIEW: We review emerging evidence regarding the impact of gut microbes on antitumor immunity, and ongoing efforts to translate this in clinical trials.<br><br>RECENT FINDINGS: Pre-clinical models and human cohort studies support a role for gut microbes in modulating overall immunity and immunotherapy response, and numerous trials are now underway exploring strategies to modulate gut microbes to enhance responses to cancer therapy. This includes the use of fecal microbiota transplant (FMT), which is being used to treat patients with Clostridium difficile infection among other non-cancer indications. The use of FMT is now being extended to modulate gut microbes in patients being treated with cancer immunotherapy, with the goal of enhancing responses and/or to ameliorate toxicity. However, significant complexities exist with such an approach and will be discussed herein. Data from ongoing studies of FMT in cancer will provide critical insights for optimization of this approach.}, }
@article {pmid32575899, year = {2020}, author = {Giannone, G and Ghisoni, E and Genta, S and Scotto, G and Tuninetti, V and Turinetto, M and Valabrega, G}, title = {Immuno-Metabolism and Microenvironment in Cancer: Key Players for Immunotherapy.}, journal = {International journal of molecular sciences}, volume = {21}, number = {12}, pages = {}, doi = {10.3390/ijms21124414}, pmid = {32575899}, issn = {1422-0067}, abstract = {Immune checkpoint inhibitors (ICIs) have changed therapeutic algorithms in several malignancies, although intrinsic and secondary resistance is still an issue. In this context, the dysregulation of immuno-metabolism plays a leading role both in the tumor microenvironment (TME) and at the host level. In this review, we summarize the most important immune-metabolic factors and how they could be exploited therapeutically. At the cellular level, an increased concentration of extracellular adenosine as well as the depletion of tryptophan and uncontrolled activation of the PI3K/AKT pathway induces an immune-tolerant TME, reducing the response to ICIs. Moreover, aberrant angiogenesis induces a hypoxic environment by recruiting VEGF, Treg cells and immune-suppressive tumor associated macrophages (TAMs). On the other hand, factors such as gender and body mass index seem to affect the response to ICIs, while the microbiome composition (and its alterations) modulates both the response and the development of immune-related adverse events. Exploiting these complex mechanisms is the next goal in immunotherapy. The most successful strategy to date has been the combination of antiangiogenic drugs and ICIs, which prolonged the survival of patients with non-small-cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC), while results from tryptophan pathway inhibition studies are inconclusive. New exciting strategies include targeting the adenosine pathway, TAMs and the microbiota with fecal microbiome transplantation.}, }
@article {pmid32483373, year = {2020}, author = {Burberry, A and Wells, MF and Limone, F and Couto, A and Smith, KS and Keaney, J and Gillet, G and van Gastel, N and Wang, JY and Pietilainen, O and Qian, M and Eggan, P and Cantrell, C and Mok, J and Kadiu, I and Scadden, DT and Eggan, K}, title = {C9orf72 suppresses systemic and neural inflammation induced by gut bacteria.}, journal = {Nature}, volume = {582}, number = {7810}, pages = {89-94}, doi = {10.1038/s41586-020-2288-7}, pmid = {32483373}, issn = {1476-4687}, support = {5R01NS089742/NH/NIH HHS/United States ; 5K99AG057808-02/NH/NIH HHS/United States ; 1K99MH119327-01/NH/NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/genetics/pathology ; Animals ; Anti-Bacterial Agents/pharmacology ; Autoimmunity/drug effects/genetics/immunology ; C9orf72 Protein/*genetics ; Cell Movement/drug effects ; Cytokines/immunology ; Fecal Microbiota Transplantation ; Female ; Frontotemporal Dementia/genetics/pathology ; Gastrointestinal Microbiome/drug effects/immunology/*physiology ; Gliosis/genetics/*microbiology/*pathology/prevention &amp; control ; Inflammation/*genetics/*microbiology/pathology/prevention &amp; control ; Loss of Function Mutation/genetics ; Male ; Mice ; Microglia/immunology/microbiology/pathology ; Spinal Cord/immunology/microbiology/*pathology ; Survival Rate ; }, abstract = {A hexanucleotide-repeat expansion in C9ORF72 is the most common genetic variant that contributes to amyotrophic lateral sclerosis and frontotemporal dementia1,2. The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are implicated in neural degeneration3-9. The expansion is transcribed into a long repetitive RNA, which negatively sequesters RNA-binding proteins5 before its non-canonical translation into neural-toxic dipeptide proteins3,4. The failure of RNA polymerase to read through the mutation also reduces the abundance of the endogenous C9ORF72 gene product, which functions in endolysosomal pathways and suppresses systemic and neural inflammation6-9. Notably, the effects of the repeat expansion act with incomplete penetrance in families with a high prevalence of amyotrophic lateral sclerosis or frontotemporal dementia, indicating that either genetic or environmental factors modify the risk of disease for each individual. Identifying disease modifiers is of considerable translational interest, as it could suggest strategies to diminish the risk of developing amyotrophic lateral sclerosis or frontotemporal dementia, or to slow progression. Here we report that an environment with reduced abundance of immune-stimulating bacteria10,11 protects C9orf72-mutant mice from premature mortality and significantly ameliorates their underlying systemic inflammation and autoimmunity. Consistent with C9orf72 functioning to prevent microbiota from inducing a pathological inflammatory response, we found that reducing the microbial burden in mutant mice with broad spectrum antibiotics-as well as transplanting gut microflora from a protective environment-attenuated inflammatory phenotypes, even after their onset. Our studies provide further evidence that the microbial composition of our gut has an important role in brain health and can interact in surprising ways with well-known genetic risk factors for disorders of the nervous system.}, }
@article {pmid32574836, year = {2020}, author = {Zhang, F and Chen, H and Zhang, R and Liu, Y and Kong, N and Guo, Y and Xu, M}, title = {5-Fluorouracil induced dysregulation of the microbiome-gut-brain axis manifesting as depressive like behaviors in rats.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {}, number = {}, pages = {165884}, doi = {10.1016/j.bbadis.2020.165884}, pmid = {32574836}, issn = {1879-260X}, abstract = {Disturbances of the gut microbiome have been widely suggested to be associated with 5-fluorouracil (5-Fu) induced digestive pathologies. Furthermore, it has been elucidated that the gut microbiome may play a key role in the pathogenesis of depressive disorders via the microbiota-gut-brain axis. Despite the speculation, there exists no direct evidence proving the causality between disturbances in the gut microbiome induced by 5-Fu and depressive mood dysregulation. Herein, behavioral testing was used to evaluate depressive-like behaviors in 5-Fu treated rats. Subsequently, the gut microbiota and prefrontal cortex (PFC) metabolic were analyzed by 16S rRNA sequencing and 1H nuclear magnetic resonance (1H NMR). To clarify the association between the gut microbiota and their role on depressive-like behaviors caused by 5-Fu, a fecal microbiota transplantation (FMT) experiment was carried out. The results suggested that 5-Fu could significantly alter the diversity and abundance of the gut microbiome, and induce PFC metabolic disorders, as well as depressive behaviors in rats. Transplantation of fecal microbiota from healthy control into 5-Fu treated rats significantly alleviated the PFC metabolic disorder and depressive-like behaviors. In conclusion, this study demonstrated that the gut microbiome was actively involved in the occurrence of 5-Fu induced depressive-like behaviors, and manipulation of specific gut microbiome parameters may serve as a promising novel target for side effects of 5-Fu treatment.}, }
@article {pmid32574415, year = {2020}, author = {Bilinski, J and Lis, K and Tomaszewska, A and Pechcinska, A and Grzesiowski, P and Dzieciatkowski, T and Walesiak, A and Gierej, B and Ziarkiewicz-Wróblewska, B and Tyszka, M and Kacprzyk, P and Chmielewska, L and Waszczuk-Gajda, A and Wiktor-Jedrzejczak, W and Basak, GW}, title = {Eosinophilic gastroenteritis and graft-versus-host disease induced by transmission of Norovirus with fecal microbiota transplant.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {}, number = {}, pages = {e13386}, doi = {10.1111/tid.13386}, pmid = {32574415}, issn = {1399-3062}, abstract = {Fecal microbiota transplantation (FMT) was performed to decolonize gastrointestinal tract from antibiotic-resistant bacteria before allogeneic hematopoietic cells transplantation (alloHCT). AlloHCT was complicated by Norovirus gastroenteritis, acute graft-versus-host-disease and eosinophilic pancolitis. Norovirus was identified in samples from FMT material. Symptoms resolved after steroids course and second norovirus-free FMT from another donor.}, }
@article {pmid32572461, year = {2020}, author = {Mangioni, D and Alagna, L and Gori, A and Bandera, A}, title = {Fecal Microbiota Transplant: keep calm and carry on, learning from experience.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaa846}, pmid = {32572461}, issn = {1537-6591}, }
@article {pmid32570299, year = {2020}, author = {Shasthry, SM}, title = {Fecal microbiota transplantation in alcohol related liver diseases.}, journal = {Clinical and molecular hepatology}, volume = {}, number = {}, pages = {}, doi = {10.3350/cmh.2020.0057}, pmid = {32570299}, issn = {2287-285X}, abstract = {The current standard of care for severe alcoholic hepatitis (SAH) has several limitations in that only up to one-third of patients are eligible for steroid therapy. Additionally, steroids have their own issues: a portion of patients do not respond, while there is doubtful long-term benefit in those who do and a large proportion are ineligible to receive steroids entirely and hence have no definitive options for treatment. As such, there is a large gap between the problem and the available solutions. Alcohol causes dysbiosis and also disrupts gut barrier function, consequently promoting the translocation of microbial lipopolysaccharide into the portal circulation and liver. Therefore, probiotics, prebiotics, antibiotics, or transplantation of gut microbiota are likely to attenuate the dysbiosis-related liver insult. Fecal microbiota transplantation (FMT) is expected to have a role in managing alcoholic liver disease in general and SAH in particular by correcting dysbiosis, the primary insult. Results from mouse studies have suggested beyond doubt that alcohol-related liver injury is transferrable and also treatable by adopting FMT from suitable donors. Initial human trials from our center have affirmed benefits in human subjects with SAH as well, with both improvements in disease severity and as well as the rate of survival. Further studies addressing the head-to-head comparison of steroids and FMT are ongoing. Available preliminary data are promising and FMT and/or gut microbial modulation might become the standard of care in the near future for managing alcohol-related liver diseases, especially alcoholic hepatitis, with greater applicability, improved acceptability, and minimal side effects.}, }
@article {pmid31978342, year = {2020}, author = {Walter, J and Armet, AM and Finlay, BB and Shanahan, F}, title = {Establishing or Exaggerating Causality for the Gut Microbiome: Lessons from Human Microbiota-Associated Rodents.}, journal = {Cell}, volume = {180}, number = {2}, pages = {221-232}, doi = {10.1016/j.cell.2019.12.025}, pmid = {31978342}, issn = {1097-4172}, support = {//CIHR/Canada ; }, mesh = {Animals ; Disease/etiology ; Dysbiosis/*microbiology ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Mice ; Microbiota/physiology ; Models, Animal ; Rats ; Rodentia/*microbiology ; }, abstract = {Human diseases are increasingly linked with an altered or &quot;dysbiotic&quot; gut microbiota, but whether such changes are causal, consequential, or bystanders to disease is, for the most part, unresolved. Human microbiota-associated (HMA) rodents have become a cornerstone of microbiome science for addressing causal relationships between altered microbiomes and host pathology. In a systematic review, we found that 95% of published studies (36/38) on HMA rodents reported a transfer of pathological phenotypes to recipient animals, and many extrapolated the findings to make causal inferences to human diseases. We posit that this exceedingly high rate of inter-species transferable pathologies is implausible and overstates the role of the gut microbiome in human disease. We advocate for a more rigorous and critical approach for inferring causality to avoid false concepts and prevent unrealistic expectations that may undermine the credibility of microbiome science and delay its translation.}, }
@article {pmid31211700, year = {2019}, author = {Mishima, Y and Oka, A and Liu, B and Herzog, JW and Eun, CS and Fan, TJ and Bulik-Sullivan, E and Carroll, IM and Hansen, JJ and Chen, L and Wilson, JE and Fisher, NC and Ting, JP and Nochi, T and Wahl, A and Garcia, JV and Karp, CL and Sartor, RB}, title = {Microbiota maintain colonic homeostasis by activating TLR2/MyD88/PI3K signaling in IL-10-producing regulatory B cells.}, journal = {The Journal of clinical investigation}, volume = {129}, number = {9}, pages = {3702-3716}, pmid = {31211700}, issn = {1558-8238}, support = {R01 CA156330/CA/NCI NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; R01 AI123010/AI/NIAID NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; R01 AI140799/AI/NIAID NIH HHS/United States ; R01 DK053347/DK/NIDDK NIH HHS/United States ; R01 AI111899/AI/NIAID NIH HHS/United States ; P30 DK056350/DK/NIDDK NIH HHS/United States ; R01 MH108179/MH/NIMH NIH HHS/United States ; P01 DK094779/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; B-Lymphocytes, Regulatory/immunology/*microbiology ; Colitis/microbiology ; Cytokines/metabolism ; Down-Regulation ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Germ-Free Life ; Green Fluorescent Proteins/metabolism ; Immunity, Innate ; Inflammation ; Interleukin-10/*metabolism ; Intestines/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Differentiation Factor 88/*metabolism ; Phosphatidylinositol 3-Kinases/*metabolism ; Toll-Like Receptor 2/*metabolism ; Toll-Like Receptor 9/metabolism ; }, abstract = {Resident microbiota activate regulatory cells that modulate intestinal inflammation and promote and maintain intestinal homeostasis. IL-10 is a key mediator of immune regulatory function. Our studies described the functional importance and mechanisms by which gut microbiota and specific microbial components influenced the development of intestinal IL-10-producing B cells. We used fecal transplant to germ-free (GF) Il10+/EGFP reporter and Il10-/- mice to demonstrate that microbiota from specific pathogen-free mice primarily stimulated IL-10-producing colon-specific B cells and T regulatory-1 cells in ex-GF mice. IL-10 in turn down-regulated microbiota-activated mucosal inflammatory cytokines. TLR2/9 ligands and enteric bacterial lysates preferentially induced IL-10 production and regulatory capacity of intestinal B cells. Analysis of Il10+/EGFP mice crossed with additional gene-deficient strains and B cell co-transfer studies demonstrated that microbiota-induced IL-10-producing intestinal B cells ameliorated chronic T cell-mediated colitis in a TLR2, MyD88 and PI3K-dependent fashion. In vitro studies implicated PI3Kp110δ and AKT downstream signaling. These studies demonstrated that resident enteric bacteria activated intestinal IL-10-producing B cells through TLR2, MyD88 and PI3K pathways. These B cells reduced colonic T cell activation and maintained mucosal homeostasis in response to intestinal microbiota.}, }
@article {pmid32564632, year = {2020}, author = {Suraya, R and Nagano, T and Kobayashi, K and Nishimura, Y}, title = {Microbiome as a Target for Cancer Therapy.}, journal = {Integrative cancer therapies}, volume = {19}, number = {}, pages = {1534735420920721}, doi = {10.1177/1534735420920721}, pmid = {32564632}, issn = {1552-695X}, abstract = {Recently, the microbiome has been gaining traction as a major player regulating various functions that correlate with many pathological conditions, including cancer. The central gut microbiota population has the capability to regulate normal inflammatory, immune, and metabolic functions, and disturbance in the balance of the normal microbiota population can subsequently induce pathological responses that closely relate with the mechanistic development and progression of cancer in various forms and sites. As a disease with major socioeconomic burden partly due to its current therapeutic options, modulating the imbalanced gut microbiota represents a novel option not only as an adjuvant therapy to relieve cancer treatment-related symptoms but also to influence cancer progression itself. In this review, we will discuss how the microbiome, specifically the gut microbiota, could affect cancer pathogenesis and what the effect of gut microbiota-targeting treatment options have on the many aspects of cancer pathologies based on the knowledge of recent years.}, }
@article {pmid32071279, year = {2020}, author = {Madhusoodanan, J}, title = {News Feature: Editing the microbiome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {7}, pages = {3345-3348}, pmid = {32071279}, issn = {1091-6490}, mesh = {Bacteria/*genetics/metabolism ; Bacteriophages/physiology ; Clostridium Infections/*microbiology/therapy ; Clostridium difficile/physiology/virology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Phage Therapy ; Plasmids/genetics/metabolism ; }, }
@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 decolonisation of a patient with osteitis caused by a carbapenemase-producing Klebsiella pneumoniae isolate harbouring both NDM-1 and OXA-48 enzymes.}, journal = {Journal of global antimicrobial resistance}, volume = {18}, number = {}, pages = {225-229}, doi = {10.1016/j.jgar.2019.06.001}, pmid = {31201994}, issn = {2213-7173}, mesh = {Adult ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacterial Proteins/adverse effects/genetics/metabolism ; Carbapenems/therapeutic use ; Drug Resistance, Multiple, Bacterial/drug effects/genetics ; Fecal Microbiota Transplantation/methods ; Humans ; Klebsiella pneumoniae/enzymology/*genetics/*metabolism/pathogenicity ; Male ; Microbial Sensitivity Tests ; Osteitis/chemically induced/*microbiology/*therapy ; Plasmids/genetics ; Whole Genome Sequencing ; beta-Lactamases/adverse effects/*genetics/*metabolism ; }, abstract = {OBJECTIVES: Carbapenem resistance in Klebsiella pneumoniae is an increasing problem worldwide and infections caused by this bacterium can be difficult to treat. This study reported the case of a patient from Romania, who was hospitalised in Bulgaria after an accident trauma. He then came to France for treatment of an osteitis caused by a Klebsiella pneumoniae carrying both blaNDM-1 and blaOXA-48.<br><br>METHOD: The resistome of this extremely drug-resistant bacterium was analysed both with phenotypic (large antibiotic susceptibility testing) and genomic methods (genome sequencing). The genetic environment of the two carbapenemases was studied.<br><br>RESULTS: Klebsiella pneumoniae ST307 carrying both a blaNDM-1 and blaOXA-48 gene was located on two different plasmids: Inc L/M and IncFII. The patient was successfully treated by a combination of intravenous colistin (9 MUI, then 4.5 MUI bd), intravenous fosfomycin (4g tds) and oral doxycycline (100mg bd) for 3 months. Faecal microbiota transplantation was successfully conducted for stool carriage.<br><br>CONCLUSION: The ST307 type is becoming endemic in hospital environments and is frequently associated with carbapenem resistance. Treatment of infection caused by multidrug-resistant bacteria is a clinical challenge, and the use of old antibiotics associated with screening and decolonisation of the reservoirs can be an efficient therapeutic alternative.}, }
@article {pmid31097468, year = {2019}, author = {Dodiya, HB and Kuntz, T and Shaik, SM and Baufeld, C and Leibowitz, J and Zhang, X and Gottel, N and Zhang, X and Butovsky, O and Gilbert, JA and Sisodia, SS}, title = {Sex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes.}, journal = {The Journal of experimental medicine}, volume = {216}, number = {7}, pages = {1542-1560}, pmid = {31097468}, issn = {1540-9538}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R21 NS101673/NS/NINDS NIH HHS/United States ; R01 NS088137/NS/NINDS NIH HHS/United States ; R01 AG054672/AG/NIA NIH HHS/United States ; R21 NS104609/NS/NINDS NIH HHS/United States ; R01 AG051812/AG/NIA NIH HHS/United States ; }, mesh = {Amyloid Neuropathies/*pathology ; Amyloid beta-Protein Precursor/metabolism ; Animals ; Anti-Bacterial Agents/adverse effects ; Brain Diseases/*pathology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome/drug effects/physiology ; Male ; Mice ; Microglia/*pathology ; Plaque, Amyloid/metabolism ; Sex Factors ; }, abstract = {We demonstrated that an antibiotic cocktail (ABX)-perturbed gut microbiome is associated with reduced amyloid-β (Aβ) plaque pathology and astrogliosis in the male amyloid precursor protein (APP)SWE /presenilin 1 (PS1)ΔE9 transgenic model of Aβ amyloidosis. We now show that in an independent, aggressive APPSWE/PS1L166P (APPPS1-21) mouse model of Aβ amyloidosis, an ABX-perturbed gut microbiome is associated with a reduction in Aβ pathology and alterations in microglial morphology, thus establishing the generality of the phenomenon. Most importantly, these latter alterations occur only in brains of male mice, not in the brains of female mice. Furthermore, ABX treatment lead to alterations in levels of selected microglial expressed transcripts indicative of the &quot;M0&quot; homeostatic state in male but not in female mice. Finally, we found that transplants of fecal microbiota from age-matched APPPS1-21 male mice into ABX-treated APPPS1-21 male restores the gut microbiome and partially restores Aβ pathology and microglial morphology, thus demonstrating a causal role of the microbiome in the modulation of Aβ amyloidosis and microglial physiology in mouse models of Aβ amyloidosis.}, }
@article {pmid30683453, year = {2019}, author = {Ghosh, C and Sarkar, P and Issa, R and Haldar, J}, title = {Alternatives to Conventional Antibiotics in the Era of Antimicrobial Resistance.}, journal = {Trends in microbiology}, volume = {27}, number = {4}, pages = {323-338}, doi = {10.1016/j.tim.2018.12.010}, pmid = {30683453}, issn = {1878-4380}, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Antimicrobial Cationic Peptides/therapeutic use ; Bacterial Infections/*therapy ; Bacteriocins/therapeutic use ; Bacteriophages ; Biological Therapy/*methods ; Biotechnology ; CRISPR-Cas Systems ; Disease Models, Animal ; *Drug Resistance, Bacterial/drug effects ; Fecal Microbiota Transplantation ; Genetic Engineering ; Humans ; Microbiota ; Oligonucleotides/therapeutic use ; Phage Therapy/methods ; Probiotics/therapeutic use ; }, abstract = {As more antibiotics are rendered ineffective by drug-resistant bacteria, focus must be shifted towards alternative therapies for treating infections. Although several alternatives already exist in nature, the challenge is to implement them in clinical use. Advancements within biotechnology, genetic engineering, and synthetic chemistry have opened up new avenues towards the search for therapies that can substitute for antibiotics. This review provides an introduction to the various promising approaches that have been adopted in this regard. Whilst the use of bacteriophages and antibodies has been partly implemented, other promising strategies, such as probiotics, lysins, and antimicrobial peptides, are in various stages of development. Propitious concepts such as genetically modified phages, antibacterial oligonucleotides, and CRISPR-Cas9 are also discussed.}, }
@article {pmid32563025, year = {2020}, author = {Wang, Y and Ren, R and Sun, G and Peng, L and Tian, Y and Yang, Y}, title = {Pilot study of cytokine changes evaluation after fecal microbiota transplantation in patients with ulcerative colitis.}, journal = {International immunopharmacology}, volume = {85}, number = {}, pages = {106661}, doi = {10.1016/j.intimp.2020.106661}, pmid = {32563025}, issn = {1878-1705}, abstract = {AIMS: To evaluate the changes of serum cytokines levels after fecal microbiota transplantation (FMT) in patients with active ulcerative colitis (UC) and the correlation with UC disease activity.<br><br>METHODS: Patients with active UC who meet the inclusion and exclusion criteria were recruited, and received FMT from a single donor for three times with an interval of 2-3 months. Serum samples were collected before every FMT. Clinical responses to FMT were assessed according to the criteria of Mayo score. 41 serum cytokines, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were quantitatively detected. Changes in serum cytokines levels after FMT and their correlation with CRP, ESR and Mayo scores were investigated.<br><br>RESULTS: 16 active UC patients were enrolled, and 14(87.5%) patients achieved clinical response to FMT. Compared with those before FMT, serum concentrations of IL-1Ra, IL-6, IP-10 and ENA-78 decreased significantly after the second FMT (P < 0.05), and serum concentrations of MEC, VCAM-1 and G-CSF decreased significantly after both the first and second FMT (P < 0.05). Serum levels of IL-6, IL-1Ra and VCAM-1 were all significantly positively correlated with CRP and ESR. Serum level of IP-10 was significantly positively correlated with CRP, ESR and Mayo score. Serum level of G-CSF was significantly positively correlated with Mayo score.<br><br>CONCLUSIONS: FMT may play a therapeutic role partly through modulating the host immune response. IL-6, IL-1Ra, IP-10, VCAM-1 and G-CSF may be biomarkers to evaluate the effect of FMT on UC.}, }
@article {pmid32553109, year = {2020}, author = {Watterson, WJ and Tanyeri, M and Watson, AR and Cham, CM and Shan, Y and Chang, EB and Eren, AM and Tay, S}, title = {Droplet-based high-throughput cultivation for accurate screening of antibiotic resistant gut microbes.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, doi = {10.7554/eLife.56998}, pmid = {32553109}, issn = {2050-084X}, support = {DK42086/DK/NIDDK NIH HHS/United States ; RC2 DK122394-01/DK/NIDDK NIH HHS/United States ; 2018-2019//Samuel and Emma Winters Foundation/ ; T32 DK07074/DK/NIDDK NIH HHS/United States ; }, abstract = {Traditional cultivation approaches in microbiology are labor-intensive, low-throughput, and yield biased sampling of environmental microbes due to ecological and evolutionary factors. New strategies are needed for ample representation of rare taxa and slow-growers that are often outcompeted by fast-growers in cultivation experiments. Here we describe a microfluidic platform that anaerobically isolates and cultivates microbial cells in millions of picoliter droplets and automatically sorts them based on colony density to enhance slow-growing organisms. We applied our strategy to a fecal microbiota transplant (FMT) donor stool using multiple growth media, and found significant increase in taxonomic richness and larger representation of rare and clinically relevant taxa among droplet-grown cells compared to conventional plates. Furthermore, screening the FMT donor stool for antibiotic resistance revealed 21 populations that evaded detection in plate-based assessment of antibiotic resistance. Our method improves cultivation-based surveys of diverse microbiomes to gain deeper insights into microbial functioning and lifestyles.}, }
@article {pmid32552337, year = {2020}, author = {Allegretti, JR and Elliott, RJ and Ladha, A and Njenga, M and Warren, K and O'Brien, K and Budree, S and Osman, M and Fischer, M and Kelly, CR and Kassam, Z}, title = {Stool processing speed and storage duration do not impact the clinical effectiveness of fecal microbiota transplantation.}, journal = {Gut microbes}, volume = {}, number = {}, pages = {1-3}, doi = {10.1080/19490976.2020.1768777}, pmid = {32552337}, issn = {1949-0984}, }
@article {pmid32550753, year = {2020}, author = {Little, R and Wine, E and Kamath, BM and Griffiths, AM and Ricciuto, A}, title = {Gut microbiome in primary sclerosing cholangitis: A review.}, journal = {World journal of gastroenterology}, volume = {26}, number = {21}, pages = {2768-2780}, doi = {10.3748/wjg.v26.i21.2768}, pmid = {32550753}, issn = {2219-2840}, abstract = {Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by biliary inflammation and stricturing. Exploration of the pathogenesis of PSC in light of its association with inflammatory bowel disease (IBD) and the &quot;gut-liver&quot; axis is an emerging area of interest. A growing number of studies have begun to elucidate the role of the gut microbiota, its metabolites and its influence on host immune responses in the development of PSC and PSC-IBD. Studies of the fecal microbiota have highlighted enriched levels of certain species, including Veillonella, Streptococcus and Enterococcus, among others. A heightened immune response to enteric dysbiosis and bacterial translocation have also been implicated. For example, Klebsiella pneumoniae strains derived from gnotobiotic mice transplanted with PSC-IBD microbiota were found to induce pore formation in human intestinal epithelial cells and enhanced Th17 responses. Gut microbes have additionally been hypothesized to be implicated in PSC pathogenesis through their role in the synthesis of various metabolites, including bile acids (BAs), which function as signaling molecules with important gut and hepatic effects. An expanded knowledge of the gut microbiome as it relates to PSC offers critical insight into the development of microbe-altering therapeutic interventions, such as antibiotics, nutritional interventions and fecal microbial transplantation. Some of these have already shown some preliminary evidence of benefit. Despite exciting progress in the field, much work remains to be done; areas that are particularly lacking include functional characterization of the microbiome and examination of pediatric populations. In this review, we summarize studies that have investigated the microbiome in PSC and PSC-IBD as well as putative mechanisms, including the potential role of metabolites, such as BAs. We then briefly review the evidence for interventions with microbe-altering properties for treating PSC.}, }
@article {pmid30658733, year = {2019}, author = {Gustot, T and Jalan, R}, title = {Acute-on-chronic liver failure in patients with alcohol-related liver disease.}, journal = {Journal of hepatology}, volume = {70}, number = {2}, pages = {319-327}, doi = {10.1016/j.jhep.2018.12.008}, pmid = {30658733}, issn = {1600-0641}, mesh = {Acute-On-Chronic Liver Failure/drug therapy/*epidemiology/*etiology/physiopathology ; Adrenal Cortex Hormones/therapeutic use ; Alcohol Drinking/*adverse effects ; Bacterial Infections/*complications ; Cytokines/metabolism ; Fecal Microbiota Transplantation ; Female ; Humans ; Inflammation/immunology ; Leukocytes/immunology ; Liver Diseases, Alcoholic/*complications ; Liver Transplantation ; Macrophages/immunology ; Male ; Prognosis ; }, abstract = {The spectrum of alcohol-related liver diseases (ALD) includes steatosis, steatohepatitis, progressive liver fibrosis, and cirrhosis. Acute-on-chronic liver failure (ACLF) is a recently defined entity that occurs in patients with chronic liver diseases and is characterised by acute decompensation, organ failures and a high risk of short-term mortality. Active alcohol consumption, alcoholic hepatitis and bacterial infections are the most frequent events precipitating the development of ACLF in the context of ALD (ALD-ACLF). The specific management of this entity remains unknown and the place of salvage liver transplantation controversial. This overview details the current knowledge on specific aspects of epidemiology, pathophysiology, prognosis and management of ALD-ACLF.}, }
@article {pmid30658731, year = {2019}, author = {Singal, AK and Shah, VH}, title = {Current trials and novel therapeutic targets for alcoholic hepatitis.}, journal = {Journal of hepatology}, volume = {70}, number = {2}, pages = {305-313}, doi = {10.1016/j.jhep.2018.10.026}, pmid = {30658731}, issn = {1600-0641}, mesh = {Adrenal Cortex Hormones/therapeutic use ; Anti-Inflammatory Agents/therapeutic use ; Antioxidants/therapeutic use ; Clinical Trials as Topic ; Drug Therapy, Combination ; Ethanol/pharmacology ; Fecal Microbiota Transplantation ; Gastrointestinal Agents/therapeutic use ; Gastrointestinal Microbiome/drug effects ; Hepatitis, Alcoholic/*drug therapy/*physiopathology ; Humans ; Tumor Necrosis Factor Inhibitors/therapeutic use ; Zinc/therapeutic use ; }, abstract = {Alcoholic hepatitis is a clinical syndrome in which patients present with acute-on-chronic liver failure and a high risk of short-term mortality. The current treatment of alcoholic hepatitis is suboptimal. Results recently published from the STOPAH study have improved our understanding of how best to design clinical trials for this condition. Although emerging data on liver transplantation for patients with alcoholic hepatitis are encouraging, less than 2% of these patients qualify. Clearly, there is an unmet need for novel treatments to improve the survival of these patients. Changes in the gut microbiota, inflammatory and cytokine signalling, oxidative stress and mitochondrial dysfunction, and abnormalities in the hepatic regenerative capacity alone or in combination contribute to the pathology of alcoholic hepatitis. In this chapter, we will describe the novel therapeutic agents targeting various pathways in the pathophysiology of alcoholic hepatitis. Specifically, we will describe the ongoing clinical trials in which some of these agents are being studied.}, }
@article {pmid30658727, year = {2019}, author = {Sarin, SK and Pande, A and Schnabl, B}, title = {Microbiome as a therapeutic target in alcohol-related liver disease.}, journal = {Journal of hepatology}, volume = {70}, number = {2}, pages = {260-272}, doi = {10.1016/j.jhep.2018.10.019}, pmid = {30658727}, issn = {1600-0641}, support = {R01 AA020703/AA/NIAAA NIH HHS/United States ; R01 AA024726/AA/NIAAA NIH HHS/United States ; U01 AA021856/AA/NIAAA NIH HHS/United States ; U01 AA026939/AA/NIAAA NIH HHS/United States ; }, mesh = {Adrenal Cortex Hormones/therapeutic use ; Animals ; Anti-Bacterial Agents/therapeutic use ; Dysbiosis/chemically induced/microbiology ; Ethanol/*pharmacology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Humans ; Liver Diseases, Alcoholic/*diet therapy/*drug therapy/metabolism/microbiology ; Metabolome/drug effects ; Probiotics/therapeutic use ; }, abstract = {Alcohol-related liver disease is associated with significant changes in gut microbial composition. The transmissibility of ethanol-induced liver disease has been demonstrated using faecal microbiota transfer in preclinical models. This technique has also led to improved survival in patients with severe alcoholic hepatitis, suggesting that changes in the composition and function of the gut microbiota are causatively linked to alcohol-related liver disease. A major mechanism by which gut microbiota influence the development of alcohol-related liver disease is through a leaky intestinal barrier. This permits translocation of viable bacteria and microbial products to the liver, where they induce and promote inflammation, as well as contribute to hepatocyte death and the fibrotic response. In addition, gut dysbiosis is associated with changes in the metabolic function of the intestinal microbiota, bile acid composition and circulation, immune dysregulation during onset and progression of alcohol-related liver disease. Findings from preclinical and human studies will be used to demonstrate how alcohol causes intestinal pathology and contributes to alcohol-related liver disease and how the latter is self-perpetuating. Additionally, we summarise the effects of untargeted treatment approaches on the gut microbiota, such as diet, probiotics, antibiotics and faecal microbial transplantation in alcohol-related liver disease. We further discuss how targeted approaches can restore intestinal homeostasis and improve alcohol-related liver disease. These approaches are likely to add to the therapeutic options for alcohol-related liver disease independently or in conjunction with steroids.}, }
@article {pmid31245969, year = {2019}, author = {Taylor, VH}, title = {The microbiome and mental health: Hope or hype?.}, journal = {Journal of psychiatry &amp; neuroscience : JPN}, volume = {44}, number = {4}, pages = {219-222}, pmid = {31245969}, issn = {1488-2434}, mesh = {Dysbiosis/*complications/therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Mental Disorders/*etiology/therapy ; *Probiotics/therapeutic use ; }, }
@article {pmid32548192, year = {2020}, author = {Massaro, M and Vansia, J and McGill, S}, title = {Ulcerative Proctitis in a Patient With a History of Fecal Microbiota Transplant for Clostridioides difficile Infection.}, journal = {ACG case reports journal}, volume = {7}, number = {4}, pages = {e00364}, doi = {10.14309/crj.0000000000000364}, pmid = {32548192}, issn = {2326-3253}, abstract = {Fecal microbiota transplantation (FMT) effectively treats Clostridioides difficile infection and alters the gut microbiota in the long term, but potential adverse effects are poorly understood. We report a man with a family history of ulcerative colitis who developed ulcerative proctitis within a year of FMT.}, }
@article {pmid32548190, year = {2020}, author = {Fasanello, MK and Robillard, KT and Boland, PM and Bain, AJ and Kanehira, K}, title = {Use of Fecal Microbial Transplantation for Immune Checkpoint Inhibitor Colitis.}, journal = {ACG case reports journal}, volume = {7}, number = {4}, pages = {e00360}, doi = {10.14309/crj.0000000000000360}, pmid = {32548190}, issn = {2326-3253}, abstract = {Immune checkpoint inhibitors (ICIs) can result in immune-related adverse events which require rapid identification and treatment. Gastrointestinal immune-related adverse events are among the most frequent and severe of these events. ICI colitis can be refractory to current therapies such as corticosteroids and biologic therapy. Fecal microbiota transplantation (FMT) is currently used in cases of recurrent Clostridioides difficile colitis. Many investigations are underway to test the utility of FMT for additional indications, including inflammatory bowel disease (IBD). We present a 71-year-old man with ICI colitis that was nonresponsive to currently defined management options and treated with benefit from FMT.}, }
@article {pmid32539741, year = {2020}, author = {Chinna Meyyappan, A and Forth, E and Wallace, CJK and Milev, R}, title = {Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review.}, journal = {BMC psychiatry}, volume = {20}, number = {1}, pages = {299}, doi = {10.1186/s12888-020-02654-5}, pmid = {32539741}, issn = {1471-244X}, abstract = {BACKGROUND: The Gut-Brain-Axis is a bidirectional signaling pathway between the gastrointestinal (GI) tract and the brain. The hundreds of trillions of microorganisms populating the gastrointestinal tract are thought to modulate this connection, and have far reaching effects on the immune system, central and autonomic nervous systems, and GI functioning. These interactions Diagnostic and statistical manual of mental disorders have also been linked to various psychiatric illnesses such as depression, anxiety, substance abuse, autism spectrum disorder, and eating disorders. It is hypothesized that techniques aimed at strengthening and repopulating the gut microbiome, such as Fecal Microbiota Transplant (FMT), may be useful in the prevention and treatment of psychiatric illnesses.<br><br>METHODS: A systematic search of five databases was conducted using key terms related to FMT and psychiatric illnesses. All results were then evaluated based on specific eligibility criteria.<br><br>RESULTS: Twenty-one studies met the eligibility criteria and were analysed for reported changes in mood and behavioural measures indicative of psychiatric wellbeing. The studies included were either entirely clinical (n = 8), preclinical with human donors (n = 9), or entirely preclinical (n = 11). All studies found a decrease in depressive and anxiety-like symptoms and behaviours resulting from the transplantation of healthy microbiota. The inverse was also found, with the transmission of depressive and anxiety-like symptoms and behaviours resulting from the transplantation of microbiota from psychiatrically ill donors to healthy recipients.<br><br>CONCLUSION: There appears to be strong evidence for the treatment and transmission of psychiatric illnesses through FMT. Further research with larger sample sizes and stronger scientific design is warranted in order to fully determine the efficacy and safety of this potential treatment. Registered on PROSPERO, IRD: CRD42019126795.}, }
@article {pmid32537754, year = {2020}, author = {Wong, SH and Yu, J}, title = {Proton-pump inhibitor use before fecal microbiota transplant: A wonder drug, a necessary evil, or a needless prescription?.}, journal = {Journal of gastroenterology and hepatology}, volume = {35}, number = {6}, pages = {913-914}, doi = {10.1111/jgh.15103}, pmid = {32537754}, issn = {1440-1746}, }
@article {pmid32535631, year = {2020}, author = {Uchiyama, K and Wakino, S and Irie, J and Miyamoto, J and Matsui, A and Tajima, T and Itoh, T and Oshima, Y and Yoshifuji, A and Kimura, I and Itoh, H}, title = {Contribution of uremic dysbiosis to insulin resistance and sarcopenia.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {}, number = {}, pages = {}, doi = {10.1093/ndt/gfaa076}, pmid = {32535631}, issn = {1460-2385}, abstract = {BACKGROUND: Chronic kidney disease (CKD) leads to insulin resistance (IR) and sarcopenia, which are associated with a high mortality risk in CKD patients; however, their pathophysiologies remain unclear. Recently, alterations in gut microbiota have been reported to be associated with CKD. We aimed to determine whether uremic dysbiosis contributes to CKD-associated IR and sarcopenia.<br><br>METHODS: CKD was induced in specific pathogen-free mice via an adenine-containing diet; control animals were fed a normal diet. Fecal microbiota transplantation (FMT) was performed by oral gavage in healthy germ-free mice using cecal bacterial samples obtained from either control mice (control-FMT) or CKD mice (CKD-FMT). Vehicle mice were gavaged with sterile phosphate-buffered saline. Two weeks after inoculation, mice phenotypes, including IR and sarcopenia, were evaluated.<br><br>RESULTS: IR and sarcopenia were evident in CKD mice compared with control mice. These features were reproduced in CKD-FMT mice compared with control-FMT and vehicle mice with attenuated insulin-induced signal transduction and mitochondrial dysfunction in skeletal muscles. Intestinal tight junction protein expression and adipocyte sizes were lower in CKD-FMT mice than in control-FMT mice. Furthermore, CKD-FMT mice showed systemic microinflammation, increased concentrations of serum uremic solutes, fecal bacterial fermentation products and elevated lipid content in skeletal muscle. The differences in gut microbiota between CKD and control mice were mostly consistent between CKD-FMT and control-FMT mice.<br><br>CONCLUSIONS: Uremic dysbiosis induces IR and sarcopenia, leaky gut and lipodystrophy.}, }
@article {pmid32535405, year = {2020}, author = {Liu, L and Wang, Q and Wu, X and Qi, H and Das, R and Lin, H and Shi, J and Wang, S and Yang, J and Xue, Y and Mao, D and Luo, Y}, title = {Vancomycin exposure caused opportunistic pathogens bloom in intestinal microbiome by simulator of the human intestinal microbial ecosystem (SHIME).}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {265}, number = {Pt B}, pages = {114399}, doi = {10.1016/j.envpol.2020.114399}, pmid = {32535405}, issn = {1873-6424}, abstract = {Antibiotics are emerging organic pollutants posing high health risks to humans by causing human intestinal microbial disorders with increasing abundances of opportunistic pathogens, and fecal microbiota transplantation (FMT) has been confirmed to restore the dysbiosis of gut flora in many kinds of intestinal disease. However, to date, few studies have focused on the bloomed opportunistic pathogens associated human disease-related pathways as well as antibiotic resistance genes (ARGs) after vancomycin exposure, and there is limited information on using FMT for restoration of intestinal microbiome affected by antibiotics. Therefore, this study investigated effects of vancomycin on the opportunistic pathogens, human disease-related pathways as well as ARGs in human gut, and the restoration of intestinal microbiome by FMT. Results indicated that vancomycin treatment substantially increased human disease-related pathways and decreased abundances of ARGs. Besides, the bloomed opportunistic pathogens including Achromobacter, Klebsiella, and Pseudomonas, caused by vancomycin exposure, were positively correlated with human disease-related pathways. The microbiota abundance and genes of human disease-related pathways and antibiotic resistance showed a remarkable return towards baseline after FMT, but not for natural recovery. These findings suggest that impacts of vancomycin on human gut are profound and FMT will be a promising strategy in clinical application that can restore the dysbiosis of gut microbiota, which may be valuable for directing future work.}, }
@article {pmid32529941, year = {2020}, author = {Li, X and He, C and Li, N and Ding, L and Chen, H and Wan, J and Yang, X and Xia, L and He, W and Xiong, H and Shu, X and Zhu, Y and Lu, N}, title = {The interplay between the gut microbiota and NLRP3 activation affects the severity of acute pancreatitis in mice.}, journal = {Gut microbes}, volume = {}, number = {}, pages = {1-16}, doi = {10.1080/19490976.2020.1770042}, pmid = {32529941}, issn = {1949-0984}, abstract = {Early dysbiosis of the gut microbiota is associated with the severity of acute pancreatitis (AP), although the underlying mechanism is unclear. Here, we investigated the role of crosstalk between NLRP3 and the gut microbiota in the development of AP utilizing gut microbiota deficient mice, as well as NLRP3 knockout (KO) mouse models. Pancreatic damage and systemic inflammation were improved in antibiotic-treated (Abx) and germ-free (GF) mice, accompanied by weakened activity of the intestinal NLRP3 inflammasome. Interestingly, fecal microbiota transplantation (FMT) reactivated the intestinal NLRP3 inflammasome and exacerbated the disease in Abx and GF mice. Although the gut barrier in GF and Abx mice was disrupted, gut microbiota deficiency ameliorated the severity of AP, probably due to the reduction in bacterial translocation from the gut to the pancreas. The composition of the gut microbiota was significantly different between NLRP3 KO mice and wild-type (WT) mice at baseline, and there were alterations in response to the induction of AP. While a dramatic shift in the gut microbiota with overgrowth of Escherichia-Shigella was observed in WT mice suffering from AP, there was no significant change in NLRP3 KO mice with or without AP, suggesting that NLRP3 deficiency counteracts AP-induced microbial disturbance. With a strengthened gut barrier and decreased systemic inflammation, NLRP3 KO mice showed less severe AP, as revealed by reduced pancreatic neutrophilic infiltration and necrosis. Taken together, these results identified the bidirectional modulation between the gut microbiota and NLRP3 in the progression of AP, which suggests the interplay of the host and microbiome during AP.}, }
@article {pmid32527171, year = {2020}, author = {Biernat, MM and Urbaniak-Kujda, D and Dybko, J and Kapelko-Słowik, K and Prajs, I and Wróbel, T}, title = {Fecal microbiota transplantation in the treatment of intestinal steroid-resistant graft-versus-host disease: two case reports and a review of the literature.}, journal = {The Journal of international medical research}, volume = {48}, number = {6}, pages = {300060520925693}, doi = {10.1177/0300060520925693}, pmid = {32527171}, issn = {1473-2300}, abstract = {Acute graft-versus-host disease (aGvHD) reduces the efficiency and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In recent years, attempts have been made to transplant fecal microbiota from healthy donors to treat intestinal GvHD. This study presented two cases of patients undergoing allo-HSCT who were later selected for fecal microbiota transplantation (FMT). In the first patient, FMT resulted in the complete resolution of symptoms, whereas therapeutic efficacy was not achieved in the second patient. FMT eliminated drug-resistant pathogens, namely very drug-resistant Enterococcus spp., but not multidrug-resistant Acinetobacter baumannii or Candida spp. Further research is needed, particularly on the safety of FMT in patients with intestinal steroid-resistant GvHD and on the distant impact of transplanted microflora on the outcomes of allo-HSCT. FMT appears promising for the treatment of patients with steroid-resistant GvHD.}, }
@article {pmid32407705, year = {2020}, author = {Fritsch, J and Abreu, MT}, title = {Candida in IBD: Friend or Foe?.}, journal = {Cell host &amp; microbe}, volume = {27}, number = {5}, pages = {689-691}, doi = {10.1016/j.chom.2020.04.018}, pmid = {32407705}, issn = {1934-6069}, mesh = {Candida ; *Colitis, Ulcerative ; *Fecal Microbiota Transplantation ; Humans ; Inflammation ; }, abstract = {In this issue of Cell Host &amp; Microbe, Leonardi et al. demonstrate ulcerative colitis patients with high Candida responded best to fecal microbial transplant (FMT). However, decreased Candida post-treatment was associated with improved disease-suggesting that Candida reductions are associated with less inflammation. Pre-FMT Candida levels may identify FMT responders.}, }
@article {pmid32523094, year = {2020}, author = {Pérez-Matute, P and Íñiguez, M and de Toro, M and Recio-Fernández, E and Oteo, JA}, title = {Autologous fecal transplantation from a lean state potentiates caloric restriction effects on body weight and adiposity in obese mice.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {9388}, doi = {10.1038/s41598-020-64961-x}, pmid = {32523094}, issn = {2045-2322}, abstract = {Autologous fecal transplantation (FT-A) emerges as a promising strategy to modulate gut microbiota with minimal side effects since individual´s own feces are transplanted. With the premise of improving obesity and its associated disorders, we investigated if fecal microbiota transplantation (FMT), heterologous and autologous, potentiates the effects of a moderate caloric restriction (CR) in high-fat diet (HFD)-induced obese mice. Mice were randomized into control, HFD, CR (12 weeks on HFD and 6 weeks under CR), FT-H (similar to CR and FMT carried out with feces from controls, weeks 17 &amp; 18), and FT-A (administration of their own feces before developing obesity at weeks 17 &amp; 18). Our study demonstrated that FMT, and, especially, FT-A potentiates the effects of a moderate CR on weight loss and adiposity in the short term, by decreasing feed efficiency and increasing adipose tissue lipolysis. Although FT-A produced a significant increase in bacterial richness/diversity, FMT did not significantly modify gut microbiota composition compared to the CR at phyla and bacteria genera levels, and only significant increases in Bifidobacterium and Blautia genera were observed. These results could suggest that other mechanisms different from bacterial microbiota engraftment participates in these beneficial effects. Thus, FT-A represents a very positive synergetic approach for obese patients that do not respond well to moderate restrictive diets.}, }
@article {pmid32519746, year = {2020}, author = {Su, X and Zhao, Y and Li, Y and Ma, S and Wang, Z}, title = {Gut dysbiosis is associated with primary hypothyroidism with interaction on gut-thyroid axis.}, journal = {Clinical science (London, England : 1979)}, volume = {}, number = {}, pages = {}, doi = {10.1042/CS20200475}, pmid = {32519746}, issn = {1470-8736}, abstract = {BACKGROUND: Previous studies have shown that the gut microbiome is associated with thyroid diseases, including Graves' disease, Hashimoto's disease, thyroid nodules, and thyroid cancer. However, the association between intestinal flora and primary hypothyroidism remains elusive. We aimed to characterize gut microbiome in primary hypothyroidism patients.<br><br>METHODS: Fifty-two primary hypothyroidism patients and 40 healthy controls were recruited. The differences in gut microbiota between the two groups were analyzed by 16S rRNA sequencing technology. Fecal microbiota transplantation (FMT) was performed in mice using flora from both groups; changes in thyroid function were then assessed in the mice.<br><br>RESULTS: There were significant differences in α and β diversities of gut microbiota between primary hypothyroidism patients and healthy individuals. The random forest analysis indicated that four intestinal bacteria (Veillonella, Paraprevotella, Neisseria, and Rheinheimera) could distinguish untreated primary hypothyroidism patients from healthy individuals with the highest accuracy; this was confirmed by receiver operator characteristic curve analysis. The short chain fatty acid producing ability of the primary hypothyroidism patients' gut was significantly decreased, which resulted in the increased serum lipopolysaccharides (LPS) levels. The FMT showed that mice receiving the transplant from primary hypothyroidism patients displayed decreased total thyroxine levels.<br><br>CONCLUSIONS: Our study suggests that primary hypothyroidism causes changes in gut microbiome. In turn, an altered flora can affect thyroid function in mice. These findings could help understand the development of primary hypothyroidism and might be further used to develop potential probiotics to facilitate the adjuvant treatment of this disease.}, }
@article {pmid32518854, year = {2020}, author = {Kates, AE and Gaulke, I and De Wolfe, T and Zimbric, M and Haight, K and Watson, L and Suen, G and Kim, K and Safdar, N}, title = {Fecal microbiota transplantation for patients on antibiotic treatment with C. difficile infection history (GRAFT): Study protocol for a phase II, randomized, double-blind, placebo-controlled trial to prevent recurrent C. difficile infections.}, journal = {Contemporary clinical trials communications}, volume = {18}, number = {}, pages = {100576}, doi = {10.1016/j.conctc.2020.100576}, pmid = {32518854}, issn = {2451-8654}, abstract = {Recurrent Clostridiodes difficile infections (rCDIs) are a burdensome problem. Patients with a history of CDI that are prescribed antibiotics are at a high risk for recurrence. Fecal microbiota transplantation (FMT) has been shown to be an effective treatment for rCDI, though there is little information on the impact of FMT with antibiotics on the gut microbiome. We are conducting a clinical trial of FMT to prevent rCDI in patients with a history of CDI currently taking antibiotics. Our primary objective is to determine the effect of FMT on the gut microbiome during antibiotic exposure. Our secondary aim is to assess safety and feasibility of using FMT as a prophylaxis for CDI. We plan to enroll 30 patients into a phase II randomized, double-blind, placebo-controlled trial with three arms: (1) 5 FMT capsules per day during antibiotic treatment and for 7 days post antibiotic cessation, (2) a one-time dose of 30 FMT capsules 48-72 h post cessation of antibiotic treatment, or (3) 5 placebo capsules per day during antibiotic treatment and for 7 days post antibiotic treatment. Patients provide stool samples throughout the duration of the study and are cultured C. difficile. Sequencing of the V4 region of the 16S rRNA gene will be carried out to assess the gut microbiota. Results of this study will provide information on the impact of FMT on the gut microbiome as well as the necessary data to examine whether or not prophylactic FMT should be explored further as a way to prevent CDI recurrence.}, }
@article {pmid32517023, year = {2020}, author = {Bibbò, S and Settanni, CR and Porcari, S and Bocchino, E and Ianiro, G and Cammarota, G and Gasbarrini, A}, title = {Fecal Microbiota Transplantation: Screening and Selection to Choose the Optimal Donor.}, journal = {Journal of clinical medicine}, volume = {9}, number = {6}, pages = {}, doi = {10.3390/jcm9061757}, pmid = {32517023}, issn = {2077-0383}, abstract = {In the past decade, fecal microbiota transplantation (FMT) has rapidly spread worldwide in clinical practice as a highly effective treatment option against recurrent Clostridioides difficile infection. Moreover, new evidence also supports a role for FMT in other conditions, such as inflammatory bowel disease, functional gastrointestinal disorders, or metabolic disorders. Recently, some studies have identified specific microbial characteristics associated with clinical improvement after FMT, in different disorders, paving the way for a microbiota-based precision medicine approach. Moreover, donor screening has become increasingly more complex over years, along with standardization of FMT and the increasing number of stool banks. In this narrative review, we discuss most recent evidence on the screening and selection of the stool donor, with reference to recent studies that have identified specific microbiological features for clinical conditions such as Clostridioides difficile infection, irritable bowel syndrome, inflammatory bowel disease, and metabolic disorders.}, }
@article {pmid32516027, year = {2020}, author = {Zoll, J and Read, MR and Heywood, SE and Estevez, E and Marshall, JP and Kammoun, HL and Allen, TL and Holmes, AJ and Febbraio, MA and Henstridge, DC}, title = {Fecal microbiota transplantation from high caloric-fed donors alters glucose metabolism in recipient mice, independently of adiposity or exercise status.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpendo.00037.2020}, pmid = {32516027}, issn = {1522-1555}, support = {Y15G-HEND//Diabetes Australia/ ; APP1116936//Department of Health, Australian Government | National Health and Medical Research Council (NHMRC)/ ; //Department of Health, Victorian State Government (Victorian Department of Health)/ ; }, abstract = {Studies suggest gut microbiota contributes to the development of obesity and the metabolic syndrome. Exercise alters microbiota composition and diversity and is protective of these maladies. We tested whether the protective metabolic effects of exercise are mediated through fecal components through assessment of body composition and metabolism in recipients of fecal microbiota transplantation (FMT) from exercise-trained (ET) mice fed normal or high energy diets. Donor C57BL/6J mice were fed a chow or high fat, high sucrose (HFHS) diet for 4wk to induce obesity and glucose intolerance. Mice were divided into sedentary (Sed) or ET groups [6wk treadmill-based ET] while maintaining their diets, resulting in four donor groups; chow sedentary (NC-Sed) or ET (NC-ET) and HFHS sedentary (HFHS-Sed) or ET (HFHS-ET). Chow-fed recipient mice were gavaged with feces from the respective donor groups weekly, creating four groups (NC-Sed-R, NC-ET-R, HFHS-Sed-R, HFHS-ET-R) and body composition and metabolism assessed. The HFHS diet led to glucose intolerance and obesity in the donors, while exercise training (ET) restrained adiposity and improved glucose tolerance. No donor group FMT altered recipient body composition. Despite unaltered adiposity, glucose levels were disrupted when challenged in mice receiving feces from HFHS-fed donors, irrespective of donor-ET status, with a decrease in insulin-stimulated glucose clearance into white adipose tissue and large intestine and specific changes in the recipient's microbiota composition. FMT can transmit HFHS-induced disrupted glucose metabolism to recipient mice independently of any change in adiposity. However, the protective metabolic effect of ET on glucose metabolism is not mediated through fecal factors.}, }
@article {pmid32514151, year = {2020}, author = {Fong, W and Li, Q and Yu, J}, title = {Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer.}, journal = {Oncogene}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41388-020-1341-1}, pmid = {32514151}, issn = {1476-5594}, support = {81972576//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Research about the role of gut microbiome in colorectal cancer (CRC) is a newly emerging field of study. Gut microbiota modulation, with the aim to reverse established microbial dysbiosis, is a novel strategy for prevention and treatment of CRC. Different strategies including probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT) have been employed. Although these strategies show promising results, mechanistically by correcting microbiota composition, modulating innate immune system, enhancing gut barrier function, preventing pathogen colonization and exerting selective cytotoxicity against tumor cells, it should be noted that they are accompanied by risks and controversies that can potentially introduce clinical complications. During bench-to-bedside translation, evaluation of risk-and-benefit ratio, as well as patient selection, should be carefully performed. In view of the individualized host response to gut microbiome intervention, developing personalized microbiome therapy may be the key to successful clinical treatment.}, }
@article {pmid31596195, year = {2019}, author = {Lei, S and Twitchell, EL and Ramesh, AK and Bui, T and Majette, E and Tin, CM and Avery, R and Arango-Argoty, G and Zhang, L and Becker-Dreps, S and Azcarate-Peril, MA and Jiang, X and Yuan, L}, title = {Enhanced GII.4 human norovirus infection in gnotobiotic pigs transplanted with a human gut microbiota.}, journal = {The Journal of general virology}, volume = {100}, number = {11}, pages = {1530-1540}, pmid = {31596195}, issn = {1465-2099}, support = {R01 AI089634/AI/NIAID NIH HHS/United States ; R01 AI123661/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Blood/virology ; Caliciviridae Infections/complications/*pathology ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Disease Models, Animal ; Duodenum/virology ; *Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Genotype ; Germ-Free Life ; Humans ; Ileum/virology ; *Microbial Interactions ; *Microbiota ; Norovirus/classification/genetics/*growth &amp; development ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Swine ; Time Factors ; Viral Load ; Virus Shedding ; }, abstract = {The role of commensal microbiota in enteric viral infections has been explored extensively, but the interaction between human gut microbiota (HGM) and human norovirus (HuNoV) is poorly understood. In this study, we established an HGM-Transplanted gnotobiotic (Gn) pig model of HuNoV infection and disease, using an infant stool as HGM transplant and a HuNoV GII.4/2006b strain for virus inoculation. Compared to germ-free Gn pigs, HuNoV inoculation in HGMT Gn pigs resulted in increased HuNoV shedding, characterized by significantly higher shedding titres on post inoculation day (PID) 3, 4, 6, 8 and 9, and significantly longer mean duration of virus shedding. In addition, virus titres were significantly higher in duodenum and distal ileum of HGMT Gn pigs on PID10, while comparable and transient HuNoV viremia was detected in both groups. 16S rRNA gene sequencing demonstrated that HuNoV infection dramatically altered intestinal microbiota in HGMT Gn pigs at the phylum (Proteobacteria, Firmicutes and Bacteroidetes) and genus (Enterococcus, Bifidobacterium, Clostridium, Ruminococcus, Anaerococcus, Bacteroides and Lactobacillus) levels. In summary, enhanced GII.4 HuNoV infection was observed in the presence of HGM, and host microbiota was susceptible to disruption upon HuNoV infection.}, }
@article {pmid32511695, year = {2020}, author = {Bar-Yoseph, H and Carasso, S and Shklar, S and Korytny, A and Even Dar, R and Daoud, H and Nassar, R and Maharshak, N and Hussein, K and Geffen, Y and Chowers, Y and Geva-Zatorsky, N and Paul, M}, title = {Oral capsulized Fecal microbiota transplantation for eradication of carbapenemase-producing Enterobacteriaceae colonization with a metagenomic perspective.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaa737}, pmid = {32511695}, issn = {1537-6591}, abstract = {BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) infections lead to considerable morbidity and mortality. We assessed the potential of fecal microbiota transplantation (FMT) to eradicate CPE carriage and aimed to explain failure or success through microbiome analyses.<br><br>METHODS: In this prospective cohort study, all consenting eligible CPE carriers were treated with oral capsulized FMT for 2 days. The primary outcome was CPE eradication at 1 month, defined by 3 consecutive negative rectal swabs, the last also negative for carbapenemase gene by PCR. Comprehensive metagenomics analysis of the intestinal microbiome of donors and recipients before and after FMT was performed.<br><br>RESULTS: Fifteen CPE carriers received FMT, 13 of which completed 2 days of treatment. CPE eradication at 1 month was successful in 9/15 and 9/13, respectively. Bacterial communities showed significant changes in both beta and alpha diversity metrics among participants achieving CPE eradication that were not observed among failures. Post-FMT samples' beta-diversity clustered according to the treatment outcome, both in taxonomy and in function. We observed a significant decrease in beta diversity in participants who received post-FMT antibiotics. Enterobacteriaceae abundance decreased in post-FMT samples of the responders, but increased among failures. Functionally, a clear demarcation between responders (who were similar to the donors) and failures was shown, driven by antimicrobial resistance genes.<br><br>CONCLUSION: Our study provides the biological explanation for the effect of FMT against CPE carriage. Decolonization of CPE by FMT is likely mediated by compositional and functional shifts in the microbiome. Thus, FMT might be an efficient strategy for sustained CPE eradication.}, }
@article {pmid32509162, year = {2020}, author = {Wang, H and Zhou, C and Huang, J and Kuai, X and Shao, X}, title = {The potential therapeutic role of Lactobacillus reuteri for treatment of inflammatory bowel disease.}, journal = {American journal of translational research}, volume = {12}, number = {5}, pages = {1569-1583}, pmid = {32509162}, issn = {1943-8141}, abstract = {Inflammatory bowel disease (IBD) is a chronic intestinal disease of unknown etiology. However, recent studies have established a pathological role of disordered intestinal microbiota and immune dysregulation. Clinical studies have suggested that the reconstruction of the normal intestinal flora in patients with IBD can reverse the dysbiosis caused by genetic, environmental, dietary, or antibiotic factors to ameliorate the symptoms of IBD. Lactobacillus reuteri is widely present in the intestines of healthy individuals and regulates the intestinal immune system, reducing inflammation through multiple mechanisms. This review summarizes the current knowledge of the role of L. reuteri in maintaining intestinal homeostasis and considers its possible value as a new therapeutic agent for patients with IBD.}, }
@article {pmid32508773, year = {2020}, author = {Liu, H and Wang, HH}, title = {Impact of Microbiota Transplant on Resistome of Gut Microbiota in Gnotobiotic Piglets and Human Subjects.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {932}, doi = {10.3389/fmicb.2020.00932}, pmid = {32508773}, issn = {1664-302X}, abstract = {Microbiota transplant is becoming a popular process to restore or initiate &quot;healthy&quot; gut microbiota and immunity. But, the potential risks of the related practices need to be carefully evaluated. This study retrospectively examined the resistomes of donated fecal microbiota for treating intestinal disorders, vaginal microbiota of pregnant women, and infant fecal microbiota from rural and urban communities, as well as the impact of transplants on the fecal resistome of human and animal recipients. Antibiotic resistance (AR) genes were found to be abundant in all donor microbiota. An overall surge of resistomes with higher prevalence and abundance of AR genes was observed in the feces of all transplanted gnotobiotic pigs as well as in the feces of infant subjects, compared to those in donor fecal and maternal vaginal microbiota. Surprisingly, transplants using rural Amish microbiota led to more instead of less AR genes in the fecal microbiota of gnotobiotic pigs than did transplants using urban microbiota. New AR gene subtypes undetected originally also appeared in gnotobiotic pigs, in Crohn's Disease (CD) patients after transplant, and in feces of infant subjects. The data illustrated the key role of the host gastrointestinal tract system in amplifying the ever-increasing AR gene pool, even without antibiotic exposure. The data further suggest that the current approaches of microbiota transplant can introduce significant health risk factor(s) to the recipients, and newborn human and animal hosts with naïve gut microbiota were especially susceptible. Given the illustrated public health risks of microbiota transplant, minimizing massive and unnecessary damages to gut microbiota by oral antibiotics and other gut impacting drugs becomes important. Since eliminating risk factors including AR bacteria and opportunistic pathogens directly from donor microbiota is still difficult to achieve, developing microbial cocktails with defined organisms and functions has further become an urgent need, should microbiota transplantation become necessary.}, }
@article {pmid31573550, year = {2019}, author = {Dabke, K and Hendrick, G and Devkota, S}, title = {The gut microbiome and metabolic syndrome.}, journal = {The Journal of clinical investigation}, volume = {129}, number = {10}, pages = {4050-4057}, pmid = {31573550}, issn = {1558-8238}, mesh = {Animals ; Diet ; Dyslipidemias/etiology/microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Host Microbial Interactions/physiology ; Humans ; Inflammation/etiology/microbiology ; Insulin Resistance ; Metabolic Syndrome/*etiology/metabolism/microbiology ; Models, Biological ; Obesity/etiology/microbiology ; }, abstract = {The metabolic syndrome (MetS) is a constellation of risk factors that, if left untreated, will often progress to greater metabolic defects such as type 2 diabetes and nonalcoholic fatty liver disease. While these risk factors have been established for over 40 years, the definition of MetS warrants reconsideration in light of the substantial data that have emerged from studies of the gut microbiome. In this Review we present the existing recent literature that supports the gut microbiome's potential influence on the various risk factors of MetS. The interplay of the intestinal microbiota with host metabolism has been shown to be mediated by a myriad of factors, including a defective gut barrier, bile acid metabolism, antibiotic use, and the pleiotropic effects of microbially produced metabolites. These data show that events that start in the gut, often in response to external cues such as diet and circadian disruption, have far-reaching effects beyond the gut.}, }
@article {pmid32501140, year = {2020}, author = {Reygner, J and Charrueau, C and Delannoy, J and Mayeur, C and Robert, V and Cuinat, C and Meylheuc, T and Mauras, A and Augustin, J and Nicolis, I and Modoux, M and Joly, F and Waligora-Dupriet, AJ and Thomas, M and Kapel, N}, title = {Freeze-dried fecal samples are biologically active after long-lasting storage and suited to fecal microbiota transplantation in a preclinical murine model of Clostridioides difficile infection.}, journal = {Gut microbes}, volume = {}, number = {}, pages = {1-18}, doi = {10.1080/19490976.2020.1759489}, pmid = {32501140}, issn = {1949-0984}, abstract = {Fecal microbiota transplantation is now recommended for treating recurrent forms of Clostridioides difficile infection. Recent studies have reported protocols using capsules of either frozen or freeze-dried stool allowing oral administration in in- and out-patient settings. However, a central question remains the viability, engraftment, and efficacy of the microbiome over time during storage life. This study shows that both the freeze-drying and freezing procedures for fecal samples allowed preserving viability, short-chain fatty acids concentration, and anti-Clostridioides difficile properties of microbiota without significant alteration after storage for 12 months. Fecal transplantation with freeze-dried microbiota allowed engraftment of microbiota leading to clearance of Clostridioides difficile infection in a preclinical murine model with a survival rate of 70% versus 53-60% in mice treated with frozen inocula, and 20% in the untreated group. Moreover, the freeze-dried powder can be used to fill oral hard capsules using a very low amount (0.5%) of glidant excipient, allowing oral formulation. Altogether, this study showed that freeze-dried inocula can be used for the treatment of Clostridioides difficile infection with long-lasting stability of the fecal microbiota. This formulation facilitates biobanking and allows the use of hard capsules, an essential step to simplify patient access to treatment.}, }
@article {pmid32500988, year = {2020}, author = {Piekarska, A and Panasiuk, A and Stępień, PM}, title = {Clinical practice guidelines for Clostridioides (Clostridium) difficile infection and fecal microbiota transplant protocol - recommendations of the Polish Society od Epidemiology and Infectious Diseases.}, journal = {Przeglad epidemiologiczny}, volume = {74}, number = {1}, pages = {69-87}, doi = {10.32394/pe.74.06}, pmid = {32500988}, issn = {0033-2100}, abstract = {Symptomatic Clostridium difficile infection (CDI) is an acute inflammatory disease of the gastrointestinal tract, manifesting in at least 3 unformed stools within 24 hours. Predicting factors for CDI include contact with medical care (mainly hospitalization), antibiotic therapy in the last 12 weeks, use of proton pump inhibitors (PPI), H2 blockers, cancer chemotherapy, especially in the neutropenia stage, gastrointestinal surgery, advanced age and concomitant chronic diseases (renal failure, liver failure, chronic inflammatory bowel disease - especially ulcerative bowel disease, cancer, HIV infection, cachexia and hypoalbuminaemia) and vitamin D deficiency. Clinical classification distinguishes three types of CDI - mild / moderate, severe, and fulminant. The principles of treatment of the first and subsequent CDI incidents depending on the clinical course are based on oral vancomycin. CDI is recurrent. The basis for treating CDI relapses is vancomycin administered orally at a dose of 4x125 mg for 10 days followed by concomitant vancomycin dose reduction therapy. The use of fecal microbiota transfer (FMT) in the treatment of CDI relapses is considered to be the most effective therapy for recurrent CDI. An indication for FMT is antibiotic-resistant C. difficile infection, regardless of the number of incidents CDI. The panel of tests recommended for a bacterial flora donor is presented in the recommendations.}, }
@article {pmid32499711, year = {2020}, author = {Cheung, MK and Yue, GGL and Chiu, PWY and Lau, CBS}, title = {A Review of the Effects of Natural Compounds, Medicinal Plants, and Mushrooms on the Gut Microbiota in Colitis and Cancer.}, journal = {Frontiers in pharmacology}, volume = {11}, number = {}, pages = {744}, doi = {10.3389/fphar.2020.00744}, pmid = {32499711}, issn = {1663-9812}, abstract = {The human gastrointestinal tract harbors a diverse array of microorganisms that play fundamental roles in health and disease. Imbalance in the gut microbiota, namely dysbiosis, can lead to various diseases, including cancer and gastrointestinal tract disorders. Approaches to improve gut dysbiosis, such as dietary intervention, intake of probiotics, and fecal microbiota transplantation are emerging strategies to treat these diseases. Various medicinal botanicals have reported anti-cancer and/or anti-inflammatory properties. Preclinical studies have illustrated that some of these natural products are also capable to modulate the gut microbiota, suggesting their use as possible alternative approach to improve gut dysbiosis and thereby assist diseases treatment. In this review article, we have summarized the current knowledge on the effects of natural compounds, medicinal plants, and mushrooms on the gut microbiota in various cancers and colitis in preclinical animal models. Challenges towards the clinical use of these medicinal botanicals as modulators of the gut microbiota in cancer and colitis treatment are also discussed.}, }
@article {pmid32499362, year = {2020}, author = {Simpson, E and Sanjar, F and Wylie, D and Park, S and Koh, H and Bae, J and Kook, SY and Kim, S and Kim, HJ}, title = {Draft Genome Sequences of Two Strains of Bifidobacterium dentium Isolated from a Crude Fecal Extract Used for Fecal Microbiota Transplantation in the Republic of Korea.}, journal = {Microbiology resource announcements}, volume = {9}, number = {23}, pages = {}, doi = {10.1128/MRA.00197-20}, pmid = {32499362}, issn = {2576-098X}, abstract = {We present the draft genome sequences of two Bifidobacterium dentium strains isolated from a fecal extract for fecal microbiota transplantation at a hospital in the Republic of Korea. Phylogenetic and functional analyses were performed to understand the physiological characteristics and functions of Bifidobacterium spp. in the human intestine.}, }
@article {pmid31657769, year = {2019}, author = {Kuijper, EJ and Allegretii, J and Hawkey, P and Sokol, H and Goldenberg, S and Ianiro, G and Gasbarrini, A and Kump, P and Costello, SP and Keller, J and Vehreschild, MJGT}, title = {A necessary discussion after transmission of multidrug-resistant organisms through faecal microbiota transplantations.}, journal = {The Lancet. Infectious diseases}, volume = {19}, number = {11}, pages = {1161-1162}, doi = {10.1016/S1473-3099(19)30545-6}, pmid = {31657769}, issn = {1474-4457}, mesh = {*Drug Resistance, Multiple, Bacterial ; Fecal Microbiota Transplantation/*adverse effects/methods/standards ; Government Regulation ; Humans ; Immunocompromised Host ; Microbial Sensitivity Tests ; Patient Safety ; United States ; United States Food and Drug Administration ; }, }
@article {pmid31138018, year = {2020}, author = {Paik, J and Meeker, S and Hsu, CC and Seamons, A and Pershutkina, O and Snyder, JM and Brabb, T and Maggio-Price, L}, title = {Validation studies for germ-free Smad3-/- mice as a bio-assay to test the causative role of fecal microbiomes in IBD.}, journal = {Gut microbes}, volume = {11}, number = {1}, pages = {21-31}, pmid = {31138018}, issn = {1949-0984}, support = {K01 OD021420/OD/NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biological Assay ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Inflammatory Bowel Diseases/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Smad3 Protein/*genetics ; }, abstract = {While the association between microbiomes and inflammatory bowel disease (IBD) is well known, establishing causal relationships between the two is difficult in humans. Germ-free (GF) mice genetically susceptible to IBD can address this question. Smad3-/- mice with defective transforming growth factor ß signaling are a model of IBD and colon cancer. They develop IBD upon colonization with Helicobacter under specific pathogen-free conditions, suggesting a role of the microbiome in IBD in this model. Thus, we rederived Smad3-/- mice GF to determine the potential of using these mice for testing the causative role of microbiomes in IBD. We found that fecal microbiomes from mice with IBD cause more severe gut inflammation in GF Smad3-/- and wild type mice compared to microbiomes from healthy mice and that Helicobacter induces gut inflammation within the context of other microbiomes but not by itself. Unexpectedly, GF Smad3+/+ and Smad3+/- mice given IBD microbiomes develop IBD despite their lack of disease in SPF conditions upon Helicobacter infection. This was not unique to the background strain of our Smad3 model (129); both wild type C57BL/6 and 129 strains developed IBD upon fecal transfer. However, wild type Swiss Webster stock was not susceptible, indicating that the genetic background of recipient mice influences the severity of IBD following fecal transfer. Our data suggest that the microbiome is an independent risk factor contributing to IBD development, and careful characterization of new GF models is needed to understand potential sources of confounding factors influencing microbiome studies in these mice.}, }
@article {pmid32496421, year = {2020}, author = {Assimakopoulos, SF and Papadopoulou, I and Bantouna, D and de Lastic, AL and Rodi, M and Mouzaki, A and Gogos, CA and Zolota, V and Maroulis, I}, title = {Fecal Microbiota Transplantation and Hydrocortisone Ameliorate Intestinal Barrier Dysfunction and Improve Survival in a Rat Model of Cecal Ligation and Puncture-Induced Sepsis.}, journal = {Shock (Augusta, Ga.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/SHK.0000000000001566}, pmid = {32496421}, issn = {1540-0514}, abstract = {INTRODUCTION: Sepsis is a life-threatening syndrome which can progress to multiple organ dysfunction with high mortality. Intestinal barrier failure exerts a central role in the pathophysiological sequence of events that lead from sepsis to multiple organ dysfunction. The present study investigated the role of hydrocortisone (HC) administration and fecal microbiota transplantation (FMT) in several parameters of the gut barrier integrity, immune activation and survival, in a model of polymicrobial sepsis in rats.<br><br>METHODS: Forty adults male Wistar rats were randomly divided into four groups: sham (group I), cecal ligation and puncture (CLP) (group II), CLP + HC (2.8 mg/kg, intraperitoneally single dose at 6 hours) (group III) and CLP + FMT at 6 hours (group IV). At 24 h post-CLP, ileal tissues were harvested for histological and immunohistochemical analyses while endotoxin, IL-6 and IL-10 levels in systemic circulation were determined. In a second experiment the same groups were observed for seven days for mortality, with daily administration of hydrocortisone (group III) and FMT (group IV) in surviving rats.<br><br>RESULTS: HC administration and FMT significantly reduced mortality of septic rats by 50%. These interventions totally reversed intestinal mucosal atrophy by increasing villous density and mucosal thickness (μm, mean ± SD: Group I: 620 ± 35, Group II: 411 ± 52, Group III: 622 ± 19, Group IV:617 ± 44). HC and FMT reduced the apoptotic body count in intestinal crypts whereas increased the mitotic/apoptotic index. Activated caspase-3 expression in intestinal crypts was significantly reduced by HC or FMT (activated caspase-3 (+) enterocytes/10 crypts, mean ± SD: Group I: 1,6 ± 0,5, Group II: 5,8 ± 2,4, Group III: 3,6 ± 0,9, Group IV:2,3 ± 0,6). Both treatments increased Paneth cell count and decreased intraepithelial CD3(+) T lymphocytes and inflammatory infiltration of lamina propria to control levels. In the sham group almost the total of intestinal epithelial cells expressed occludin (92 ± 8%) and claudin-1 (98 ± 4%) and CLP reduced this expression to 34 ± 12% for occludin and 35 ± 7% for claudin-1. Administration of HC significantly increased occludin (51 ± 17%) and claudin-1 (77 ± 9%) expression. FMT exerted also a significant restoring effect in TJ by increasing occludin (56 ± 15%) and claudin-1 (84 ± 7%) expression. The beneficial effects of these treatments on gut barrier function led to significant reduction of systemic endotoxemia (EU/ml, mean ± SD: Group I: 0,93 ± 0,36, Group II: 2,14 ± 1,74, Group III: 1,48 ± 0,53, Group IV: 1,61 ± 0,58,), while FMT additionally decreased IL-6 and IL-10 levels.<br><br>CONCLUSION: Fecal microbiota transplantation and stress dose hydrocortisone administration in septic rats induce a multifactorial improvement of the gut mechanical and immunological barriers, preventing endotoxemia and leading to improved survival.}, }
@article {pmid32495834, year = {2020}, author = {Rasmussen, TS and Koefoed, AK and Jakobsen, RR and Deng, L and Castro-Mejía, JL and Brunse, A and Neve, H and Vogensen, FK and Nielsen, DS}, title = {Bacteriophage-mediated manipulation of the gut microbiome - promises and presents limitations.}, journal = {FEMS microbiology reviews}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsre/fuaa020}, pmid = {32495834}, issn = {1574-6976}, abstract = {Gut microbiome (GM) composition and function are linked to human health and disease, and routes for manipulating the GM have become an area of intense research. Due to its high treatment efficacy, the use of fecal microbiota transplantation (FMT) is generally accepted as a promising experimental treatment for patients suffering from GM imbalances (dysbiosis), e.g. caused by recurrent Clostridioides difficile infections (rCDI). Mounting evidence suggests that bacteriophages (phages) play a key role in successful FMT treatment by restoring the dysbiotic bacterial GM. As a refinement to FMT, removing the bacterial component of donor feces by sterile filtration, also referred to as fecal virome transplantation (FVT), decreases the risk of invasive infections caused by bacteria. However, eukaryotic viruses and prophage-encoded virulence factors remain a safety issue. Recent in vivo studies show how cascading effects are initiated when phage communities are transferred to the gut by e.g. FVT, which leads to changes in the GM composition, host metabolome, and improve host health such as alleviating symptoms of obesity and type-2-diabetes (T2D). In this review, we discuss the promises and limitations of FVT along with the perspectives of using FVT to treat various diseases associated with GM dysbiosis.}, }
@article {pmid32495743, year = {2020}, author = {Chinna Meyyappan, A and Milev, R}, title = {The Safety, Efficacy, and Tolerability of Microbial Ecosystem Therapeutic-2 in People With Major Depression and/or Generalized Anxiety Disorder: Protocol for a Phase 1, Open-Label Study.}, journal = {JMIR research protocols}, volume = {9}, number = {6}, pages = {e17223}, doi = {10.2196/17223}, pmid = {32495743}, issn = {1929-0748}, abstract = {BACKGROUND: The bidirectional signaling between the gut microbiota and the brain, known as the gut-brain axis, is being heavily explored in current neuropsychiatric research. Analyses of the human gut microbiota have shown considerable individual variability in bacterial content, which is hypothesized to influence brain function, and potentially mood and anxiety symptoms, through gut-brain axis communication. Preclinical and clinical research examining these effects suggests that fecal microbiota transplant (FMT) may aid in improving the severity of depression and anxiety symptoms by recolonizing the gastrointestinal (GI) tract with healthy bacteria. The microbial ecosystem therapeutic (ie, microbial ecosystem therapeutic-2 [MET-2]) used in this study is an alternative treatment to FMT, which comprises 40 different strains of gut bacteria from a healthy donor.<br><br>OBJECTIVE: The primary objective of this study is to assess subjective changes in mood and anxiety symptoms before, during, and after administration of MET-2. The secondary objectives of this study are to assess the changes in metabolic functioning and the level of repopulation of healthy gut bacteria, the safety and tolerability of MET-2, and the effects of early stress on biomarkers of depression/anxiety and the response to treatment.<br><br>METHODS: Adults experiencing depressive or anxiety symptoms will be recruited from the Kingston area. These participants will orally consume an encapsulated MET-2 once daily-containing 40 strains of purified and laboratory-grown bacteria from a single healthy donor-for 8 weeks, followed by a 2-week treatment-free follow-up period. Participants will undergo a series of clinical assessments measuring mood, anxiety, and GI symptoms using validated clinical scales and questionnaires. Molecular data will be collected from blood and fecal samples to assess metabolic changes, neurotransmitter levels, inflammatory markers, and the level of engraftment of the fecal samples that may predict outcomes in depression or anxiety.<br><br>RESULTS: Given the association between the gut bacteria and the risk factors of depression, we expect to observe an improvement in the severity of depressive and anxiety symptoms following treatment, and we expect that this improvement is mediated by the recolonization of the GI tract with healthy bacteria. The recruitment for this study has been completed, and the data obtained are currently being analyzed.<br><br>CONCLUSIONS: This is the first time MET-2 is being tested in psychiatric indications, specifically depression and anxiety. As such, this may be the first study to show the potential effects of microbial therapy in alleviating psychiatric symptoms as well as its safety and tolerability.<br><br>DERR1-10.2196/17223.}, }
@article {pmid32493442, year = {2020}, author = {Trang-Poisson, C and Kerdreux, E and Poinas, A and Planche, L and Sokol, H and Bemer, P and Cabanas, K and Hivernaud, E and Biron, L and Flet, L and Montassier, E and Le Garcasson, G and Chiffoleau, A and Jobert, A and Lepelletier, D and Caillon, J and Le Pape, P and Imbert, BM and Bourreille, A}, title = {Impact of fecal microbiota transplantation on chronic recurrent pouchitis in ulcerative colitis with ileo-anal anastomosis: study protocol for a prospective, multicenter, double-blind, randomized, controlled trial.}, journal = {Trials}, volume = {21}, number = {1}, pages = {455}, doi = {10.1186/s13063-020-04330-1}, pmid = {32493442}, issn = {1745-6215}, support = {16-267//Ministère des Affaires Sociales, de la Santé et des Droits des Femmes/ ; }, abstract = {BACKGROUND: Almost 15% of patients with ulcerative colitis (UC) will require a proctocolectomy with ileal pouch-anal anastomosis (IPAA) as a result of fulminant colitis, dysplasia, cancer, or medical refractory diseases. Around 50% will experience pouchitis, an idiopathic inflammatory condition involving the ileal reservoir, responsible for digestive symptoms, deterioration in quality of life, and disability. Though the majority of initial cases of pouchitis are easily managed with a short course of antibiotics, in about 10% of cases, inflammation of the pouch becomes chronic with very few treatments available. Previous studies have suggested that manipulating the composition of intestinal flora through antibiotics, probiotics, and prebiotics achieved significant results for treating acute episodes of UC-associated pouchitis. However, there is currently no established effective treatment for chronic antibiotic-dependent pouchitis. Fecal microbiota transplantation (FMT) is a novel therapy involving the transfer of normal intestinal flora from a healthy donor to a patient with a medical condition potentially caused by the disrupted homeostasis of intestinal microbiota or dysbiosis.<br><br>METHODS: Our project aims to compare the delay of relapse of chronic recurrent pouchitis after FMT versus sham transplantation. Forty-two patients with active recurrent pouchitis after having undergone an IPAA for UC will be enrolled at 12 French centers. The patients who respond to antibiotherapy will be randomized at a ratio of 1:1 to receive either FMT or sham transplantation.<br><br>DISCUSSION: On April 30, 2014, the World Health Organization published an alarming report on antibiotic resistance. Finding an alternative medical treatment to antibiotics in order to prevent relapses of pouchitis is therefore becoming increasingly important given the risk posed by multiresistant bacteria. Moreover, if the results of this study are conclusive, FMT, which is less expensive than biologics, could become a routine treatment in the future.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, NCT03524352. Registered on 14 May 2018.}, }
@article {pmid32492490, year = {2020}, author = {Gulati, M and Singh, SK and Corrie, L and Kaur, IP and Chandwani, L}, title = {Delivery routes for faecal microbiota transplants: Available, anticipated and aspired.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {104954}, doi = {10.1016/j.phrs.2020.104954}, pmid = {32492490}, issn = {1096-1186}, abstract = {Fecal microbiota transplant (FMT) has seen a historic emergence in last decade with its sojourn recently entering into a chequered path, due to a few reports of infection and subsequent mortality. Though FMT has been extensively reported, there is no comprehensive report on the delivery routes available for this non-pharmacological treatment option. Safety, efficacy and cost of FMT not only depend on the quality of contents but also on the delivery route employed. A number of delivery routes are in use for conducting FMT, which include upper gastrointestinal routes (UGI) i.e. nasogastric/nasojejunal tube, endoscopy, oral capsules and lower gastrointestinal routes (LGI) like retention enema, sigmoidoscopy or colonoscopy. Capsules, both conventional as well as colon targeted have been the most commonly used formulations. Surprisingly, the success rates with conventional gastric delivery capsules and colon targeted capsules were found to be quite similar indicating the sufficiency of the inoculum size to withstand the microbial loss in the gastric milieu. Patient compliance, cost effectiveness, comfort of administration, level of invasiveness, patient's hospital admission, risk of aspiration and infections, multiplicity of administration required, recurrence rate are the main factors that seem to influence the choice for route of administration of physicians. The best route for FMT has not been established yet. Extensive studies are required to understand the interplay of route adopted, type of donor, physical nature of sample (fresh or frozen), patient compliance and cost effectiveness to design an approach for the risk free, convenient and cost-effective administration route for FMT.}, }
@article {pmid32487252, year = {2020}, author = {Adelman, MW and Woodworth, MH and Langelier, C and Busch, LM and Kempker, JA and Kraft, CS and Martin, GS}, title = {The gut microbiome's role in the development, maintenance, and outcomes of sepsis.}, journal = {Critical care (London, England)}, volume = {24}, number = {1}, pages = {278}, doi = {10.1186/s13054-020-02989-1}, pmid = {32487252}, issn = {1466-609X}, support = {K23AI144036//National Institute of Allergy and Infectious Diseases/ ; K08 HS-025240//Agency for Healthcare Research and Quality (US)/ ; K23HL138461-01A1/HL/NHLBI NIH HHS/United States ; UL1 TR-002378/TR/NCATS NIH HHS/United States ; }, abstract = {The gut microbiome regulates a number of homeostatic mechanisms in the healthy host including immune function and gut barrier protection. Loss of normal gut microbial structure and function has been associated with diseases as diverse as Clostridioides difficile infection, asthma, and epilepsy. Recent evidence has also demonstrated a link between the gut microbiome and sepsis. In this review, we focus on three key areas of the interaction between the gut microbiome and sepsis. First, prior to sepsis onset, gut microbiome alteration increases sepsis susceptibility through several mechanisms, including (a) allowing for expansion of pathogenic intestinal bacteria, (b) priming the immune system for a robust pro-inflammatory response, and (c) decreasing production of beneficial microbial products such as short-chain fatty acids. Second, once sepsis is established, gut microbiome disruption worsens and increases susceptibility to end-organ dysfunction. Third, there is limited evidence that microbiome-based therapeutics, including probiotics and selective digestive decontamination, may decrease sepsis risk and improve sepsis outcomes in select patient populations, but concerns about safety have limited uptake. Case reports of a different microbiome-based therapy, fecal microbiota transplantation, have shown correlation with gut microbial structure restoration and decreased inflammatory response, but these results require further validation. While much of the evidence linking the gut microbiome and sepsis has been established in pre-clinical studies, clinical evidence is lacking in many areas. To address this, we outline a potential research agenda for further investigating the interaction between the gut microbiome and sepsis.}, }
@article {pmid32486476, year = {2020}, author = {Okahara, K and Ishikawa, D and Nomura, K and Ito, S and Haga, K and Takahashi, M and Shibuya, T and Osada, T and Nagahara, A}, title = {Matching between Donors and Ulcerative Colitis Patients Is Important for Long-Term Maintenance after Fecal Microbiota Transplantation.}, journal = {Journal of clinical medicine}, volume = {9}, number = {6}, pages = {}, doi = {10.3390/jcm9061650}, pmid = {32486476}, issn = {2077-0383}, support = {JP16K09328//Japan Society for the Promotion of Science/ ; }, abstract = {We previously demonstrated that fresh fecal microbiota transplantation (FMT) following triple antibiotic therapy (amoxicillin, fosfomycin, metronidazole (AFM); A-FMT) resulted in effective colonization of Bacteroidetes species, leading to short-term clinical response in ulcerative colitis (UC). Its long-term efficacy and criteria for donor selection are unknown. Here, we analyzed the long-term efficacy of A-FMT compared to AFM monotherapy (mono-AFM). AFM was administered to patients with mild to severe UC for 2 weeks until 2 days before fresh FMT. Clinical response and efficacy maintenance were defined by the decrease and no exacerbation in clinical activity index. The population for intention-to-treat analysis comprised 92 patients (A-FMT, n = 55; mono-AFM, n = 37). Clinical response was observed at 4 weeks post-treatment (A-FMT, 56.3%; mono-AFM, 48.6%). Maintenance rate of responders at 24 months post-treatment was significantly higher with A-FMT than mono-AFM (p = 0.034). Significant differences in maintenance rate according to the age difference between donors and patients were observed. Additionally, sibling FMT had a significantly higher maintenance rate than parent-child FMT. Microbial analysis of patients who achieved long-term maintenance showed that some exhibited similarity to their donors, particularly Bacteroidetes species. Thus, A-FMT exhibited long-term efficacy. Therefore, matching between donors and UC patients may be helpful in effectively planning the FMT regimen.}, }
@article {pmid32485282, year = {2020}, author = {Wang, MX and Lin, L and Chen, YD and Zhong, YP and Lin, YX and Li, P and Tian, X and Han, B and Xie, ZY and Liao, QF}, title = {Evodiamine has therapeutic efficacy in ulcerative colitis by increasing Lactobacillus acidophilus levels and acetate production.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {104978}, doi = {10.1016/j.phrs.2020.104978}, pmid = {32485282}, issn = {1096-1186}, abstract = {Emerging evidence implicates gut microbiota have an important role in ulcerative colitis (UC). Previous study indicated that Evodiamine (EVO) can alleviate colitis through downregulating inflammatory pathways. However, specific relationship between EVO-treated colitis relief and regulation of gut microbiota is still unclear. Here, our goal was to determine the potential role of gut microbiota in the relief of UC by EVO. By using pathology-related indicators, 16S rRNA sequencing and metabolomics profiling, we assessed the pharmacological effect of EVO on dextran sulfate sodium (DSS)-induced colitis rats as well as on the change of gut microbiota and metabolism. Fecal derived from EVO-treated rats was transplanted into colitis rats to verify the effect of EVO on gut microbiota, and 'driver bacteria' was found and validated by 16S rRNA sequencing, metagenome and qRT-PCR. The effect of Lactobacillus acidophilus (L. acidophilus) was investigated by vivo experiment, microbiota analysis, Short-chain fatty acids (SCFAs) quantification and colon transcriptomics. EVO reduced the susceptibility to DSS-induced destruction of epithelial integrity and severe inflammatory response, and regulated the gut microbiota and metabolites. Fecal Microbiota Transplantation (FMT) alleviated DSS-induced colitis, increased the abundance of L. acidophilus and the level of acetate. Furthermore, gavaged with L. acidophilus reduced pro-inflammatory cytokines, promoted the increase of goblet cells and the secretion of antimicrobial peptides, regulated the ratio of Firmicutes/Bacteroidetes and increased the level of acetate. Our results indicated that EVO mitigation of DSS-induced colitis is associated with increased in L. acidophilus and protective acetate production, which may be a promising strategy for treating UC.}, }
@article {pmid31326345, year = {2019}, author = {Aroniadis, OC and Brandt, LJ and Oneto, C and Feuerstadt, P and Sherman, A and Wolkoff, AW and Kassam, Z and Sadovsky, RG and Elliott, RJ and Budree, S and Kim, M and Keller, MJ}, title = {Faecal microbiota transplantation for diarrhoea-predominant irritable bowel syndrome: a double-blind, randomised, placebo-controlled trial.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {4}, number = {9}, pages = {675-685}, doi = {10.1016/S2468-1253(19)30198-0}, pmid = {31326345}, issn = {2468-1253}, mesh = {Abdominal Pain/etiology ; Adult ; Cross-Over Studies ; Diarrhea/*therapy ; Double-Blind Method ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/*therapy ; Male ; Middle Aged ; Nausea/etiology ; Severity of Illness Index ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) has shown promise in alleviating the symptoms of irritable bowel syndrome (IBS); however, controlled data on this technique are scarce. The aim of this clinical trial was to assess the efficacy of FMT in alleviating diarrhoea-predominant IBS (IBS-D).<br><br>METHODS: We did a double-blind, randomised, placebo-controlled crossover trial in patients aged 18-65 years with moderate-to-severe IBS-D defined by an IBS-Symptom Severity Score (IBS-SSS) of more than 175, recruited from three US centres. Patients were randomly assigned (1:1) in blocks of four with a computer-generated randomisation sequence to receive FMT capsules followed by identical-appearing placebo capsules, or placebo capsules followed by FMT capsules. All participants and study team members were masked to randomisation. An independent staff member assigned the treatments according to consecutive numbers. Patients received either 75 FMT capsules (each capsule contained approximately 0·38 g of minimally processed donor stool) or 75 placebo capsules over 3 days (25 capsules per day). All patients crossed over to the alternate treatment at 12 weeks. The primary outcome was difference in IBS-SSS between the groups at 12 weeks. Intention-to-treat analyses were done and all patients who received study drug were included in an adverse events analysis. The trial was terminated during recruitment because results from an interim analysis revealed futility. The study is registered with ClinicalTrials.gov, number NCT02328547.<br><br>FINDINGS: From May 28, 2015, to April 21, 2017, 48 patients were randomly assigned to receive FMT first (n=25) or placebo first (n=23). Three participants were lost to follow-up in the FMT group. IBS-SSS did not differ between FMT recipients (mean 221 [SD 105]) and placebo recipients (236 [95]) at 12 weeks (p=0·65), after adjustment for baseline scores. The most common drug-related adverse events included abdominal pain (five [10%] of the 48 participants while receiving FMT capsules vs four [8%] while receiving placebo), nausea (four [8%] vs two [4%]), and exacerbation of diarrhoea (three [6%] vs eight [17%]). One serious adverse event that was unrelated to study drug (acute cholecystitis) was reported in a patient while receiving placebo capsules.<br><br>INTERPRETATION: FMT was safe, but did not induce symptom relief at 12 weeks compared with placebo. Additional studies are needed to determine the efficacy of FMT for IBS-D.<br><br>FUNDING: National Institutes of Health.}, }
@article {pmid31238017, year = {2019}, author = {Wang, Y and Zhao, W and Shi, J and Wang, J and Hao, J and Pang, X and Huang, X and Chen, X and Li, Y and Jin, R and Ge, Q}, title = {Intestinal microbiota contributes to altered glucose metabolism in simulated microgravity mouse model.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {33}, number = {9}, pages = {10140-10151}, doi = {10.1096/fj.201900238RR}, pmid = {31238017}, issn = {1530-6860}, mesh = {Acute-Phase Proteins ; Animals ; Bifidobacterium/isolation &amp; purification ; Carrier Proteins/blood ; Corticosterone/blood ; Dysbiosis/*metabolism ; Endotoxemia/prevention &amp; control ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Glucose/*metabolism ; Glucose Intolerance/*etiology ; Head-Down Tilt ; Hepatitis/prevention &amp; control ; Housing, Animal ; Insulin Resistance ; Liver/metabolism ; Male ; Membrane Glycoproteins/blood ; Mice ; Mice, Inbred C57BL ; Norepinephrine/blood ; Probiotics ; Random Allocation ; Specific Pathogen-Free Organisms ; Verrucomicrobia/isolation &amp; purification ; *Weightlessness/adverse effects ; }, abstract = {Exposure to space environment induces alterations in glucose and lipid metabolism that contribute to muscular atrophy, bone loss, and cardiovascular disorders. Intestinal microbiota is also changed, but its impact on spaceflight-related metabolic disorder is not clear. We investigated the relationship between glucose metabolic changes and gut dysbiosis in a hind limb-unloading (HU) mouse model, a well-accepted ground-based spaceflight analog. Impaired body weight gain, glucose intolerance, and peripheral insulin resistance were found in 2-4-wk HU mice. Reduced abundance of gut Bifidobacterium spp. and Akkermansia muciniphila was observed within 3 d of HU. The ground-based control (Ctrl) mice that were cohoused with HU mice showed similar patterns of dysbiosis and metabolic changes. Compared with the Ctrls, higher levels of plasma LPS-binding protein and altered transcription of Tnfa and glucose metabolism-related genes in the liver were observed in HU mice. The supplementation of Bifidobacterium spp. suppressed endotoxemia and liver inflammation and improved glucose tolerance in HU mice. The results indicate a close relationship between dysbiosis and altered glucose metabolism in the HU model and also emphasize the importance of evaluating intestinal microbiota in astronauts and its effect on glucose metabolism.-Wang, Y., Zhao, W., Shi, J., Wang, J., Hao, J., Pang, X., Huang, X., Chen, X., Li, Y., Jin, R., Ge, Q. Intestinal microbiota contributes to altered glucose metabolism in simulated microgravity mouse model.}, }
@article {pmid31167080, year = {2019}, author = {Duan, Y and Zhong, Y and Xiao, H and Zheng, C and Song, B and Wang, W and Guo, Q and Li, Y and Han, H and Gao, J and Xu, K and Li, T and Yin, Y and Li, F and Yin, J and Kong, X}, title = {Gut microbiota mediates the protective effects of dietary β-hydroxy-β-methylbutyrate (HMB) against obesity induced by high-fat diets.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {33}, number = {9}, pages = {10019-10033}, doi = {10.1096/fj.201900665RR}, pmid = {31167080}, issn = {1530-6860}, mesh = {Adipose Tissue/drug effects/metabolism ; Adipose Tissue, Brown/metabolism ; Animals ; Bacteroidetes/isolation &amp; purification ; Diet, High-Fat/*adverse effects ; Dysbiosis/etiology/*metabolism/microbiology ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Firmicutes/isolation &amp; purification ; Gastrointestinal Microbiome/*physiology ; Gene Expression Profiling ; Insulin Resistance ; Lipid Metabolism/genetics ; Male ; Mice ; Mice, Inbred ICR ; Obesity/etiology/microbiology/*prevention &amp; control ; Propionates/metabolism/pharmacology ; RNA, Messenger/biosynthesis ; Random Allocation ; Valerates/*pharmacology/therapeutic use ; }, abstract = {Obesity increases the risk of developing insulin resistance and diabetes and is a major public health concern. Our previous study shows that dietary β-hydroxy-β-methylbutyrate (HMB) improves lipid metabolism in a pig model. However, it remains unclear whether HMB blocks obesity through gut microbiota. In this study, we found that HMB reduced body weight, alleviated the whitening of brown adipose tissue, and improved insulin resistance in mice fed a high-fat diet (HFD). High-throughput pyrosequencing of the 16S rRNA demonstrated that HMB administration significantly reversed the gut microbiota dysbiosis in HFD-fed mice, including the diversity of gut microbiota and relative abundances of Bacteroidetes and Firmicutes. Moreover, microbiota transplantation from HMB-treated mice attenuated HFD-induced lipid metabolic disorders. Furthermore, HFD-fed mice showed lower short-chain fatty acids, whereas administration of HMB increased the propionic acid production. Correlation analysis identified a significant correlation between propionic acid production and the relative Bacteroidetes abundance. Sodium propionate treatment also attenuated HFD-induced lipid metabolic disorders. Collectively, our results indicated that HMB might be used as a probiotic agent to reverse HFD-induced obesity, and the potential mechanism was associated with reprogramming gut microbiota and metabolism, especially Bacteroidetes-mediated propionic acid production. In future studies, more efforts should be made to confirm and expand the beneficial effects of HMB to human models.-Duan, Y., Zhong, Y., Xiao, H., Zheng, C., Song, B., Wang, W., Guo, Q., Li, Y., Han, H., Gao, J., Xu, K., Li, T., Yin, Y., Li, F., Yin, J., Kong, X. Gut microbiota mediates the protective effects of dietary β-hydroxy-β-methylbutyrate (HMB) against obesity induced by high-fat diets.}, }
@article {pmid32474336, year = {2020}, author = {Lin, H and Wang, Q and Yuan, M and Liu, L and Chen, Z and Zhao, Y and Das, R and Duan, Y and Xu, X and Xue, Y and Luo, Y and Mao, D}, title = {The prolonged disruption of a single-course amoxicillin on mice gut microbiota and resistome, and recovery by inulin, Bifidobacterium longum and fecal microbiota transplantation.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {265}, number = {Pt A}, pages = {114651}, doi = {10.1016/j.envpol.2020.114651}, pmid = {32474336}, issn = {1873-6424}, abstract = {The usages of antibiotics in treating the pathogenic infections could alter the gut microbiome and associated resistome, causing long term adverse impact on human health. In this study, mice were treated with human-simulated regimen 25.0 mg kg-1 of amoxicillin for seven days, and their gut microbiota and resistome were characterized using the 16S rRNA amplicons sequencing and the high-throughput qPCR, respectively. Meanwhile, the flora restorations after individual applications of inulin, Bifidobacterium longum (B. longum), and fecal microbiota transplantation (FMT) were analyzed for up to 35 days. The results revealed the prolonged negative impact of single course AMX exposure on mice gut microbiota and resistome. To be specific, pathobionts of Klebsiella and Escherichia-Shigella were significantly enriched, while prebiotics of Bifidobacterium and Lactobacillus were dramatically depleted. Furthermore, β-lactam resistance genes and efflux resistance genes were obviously enriched after amoxicillin exposure. Compared to B. longum, FMT and inulin were demonstrated to preferably restore the gut microbiota via reconstituting microbial community and stimulating specific prebiotic respectively. Such variation of microbiome caused their distinct alleviations on resistome alteration. Inulin earned the greatest elimination on AMX induced ARG abundance and diversity enrichment. FMT and B. longum caused remove of particular ARGs such as ndm-1, blaPER. Network analysis revealed that most of the ARGs were prone to be harbored by Firmicutes and Proteobacteria. In general, gut resistome shift was partly associated with the changing bacterial community structures and transposase and integron. Taken together, these results demonstrated the profound disruption of gut microbiota and resistome after single-course amoxicillin treatment and different restoration by inulin, B. longum and FMT.}, }
@article {pmid32468608, year = {2020}, author = {Kragsnaes, MS and Nilsson, AC and Kjeldsen, J and Holt, HM and Rasmussen, KF and Georgsen, J and Ellingsen, T and Holm, DK}, title = {How do I establish a stool bank for fecal microbiota transplantation within the blood- and tissue transplant service?.}, journal = {Transfusion}, volume = {}, number = {}, pages = {}, doi = {10.1111/trf.15816}, pmid = {32468608}, issn = {1537-2995}, support = {//Odense University Hospital/ ; }, abstract = {Worldwide, there is a rising demand for thoroughly screened, high-quality fecal microbiota transplantation (FMT) products that can be obtained at a reasonable cost. In the light of this evolving therapeutic area of the intestinal microbiota, both private and public stool banks have emerged. However, some of the larger difficulties when establishing stool banks are caused by the absence of or international disagreement on regulation and legislative formalities. In this context, the establishment of a stool bank within a nonprofit blood and tissue transplant service has several advantages. Especially, this setting can ensure that every step of the donation process, laboratory handling, and donor-traceability is in agreement with the current expert guidelines and meets the requirements of the European Union's regulative directives on human cells and tissues. Although safety and documentation are the top priority of the stool bank setup presented here, cost-effectiveness of the production is possible due to a high donor screening success rate and the knowhow, infrastructure, facilities, personnel, and laboratory- and quality-management systems that were already in place. Overall, our experience is that a centralized, nonprofit, blood and tissue transplant service is an ideal and safe facility to run a stool bank of high quality FMT products that are based on stool donations from volunteer, unpaid, healthy, blood donors.}, }
@article {pmid32466801, year = {2020}, author = {Jian, X and Zhu, Y and Ouyang, J and Wang, Y and Lei, Q and Xia, J and Guan, Y and Zhang, J and Guo, J and He, Y and Wang, J and Li, J and Lin, J and Su, M and Li, G and Wu, M and Qiu, L and Xiang, J and Xie, L and Jia, W and Zhou, W}, title = {Alterations of gut microbiome accelerate multiple myeloma progression by increasing the relative abundances of nitrogen-recycling bacteria.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {74}, doi = {10.1186/s40168-020-00854-5}, pmid = {32466801}, issn = {2049-2618}, support = {31900102//National Natural Science Foundation of China/ ; 81570205, 81630007//National Natural Science Foundation of China/ ; 81800209//National Natural Science Foundation of China/ ; 2019M652792//China Postdoctoral Science Foundation/ ; ZLXD2017004//Strategic Priority Research Program of Central South University/ ; }, abstract = {BACKGROUND: Gut microbiome alterations are closely related to human health and linked to a variety of diseases. Although great efforts have been made to understand the risk factors for multiple myeloma (MM), little is known about the role of the gut microbiome and alterations of its metabolic functions in the development of MM.<br><br>RESULTS: Here, in a cohort of newly diagnosed patients with MM and healthy controls (HCs), significant differences in metagenomic composition were discovered, for the first time, with higher bacterial diversity in MM. Specifically, nitrogen-recycling bacteria such as Klebsiella and Streptococcus were significantly enriched in MM. Also, the bacteria enriched in MM were significantly correlated with the host metabolome, suggesting strong metabolic interactions between microbes and the host. In addition, the MM-enriched bacteria likely result from the regulation of urea nitrogen accumulated during MM progression. Furthermore, by performing fecal microbiota transplantation (FMT) into 5TGM1 mice, we proposed a mechanistic explanation for the interaction between MM-enriched bacteria and MM progression via recycling urea nitrogen. Further experiments validated that Klebsiella pneumoniae promoted MM progression via de novo synthesis of glutamine in mice and that the mice fed with glutamine-deficient diet exhibited slower MM progression.<br><br>CONCLUSIONS: Overall, our findings unveil a novel function of the altered gut microbiome in accelerating the malignant progression of MM and open new avenues for novel treatment strategies via manipulation of the intestinal microbiota of MM patients. Video abstract.}, }
@article {pmid32466620, year = {2020}, author = {Nance, CL and Deniskin, R and Diaz, VC and Paul, M and Anvari, S and Anagnostou, A}, title = {The Role of the Microbiome in Food Allergy: A Review.}, journal = {Children (Basel, Switzerland)}, volume = {7}, number = {6}, pages = {}, doi = {10.3390/children7060050}, pmid = {32466620}, issn = {2227-9067}, abstract = {Food allergies are common and estimated to affect 8% of children and 11% of adults in the United States. They pose a significant burden-physical, economic and social-to those affected. There is currently no available cure for food allergies. Emerging evidence suggests that the microbiome contributes to the development and manifestations of atopic disease. According to the hygiene hypothesis, children growing up with older siblings have a lower incidence of allergic disease compared with children from smaller families, due to their early exposure to microbes in the home. Research has also demonstrated that certain environmental exposures, such as a farming environment, during early life are associated with a diverse bacterial experience and reduced risk of allergic sensitization. Dysregulation in the homeostatic interaction between the host and the microbiome or gut dysbiosis appears to precede the development of food allergy, and the timing of such dysbiosis is critical. The microbiome affects food tolerance via the secretion of microbial metabolites (e.g., short chain fatty acids) and the expression of microbial cellular components. Understanding the biology of the microbiome and how it interacts with the host to maintain gut homeostasis is helpful in developing smarter therapeutic approaches. There are ongoing trials evaluating the benefits of probiotics and prebiotics, for the prevention and treatment of atopic diseases to correct the dysbiosis. However, the routine use of probiotics as an intervention for preventing allergic disease is not currently recommended. A new approach in microbial intervention is to attempt a more general modification of the gut microbiome, such as with fecal microbiota transplantation. Developing targeted bacterial therapies for food allergy may be promising for both the treatment and prevention of food allergy. Similarly, fecal microbiota transplantation is being explored as a potentially beneficial interventional approach. Overall, targeted bacterial therapies for food allergy may be promising for both the treatment and prevention of food allergy.}, }
@article {pmid32460890, year = {2020}, author = {Li, M and Li, C and Wu, X and Chen, T and Ren, L and Xu, B and Cao, J}, title = {Microbiota-driven interleukin-17 production provides immune protection against invasive candidiasis.}, journal = {Critical care (London, England)}, volume = {24}, number = {1}, pages = {268}, doi = {10.1186/s13054-020-02977-5}, pmid = {32460890}, issn = {1466-609X}, support = {81722001//National Natural Science Foundation of China/ ; 81572038//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: The intestinal microbiota plays a crucial role in human health, which could affect host immunity and the susceptibility to infectious diseases. However, the role of intestinal microbiota in the immunopathology of invasive candidiasis remains unknown.<br><br>METHODS: In this work, an antibiotic cocktail was used to eliminate the intestinal microbiota of conventional-housed (CNV) C57/BL6 mice, and then both antibiotic-treated (ABX) mice and CNV mice were intravenously infected with Candida albicans to investigate their differential responses to infection. Furthermore, fecal microbiota transplantation (FMT) was applied to ABX mice in order to assess its effects on host immunity against invasive candidiasis after restoring the intestinal microbiota, and 16S ribosomal RNA gene sequencing was conducted on fecal samples from both uninfected ABX and CNV group of mice to analyze their microbiomes.<br><br>RESULTS: We found that ABX mice displayed significantly increased weight loss, mortality, and organ damage during invasive candidiasis when compared with CNV mice, which could be alleviated by FMT. In addition, the level of IL-17A in ABX mice was significantly lower than that in the CNV group during invasive candidiasis. Treatment with recombinant IL-17A could improve the survival of ABX mice during invasive candidiasis. Besides, the microbial diversity of ABX mice was significantly reduced, and the intestinal microbiota structure of ABX mice was significantly deviated from the CNV mice.<br><br>CONCLUSIONS: Our data revealed that intestinal microbiota plays a protective role in invasive candidiasis by enhancing IL-17A production in our model system.}, }
@article {pmid32457246, year = {2020}, author = {Abhyankar, MM and Ma, JZ and Scully, KW and Nafziger, AJ and Frisbee, AL and Saleh, MM and Madden, GR and Hays, AR and Poulter, M and Petri, WA}, title = {Immune Profiling To Predict Outcome of Clostridioides difficile Infection.}, journal = {mBio}, volume = {11}, number = {3}, pages = {}, doi = {10.1128/mBio.00905-20}, pmid = {32457246}, issn = {2150-7511}, abstract = {There is a pressing need for biomarker-based models to predict mortality from and recurrence of Clostridioides difficile infection (CDI). Risk stratification would enable targeted interventions such as fecal microbiota transplant, antitoxin antibodies, and colectomy for those at highest risk. Because severity of CDI is associated with the immune response, we immune profiled patients at the time of diagnosis. The levels of 17 cytokines in plasma were measured in 341 CDI inpatients. The primary outcome of interest was 90-day mortality. Increased tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), C-C motif chemokine ligand 5 (CCL-5), suppression of tumorigenicity 2 receptor (sST-2), IL-8, and IL-15 predicted mortality by univariate analysis. After adjusting for demographics and clinical characteristics, the mortality risk (as indicated by the hazard ratio [HR]) was higher for patients in the top 25th percentile for TNF-α (HR = 8.35, P = 0.005) and IL-8 (HR = 4.45, P = 0.01) and lower for CCL-5 (HR = 0.18, P ≤ 0.008). A logistic regression risk prediction model was developed and had an area under the receiver operating characteristic curve (AUC) of 0.91 for 90-day mortality and 0.77 for 90-day recurrence. While limited by being single site and retrospective, our work resulted in a model with a substantially greater predictive ability than white blood cell count. In conclusion, immune profiling demonstrated differences between patients in their response to CDI, offering the promise for precision medicine individualized treatment.IMPORTANCEClostridioides difficile infection is the most common health care-associated infection in the United States with more than 20% patients experiencing symptomatic recurrence. The complex nature of host-bacterium interactions makes it difficult to predict the course of the disease based solely on clinical parameters. In the present study, we built a robust prediction model using representative plasma biomarkers and clinical parameters for 90-day all-cause mortality. Risk prediction based on immune biomarkers and clinical variables may contribute to treatment selection for patients as well as provide insight into the role of immune system in C. difficile pathogenesis.}, }
@article {pmid32453670, year = {2020}, author = {Kaźmierczak-Siedlecka, K and Daca, A and Fic, M and van de Wetering, T and Folwarski, M and Makarewicz, W}, title = {Therapeutic methods of gut microbiota modification in colorectal cancer management - fecal microbiota transplantation, prebiotics, probiotics, and synbiotics.}, journal = {Gut microbes}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/19490976.2020.1764309}, pmid = {32453670}, issn = {1949-0984}, abstract = {The link between gut microbiota and the development of colorectal cancer has been investigated. An imbalance in the gut microbiota promotes the progress of colorectal carcinogenesis via multiple mechanisms, including inflammation, activation of carcinogens, and tumorigenic pathways as well as damaging host DNA. Several therapeutic methods are available with which to alter the composition and the activity of gut microbiota, such as administration of prebiotics, probiotics, and synbiotics; these can confer various benefits for colorectal cancer patients. Nowadays, fecal microbiota transplantation is the most modern way of modulating the gut microbiota. Even though data regarding fecal microbiota transplantation in colorectal cancer patients are still rather limited, it has been approved as a clinical method of treatment-recurrent Clostridium difficile infection, which may also occur in these patients. The major benefits of fecal microbiota transplantation include modulation of immunotherapy efficacy, amelioration of bile acid metabolism, and restoration of intestinal microbial diversity. Nonetheless, more studies are needed to assess the long-term effects of fecal microbiota transplantation. In this review, the impact of gut microbiota on the efficiency of anti-cancer therapy and colorectal cancer patients' overall survival is also discussed.}, }
@article {pmid31439276, year = {2019}, author = {Li, J and Hu, FB}, title = {Research digest: reshaping the gut microbiota.}, journal = {The lancet. Diabetes &amp; endocrinology}, volume = {7}, number = {9}, pages = {671}, doi = {10.1016/S2213-8587(19)30270-0}, pmid = {31439276}, issn = {2213-8595}, mesh = {Biomedical Research ; Dysbiosis/*microbiology/physiopathology ; Fecal Microbiota Transplantation/trends ; Feces/*microbiology ; Gastrointestinal Microbiome/immunology/*physiology ; Humans ; Immune System Diseases/*microbiology ; Inflammation/immunology/*microbiology ; Mental Disorders/*microbiology ; Metabolic Diseases/*microbiology ; Nutritional Physiological Phenomena ; }, }
@article {pmid32448639, year = {2020}, author = {Castro Rocha, FA and Duarte-Monteiro, AM and Henrique da Mota, LM and Matias Dinelly Pinto, AC and Fonseca, JE}, title = {Microbes, helminths, and rheumatic diseases.}, journal = {Best practice &amp; research. Clinical rheumatology}, volume = {}, number = {}, pages = {101528}, doi = {10.1016/j.berh.2020.101528}, pmid = {32448639}, issn = {1532-1770}, abstract = {There has been a progressive interest on modifications of the human defense system following insults occurring in the interface between our body and the external environment, as they may provoke or worsen disease states. Studies suggest that billions of germs, which compose the gut microbiota influence one's innate and adaptive immune responses at the intestinal level, but these microorganisms may also impact rheumatic diseases. The microbiota of the skin, respiratory, and urinary tracts may also be relevant in rheumatology. Evidence indicates that changes in the gut microbiome alter the pathogenesis of immune-mediated diseases such as rheumatoid arthritis and ankylosing spondylitis but also of other disorders like atherosclerosis and osteoarthritis. Therapeutic strategies to modify the microbiota, including probiotics and fecal microbiota transplantation, have been received with skepticism, which, in turn, has drawn attention back to previously developed interventions such as antibiotics. Helminths adapted to humans over the evolution process, but their role in disease modulation, particularly immune-mediated diseases, remains to be understood. The present review focuses on data concerning modifications of the immune system induced by interactions with microbes and pluricellular organisms, namely helminths, and their impact on rheumatic diseases. Practical aspects, including specific microbiota-targeted therapies, are also discussed.}, }
@article {pmid31612528, year = {2019}, author = {Tixier, EN and Verheyen, E and Ungaro, RC and Grinspan, AM}, title = {Faecal microbiota transplant decreases mortality in severe and fulminant Clostridioides difficile infection in critically ill patients.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {50}, number = {10}, pages = {1094-1099}, pmid = {31612528}, issn = {1365-2036}, support = {K23 DK111995/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/epidemiology/*mortality/*therapy ; *Clostridium difficile/pathogenicity ; Cohort Studies ; Critical Illness/*mortality/*therapy ; *Fecal Microbiota Transplantation/mortality/statistics &amp; numerical data ; Female ; Humans ; Intensive Care Units/statistics &amp; numerical data ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Tertiary Care Centers ; Treatment Outcome ; }, abstract = {BACKGROUND: Severe and fulminant Clostridioides difficile infection is associated with high mortality rates. While faecal microbiota transplant has been shown to be effective for recurrent C difficile infection, there is little data on the utility of faecal microbiota transplant in severe or fulminant C difficile infection.<br><br>AIM: To compare the outcomes of antibiotics and faecal microbiota transplantation vs antibiotics alone (standard of care) in critically ill patients with severe or fulminant C difficile infection.<br><br>METHODS: This was a retrospective, matched cohort study in one urban tertiary academic care centre including 48 patients hospitalised with severe or fulminant C difficile infection who required care in intensive care unit.<br><br>RESULTS: Patients who received faecal microbiota transplantation (n = 16) had a 77% decrease in odds for mortality (OR 0.23, 95% CI 0.06-0.97) with a number needed to treat of 3 to prevent one death.<br><br>CONCLUSIONS: Faecal microbiota transplantation provides mortality benefit over standard of care for severe and fulminant C difficile infection and should be considered in critically ill patients.}, }
@article {pmid31328778, year = {2019}, author = {Pebenito, AM and Liu, M and Nazzal, L and Blaser, MJ}, title = {Development of a Humanized Murine Model for the Study of Oxalobacter formigenes Intestinal Colonization.}, journal = {The Journal of infectious diseases}, volume = {220}, number = {11}, pages = {1848-1858}, pmid = {31328778}, issn = {1537-6613}, support = {U54 DK083908/DK/NIDDK NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Carrier State/*microbiology ; Fecal Microbiota Transplantation/methods ; Feces/microbiology ; Gastrointestinal Microbiome ; Gram-Negative Bacterial Infections/*microbiology ; Intestines/*microbiology ; Mice, Inbred C57BL ; *Models, Animal ; Oxalobacter formigenes/*growth &amp; development ; }, abstract = {BACKGROUND: Oxalobacter formigenes are bacteria that colonize the human gut and degrade oxalate, a component of most kidney stones. Findings of clinical and epidemiological studies suggest that O. formigenes colonization reduces the risk for kidney stones. We sought to develop murine models to allow investigating O. formigenes in the context of its native human microbiome.<br><br>METHODS: For humanization, we transplanted pooled feces from healthy, noncolonized human donors supplemented with a human O. formigenes strain into recipient mice. We transplanted microbiota into mice that were treated with broad-spectrum antibiotics to suppress their native microbiome, were germ free, or received humanization without pretreatment or received sham gavage (controls).<br><br>RESULTS: All humanized mice were stably colonized with O. formigenes through 8 weeks after gavage, whereas mice receiving sham gavage remained uncolonized (P < .001). Humanization significantly changed the murine intestinal microbial community structure (P < .001), with humanized germ-free and antibiotic-treated groups overlapping in β-diversity. Both germ-free and antibiotic-treated mice had significantly increased numbers of human species compared with sham-gavaged mice (P < .001).<br><br>CONCLUSIONS: Transplanting mice with human feces and O. formigenes introduced new microbial populations resembling the human microbiome, with stable O. formigenes colonization; such models can define optimal O. formigenes strains to facilitate clinical trials.}, }
@article {pmid32443576, year = {2020}, author = {Kløve, S and Genger, C and Mousavi, S and Weschka, D and Bereswill, S and Heimesaat, MM}, title = {Toll-Like Receptor-4 Dependent Intestinal and Systemic Sequelae Following Peroral Campylobacter coli Infection of IL10 Deficient Mice Harboring a Human Gut Microbiota.}, journal = {Pathogens (Basel, Switzerland)}, volume = {9}, number = {5}, pages = {}, doi = {10.3390/pathogens9050386}, pmid = {32443576}, issn = {2076-0817}, support = {ZIM; ZF4117904 AJ8//Bundesministerium für Forschung und Technologie/ ; Zoonoses research consortium PAC-Campylobacter, IP7/ 01KI1725D//Bundesministerium für Bildung, Wissenschaft und Forschung/ ; }, abstract = {Zoonotic Campylobacter, including C. jejuni and C. coli, are among the most prevalent agents of food-borne enteritis worldwide. The immunopathological sequelae of campylobacteriosis are caused by Toll-like Receptor-4 (TLR4)-dependent host immune responses, induced by bacterial lipooligosaccharide (LOS). In order to investigate C. coli-host interactions, including the roles of the human gut microbiota and TLR4, upon infection, we applied a clinical acute campylobacteriosis model, and subjected secondary abiotic, TLR4-deficient IL10-/- mice and IL10-/- controls to fecal microbiota transplantation derived from human donors by gavage, before peroral C. coli challenge. Until day 21 post-infection, C. coli could stably colonize the gastrointestinal tract of human microbiota-associated (hma) mice of either genotype. TLR4-deficient IL10-/- mice, however, displayed less severe clinical signs of infection, that were accompanied by less distinct apoptotic epithelial cell and innate as well as adaptive immune cell responses in the colon, as compared to IL10-/- counterparts. Furthermore, C. coli infected IL10-/-, as opposed to TLR4-deficient IL10-/-, mice displayed increased pro-inflammatory cytokine concentrations in intestinal and, strikingly, systemic compartments. We conclude that pathogenic LOS might play an important role in inducing TLR4-dependent host immune responses upon C. coli infection, which needs to be further addressed in more detail.}, }
@article {pmid32440192, year = {2020}, author = {Elsalem, L and Jum'ah, AA and Alfaqih, MA and Aloudat, O}, title = {The Bacterial Microbiota of Gastrointestinal Cancers: Role in Cancer Pathogenesis and Therapeutic Perspectives.}, journal = {Clinical and experimental gastroenterology}, volume = {13}, number = {}, pages = {151-185}, doi = {10.2147/CEG.S243337}, pmid = {32440192}, issn = {1178-7023}, abstract = {The microbiota has an essential role in the pathogenesis of many gastrointestinal diseases including cancer. This effect is mediated through different mechanisms such as damaging DNA, activation of oncogenic pathways, production of carcinogenic metabolites, stimulation of chronic inflammation, and inhibition of antitumor immunity. Recently, the concept of &quot;pharmacomicrobiomics&quot; has emerged as a new field concerned with exploring the interplay between drugs and microbes. Mounting evidence indicates that the microbiota and their metabolites have a major impact on the pharmacodynamics and therapeutic responses toward anticancer drugs including conventional chemotherapy and molecular-targeted therapeutics. In addition, microbiota appears as an attractive target for cancer prevention and treatment. In this review, we discuss the role of bacterial microbiota in the pathogenesis of different cancer types affecting the gastrointestinal tract system. We also scrutinize the evidence regarding the role of microbiota in anticancer drug responses. Further, we discuss the use of probiotics, fecal microbiota transplantation, and antibiotics, either alone or in combination with anticancer drugs for prevention and treatment of gastrointestinal tract cancers.}, }
@article {pmid32437393, year = {2020}, author = {Fretheim, H and Chung, BK and Didriksen, H and Bækkevold, ES and Midtvedt, Ø and Brunborg, C and Holm, K and Valeur, J and Tennøe, AH and Garen, T and Midtvedt, T and Trøseid, M and Zarè, H and Lund, MB and Hov, JR and Lundin, KEA and Molberg, Ø and Hoffmann-Vold, AM}, title = {Fecal microbiota transplantation in systemic sclerosis: A double-blind, placebo-controlled randomized pilot trial.}, journal = {PloS one}, volume = {15}, number = {5}, pages = {e0232739}, doi = {10.1371/journal.pone.0232739}, pmid = {32437393}, issn = {1932-6203}, abstract = {OBJECTIVES: Systemic sclerosis (SSc) is an auto-immune, multi organ disease marked by severe gastrointestinal (GI) involvement and gut dysbiosis. Here, we aimed to determine the safety and efficacy of fecal microbiota transplantation (FMT) using commercially-available anaerobic cultivated human intestinal microbiota (ACHIM) in SSc.<br><br>METHODS: Ten patients with SSc were randomized to ACHIM (n = 5) or placebo (n = 5) in a double-blind, placebo-controlled 16-week pilot. All patients had mild to severe upper and lower GI symptoms including diarrhea, distention/bloating and/or fecal incontinence at baseline. Gastroduodenoscopy transfer of ACHIM or placebo was performed at weeks 0 and 2. Primary endpoints were safety and clinical efficacy on GI symptoms assessed at weeks 4 and 16. Secondary endpoints included changes in relative abundance of total, immunoglobulin (Ig) A- and IgM-coated fecal bacteria measured by 16s rRNA sequencing.<br><br>RESULTS: ACHIM side effects were mild and transient. Two placebo controls experienced procedure-related serious adverse events; one developed laryngospasms at week 0 gastroduodenoscopy necessitating study exclusion whilst one encountered duodenal perforation during gastroduodenoscopy at the last study visit (week 16). Decreased bloating, diarrhea and/or fecal incontinence was observed in four of five patients in the FMT group (week 4 or/and 16) and in two of four in the placebo group (week 4 or 16). Relative abundance, richness and diversity of total and IgA-coated and IgM-coated bacteria fluctuated more after FMT, than after placebo.<br><br>CONCLUSIONS: FMT of commercially-available ACHIM is associated with gastroduodenoscopy complications but reduces lower GI symptoms by possibly altering the gut microbiota in patients with SSc.}, }
@article {pmid32434586, year = {2020}, author = {Xiao, HW and Cui, M and Li, Y and Dong, JL and Zhang, SQ and Zhu, CC and Jiang, M and Zhu, T and Wang, B and Wang, HC and Fan, SJ}, title = {Gut microbiota-derived indole 3-propionic acid protects against radiation toxicity via retaining acyl-CoA-binding protein.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {69}, doi = {10.1186/s40168-020-00845-6}, pmid = {32434586}, issn = {2049-2618}, support = {P30 CA196521/CA/NCI NIH HHS/United States ; OCM-094//Centers for Medicare and Medicaid Services/ ; }, abstract = {BACKGROUND: We have proved fecal microbiota transplantation (FMT) is an efficacious remedy to mitigate acute radiation syndrome (ARS); however, the mechanisms remain incompletely characterized. Here, we aimed to tease apart the gut microbiota-produced metabolites, underpin the therapeutic effects of FMT to radiation injuries, and elucidate the underlying molecular mechanisms.<br><br>RESULTS: FMT elevated the level of microbial-derived indole 3-propionic acid (IPA) in fecal pellets from irradiated mice. IPA replenishment via oral route attenuated hematopoietic system and gastrointestinal (GI) tract injuries intertwined with radiation exposure without precipitating tumor growth in male and female mice. Specifically, IPA-treated mice represented a lower system inflammatory level, recuperative hematogenic organs, catabatic myelosuppression, improved GI function, and epithelial integrity following irradiation. 16S rRNA gene sequencing and subsequent analyses showed that irradiated mice harbored a disordered enteric bacterial pattern, which was preserved after IPA administration. Notably, iTRAQ analysis presented that IPA replenishment retained radiation-reprogrammed protein expression profile in the small intestine. Importantly, shRNA interference and hydrodynamic-based gene delivery assays further validated that pregnane X receptor (PXR)/acyl-CoA-binding protein (ACBP) signaling played pivotal roles in IPA-favored radioprotection in vitro and in vivo.<br><br>CONCLUSIONS: These evidences highlight that IPA is a key intestinal microbiota metabolite corroborating the therapeutic effects of FMT to radiation toxicity. Owing to the potential pitfalls of FMT, IPA might be employed as a safe and effective succedaneum to fight against accidental or iatrogenic ionizing ARS in clinical settings. Our findings also provide a novel insight into microbiome-based remedies toward radioactive diseases. Video abstract.}, }
@article {pmid32433272, year = {2020}, author = {Khanna, S and Pardi, D}, title = {Fecal Microbiota Transplantation for Recurrent Clostridioides difficile infection: The COVID-19 Era.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000000689}, pmid = {32433272}, issn = {1572-0241}, }
@article {pmid32427675, year = {2020}, author = {Craven, L and Rahman, A and Nair Parvathy, S and Beaton, M and Silverman, J and Qumosani, K and Hramiak, I and Hegele, R and Joy, T and Meddings, J and Urquhart, B and Harvie, R and McKenzie, C and Summers, K and Reid, G and Burton, JP and Silverman, M}, title = {Allogenic Fecal Microbiota Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000000661}, pmid = {32427675}, issn = {1572-0241}, abstract = {INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability.<br><br>METHODS: Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT.<br><br>RESULTS: There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT.<br><br>DISCUSSION: FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.}, }
@article {pmid32425906, year = {2020}, author = {Sun, Z and Li, J and Dai, Y and Wang, W and Shi, R and Wang, Z and Ding, P and Lu, Q and Jiang, H and Pei, W and Zhao, X and Guo, Y and Liu, J and Tan, X and Mao, T}, title = {Indigo Naturalis Alleviates Dextran Sulfate Sodium-Induced Colitis in Rats via Altering Gut Microbiota.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {731}, doi = {10.3389/fmicb.2020.00731}, pmid = {32425906}, issn = {1664-302X}, abstract = {Ulcerative colitis is a gastrointestinal disorder intricately associated with intestinal dysbiosis, but effective treatments are currently limited. Indigo naturalis, a traditional Chinese medicine derived from indigo plants, has been widely used in the treatment of ulcerative colitis. However, the specific mechanisms have not yet been identified. Accordingly, in this study, we evaluated the effects and mechanisms of indigo naturalis on dextran sulfate sodium (DSS)-induced colitis in rats. Our results showed that indigo naturalis potently alleviated DSS-induced colitis in rats, and reversed DSS-induced intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing. The protective effects of indigo naturalis were gut microbiota dependent, as demonstrated by antibiotic treatments and fecal microbiota transplantation. Depletion of the gut microbiota through a combination of antibiotic treatments blocked the anti-inflammatory effect of indigo naturalis on the DSS-induced colitis, and the recipients of the gut microbiota from indigo naturalis-treated rats displayed a significantly attenuated intestinal inflammation, which was actively responsive to therapeutic interventions with indigo naturalis. Notably, supplement with indigo naturalis greatly increased the levels of feces butyrate, which was positively correlated with the relative abundances of Ruminococcus_1 and Butyricicoccus. We further showed that indigo naturalis-dependent attenuation of colitis was associated with elevated expression of short-chain fatty acid-associated receptors GPR41 and GPR43. Collectively, these results suggested that indigo naturalis alleviates DSS-induced colitis in rats through a mechanism of the microbiota-butyrate axis, particularly alterations in Ruminococcus_1 and Butyricicoccus abundances, and target-specific microbial species may have unique therapeutic promise for ulcerative colitis.}, }
@article {pmid32423189, year = {2020}, author = {Zhang, W and Zou, G and Li, B and Du, X and Sun, Z and Sun, Y and Jiang, X}, title = {Fecal Microbiota Transplantation (FMT) alleviates experimental colitis in mice by gut microbiota regulation.}, journal = {Journal of microbiology and biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.4014/jmb.2002.02044}, pmid = {32423189}, issn = {1738-8872}, abstract = {Inflammatory bowel disease (IBD) is an increasing global burden and a predisposing factor to colorectal cancer. Although a number of treatment options are available, the side effects could be considerable. Studies on the fecal microbiota transplantation (FMT) as an IBD intervention protocol require further validation as the underlying mechanisms for its attenuating effects remain unclear. This study thus aims to demonstrate the ameliorative role of FMT in an ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) and elucidate its relative mechanisms in a mouse model. It was shown that FMT intervention decreased disease activity index (DAI) levels and increased the body weight, colon weight and colon length of experimental animals. It also alleviated histopathological changes, reduced key cytokine expression and oxidative status in the colon. A down-regulated expression level of genes associated with NF-κB signaling pathway was also observed. The results of 16S rRNA gene sequencing showed that FMT intervention restored the gut microbiota to the pattern of the control group by increasing the relative abundance of Firmicutes and decreasing the abundances of Bacteroidetes and Proteobacteria. The relative abundances of the genera Lactobacillus, Butyricicoccus, Lachnoclostridium, Olsenella and Odoribacter were upregulated but Helicobacter, Bacteroides and Clostridium were reduced after FMT administration. Furthermore, FMT administration elevated the contents of SCFAs in the colon. In conclusion, FMT intervention could be suitable for UC control, but further validations via clinical trials are recommended.}, }
@article {pmid32421966, year = {2019}, author = {Akash, MSH and Fiayyaz, F and Rehman, K and Sabir, S and Rasool, MH}, title = {Gut Microbiota and Metabolic Disorders: Advances in Therapeutic Interventions.}, journal = {Critical reviews in immunology}, volume = {39}, number = {4}, pages = {223-237}, doi = {10.1615/CritRevImmunol.2019030614}, pmid = {32421966}, issn = {1040-8401}, abstract = {Human gut microbiota consist of numerous microorganisms, but the most abundant species are Bacteroides and Firmicutes. Each human possesses a specific gut microbiota, which can be altered by diet, antibiotics, lifestyle, and genetic background. Gut microbiota perform vital functions, but in this article, we aimed to elaborate the effects of modified composition of microbiota on host metabolism. Ligands for G protein coupled receptors (GPCRs) are short-chain fatty acids (SCFAs) located on endocrine glands, epithelial cells, and adipocytes. SCFAs are produced in the distal gut by bacterial fermentation of nondigestible polysaccharides; they induce the various beneficial effects including decrease serum glucose level, insulin resistance, as well as inflammation; and they increase glucagon-like peptide-1 (GLP-1) secretion. Fasting-induced adipose factor (FIAF) is suppressed by gut microbiota and results in the increased storage of fatty acids in the adipose tissues and liver. An increased lipopolysaccharide level due to altered gut microflora cause the initiation of inflammation associated with type 2 diabetes mellitus (T2DM). Intestinal dysbiosis and metabolic endotoxemia are considered key mechanisms that seem to be associated with the development of T2DM and obesity. Therapeutic interventions that can be used for the treatment of diabetes include metformin, dietary modulation, probiotics, prebiotics, fecal microbiota transplantation and bariatric surgery.}, }
@article {pmid31373710, year = {2019}, author = {Koopman, N and Molinaro, A and Nieuwdorp, M and Holleboom, AG}, title = {Review article: can bugs be drugs? The potential of probiotics and prebiotics as treatment for non-alcoholic fatty liver disease.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {50}, number = {6}, pages = {628-639}, doi = {10.1111/apt.15416}, pmid = {31373710}, issn = {1365-2036}, support = {016.146.327//ZONMW-VIDI/International ; //Dutch Heart Foundation/International ; //Gilead Research scholarship/International ; //Amsterdam UMC Fellowship/International ; //TKI-PPP/International ; }, mesh = {Animals ; Bariatric Surgery ; Fecal Microbiota Transplantation ; Humans ; Microbiota ; Non-alcoholic Fatty Liver Disease/*therapy ; *Prebiotics ; Probiotics/*therapeutic use ; Synbiotics ; }, abstract = {BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver condition. A major current research effort is ongoing to find potential strategies to treat NAFLD-non-alcoholic steatohepatitis (NASH), with special attention to the gut microbiota. Multiple animal studies and pilot clinical trials are assessing different gut microbiota modulating strategies such as faecal microbiota transplantation, antibiotics, probiotics, prebiotics and synbiotics.<br><br>AIM: To review the role of microbiota in NAFLD-NASH and determine whether pro- and prebiotics have potential as treatment METHODS: Information was obtained from critically reviewing literature on PubMed on targeting the gut microbiota in NAFLD. Search terms included NAFLD, NASH, non-alcoholic fatty liver disease, steatohepatitis; combined with microbiome, microbiota, gut bacteria, probiotics and prebiotics.<br><br>RESULTS: Animal studies and the first emerging studies in humans show promising results for both the common probiotics Lactobacillus, Bifidobacterium and Streptococci as for short chain fatty acid (SCFA) butyrate-producing bacteria. Also, prebiotics have positive effects on different mechanisms underlying NAFLD-NASH.<br><br>CONCLUSIONS: The most promising strategies thus far developed to alter the microbiome in NAFLD-NASH are probiotics and prebiotics. However, pre- and probiotic treatment of NAFLD-NASH is relatively new and still under development. Actual understanding of the involved mechanisms is lacking and changes in the intestinal microbiota composition after treatment are rarely measured. Furthermore, large clinical trials with comparative endpoints are unavailable. Personalised treatment based on metagenomics gut microbiota analysis will probably be part of the future diagnosis and treatment of NAFLD-NASH.}, }
@article {pmid31361420, year = {2019}, author = {Ooijevaar, RE and van Rossen, TM and Vandenbroucke-Grauls, CMJE and Budding, AE and Kneepkens, CMF and de Meij, TGJ}, title = {[Faecal transplants for children with recurrent infections].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {163}, number = {}, pages = {}, pmid = {31361420}, issn = {1876-8784}, mesh = {Adolescent ; Anti-Bacterial Agents/adverse effects ; Child, Preschool ; Clostridium Infections/chemically induced/microbiology/*therapy ; Clostridium difficile ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Otitis Media/drug therapy ; Recurrence ; }, abstract = {BACKGROUND: Clostridioides difficile infection is a relatively rare cause of diarrhoea in children, but there are frequent recurrences when it occurs, despite targeted antibiotic treatment.<br><br>CASE DESCRIPTIONS: A 2-year-old boy with concomitant motility disorder and a 14-year-old girl with Down syndrome experienced several infections with C. difficile, respectively after the use of antibiotics for otitis media and extended use of antibiotics in addition to chemotherapy. Both were treated successfully with faecal transplants.<br><br>CONCLUSION: Clostridioides difficile infections occur in children, mainly after extended use of antibiotics or when the immune system is impaired. In case of recurring C. difficile infections, children can be treated safely and effectively with faecal transplants.}, }
@article {pmid32422097, year = {2020}, author = {Talley, NJ and Irani, M}, title = {In irritable bowel syndrome, fecal microbiota transplantation improved symptoms at 3 months.}, journal = {Annals of internal medicine}, volume = {172}, number = {10}, pages = {JC52}, doi = {10.7326/ACPJ202005190-052}, pmid = {32422097}, issn = {1539-3704}, abstract = {SOURCE CITATION: El-Salhy M, Hatlebakk JG, Gilja OH, Bråthen Kristoffersen A, Hausken T. Efficacy of faecal microbiota transplantation for patients with irritable bowel syndrome in a randomised, double-blind, placebo-controlled study. Gut. 2020;69:859-67. 31852769.}, }
@article {pmid32421761, year = {2020}, author = {Bauer, CM and Zhang, X and Long, MD and Sandler, RS}, title = {Characteristics of Fecal Microbiota Transplantation Use in Inflammatory Bowel Disease Cohort.}, journal = {Crohn's &amp; colitis 360}, volume = {2}, number = {2}, pages = {otaa024}, doi = {10.1093/crocol/otaa024}, pmid = {32421761}, issn = {2631-827X}, abstract = {Background: There is a growing interest in the role of gut bacteria in a number of diseases and an emerging hypothesis that inflammatory bowel disease (IBD) is triggered by microbial dysbiosis in genetically susceptible individuals. Currently, fecal microbiota transplantation (FMT) is utilized for the treatment of Clostridium difficile colitis. Data on the efficacy of FMT for IBD are mixed, but patients are interested in its use for the treatment of IBD. We sought to describe the use of FMT (self or medical professional administered) in individuals with IBD using IBD Partners, an Internet-based cohort.<br><br>Methods: Patients enrolled in the IBD Partners cohort were offered the opportunity to complete an optional survey on the use of FMT between January 2017 to September 2018 (n = 5430). A cross-sectional analysis was performed within patients who completed the survey and did not have a pouch or ostomy. Patients' demographic characteristics, disease activity and phenotype, mode of FMT delivery, and patient-reported efficacy were compared.<br><br>Results: Among 3274 eligible patients, 51 (1.6%) responded that they had an FMT in the past. Of patients undergoing FMT, 22 patients had the FMT for C. difficile while 29 reported that the FMT was for another indication. Most patients receiving FMT for an indication other than C. difficile had ulcerative colitis/indeterminate colitis (25, 86.2%). Colonoscopy (68.2%) and nasogastric tube (18.2%) were the most common routes of administration for patients receiving FMT for C. difficile colitis. Self-administration (72.4%) and enemas (17.2%) were the most common routes of administration in patients receiving FMT for an alternate indication. Patients reporting FMT for an indication other than C. difficile were less likely to have a physician directing their FMT treatment (20.6%) as compared to patients receiving FMT for C. difficile (86.3%). Patient-reported efficacy was lower for FMT given for a non-C. difficile indication.<br><br>Conclusions: Patients undergoing FMT for an indication other than C. difficile infection were more likely to have ulcerative colitis, self-administer FMT, and were less likely to be receiving FMT under the guidance of a medical professional. FMT was not as effective for symptoms when given for a non-C. difficile indication. Patients should be counseled on potential harms and lack of proven benefit associated with FMT for IBD indications to try to discourage self-administered FMT without proper medical oversite.}, }
@article {pmid32419454, year = {2020}, author = {Liu, Y and Luo, L and Luo, Y and Zhang, J and Wang, X and Sun, K and Zeng, L}, title = {The Prebiotic Properties of Green and Dark Tea Contribute to The Protective Effects in Chemical-Induced Colitis in Mice: A Fecal Microbiota Transplantation Study.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.0c02336}, pmid = {32419454}, issn = {1520-5118}, abstract = {Green and dark tea extract (GTE/DTE) ameliorate chemical induced-colitis in mice; however, the role of gut microbiota on the anti-colitis effects of green and dark tea in mice remains unclear. This study aims to explore the role of modulations in gut microbes mediated by green and dark tea in colitis mice by a fecal microbiota transplantation (FMT). Our results indicated that GTE and DTE (5 mg/kg bodyweight/day for 4 weeks) exhibited prebiotic effects on the donor mice. Moreover, the FMT treatments (transferring the microbiota daily from the 1g/kg bodyweight fecal sample to each recipient) indicated that, compared with the fecal microbiota from the normal diet treated donor mice, the fecal microbiota from the GTE and DTE treated donor mice significantly ameliorate colitis-related symptoms (e.g., loss of bodyweight, colonic inflammation, loss of barrier integrity, and gut microbiota dysbiosis) and downregulated TLR4/MyD88/NF-κB pathway. Collectively, GTE and DTE ameliorate chemical induced-colitis by modulating gut microbiota.}, }
@article {pmid32418496, year = {2020}, author = {Sharma, RK and Oliveira, AC and Yang, T and Karas, MM and Li, J and Lobaton, GO and Aquino, VP and Robles-Vera, I and de Kloet, AD and Krause, EG and Bryant, AJ and Verma, A and Li, Q and Richards, EM and Raizada, MK}, title = {Gut Pathology and Its Rescue by ACE2 (Angiotensin-Converting Enzyme 2) in Hypoxia-Induced Pulmonary Hypertension.}, journal = {Hypertension (Dallas, Tex. : 1979)}, volume = {}, number = {}, pages = {HYPERTENSIONAHA12014931}, doi = {10.1161/HYPERTENSIONAHA.120.14931}, pmid = {32418496}, issn = {1524-4563}, abstract = {Therapeutic advances for pulmonary hypertension (PH) have been incremental because of the focus on the pulmonary vasculature in PH pathology. Here, we evaluate the concept that PH is, rather, a systemic disorder involving interplay among multiorgan systems, including brain, gut, and lungs. Therefore, the objective of this study was to evaluate the hypothesis that PH is associated with a dysfunctional brain-gut-lung axis and that global overexpression of ACE2 (angiotensin-converting enzyme 2) rebalances this axis and protects against PH. ACE2 knockin and wild-type (WT; C57BL/6) mice were subjected to chronic hypoxia (10% FIO2) or room air for 4 weeks. Cardiopulmonary hemodynamics, histology, immunohistochemistry, and fecal 16S rRNA microbial gene analyses were evaluated. Hypoxia significantly increased right ventricular systolic pressure, sympathetic activity as well as the number and activation of microglia in the paraventricular nucleus of the hypothalamus in WT mice. This was associated with a significant increase in muscularis layer thickening and decreases in both villi length and goblet cells and altered gut microbiota. Global overexpression of ACE2 prevented changes in hypoxia-induced pulmonary and gut pathophysiology and established distinct microbial communities from WT hypoxia mice. Furthermore, WT mice subjected to fecal matter transfer from ACE2 knockin mice were resistant to hypoxia-induced PH compared with their controls receiving WT fecal matter transfer. These observations demonstrate that ACE2 ameliorates these hypoxia-induced pathologies and attenuates PH. The data implicate dysfunctional brain-gut-lung communication in PH and provide novel avenues for therapeutic interventions.}, }
@article {pmid30666959, year = {2019}, author = {Lavoie, S and Conway, KL and Lassen, KG and Jijon, HB and Pan, H and Chun, E and Michaud, M and Lang, JK and Gallini Comeau, CA and Dreyfuss, JM and Glickman, JN and Vlamakis, H and Ananthakrishnan, A and Kostic, A and Garrett, WS and Xavier, RJ}, title = {The Crohn's disease polymorphism, ATG16L1 T300A, alters the gut microbiota and enhances the local Th1/Th17 response.}, journal = {eLife}, volume = {8}, number = {}, pages = {}, pmid = {30666959}, issn = {2050-084X}, support = {DK097485/NH/NIH HHS/United States ; DK105653/NH/NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; F31 DK105653/DK/NIDDK NIH HHS/United States ; R01 DK092405/DK/NIDDK NIH HHS/United States ; CA154426/NH/NIH HHS/United States ; P30 DK036836/DK/NIDDK NIH HHS/United States ; DK110499/NH/NIH HHS/United States ; R01 CA154426/CA/NCI NIH HHS/United States ; Smith Family Foundation Award for Excellence in Biomedical Research//Richard and Susan Smith Family Foundation/International ; DK092405/NH/NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; R01 DK097485/DK/NIDDK NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Autophagy-Related Proteins/*genetics ; Bacteroides ; Crohn Disease/*genetics/*microbiology ; Dysbiosis/genetics/microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Gene Knock-In Techniques ; Genotype ; Humans ; Immune System ; Mice ; Polymorphism, Genetic ; Risk ; Th1 Cells/*cytology/microbiology ; Th17 Cells/*cytology/microbiology ; }, abstract = {Inflammatory bowel disease (IBD) is driven by dysfunction between host genetics, the microbiota, and immune system. Knowledge gaps remain regarding how IBD genetic risk loci drive gut microbiota changes. The Crohn's disease risk allele ATG16L1 T300A results in abnormal Paneth cells due to decreased selective autophagy, increased cytokine release, and decreased intracellular bacterial clearance. To unravel the effects of ATG16L1 T300A on the microbiota and immune system, we employed a gnotobiotic model using human fecal transfers into ATG16L1 T300A knock-in mice. We observed increases in Bacteroides ovatus and Th1 and Th17 cells in ATG16L1 T300A mice. Association of altered Schaedler flora mice with B. ovatus specifically increased Th17 cells selectively in ATG16L1 T300A knock-in mice. Changes occur before disease onset, suggesting that ATG16L1 T300A contributes to dysbiosis and immune infiltration prior to disease symptoms. Our work provides insight for future studies on IBD subtypes, IBD patient treatment and diagnostics.}, }
@article {pmid32415349, year = {2020}, author = {Chen, H and Xu, C and Zhang, F and Liu, Y and Guo, Y and Yao, Q}, title = {The gut microbiota attenuates muscle wasting by regulating energy metabolism in chemotherapy-induced malnutrition rats.}, journal = {Cancer chemotherapy and pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00280-020-04060-w}, pmid = {32415349}, issn = {1432-0843}, support = {2017ZZ004//Chinese Medicine Research Program of Zhejiang Province/ ; 2019ZA018//Chinese Medicine Research Program of Zhejiang Province/ ; }, abstract = {BACKGROUND: Malnutrition is a common clinical symptom in cancer patients after chemotherapy, which is characterized by muscle wasting and metabolic dysregulation. The regulation of muscle metabolism by gut microbiota has been studied recently. However, there is no direct convincing evidence proving that manipulating gut microbiota homeostasis could regulate muscle metabolic disorder caused by chemotherapy. Here, we investigate the potential role of gut microbiota in the regulation of the muscle metabolism in 5-fluorouracil (5-Fu)-induced malnutrition rat model.<br><br>METHODS: Male Sprague-Dawley rats were randomly divided into two groups (n = 8/group): control group and 5-Fu group. In the 5-Fu group, rats received 5-Fu (40 mg/kg/day) by intraperitoneal injection for 4 days, and all rats were raised for 8 days. Nutritional status, muscle function, muscle metabolites, and gut microbiota were assessed. Fecal microbiota transplantation (FMT) was applied to explore the potential regulation of gut microbiota on muscle metabolism.<br><br>RESULTS: 5-Fu-treated rats exhibited loss of body weight and food intake compared to control group. 5-Fu decreased the levels of total protein and albumin in serum, and significantly increased the levels of IL-6 and TNF-α in muscle tissue. Rats that received 5-Fu displayed concurrent reduction of muscle function and fiber size. Moreover, 5-Fu group showed a distinct profile of gut microbiota compared to control group, including the relative lower abundance of Firmicutes and a higher abundance of Proteobacteria and Verrucomicrobia. Fourteen differential muscle metabolites were identified between two groups, which were mainly related to glycolysis, amino acid metabolism, and TCA cycle pathway. Furthermore, fecal transplantation from healthy rats improved nutritional status and muscle function in 5-Fu-treated rats. Notably, FMT inhibited the inflammatory response in muscle, and reversed the changes of several differential muscle metabolites and energy metabolism in 5-Fu-treated rats.<br><br>CONCLUSIONS: Our study demonstrated that gut microbiota played an important role in the regulation of muscle metabolism and promoting muscle energy production in 5-Fu-induced malnutrition rats, suggesting the potential attenuation of chemotherapy-induced muscle wasting by manipulating gut microbiota homeostasis.}, }
@article {pmid31326346, year = {2019}, author = {Moayyedi, P}, title = {Faecal microbiota transplantation for IBS: still a long way to go.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {4}, number = {9}, pages = {656-657}, doi = {10.1016/S2468-1253(19)30226-2}, pmid = {31326346}, issn = {2468-1253}, mesh = {Diarrhea ; Double-Blind Method ; *Fecal Microbiota Transplantation ; Feces ; Humans ; *Irritable Bowel Syndrome ; }, }
@article {pmid32406264, year = {2020}, author = {Pereira, FV and Melo, ACL and Silva, MB and de Melo, FM and Terra, FF and Castro, IA and Perandini, LA and Miyagi, MT and Sato, FT and Origassa, CST and Hiyane, MI and Donato, J and Wasinski, F and Araujo, RC and Festuccia, WTL and da Silva, JS and Camara, NOS}, title = {Interleukin-6 and the Gut Microbiota Influence Melanoma Progression in Obese Mice.}, journal = {Nutrition and cancer}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/01635581.2020.1764982}, pmid = {32406264}, issn = {1532-7914}, abstract = {There is a strong correlation between obesity and cancer. Here, we investigated the influence of IL-6 and gut microbiota of obese mice in melanoma development. We first evaluated B16F10 melanoma growth in preclinical models for obesity: mice deficient for leptin (ob/ob) or adiponectin (AdpKO) and in wild-type mice (WT, C57BL/6J) fed a high-fat diet (HFD; 60% kcal from fat) for 12 weeks. The survival rates of ob/ob and HFD-fed mice were lower than those of their respective controls. AdpKO mice also died earlier than WT control mice. We then verified the involvement of IL-6 signaling in obese mice that were inoculated with melanoma cells. Both ob/ob and AdpKO mice had higher circulating IL-6 levels than wild-type mice. Melanoma tumor volumes in IL-6 KO mice fed an HFD were reduced compared to those of WT mice subjected to the same diet. Also evaluated the effect of microbiota in tumor development. Cohousing and fecal matter transfer experiments revealed that microbiota from ob/ob mice can stimulate tumor development in lean WT mice. Taken together, our data show that in some conditions IL-6 and the gut microbiota are key mediators that link obesity and melanoma.}, }
@article {pmid32405509, year = {2020}, author = {Wilcox, MH and McGovern, BH and Hecht, GA}, title = {The Efficacy and Safety of Fecal Microbiota Transplant for Recurrent Clostridiumdifficile Infection: Current Understanding and Gap Analysis.}, journal = {Open forum infectious diseases}, volume = {7}, number = {5}, pages = {ofaa114}, doi = {10.1093/ofid/ofaa114}, pmid = {32405509}, issn = {2328-8957}, abstract = {The leading risk factor for Clostridioides (Clostridium) difficile infection (CDI) is broad-spectrum antibiotics, which lead to low microbial diversity, or dysbiosis. Current therapeutic strategies for CDI are insufficient, as they do not address the key role of the microbiome in preventing C. difficile spore germination into toxin-producing vegetative bacteria, which leads to symptomatic disease. Fecal microbiota transplant (FMT) appears to reduce the risk of recurrent CDI through microbiome restoration. However, a wide range of efficacy rates have been reported, and few placebo-controlled trials have been conducted, limiting our understanding of FMT efficacy and safety. We discuss the current knowledge gaps driven by questions around the quality and consistency of clinical trial results, patient selection, diagnostic methodologies, use of suppressive antibiotic therapy, and methods for adverse event reporting. We provide specific recommendations for future trial designs of FMT to provide improved quality of the clinical evidence to better inform treatment guidelines.}, }
@article {pmid32403888, year = {2020}, author = {Fan, LD and Liu, YM and Cheng, ML}, title = {[Probiotics enhance the efficacy of fecal microbiota transplantation in severe acute liver injury].}, journal = {Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology}, volume = {28}, number = {4}, pages = {345-350}, doi = {10.3760/cma.j.cn501113-20190823-00315}, pmid = {32403888}, issn = {1007-3418}, support = {81570543//National Natural Science Foundation of China/ ; }, abstract = {Objective: To observe the changes of gut flora in mice, and explore the outcome of fecal microbiota transplantation combined with probiotics in the intervention of severe acute liver injury. Methods: Forty male BALB/c mice were selected and randomly divided into blank control group (10 mice), model group (10 mice), ordinary fecal microbiota transplantation group (10 mice), and fecal microbiota + probiotics transplantation group (10 mice). An intraperitoneal injection of d-galactosamine (D-GalN 3.0g/kg) was given to every group except the blank control group to induce severe acute liver injury model. Simultaneously, ordinary fecal microbiota transplantation group and fecal microbiota + probiotics transplantation group and modeling group were given enema solutions (once a day). After 48 hours, fetched serum was taken to detect alanine transaminase, aspartate transaminase and total bilirubin, and liver tissue was taken for pathological detection. The colonic content was used to extract DNA for 16S V3-V4 high-throughput sequencing. The results of sequencing were analyzed by using bioinformatics analysis; including OTU cluster analysis, α diversity analysis, β diversity analysis, and linear discriminant analysis effect size (Lefse) to find the bacteria with different colonic content characteristics in different groups of mice. Differences in clinical biochemical indicators between groups were compared using t-test, and the differences between 16S V3-V4 region sequencing results were compared using Wilcoxon test. Results: Model group mice serum biochemical parameters were higher than the other three groups, and the difference was statistically significant (P < 0.05). HE staining of liver sections showed severe inflammatory changes under the microscope in the model group. Ordinary fecal microbiota transplantation group and fecal microbiota + probiotic microbiota transplantation group had low levels of inflammation than the model group. The analysis results of 16S rRNA high-throughput sequencing showed that there was no statistically significant difference in Shannon's index between the blank control and the other three groups. Observed Species difference was statistically significant, and the gut flora composition varied greatly. Species number in the mice gut flora was increased with fecal microbiota transplantation. The results of β - diversity analysis showed that the difference between the blank control group and the other three groups was greater than that between the disease groups. The difference in the structure of the gut flora of the diseased mice in the fecal microbiota + probiotic transplantation group was mostly butyrate-producing bacteria. Conclusion: Fecal microbiota + probiotics enhance the therapeutic effect of fecal microbiota transplantation, improve liver inflammation, and increase the number of butyrate-producing bacteria in the gut.}, }
@article {pmid31136009, year = {2019}, author = {Ianiro, G and Eusebi, LH and Black, CJ and Gasbarrini, A and Cammarota, G and Ford, AC}, title = {Systematic review with meta-analysis: efficacy of faecal microbiota transplantation for the treatment of irritable bowel syndrome.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {50}, number = {3}, pages = {240-248}, doi = {10.1111/apt.15330}, pmid = {31136009}, issn = {1365-2036}, mesh = {Adult ; Colitis, Ulcerative/epidemiology/microbiology/therapy ; *Fecal Microbiota Transplantation/methods/statistics &amp; numerical data ; Feces/microbiology ; Gastrointestinal Microbiome/physiology ; Humans ; Irritable Bowel Syndrome/epidemiology/microbiology/*therapy ; Randomized Controlled Trials as Topic/statistics &amp; numerical data ; Treatment Outcome ; }, abstract = {BACKGROUND: Increasing evidence supports the role of the gut microbiota in the aetiology of irritable bowel syndrome (IBS). Faecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridioides difficile infection in randomised controlled trials (RCTs), and may be beneficial in ulcerative colitis. However, its efficacy in IBS is uncertain.<br><br>AIM: To perform a systematic review and meta-analysis to examine this issue.<br><br>METHODS: We searched MEDLINE, EMBASE, EMBASE Classic, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov through to March 2019. RCTs recruiting adults with IBS, which compared FMT with placebo, were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% CI.<br><br>RESULTS: The search strategy identified 322 citations. Five RCTs were eligible for inclusion, containing 267 patients. Overall, 92.2% of included patients had IBS-D or IBS-M, and only 7.8% IBS-C. When data were pooled for all patients, irrespective of stool type, the RR of IBS symptoms not improving was 0.98 (95% CI 0.58-1.66). Placebo capsules administered orally were superior to capsules containing donor stool in two pooled trials (RR = 1.96; 95% CI 1.19-3.20). FMT from donor stool delivered via colonoscopy was superior to autologous stool in two pooled RCTs (RR = 0.63; 95% CI 0.43-0.93). FMT from donor stool via nasojejunal tube showed a trend towards a benefit over autologous stool in one trial (RR = 0.69; 95% CI 0.46-1.02).<br><br>CONCLUSIONS: Fresh or frozen donor stool delivered via colonoscopy or nasojejunal tube may be beneficial in IBS. Larger, more rigorously conducted trials of FMT in IBS are needed.}, }
@article {pmid32402927, year = {2020}, author = {Shan, B and Ai, Z and Zeng, S and Song, Y and Song, J and Zeng, Q and Liao, Z and Wang, T and Huang, C and Su, D}, title = {Gut microbiome-derived lactate promotes to anxiety-like behaviors through GPR81 receptor-mediated lipid metabolism pathway.}, journal = {Psychoneuroendocrinology}, volume = {117}, number = {}, pages = {104699}, doi = {10.1016/j.psyneuen.2020.104699}, pmid = {32402927}, issn = {1873-3360}, abstract = {Accumulating evidence suggests that chronic stress could perturb the composition of the gut microbiota and induce host anxiety- and depression-like behaviors. In particular, microorganism-derived products that can directly or indirectly signal to the nervous system. This study sought to investigate whether high levels of Lactobacillus and lactate in the gut of rats under chronic unpredictable stress (CUS) were the factors leading to anxiety behavior. We collected faeces and blood samples in a sterile laboratory bench to study the microbiome and plasma metabolome from adult male rats age and environment matched healthy individuals. We sequenced the V3 and V4 regions of the 16S rRNA gene from faeces samples. UPLC-MS metabolomics were used to examine plasma samples. Search for potential biomarkers by combining the different data types. Finally, we found a regulated signaling pathway through the relative expression of protein and mRNA. Both lactate feeding and fecal microbiota transplantation caused behavioral abnormalities such as psychomotor malaise, impaired learning and memory in the recipient animals. These rats also showed inhibition of the adenylate cyclase (AC)-protein kinase A (PKA) pathway of lipolysis after activation of G protein-coupled receptor 81 (GPR81) by lactate in the liver, as well as increased tumor necrosis factor α (TNF-α), compared with healthy controls. Furthermore, we showed that sphingosine-1-phosphate receptor 2 (S1PR2) protein expression in hippocampus was reduced in chronic unpredictable stress compared to control group and its expression negatively correlates with symptom severity. Our study suggest that the gut microbiome-derived lactate promotes to anxiety-like behaviors through GPR81 receptor-mediated lipid metabolism pathway.}, }
@article {pmid32402176, year = {2020}, author = {DeFilipp, Z and Bloom, PP and Hohmann, EL and , }, title = {Drug-Resistant Bacteremia after Fecal Microbiota Transplant. Reply.}, journal = {The New England journal of medicine}, volume = {382}, number = {20}, pages = {1961-1962}, doi = {10.1056/NEJMc2002496}, pmid = {32402176}, issn = {1533-4406}, }
@article {pmid32402175, year = {2020}, author = {Bleibtreu, A and Kapel, N and Galperine, T and , }, title = {Drug-Resistant Bacteremia after Fecal Microbiota Transplant.}, journal = {The New England journal of medicine}, volume = {382}, number = {20}, pages = {1961}, doi = {10.1056/NEJMc2002496}, pmid = {32402175}, issn = {1533-4406}, }
@article {pmid32402174, year = {2020}, author = {Chiu, CH and Chiu, CT}, title = {Drug-Resistant Bacteremia after Fecal Microbiota Transplant.}, journal = {The New England journal of medicine}, volume = {382}, number = {20}, pages = {1960-1961}, doi = {10.1056/NEJMc2002496}, pmid = {32402174}, issn = {1533-4406}, }
@article {pmid32402173, year = {2020}, author = {Janket, SJ and Ackerson, LK and Diamandis, EP}, title = {Drug-Resistant Bacteremia after Fecal Microbiota Transplant.}, journal = {The New England journal of medicine}, volume = {382}, number = {20}, pages = {1960}, doi = {10.1056/NEJMc2002496}, pmid = {32402173}, issn = {1533-4406}, }
@article {pmid31051514, year = {2019}, author = {Khoruts, A and Sadowsky, MJ}, title = {Letter to the Editor.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {69}, number = {12}, pages = {2232-2233}, doi = {10.1093/cid/ciz366}, pmid = {31051514}, issn = {1537-6591}, mesh = {*Clostridium difficile ; *Fecal Microbiota Transplantation ; }, }
@article {pmid31051032, year = {2019}, author = {Khanna, S and Tariq, R and Pardi, DS}, title = {Reply to Khoruts and Sadowsky.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {69}, number = {12}, pages = {2233-2234}, doi = {10.1093/cid/ciz367}, pmid = {31051032}, issn = {1537-6591}, mesh = {*Clostridium difficile ; Diagnostic Tests, Routine ; *Fecal Microbiota Transplantation ; }, }
@article {pmid32393794, year = {2020}, author = {Kim, SM and DeFazio, JR and Hyoju, SK and Sangani, K and Keskey, R and Krezalek, MA and Khodarev, NN and Sangwan, N and Christley, S and Harris, KG and Malik, A and Zaborin, A and Bouziat, R and Ranoa, DR and Wiegerinck, M and Ernest, JD and Shakhsheer, BA and Fleming, ID and Weichselbaum, RR and Antonopoulos, DA and Gilbert, JA and Barreiro, LB and Zaborina, O and Jabri, B and Alverdy, JC}, title = {Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {2354}, doi = {10.1038/s41467-020-15545-w}, pmid = {32393794}, issn = {2041-1723}, abstract = {Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression.}, }
@article {pmid32392712, year = {2020}, author = {Iruzubieta, P and Medina, JM and Fernández-López, R and Crespo, J and de la Cruz, F}, title = {A Role for Gut Microbiome Fermentative Pathways in Fatty Liver Disease Progression.}, journal = {Journal of clinical medicine}, volume = {9}, number = {5}, pages = {}, doi = {10.3390/jcm9051369}, pmid = {32392712}, issn = {2077-0383}, support = {BFU2017-86378-P//Ministerio de Ciencia y Tecnología/ ; Gilead Fellowship programme 2018//Gilead Sciences/ ; PI18/01304//Ministerio de Ciencia, Innovación y Universidades/ ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease in which environmental and genetic factors are involved. Although the molecular mechanisms involved in NAFLD onset and progression are not completely understood, the gut microbiome (GM) is thought to play a key role in the process, influencing multiple physiological functions. GM alterations in diversity and composition directly impact disease states with an inflammatory course, such as non-alcoholic steatohepatitis (NASH). However, how the GM influences liver disease susceptibility is largely unknown. Similarly, the impact of strategies targeting the GM for the treatment of NASH remains to be evaluated. This review provides a broad insight into the role of gut microbiota in NASH pathogenesis, as a diagnostic tool, and as a therapeutic target in this liver disease. We highlight the idea that the balance in metabolic fermentations can be key in maintaining liver homeostasis. We propose that an overabundance of alcohol-fermentation pathways in the GM may outcompete healthier, acid-producing members of the microbiota. In this way, GM ecology may precipitate a self-sustaining vicious cycle, boosting liver disease progression.}, }
@article {pmid32390701, year = {2020}, author = {Chen, HT and Huang, HL and Li, YQ and Xu, HM and Zhou, YJ}, title = {Therapeutic advances in non-alcoholic fatty liver disease: A microbiota-centered view.}, journal = {World journal of gastroenterology}, volume = {26}, number = {16}, pages = {1901-1911}, doi = {10.3748/wjg.v26.i16.1901}, pmid = {32390701}, issn = {2219-2840}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent metabolic disorder with steadily increasing incidence rates worldwide, especially in the West. There are no drugs available at present to treat NAFLD, and the primary therapeutic options include weight loss and the combination of healthy diet and exercise. Therefore, novel interventions are required that can target the underlying risk factors. Gut microbiota is an &quot;invisible organ&quot; of the human body and vital for normal metabolism and immuno-modulation. The number and diversity of microbes differ across the gastrointestinal tract from the mouth to the anus, and is most abundant in the intestine. Since dysregulated gut microbiota is an underlying pathological factor of NAFLD, it is a viable therapeutic target that can be modulated by antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and microbial metabolites. In this review, we summarize the most recent advances in gut microbiota-targeted therapies against NAFLD in clinical and experimental studies, and critically evaluate novel targets and strategies for treating NAFLD.}, }
@article {pmid31775890, year = {2019}, author = {Le Roy, T and Lécuyer, E and Chassaing, B and Rhimi, M and Lhomme, M and Boudebbouze, S and Ichou, F and Haro Barceló, J and Huby, T and Guerin, M and Giral, P and Maguin, E and Kapel, N and Gérard, P and Clément, K and Lesnik, P}, title = {The intestinal microbiota regulates host cholesterol homeostasis.}, journal = {BMC biology}, volume = {17}, number = {1}, pages = {94}, pmid = {31775890}, issn = {1741-7007}, mesh = {Animals ; Cholesterol/*metabolism ; Dyslipidemias/*metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; *Homeostasis ; Intestines/*microbiology ; Mice ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Management of blood cholesterol is a major focus of efforts to prevent cardiovascular diseases. The objective of this study was to investigate how the gut microbiota affects host cholesterol homeostasis at the organism scale.<br><br>RESULTS: We depleted the intestinal microbiota of hypercholesterolemic female Apoe-/- mice using broad-spectrum antibiotics. Measurement of plasma cholesterol levels as well as cholesterol synthesis and fluxes by complementary approaches showed that the intestinal microbiota strongly regulates plasma cholesterol level, hepatic cholesterol synthesis, and enterohepatic circulation. Moreover, transplant of the microbiota from humans harboring elevated plasma cholesterol levels to recipient mice induced a phenotype of high plasma cholesterol levels in association with a low hepatic cholesterol synthesis and high intestinal absorption pattern. Recipient mice phenotypes correlated with several specific bacterial phylotypes affiliated to Betaproteobacteria, Alistipes, Bacteroides, and Barnesiella taxa.<br><br>CONCLUSIONS: These results indicate that the intestinal microbiota determines the circulating cholesterol level and may thus represent a novel therapeutic target in the management of dyslipidemia and cardiovascular diseases.}, }
@article {pmid31467135, year = {2019}, author = {Wang, S and Lv, D and Jiang, S and Jiang, J and Liang, M and Hou, F and Chen, Y}, title = {Quantitative reduction in short-chain fatty acids, especially butyrate, contributes to the progression of chronic kidney disease.}, journal = {Clinical science (London, England : 1979)}, volume = {133}, number = {17}, pages = {1857-1870}, doi = {10.1042/CS20190171}, pmid = {31467135}, issn = {1470-8736}, mesh = {Animals ; Butyrates/blood/*metabolism ; Case-Control Studies ; Disease Models, Animal ; Fatty Acids, Volatile/blood/*metabolism ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/genetics ; Humans ; Kidney/physiopathology ; Male ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Renal Insufficiency, Chronic/*etiology/metabolism/pathology/physiopathology ; }, abstract = {Chronic kidney disease (CKD) affects 10-15% of the population worldwide, results in high morbidity and mortality, and requires costly treatment and renal replacement therapy. Glomerulosclerosis, tubulointerstitial fibrosis, and persistent intestinal flora disturbance are common in CKD. Short-chain fatty acids (SCFAs), produced by the intestinal microbiota, have been previously reported to ameliorate kidney injury; however, the specific concentrations and types that are required to improve renal function remain unknown. The present study aims to evaluate the levels of SCFAs in healthy and CKD patients, and to test the hypothesis that SCFAs play a critical role in delaying CKD progression. One hundred and twenty-seven patients with CKD and 63 healthy controls from China were enrolled in the present study. Butyrate, which is considered beneficial to humans, was almost three-times higher in healthy volunteers than that in CKD5 subjects (P=0.001). Moreover, the serum SCFA levels in controls were significantly higher than that in CKD patients (P<0.05), and the butyrate level among CKD5 patients (1.48 ± 0.60 μmol/l) was less than half of that in controls (3.44 ± 2.12 μmol/l, P<0.001). In addition, we observed an inverse correlation between butyrate level and renal function (P<0.05). A CKD rat model transplanted with microbiota obtained from CKD patients exhibited accelerated CKD progression via increased production of trimethylamine N-oxide (TMAO), which was reversed by supplementation with extra butyrate. Our results showed that SCFA levels were reduced in CKD patients and that butyrate supplementation might delay CKD progression.}, }
@article {pmid31273774, year = {2019}, author = {Kirby, TO and Brown, M and Ochoa-Repáraz, J and Roullet, JB and Gibson, KM}, title = {Microbiota Manipulation as a Metagenomic Therapeutic Approach for Rare Inherited Metabolic Disorders.}, journal = {Clinical pharmacology and therapeutics}, volume = {106}, number = {3}, pages = {505-507}, pmid = {31273774}, issn = {1532-6535}, support = {R01 EY027476/EY/NEI NIH HHS/United States ; }, mesh = {4-Aminobutyrate Transaminase/deficiency ; Amino Acid Metabolism, Inborn Errors/physiopathology/therapy ; Animals ; Developmental Disabilities/physiopathology/therapy ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Metabolism, Inborn Errors/*physiopathology/therapy ; Mice ; Prebiotics/administration &amp; dosage ; Probiotics/administration &amp; dosage ; RNA, Ribosomal, 16S/metabolism ; Rare Diseases/*physiopathology/therapy ; Severity of Illness Index ; Succinate-Semialdehyde Dehydrogenase/deficiency ; }, }
@article {pmid30897248, year = {2019}, author = {Alrafas, HR and Busbee, PB and Nagarkatti, M and Nagarkatti, PS}, title = {Resveratrol modulates the gut microbiota to prevent murine colitis development through induction of Tregs and suppression of Th17 cells.}, journal = {Journal of leukocyte biology}, volume = {106}, number = {2}, pages = {467-480}, pmid = {30897248}, issn = {1938-3673}, support = {R01 AI129788/AI/NIAID NIH HHS/United States ; R01 MH094755/MH/NIMH NIH HHS/United States ; P20 GM103641/GM/NIGMS NIH HHS/United States ; P01 AT003961/AT/NCCIH NIH HHS/United States ; R01 AT006888/AT/NCCIH NIH HHS/United States ; R01 AI123947/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Anti-Inflammatory Agents, Non-Steroidal/*pharmacology ; Biomarkers ; Colitis/*etiology/metabolism/pathology/prevention &amp; control ; Colonoscopy ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*drug effects/*immunology ; Humans ; Immunomodulation/*drug effects ; Metagenomics/methods ; Mice ; Resveratrol/*pharmacology ; T-Lymphocyte Subsets/immunology/metabolism ; T-Lymphocytes, Regulatory/drug effects/*immunology/metabolism ; Th17 Cells/drug effects/*immunology/metabolism ; }, abstract = {Inflammatory diseases of the gastrointestinal tract are often associated with microbial dysbiosis. Thus, dietary interactions with intestinal microbiota, to maintain homeostasis, play a crucial role in regulation of clinical disorders such as colitis. In the current study, we investigated if resveratrol, a polyphenol found in a variety of foods and beverages, would reverse microbial dysbiosis induced during colitis. Administration of resveratrol attenuated colonic inflammation and clinical symptoms in the murine model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Resveratrol treatment in mice with colitis led to an increase in CD4+ FOXP3+ and CD4+ IL-10+ T cells, and a decrease in CD4+ IFN-γ+ and CD4+ IL-17+ T cells. 16S rRNA gene sequencing to investigate alterations in the gut microbiota revealed that TNBS caused significant dysbiosis, which was reversed following resveratrol treatment. Analysis of cecal flush revealed that TNBS administration led to an increase in species such as Bacteroides acidifaciens, but decrease in species such as Ruminococcus gnavus and Akkermansia mucinphilia, as well as a decrease in SCFA i-butyric acid. However, resveratrol treatment restored the gut bacteria back to homeostatic levels, and increased production of i-butyric acid. Fecal transfer experiments confirmed the protective role of resveratrol-induced microbiota against colitis inasmuch as such recipient mice were more resistant to TNBS-colitis and exhibited polarization toward CD4+ FOXP3+ T cells and decreases in CD4+ IFN-γ+ and CD4+ IL-17+ T cells. Collectively, these data demonstrate that resveratrol-mediated attenuation of colitis results from reversal of microbial dysbiosis induced during colitis and such microbiota protect the host from colonic inflammation by inducing Tregs while suppressing inflammatory Th1/Th17 cells.}, }
@article {pmid32388250, year = {2020}, author = {Wang, P and Wang, J and Li, D and Ke, W and Chen, F and Hu, X}, title = {Targeting the gut microbiota with resveratrol: a demonstration of novel evidence for the management of hepatic steatosis.}, journal = {The Journal of nutritional biochemistry}, volume = {81}, number = {}, pages = {108363}, doi = {10.1016/j.jnutbio.2020.108363}, pmid = {32388250}, issn = {1873-4847}, abstract = {Resveratrol is a natural polyphenol that has been reported to reduce the risk of obesity and nonalcoholic fatty liver disease (NAFLD). Recent evidence has demonstrated that the gut microbiota plays an important role in the protection against NAFLD and other metabolic diseases. The present study aimed to investigate the relationship between the gut microbiota and the beneficial effects of resveratrol on the amelioration of NAFLD in mice. We observed marked decreases in body weight and liver steatosis and improved insulin resistance in high-fat diet (HFD)-fed mice treated with resveratrol. Furthermore, we found that resveratrol treatment alleviated NAFLD in HFD-fed mice by improving the intestinal microenvironment, including gut barrier function and gut microbiota composition. On the one hand, resveratrol improved gut intestinal barrier integrity through the repair of intestinal mucosal morphology and increased the expression of physical barrier- and physiochemical barrier-related factors in HFD-fed mice. On the other hand, in HFD-fed mice, resveratrol supplementation modulated the gut bacterial composition. The resveratrol-induced gut microbiota was characterized by a decreased abundance of harmful bacteria, including Desulfovibrio, Lachnospiraceae_NK4A316_group and Alistipes, as well as an increased abundance of short-chain fatty acid (SCFA)-producing bacteria, such as Allobaculum, Bacteroides and Blautia. Moreover, transplantation of the HFDR-microbiota into HFD-fed mice sufficiently decreased body weight, liver steatosis and low-grade inflammation and improved hepatic lipid metabolism. Collectively, resveratrol would provide a potentially dietary intervention strategy against NAFLD through modulating the intestinal microenvironment.}, }
@article {pmid32375675, year = {2020}, author = {Zhang, T and Long, C and Cui, B and Buch, H and Wen, Q and Li, Q and Ding, X and Ji, G and Zhang, F}, title = {Colonic transendoscopic tube-delivered enteral therapy (with video): a prospective study.}, journal = {BMC gastroenterology}, volume = {20}, number = {1}, pages = {135}, doi = {10.1186/s12876-020-01285-0}, pmid = {32375675}, issn = {1471-230X}, support = {81670495//National Natural Science Foundation of China/ ; 81600417//National Natural Science Foundation of China/ ; -//Jiangsu Province Creation Team and Leading Talents project/ ; LGY2017080//Top-notch Talent Research Projects/ ; -//public donated Intestine Initiative Foundation/ ; }, abstract = {BACKGROUND: Colonic transendoscopic enteral tubing (TET) refers to colonic transendoscopic tube-delivered enteral therapy. Colonic TET has been successfully used for frequent colonic administration of drugs or multiple fecal microbiota transplantations (FMTs). This prospective observational study aimed to evaluate possible factors affecting methodology, feasibility and safety of colonic TET.<br><br>METHODS: Patients who underwent colonic TET at our center from October 2014 to November 2018 were included. The feasibility, efficacy, and safety of TET were evaluated.<br><br>RESULTS: In total, 224 patients were analyzed. The success rate of TET was 100%. The median retention time of TET tube within the colonic lumen was 8.5 (IQR 7-11) days in 158 patients with tube falling out spontaneously, and the maximum retention time was up to 28 days. These patients were divided into the short-retention group (≤ 8.5 days) and the long-retention group (> 8.5 days). Univariate and multivariate analysis demonstrated that the type of endoscopic clip (p = 0.001) was an independent factor for the retention time. The larger clips as well as a greater number of clips significantly affected the retention time (p = 0.013). No severe adverse event was observed during and after TET.<br><br>CONCLUSIONS: Colonic TET is a feasible, practical, and safe colon-targeted drug delivery technique with a high degree of patients' satisfaction. Two to four large endoscopic clips are recommended to maintain stability of the TET tube within the colon for over 7 days.}, }
@article {pmid31375137, year = {2019}, author = {Lavelle, A and Hoffmann, TW and Pham, HP and Langella, P and Guédon, E and Sokol, H}, title = {Baseline microbiota composition modulates antibiotic-mediated effects on the gut microbiota and host.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {111}, pmid = {31375137}, issn = {2049-2618}, mesh = {Amoxicillin-Potassium Clavulanate Combination/*administration &amp; dosage ; Animals ; Anti-Bacterial Agents/*administration &amp; dosage ; Bacteria/classification/*drug effects ; Bacterial Physiological Phenomena ; Colon/microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Gene Expression Profiling ; Germ-Free Life ; Humans ; Male ; Mice ; *Microbiota ; }, abstract = {BACKGROUND: Normal mammalian development and homeostasis are dependent upon the gut microbiota. Antibiotics, essential for the treatment and prophylaxis of bacterial infections, can have collateral effects on the gut microbiota composition, which can in turn have far-reaching and potentially deleterious consequences for the host. However, the magnitude and duration of such collateral effects appear to vary between individuals. Furthermore, the degree to which such perturbations affect the host response is currently unclear. We aimed to test the hypothesis that different human microbiomes have different responses to a commonly prescribed antibiotic and that these differences may impact the host response.<br><br>METHODS: Germ-free mice (n = 30) humanized with the microbiota of two unrelated donors (A and B) were subjected to a 7-day antibiotic challenge with amoxicillin-clavulanate (&quot;co-amoxiclav&quot;). Microbiome and colonic transcriptome analysis was performed, pre (day 0) and post antibiotics (day 8) and subsequently into recovery (days 11 and 18).<br><br>RESULTS: Unique community profiles were evident depending upon the donor, with donor A recipient mice being dominated by Prevotella and Faecalibacterium and donor B recipient mice dominated by Bacteroides and Parabacteroides. Donor A mice underwent a marked destabilization of their microbiota following antibiotic treatment, while donor B mice maintained a more stable profile. Dramatic and overlapping alterations in the host transcriptome were apparent following antibiotic challenge in both groups. Despite this overlap, donor A mice experienced a more significant alteration in gene expression and uniquely showed correlations between host pathways and key microbial genera.<br><br>CONCLUSIONS: Germ-free mice humanized by different donor microbiotas maintain distinct microbiome profiles, which respond in distinct ways to antibiotic challenge and evince host responses that parallel microbiome disequilibrium. These results suggest that inter-individual variation in the gut microbiota may contribute to personalized host responses following microbiota perturbation.}, }
@article {pmid31234928, year = {2019}, author = {Paetzold, B and Willis, JR and Pereira de Lima, J and Knödlseder, N and Brüggemann, H and Quist, SR and Gabaldón, T and Güell, M}, title = {Skin microbiome modulation induced by probiotic solutions.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {95}, pmid = {31234928}, issn = {2049-2618}, mesh = {Adult ; Bacteria/classification/isolation &amp; purification ; Bacterial Load ; Female ; Healthy Volunteers ; Humans ; Male ; *Microbiota ; Probiotics/*administration &amp; dosage/therapeutic use ; Propionibacteriaceae ; Skin/*microbiology ; Skin Diseases/therapy ; Young Adult ; }, abstract = {BACKGROUND: The skin is colonized by a large number of microorganisms, most of which are beneficial or harmless. However, disease states of skin have specific microbiome compositions that are different from those of healthy skin. Gut microbiome modulation through fecal transplant has been proven as a valid therapeutic strategy in diseases such as Clostridium difficile infections. Therefore, techniques to modulate the skin microbiome composition may become an interesting therapeutic option in diseases affecting the skin such as psoriasis or acne vulgaris.<br><br>METHODS: Here, we have used mixtures of different skin microbiome components to alter the composition of recipient skin microbiomes.<br><br>RESULTS: We show that after sequential applications of a donor microbiome, the recipient microbiome becomes more similar to the donor. After intervention, an initial week-long phase is characterized by the dominance of donor strains. The level of engraftment depends on the composition of the recipient and donor microbiomes, and the applied bacterial load. We observed higher engraftment using a multi-strain donor solution with recipient skin rich in Cutibacterium acnes subtype H1 and Leifsonia.<br><br>CONCLUSIONS: We have demonstrated the use of living bacteria to modulate skin microbiome composition.}, }
@article {pmid30545582, year = {2019}, author = {Benavent Boladeras, R and Ariño Blasco, S}, title = {[Faecal transplantation in geriatrics].}, journal = {Revista espanola de geriatria y gerontologia}, volume = {54}, number = {2}, pages = {119-120}, doi = {10.1016/j.regg.2018.10.005}, pmid = {30545582}, issn = {1578-1747}, mesh = {Aged, 80 and over ; *Clostridium difficile ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Male ; }, }
@article {pmid32373209, year = {2020}, author = {Liu, YJ and Tang, B and Wang, FC and Tang, L and Lei, YY and Luo, Y and Huang, SJ and Yang, M and Wu, LY and Wang, W and Liu, S and Yang, SM and Zhao, XY}, title = {Parthenolide ameliorates colon inflammation through regulating Treg/Th17 balance in a gut microbiota-dependent manner.}, journal = {Theranostics}, volume = {10}, number = {12}, pages = {5225-5241}, doi = {10.7150/thno.43716}, pmid = {32373209}, issn = {1838-7640}, abstract = {Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays an important pathogenic role. However, the current drugs for IBD treatment are far from optimal. Previous researches indicated that parthenolide (PTL) had not only anti-cancer properties but also strong anti-inflammatory activities. Rationale: To investigate the protective effect of PTL on colon inflammation and demonstrate the underlying gut microbiota-dependent mechanism. Methods: Colon inflammation severity in mouse model was measured by body weight change, mortality, colon length, disease activity index (DAI) score, H&amp;E staining and colonoscopy evaluation. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and targeted metabolomics. Luminex cytokine microarray and Enzyme-linked immunosorbent assay (ELISA) were conducted to measure the colon cytokines profile. The frequency of immune cells in lamina propria (LP) and spleen were phenotyped by flow cytometry. Results: The PTL-treated mice showed significantly relieved colon inflammation, as evidenced by a reduction in body weight loss, survival rate, shortening of colon length, DAI score, histology score and colonoscopy score. Notably, when the gut microbiota was depleted using antibiotic cocktails, the protective effect of PTL on colon inflammation disappeared. PTL treatment downregulated the level of proinflammatory cytokines, including IL-1β, TNF-α, IL-6, and IL-17A and upregulated the immunosuppressive cytokine IL-10 in colon tissue. 16S rRNA sequencing indicated that PTL-treated mice exhibited much more abundant gut microbial diversity and flora composition. Targeted metabolomics analysis manifested the increased SCFAs production in PTL-treated mice. Additionally, PTL administration selectively upregulated the frequency of colonic regulatory T (Treg) cells as well as downregulated the ratio of colonic T helper type 17 (Th17) cells, improving the Treg/Th17 balance to maintain intestinal homeostasis. Gut microbiota depletion and fecal microbiota transplantation (FMT) was performed to confirm this gut microbiota-dependent mechanism. Conclusions: PTL ameliorated colon inflammation in a gut microbiota-dependent manner. The underlying protective mechanism was associated with the improved Treg/Th17 balance in intestinal mucosa mediated through the increased microbiota-derived SCFAs production. Collectively, our results demonstrated the role of PTL as a potential gut microbiota modulator to prevent and treat IBD.}, }
@article {pmid31169660, year = {2019}, author = {Kuijper, EJ and Coia, JE and Vehreschild, MJGT and Keller, J and Terveer, L}, title = {Treatment of (recurrent) Clostridioides difficile Infections in Children and Adults.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {69}, number = {2}, pages = {e57-e58}, doi = {10.1097/MPG.0000000000002387}, pmid = {31169660}, issn = {1536-4801}, mesh = {Child ; *Clostridium Infections ; *Clostridium difficile ; *Enterocolitis, Pseudomembranous ; Fecal Microbiota Transplantation ; *Gastroenterology ; Humans ; United States ; }, }
@article {pmid31169659, year = {2019}, author = {Kociolek, LK and Davidovics, ZH and Kahn, SA and Kellermayer, R}, title = {Response to: Treatment of (Recurrent) Clostridioides difficile Infections in Children and Adults.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {69}, number = {2}, pages = {e58-e59}, doi = {10.1097/MPG.0000000000002388}, pmid = {31169659}, issn = {1536-4801}, mesh = {Child ; *Clostridium Infections ; *Clostridium difficile ; *Enterocolitis, Pseudomembranous ; Fecal Microbiota Transplantation ; *Gastroenterology ; Humans ; United States ; }, }
@article {pmid32368882, year = {2020}, author = {Nakov, R and Segal, JP and Settanni, CR and Bibbò, S and Gasbarrini, A and Cammarota, G and Ianiro, G}, title = {Microbiome: what intensivists should know.}, journal = {Minerva anestesiologica}, volume = {}, number = {}, pages = {}, doi = {10.23736/S0375-9393.20.14278-0}, pmid = {32368882}, issn = {1827-1596}, abstract = {The standard conditions of critical illness (including sepsis, acute respiratory distress syndrome, and multiorgan failure) cause enormous global mortality and a growing economic burden. Increasing evidence suggests that critical illness may be associated with loss of commensal microbes and overgrowth of potentially pathogenic and inflammatory bacteria. This state could be associated with poor outcomes. Therefore, microbiota-targeted interventions are potentially attractive novel treatment options. Although the precise mechanisms of microbiome-directed treatments such as prebiotics, probiotics, and fecal microbiota transplantation remain to be determined, they can be utilized in the intensive care unit (ICU) setting. The current review aims to offer intensivists an evidenced-based approach on what we currently know about the role of the microbiome in critical illness and how the microbiome could be targeted in the clinical practice to improve ICU-related outcomes.}, }
@article {pmid31210950, year = {2019}, author = {Peri, R and Aguilar, RC and Tüffers, K and Erhardt, A and Link, A and Ehlermann, P and Angeli, W and Frank, T and Storr, M and Glück, T and Sturm, A and Rosien, U and Tacke, F and Bachmann, O and Solbach, P and Stallmach, A and Goeser, F and Vehreschild, MJ and , }, title = {The impact of technical and clinical factors on fecal microbiota transfer outcomes for the treatment of recurrent Clostridioides difficile infections in Germany.}, journal = {United European gastroenterology journal}, volume = {7}, number = {5}, pages = {716-722}, pmid = {31210950}, issn = {2050-6406}, mesh = {Age Factors ; Aged ; Aged, 80 and over ; Clostridium Infections/*therapy ; *Clostridium difficile ; *Fecal Microbiota Transplantation/adverse effects ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Secondary Prevention ; Treatment Failure ; }, abstract = {Introduction: Fecal microbiota transfer (FMT) is highly effective in the treatment and prevention of recurrent Clostridioides difficile infection (rCDI) with cure rates of about 80% after a single treatment. Nevertheless, the reasons for failure in the remaining 20% remain largely elusive. The aim of the present study was to investigate different potential clinical predictors of response to FMT in Germany.<br><br>Methods: Information was extracted from the MicroTrans Registry (NCT02681068), a retrospective observational multicenter study, collecting data from patients undergoing FMT for recurrent or refractory CDI in Germany. We performed binary logistic regression with the following covariates: age, gender, ribotype 027, Eastern Co-operative Oncology Group score, immunosuppression, preparation for FMT by use of proton pump inhibitor, antimotility agents and bowel lavage, previous recurrences, severity of CDI, antibiotic induction treatment, fresh or frozen FMT preparation, and route of application.<br><br>Results: Treatment response was achieved in 191/240 evaluable cases (79.6%) at day 30 (D30) post FMT and 78.1% at day 90 (D90) post FMT. Assessment of clinical predictors for FMT failure by forward and confirmatory backward-stepwise regression analysis yielded higher age as an independent predictor of FMT failure (p = 0.001; OR 1.060; 95%CI 1.025-1.097).<br><br>Conclusion: FMT in Germany is associated with high cure rates at D30 and D90. No specific pre-treatment, preparation or application strategy had an impact on FMT success. Only higher age was identified as an independent risk factor for treatment failure. Based on these and external findings, future studies should focus on the assessment of microbiota and microbiota-associated metabolites as factors determining FMT success.}, }
@article {pmid31028093, year = {2019}, author = {Jimenez, M and Langer, R and Traverso, G}, title = {Microbial therapeutics: New opportunities for drug delivery.}, journal = {The Journal of experimental medicine}, volume = {216}, number = {5}, pages = {1005-1009}, pmid = {31028093}, issn = {1540-9538}, mesh = {Bifidobacterium ; Clostridium ; Clostridium Infections/microbiology/*therapy ; Drug Compounding ; *Drug Delivery Systems ; Drug Dosage Calculations ; Escherichia coli ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Humans ; *Vaccines, Live, Unattenuated ; }, abstract = {With >40 clinical trials underway, we are nearing the first FDA-approved live microbial therapeutic. Here, Giovanni Traverso, MIT and Harvard Medical School Assistant Professor, and colleagues Miguel Jimenez and Institute Professor Robert Langer from MIT discuss the significant challenges of administering live microorganisms to patients and the opportunities for drug delivery of these new complex therapeutics.}, }
@article {pmid32363202, year = {2020}, author = {Chaitman, J and Ziese, AL and Pilla, R and Minamoto, Y and Blake, AB and Guard, BC and Isaiah, A and Lidbury, JA and Steiner, JM and Unterer, S and Suchodolski, JS}, title = {Fecal Microbial and Metabolic Profiles in Dogs With Acute Diarrhea Receiving Either Fecal Microbiota Transplantation or Oral Metronidazole.}, journal = {Frontiers in veterinary science}, volume = {7}, number = {}, pages = {192}, doi = {10.3389/fvets.2020.00192}, pmid = {32363202}, issn = {2297-1769}, abstract = {The aim was to characterize differences in fecal consistency, and fecal microbiota and metabolome profiles in dogs with acute diarrhea (AD) treated with either fecal microbiota transplantation as enema (FMT; n = 11) or oral metronidazole (MET; n = 7) for 7 days. On days 0, 7, and 28 fecal samples were obtained. Fecal samples from healthy dogs (HC; n = 14) were used for comparison. Samples were analyzed by the previously validated qPCR based canine Dysbiosis Index (DI; increased values indicate microbiota dysbiosis) and 16S rRNA gene sequencing. The fecal metabolome was analyzed using a previously validated targeted canine assay for fecal unconjugated bile acids, and untargeted metabolomics. Fecal consistency improved significantly in dogs treated with FMT and MET by day 7 and day 28 (p < 0.01) compared to day 0. However, on day 28 fecal consistency was significantly better in FMT compared to MET (p = 0.040). At day 0, dogs with AD had an altered microbiota indicated by significantly increased DI, decreased alpha-diversity, and altered beta-diversity. In the FMT group, the DI decreased over time, while MET led to a significant increase in the dysbiosis index at day 7 and 28 compared to FMT. Sequencing data revealed that in FMT microbial diversity and beta-diversity was similar to HC at day 28, while in MET these parameters were still significantly different from HC. In dogs treated with FMT, a decrease in cholic acid and the percentage of primary bile acids was observed, whereas treatment with metronidazole led to an increase in cholic acid at day 7 and an increase in percentage of primary bile acids over time. Based on untargeted metabolomics, dogs with AD had an altered fecal metabolome compared to HC. Dogs treated with FMT clustered closer to HC at day 28, while dogs treated with MET did not. In this pilot study, dogs with AD had significant differences in fecal microbiota and metabolome profiles. Dogs treated with MET still had altered microbial and metabolic profiles at day 28 compared to dogs treated with FMT or healthy dogs.}, }
@article {pmid32359480, year = {2020}, author = {Frisbee, AL and Petri, WA}, title = {Considering the Immune System during Fecal Microbiota Transplantation for Clostridioides difficile Infection.}, journal = {Trends in molecular medicine}, volume = {26}, number = {5}, pages = {496-507}, doi = {10.1016/j.molmed.2020.01.009}, pmid = {32359480}, issn = {1471-499X}, abstract = {Our understanding and utilization of fecal microbiota transplantation (FMT) has jump-started over the past two decades. Recent technological advancements in sequencing and metabolomics have allowed for better characterization of our intestinal microbial counterparts, triggering a surge of excitement in the fields of mucosal immunology and microbiology. This excitement is well founded, as demonstrated by 90% relapse-free cure rates in FMT treatment for recurrent Clostridioides difficile infections. Growing evidence suggests that in addition to bacterial factors, the host immune response during C. difficile infection greatly influences disease severity. In this review, we discuss recent advancements in understanding the interplay between immune cells and the microbiota and how they may relate to recovery from C. difficile through FMT therapy.}, }
@article {pmid32357144, year = {2020}, author = {Li, Y and Ning, L and Yin, Y and Wang, R and Zhang, Z and Hao, L and Wang, B and Zhao, X and Yang, X and Yin, L and Wu, S and Guo, D and Zhang, C}, title = {Age-related shifts in gut microbiota contribute to cognitive decline in aged rats.}, journal = {Aging}, volume = {12}, number = {}, pages = {}, doi = {10.18632/aging.103093}, pmid = {32357144}, issn = {1945-4589}, abstract = {Cognitive function declines during the aging process, meanwhile, gut microbiota of the elderly changed significantly. Although previous studies have reported the effect of gut microbiota on learning and memory, all the reports were based on various artificial interventions to change the gut microbiota without involvement of aging biological characteristics. Here, we investigated the effect of aged gut microbiota on cognitive function by using fecal microbiota transplantation (FMT) from aged to young rats. Results showed that FMT impaired cognitive behavior in young recipient rats; decreased the regional homogeneity in medial prefrontal cortex and hippocampus; changed synaptic structures and decreased dendritic spines; reduced expression of brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartate receptor NR1 subunit, and synaptophysin; increased expression of advanced glycation end products (AGEs) and receptor for AGEs (RAGE). All these behavioral, brain structural and functional alterations induced by FMT reflected cognitive decline. In addition, FMT increased levels of pro-inflammatory cytokines and oxidative stress in young rats, indicating that inflammation and oxidative stress may underlie gut-related cognitive decline in aging. This study provides direct evidence for the contribution of gut microbiota to the cognitive decline during normal aging and suggests that restoring microbiota homeostasis in the elderly may improve cognitive function.}, }
@article {pmid32356257, year = {2020}, author = {Agrawal, G}, title = {Fecal Microbiota Transplantation for Clostridioides difficile in High-Risk Older Adults: Treat Early, Treat Often.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-020-06291-6}, pmid = {32356257}, issn = {1573-2568}, }
@article {pmid32354351, year = {2020}, author = {Arnoriaga-Rodríguez, M and Mayneris-Perxachs, J and Burokas, A and Pérez-Brocal, V and Moya, A and Portero-Otin, M and Ricart, W and Maldonado, R and Fernández-Real, JM}, title = {Gut bacterial ClpB-like gene function is associated with decreased body weight and a characteristic microbiota profile.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {59}, doi = {10.1186/s40168-020-00837-6}, pmid = {32354351}, issn = {2049-2618}, support = {CP19/00190//Instituto de Salud Calos III, Río Hortega/ ; CP18/00009//Instituto de Salud Carlos III, Miguel Servet/ ; PI15/01934//Instituto de Salud Carlos III/ ; }, abstract = {BACKGROUND: The chaperone ClpB, a bacterial protein, is a conformational antigen-mimetic of α-melanocyte-stimulating hormone (α-MSH) implicated in body weight regulation in mice. We here investigated the potential associations of gut bacterial ClpB-like gene function with obesity status and gut microbiota in humans.<br><br>RESULTS: Gut microbiota ClpB KEGG function was negatively associated with body mass index, waist circumference, and total fat mass (DEXA). The relative abundance (RA) of several phyla and families directly associated with ClpB was decreased in subjects with obesity. Specifically, the RA of Rikenellaceae, Clostridiaceae and not assigned Firmicutes were lower in subjects with obesity and positively associated with gut bacterial ClpB-like gene function (not assigned Firmicutes (r = 0.405, FDR = 2.93 × 10-2), Rikenellaceae (r = 0.217, FDR = 0.031), and Clostridiaceae (r = 0.239, FDR = 0.017)). The gut bacterial ClpB-like gene function was also linked to specific plasma metabolites (hippuric acid and 3-indolepropionic acid) and fecal lupeol. The α-MSH-like epitope similar to that of Escherichia coli ClpB was also identified in some sequences of those bacterial families. After fecal transplantation from humans to mice, the families that more contributed to ClpB-like gene function in humans were also associated with ClpB-like gene function in mice after adjusting for the donor's body mass index (not assigned Firmicutes (r = 0.621, p = 0.003), Prevotellaceae (r = 0.725, p = 4.1 × 10-7), Rikenellaceae (r = 0.702, p = 3.9 × 10-4), and Ruminococcaceae (r = 0.526, p = 0.014)). Clostridiaceae (r = - 0.445, p = 0.038) and Prevotellaceae RA (r = - 0.479, p = 0.024) and were also negatively associated with weight gain in mice. The absolute abundance (AA) of Prevotellaceae in mice was also positively associated with the gut bacterial ClpB-like gene function in mice. DESeq2 identified species of Prevotellaceae, both negatively associated with mice' weight gain and positively with gut bacterial ClpB-like gene function.<br><br>CONCLUSIONS: In summary, gut bacterial ClpB-like gene function is associated with obesity status, a specific gut microbiota composition and a plasma metabolomics profile in humans that could be partially transplanted to mice. Video Abstract.}, }
@article {pmid32354259, year = {2020}, author = {Lee, J and d'Aigle, J and Atadja, L and Quaicoe, V and Honarpisheh, P and Ganesh, BP and Hassan, A and Graf, J and Petrosino, JF and Putluri, N and Zhu, L and Durgan, DJ and Bryan, RM and McCullough, LD and Venna, VR}, title = {Gut Microbiota-Derived Short-Chain Fatty Acids Promote Post-Stroke Recovery in Aged Mice.}, journal = {Circulation research}, volume = {}, number = {}, pages = {}, doi = {10.1161/CIRCRESAHA.119.316448}, pmid = {32354259}, issn = {1524-4571}, abstract = {Rationale: The elderly experience profound systemic responses after stroke, which contribute to higher mortality and more severe long-term disability. Recent studies have revealed that stroke outcomes can be influenced by the composition of gut microbiome. However, the potential benefits of manipulating the gut microbiome after injury is unknown. Objective:To determine if restoring youthful gut microbiota after stroke aids in recovery in aged subjects, we altered the gut microbiome through young fecal transplant gavage (young FTG) in aged mice after experimental stroke. Further, the effect of direct enrichment of selective bacteria producing short-chain fatty acids (SCFAs) was tested as a more targeted and refined microbiome therapy. Methods and Results: Aged male mice (18-20 months) were subjected to ischemic stroke by middle cerebral artery occlusion (MCAO). We performed FTG three days after MCAO using young donor biome (2-3 months) or aged biome (18-20 months). At day 14 after stroke, aged stroke mice receiving young FTG had less behavioral impairment, and reduced brain and gut inflammation. Based on data from microbial sequencing and metabolomics analysis demonstrating that young fecal transplants contained much higher SCFA levels and related bacterial strains, we selected four SCFA-producers (Bifidobacterium longum, Clostridium symbiosum, Faecalibacterium prausnitzii and Lactobacillus fermentum) for transplantation. These SCFA-producers alleviated post-stroke neurological deficits and inflammation, and elevated gut, brain and plasma SCFA concentrations in aged stroke mice. Conclusions:This is the first study suggesting that the poor stroke recovery in aged mice can be reversed via &quot;post-stroke bacteriotherapy&quot; following the replenishment of youthful gut microbiome via modulation of immunologic, microbial and metabolomic profiles in the host.}, }
@article {pmid32353108, year = {2020}, author = {Payen, M and Nicolis, I and Robin, M and Michonneau, D and Delannoye, J and Mayeur, C and Kapel, N and Berçot, B and Butel, MJ and Le Goff, J and Socié, G and Rousseau, C}, title = {Functional and phylogenetic alterations in gut microbiome are linked to graft-versus-host disease severity.}, journal = {Blood advances}, volume = {4}, number = {9}, pages = {1824-1832}, doi = {10.1182/bloodadvances.2020001531}, pmid = {32353108}, issn = {2473-9537}, abstract = {Acute graft-versus-host disease (aGVHD) is the main complication of hematopoietic stem cell transplantation (HSCT). Changes in gut microbiota composition have been associated with subsequent aGVHD, and reconstitution of healthy microbiota is currently being explored as a therapeutic approach. However, the specific actors in the intestinal ecosystem involved in the pathologic process at the time of aGVHD onset are not yet fully known. We prospectively collected stool samples from patients who underwent allogeneic HSCT. Patients sampled at aGVHD onset were compared with non-GVHD patients. To identify phylogenetic and functional signatures of the disease process, we determined fecal short-chain fatty acid (SFCA) profiles and used high-throughput DNA sequencing and real-time quantitative polymerase chain reaction to assess the microbiota composition. Microbiota alterations were highly specific of gastrointestinal (GI) aGVHD severity. Bacterial biomass and α-diversity were lower in severe aGVHD. We identified several bacterial signatures associated with severe aGVHD at disease onset; a negative correlation was observed with anaerobic bacteria of the Lachnospiraceae, especially the Blautia genus, and Ruminococcaceae families. In parallel, in severe aGVHD patients, we showed a dramatic decrease in the levels of the main SFCAs: acetate (75.8%), propionate (95.8%), and butyrate (94.6%). Mild aGVHD patients were characterized by conserved levels of propionate and Blautia propionate producers. Butyrate was significantly decreased in all GI aGVHD stages, representing a potential diagnostic marker of the disease. Specific microbiota and metabolic alterations were thus associated with aGVHD severity and may be useful for diagnostic and pathophysiologic purposes.}, }
@article {pmid32350099, year = {2020}, author = {Korach-Rechtman, H and Hreish, M and Fried, C and Gerassy-Vainberg, S and Azzam, ZS and Kashi, Y and Berger, G}, title = {Intestinal Dysbiosis in Carriers of Carbapenem-Resistant Enterobacteriaceae.}, journal = {mSphere}, volume = {5}, number = {2}, pages = {}, doi = {10.1128/mSphere.00173-20}, pmid = {32350099}, issn = {2379-5042}, abstract = {Infection with carbapenem-resistant Enterobacteriaceae (CRE) has become an important challenge in health care settings and a growing concern worldwide. Since infection is preceded by colonization, an understanding of the latter may reduce CRE infections. We aimed to characterize the gut microbiota in CRE carriers, assuming that microbiota alterations precede CRE colonization. We evaluated the gut microbiota using 16S rRNA gene sequencing extracted of fecal samples collected from hospitalized CRE carriers and two control groups, hospitalized noncarriers and healthy adults. The microbiota diversity and composition in CRE-colonized patients differed from those of the control group participants. These CRE carriers displayed lower phylogenetic diversity and dysbiotic microbiota, enriched with members of the family Enterobacteriaceae Concurrent with the enrichment in Enterobacteriaceae, a depletion of anaerobic commensals was observed. Additionally, changes in several predicted metabolic pathways were observed for the CRE carriers. Concomitantly, we found higher prevalence of bacteremia in the CRE carriers. Several clinical factors that might induce changes in the microbiota were examined and found to be insignificant between the groups. The compositional and functional changes in the microbiota of CRE-colonized patients are associated with increased risk for systemic infection. Our study results provide justification for attempts to restore the dysbiotic microbiota with probiotics or fecal transplantation.IMPORTANCE The gut microbiota plays important roles in the host's normal function and health, including protection against colonization by pathogenic bacteria. Alterations in the gut microbial profile can potentially serve as an early diagnostic tool, as well as a therapeutic strategy against colonization by and carriage of harmful bacteria, including antibiotic-resistant pathogens. Here, we show that the microbiota of hospitalized patients demonstrated specific taxa which differed between carriers of carbapenem-resistant Enterobacteriaceae (CRE) and noncarriers. The difference in the microbiota also dictates alterations in microbiome-specific metabolic capabilities, in association with increased prevalence of systemic infection. Reintroducing specific strains and/or correction of dysbiosis with probiotics or fecal transplantation may potentially lead to colonization by bacterial taxa responsible for protection against or depletion of antibiotic-resistant pathogens.}, }
@article {pmid32346376, year = {2020}, author = {Zhang, Y and Liu, Q and Yu, Y and Wang, M and Wen, C and He, Z}, title = {Early and Short-Term Interventions in the Gut Microbiota Affects Lupus Severity, Progression, and Treatment in MRL/lpr Mice.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {628}, doi = {10.3389/fmicb.2020.00628}, pmid = {32346376}, issn = {1664-302X}, abstract = {There have been attempts to reveal the possible associations between systemic lupus erythematosus (SLE) and gut microbiota. Using MRL/lpr mice, this study was performed to reveal whether early and short-term interventions in gut microbiota affect lupus. MRL/lpr mice were treated with antibiotics or fecal microbiota transplantation (FMT) before onset. Then, prednisone was used to treat the lupus mice with initially different gut microbiota compositions. The compositions of gut microbiota were assessed by the V3-V4 region of 16S rRNA gene sequence. Early and short-term antibiotics exposure aggravated lupus severity by depleting beneficial gut microbiota for lupus, such as Lactobacillus and Bifidobacterium, and enriching harmful gut microbiota for lupus, such as Klebsiella and Proteus. FMT alleviated lupus severity by renovating the antibiotic-induced dysbiosis of gut microbiota in the following 1 week after antibiotics exposure. Besides, short-term antibiotics exposure before onset imposed no significant effects on lupus progression, but the following one week of FMT suppressed lupus progression. Moreover, the short-term antibiotics or FMT before onset inhibited the therapeutic efficiency of prednisone on lupus from 9 to 13 weeks old of MRL/lpr mice. These data demonstrate that the gut microbiota before onset is important for lupus severity, progression and treatment.}, }
@article {pmid31873192, year = {2020}, author = {Hill, C}, title = {Balancing the risks and rewards of live biotherapeutics.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {17}, number = {3}, pages = {133-134}, doi = {10.1038/s41575-019-0254-3}, pmid = {31873192}, issn = {1759-5053}, mesh = {*Bacteremia ; Escherichia coli ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Reward ; }, }
@article {pmid32023228, year = {2020}, author = {Pimentel, M and Saad, RJ and Long, MD and Rao, SSC}, title = {ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth.}, journal = {The American journal of gastroenterology}, volume = {115}, number = {2}, pages = {165-178}, doi = {10.14309/ajg.0000000000000501}, pmid = {32023228}, issn = {1572-0241}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Blind Loop Syndrome/*diagnosis/*therapy ; Breath Tests ; Culture Techniques ; *Diet Therapy ; *Fecal Microbiota Transplantation ; Humans ; Hydrogen/analysis ; Intestine, Small ; Methane/analysis ; Probiotics/*therapeutic use ; Suction ; }, abstract = {Small intestinal bacterial overgrowth is defined as the presence of excessive numbers of bacteria in the small bowel, causing gastrointestinal symptoms. This guideline statement evaluates criteria for diagnosis, defines the optimal methods for diagnostic testing, and summarizes treatment options for small intestinal bacterial overgrowth. This guideline provides an evidence-based evaluation of the literature through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. In instances where the available evidence was not appropriate for a formal GRADE recommendation, key concepts were developed using expert consensus.}, }
@article {pmid31712445, year = {2019}, author = {Sobhani, I and Bergsten, E and Couffin, S and Amiot, A and Nebbad, B and Barau, C and de'Angelis, N and Rabot, S and Canoui-Poitrine, F and Mestivier, D and Pédron, T and Khazaie, K and Sansonetti, PJ}, title = {Colorectal cancer-associated microbiota contributes to oncogenic epigenetic signatures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {48}, pages = {24285-24295}, pmid = {31712445}, issn = {1091-6490}, mesh = {Animals ; Cohort Studies ; Colorectal Neoplasms/*genetics/*microbiology ; DNA Methylation ; Dysbiosis/genetics/microbiology/pathology ; *Epigenesis, Genetic ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Gene Expression Regulation ; Germ-Free Life ; Humans ; Intestinal Mucosa/metabolism/pathology ; Male ; Mice, Inbred C3H ; Promoter Regions, Genetic ; RNA, Ribosomal, 16S ; }, abstract = {Sporadic colorectal cancer (CRC) is a result of complex interactions between the host and its environment. Environmental stressors act by causing host cell DNA alterations implicated in the onset of cancer. Here we investigate the stressor ability of CRC-associated gut dysbiosis as causal agent of host DNA alterations. The epigenetic nature of these alterations was investigated in humans and in mice. Germ-free mice receiving fecal samples from subjects with normal colonoscopy or from CRC patients were monitored for 7 or 14 wk. Aberrant crypt foci, luminal microbiota, and DNA alterations (colonic exome sequencing and methylation patterns) were monitored following human feces transfer. CRC-associated microbiota induced higher numbers of hypermethylated genes in murine colonic mucosa (vs. healthy controls' microbiota recipients). Several gene promoters including SFRP1,2,3, PENK, NPY, ALX4, SEPT9, and WIF1 promoters were found hypermethylated in CRC but not in normal tissues or effluents from fecal donors. In a pilot study (n = 266), the blood methylation levels of 3 genes (Wif1, PENK, and NPY) were shown closely associated with CRC dysbiosis. In a validation study (n = 1,000), the cumulative methylation index (CMI) of these genes was significantly higher in CRCs than in controls. Further, CMI appeared as an independent risk factor for CRC diagnosis as shown by multivariate analysis that included fecal immunochemical blood test. Consequently, fecal bacterial species in individuals with higher CMI in blood were identified by whole metagenomic analysis. Thus, CRC-related dysbiosis induces methylation of host genes, and corresponding CMIs together with associated bacteria are potential biomarkers for CRC.}, }
@article {pmid31554900, year = {2019}, author = {Zachariassen, LF and Hansen, AK and Krych, L and Nielsen, DS and Holm, TL and Tougaard, P and Hansen, CHF}, title = {Cesarean section increases sensitivity to oxazolone-induced colitis in C57BL/6 mice.}, journal = {Mucosal immunology}, volume = {12}, number = {6}, pages = {1348-1357}, doi = {10.1038/s41385-019-0207-8}, pmid = {31554900}, issn = {1935-3456}, mesh = {Animals ; Cesarean Section/*adverse effects ; Colitis/*chemically induced/immunology/metabolism/microbiology ; Colon/*immunology/metabolism/microbiology/pathology ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Inflammation Mediators/metabolism ; Intestinal Mucosa/*immunology/metabolism/microbiology/pathology ; Mice, Inbred C57BL ; *Oxazolone ; Peroxidase/metabolism ; Pregnancy ; Severity of Illness Index ; Tumor Necrosis Factor-alpha/metabolism ; }, abstract = {Children born by cesarean section (CS) have an increased risk of developing inflammatory bowel disease (IBD), possibly due to skewed microbial colonization during birth and consequently impaired bacterial stimulation of the developing immune system. The aim of this study was to investigate the association between CS and experimental colitis in a murine model of IBD. It was hypothesized that CS aggravates colonic inflammation due to a change in gut microbiota (GM) composition. C57BL/6 mice, delivered by CS or vaginal delivery (VD), were intra-rectally challenged with oxazolone at 8 weeks of age and monitored for colitis symptoms. The results showed that CS delivered mice experienced an increased body weight loss and colon weight, together with higher colonic concentrations of TNF-α and MPO compared with VD mice. Increased infiltration of inflammatory cells was present in CS delivered mice, as well as a downregulation in expression of the gut integrity genes occludin and tight junction protein 1 indicative of an impaired barrier function. The GM from CS delivered mice without colitis partly contributed to the increase in colitis symptoms when inoculated into germ-free recipient mice. In conclusion, CS increased sensitivity to oxazolone induced colitis in mice.}, }
@article {pmid31501515, year = {2019}, author = {Spalinger, MR and Schwarzfischer, M and Hering, L and Shawki, A and Sayoc, A and Santos, A and Gottier, C and Lang, S and Bäbler, K and Geirnaert, A and Lacroix, C and Leventhal, GE and Dai, X and Rawlings, D and Chan, AA and Rogler, G and McCole, DF and Scharl, M}, title = {Loss of PTPN22 abrogates the beneficial effect of cohousing-mediated fecal microbiota transfer in murine colitis.}, journal = {Mucosal immunology}, volume = {12}, number = {6}, pages = {1336-1347}, doi = {10.1038/s41385-019-0201-1}, pmid = {31501515}, issn = {1935-3456}, mesh = {Animals ; Bacteria/*growth &amp; development/immunology ; Cells, Cultured ; Colitis/enzymology/genetics/microbiology/*therapy ; Colon/*enzymology/immunology/microbiology ; Dextran Sulfate ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Genotype ; *Housing, Animal ; Intestinal Mucosa/*enzymology/immunology/microbiology ; Mice, Inbred C57BL ; Mice, Knockout ; Protein Tyrosine Phosphatase, Non-Receptor Type 22/*deficiency/genetics ; Th1 Cells/immunology/metabolism/microbiology ; }, abstract = {Fecal microbiota transfer (FMT) is a very efficient approach for the treatment of severe and recurring C. difficile infections. However, the beneficial effect of FMT in other disorders such as ulcerative colitis (UC) or Crohn's disease remains unclear. Furthermore, it is currently unknown how disease-associated genetic variants in donors or recipients influence the effect of FMT. We found that bacteria-transfer from wild-type (WT) donors via cohousing was efficient in inducing recovery from colitis in WT mice, but not in mice deficient in protein-tyrosine phosphatase non-receptor type 22 (PTPN22), a known risk gene for several chronic inflammatory diseases. Also cohousing of PTPN22-deficient mice with diseased WT mice failed to induce faster recovery. Our data indicate that the genetic background of the donor and the recipient influences the outcome of microbiota transfer, and offers a potential explanation why transfer of fecal microbes from some, but not all donors is efficient in UC patients.}, }
@article {pmid30835680, year = {2019}, author = {Wallace, DJ and Sayre, NL and Patterson, TT and Nicholson, SE and Hilton, D and Grandhi, R}, title = {Spinal cord injury and the human microbiome: beyond the brain-gut axis.}, journal = {Neurosurgical focus}, volume = {46}, number = {3}, pages = {E11}, doi = {10.3171/2018.12.FOCUS18206}, pmid = {30835680}, issn = {1092-0684}, support = {IK2 BX003240/BX/BLRD VA/United States ; }, mesh = {Animals ; Bacterial Translocation ; Brain Injuries, Traumatic/microbiology ; Burns/microbiology ; Dysbiosis/complications/immunology/microbiology/therapy ; Fecal Microbiota Transplantation ; Feedback, Physiological ; *Gastrointestinal Microbiome ; Humans ; Immunity, Mucosal/immunology ; Intestinal Mucosa/immunology/microbiology ; Mice ; Probiotics/therapeutic use ; Rats ; Sepsis/etiology/microbiology ; Species Specificity ; Spinal Cord Injuries/complications/immunology/*microbiology ; Stroke/microbiology/therapy ; }, abstract = {In addition to standard management for the treatment of the acute phase of spinal cord injury (SCI), implementation of novel neuroprotective interventions offers the potential for significant reductions in morbidity and long-term health costs. A better understanding of the systemic changes after SCI could provide insight into mechanisms that lead to secondary injury. An emerging area of research involves the complex interplay of the gut microbiome and the CNS, i.e., a brain-gut axis, or perhaps more appropriately, a CNS-gut axis. This review summarizes the relevant literature relating to the gut microbiome and SCI. Experimental models in stroke and traumatic brain injury demonstrate the bidirectional communication of the CNS to the gut with postinjury dysbiosis, gastrointestinal-associated lymphoid tissue-mediated neuroinflammatory responses, and bacterial-metabolite neurotransmission. Similar findings are being elucidated in SCI as well. Experimental interventions in these areas have shown promise in improving functional outcomes in animal models. This commensal relationship between the human body and its microbiome, particularly the gut microbiome, represents an exciting frontier in experimental medicine.}, }
@article {pmid32330797, year = {2020}, author = {Wang, H and Zhang, S and Yang, F and Xin, R and Wang, S and Cui, D and Sun, Y}, title = {The gut microbiota confers protection in the CNS against neurodegeneration induced by manganism.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {127}, number = {}, pages = {110150}, doi = {10.1016/j.biopha.2020.110150}, pmid = {32330797}, issn = {1950-6007}, abstract = {Among all types of pollution, heavy metals are considered the greatest threat to human health, and heavy metals are associated with an increased risk of cardiovascular disease, coronary heart disease and neurodegenerative disorders. Manganese (Mn) exposure is well reported to exert neurotoxicity and various neurodegenerative disorders, but the mechanisms are not clear. The gut microbiota plays a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities. The changes in chemical signaling, metabolism and gut microbiota associated with Mn exposure have provided deeper insight into the neurotoxic mechanism of Mn. We observed that Mn exposure increases host manganic bioaccumulation, and β-amyloid (Aβ), receptor-interacting protein kinase 3 (RIP3) and caspase-3 production in the brain, and causes hippocampal degeneration and necrosis. Mn exposure led to decreased gut bacterial richness, especially for Prevotellaceae, Fusobacteriaceae and Lactobacillaceae. In addition, Mn exposure altered the metabolism of tryptamine, taurodeoxycholic acid, β-hydroxypyruvic acid and urocanic acid. Meanwhile, we found correlations between the abundance of certain bacterial species and the level of tryptamine, taurodeoxycholic acid, β-hydroxypyruvic acid and urocanic acid. Fecal microbiome transplantation from normal rats could alleviate the neurotoxicity of Mn exposure by shaping the gut microbiota. Our findings highlight the role of gut dysbiosis-promoted neurotoxicity in Mn exposure and suggest a novel therapeutic strategy of remodeling the gut microbiota.}, }
@article {pmid32330075, year = {2020}, author = {Nie, X and Li, L and Yi, M and Qin, W and Zhao, W and Li, F and Wu, B and Yuan, X}, title = {The Intestinal Microbiota Plays as a Protective Regulator Against Radiation Pneumonitis.}, journal = {Radiation research}, volume = {}, number = {}, pages = {}, doi = {10.1667/RR15579.1}, pmid = {32330075}, issn = {1938-5404}, abstract = {Radiation pneumonitis is a common complication of thoracic irradiation for lung cancer patients. The healthy gut microbiota plays an important role in the local mucosal defense process as well as pulmonary immunomodulation of the host. However, the effect of the intestinal microbiota on radiation pneumonitis is not well understood. Here we studied how the intestinal microbiota affected the host response to radiation pneumonitis. C57BL/6 mice were administered antibiotics to induce disequilibrium in the gut microbiota, and subsequently irradiated. We found that the intestinal microbiota served as a protective mediator against radiation pneumonitis, as indicated by decreased body weight and increased mortality in antibiotic-treated mice. In mice with gut microbiota disequilibrium, more serious pathological lung damage was observed at two and four weeks postirradiation. Fecal microbiota transplantation into irradiated mice led to improvement from radiation-induced inflammation two weeks postirradiation. High-throughput sequencing of murine feces displayed conversion of flora diversity, bacterial composition and community structure in the absence of normal intestinal flora. We filtered the potentially important species among the gut microbiota and considered that the tissue-type plasminogen activator might be involved in the inflammatory process. This study reveals that the gut microbiota functions as a protective regulator against radiation pneumonitis. Additionally, fecal microbiota transplantation was shown to alleviate lung injury in the irradiated model. The protective role of the healthy gut microbiota and the utilization of the gut-lung axis show potential for innovative therapeutic strategies in radiation-induced lung injury.}, }
@article {pmid32326509, year = {2020}, author = {Nicco, C and Paule, A and Konturek, P and Edeas, M}, title = {From Donor to Patient: Collection, Preparation and Cryopreservation of Fecal Samples for Fecal Microbiota Transplantation.}, journal = {Diseases (Basel, Switzerland)}, volume = {8}, number = {2}, pages = {}, doi = {10.3390/diseases8020009}, pmid = {32326509}, issn = {2079-9721}, abstract = {Fecal Microbiota Transplantation (FMT) is suggested as an efficacious therapeutic strategy for restoring intestinal microbial balance, and thus for treating disease associated with alteration of gut microbiota. FMT consists of the administration of fresh or frozen fecal microorganisms from a healthy donor into the intestinal tract of diseased patients. At this time, in according to healthcare authorities, FMT is mainly used to treat recurrent Clostridium difficile. Despite the existence of a few existing stool banks worldwide and many studies of the FMT, there is no standard method for producing material for FMT, and there are a multitude of factors that can vary between the institutions. The main constraints for the therapeutic uses of FMT are safety concerns and acceptability. Technical and logistical issues arise when establishing such a non-standardized treatment into clinical practice with safety and proper governance. In this context, our manuscript describes a process of donor safety screening for FMT compiling clinical and biological examinations, questionnaires and interviews of donors. The potential risk of transmission of SARS-CoV-2 virus by the use of fecal microbiota for transplantation must be taken urgently into consideration. We discuss a standardized procedure of collection, preparation and cryopreservation of fecal samples through to the administration of material to patients, and explore the risks and limits of this method of FMT. The future success of medicine employing microbiota transplantation will be tightly related to its modulation and manipulation to combat dysbiosis. To achieve this goal, standard and strict methods need to be established before performing any type of FMT.}, }
@article {pmid31749279, year = {2020}, author = {Quaranta, G and Fancello, G and Ianiro, G and Graffeo, R and Gasbarrini, A and Cammarota, G and Sanguinetti, M and Masucci, L}, title = {Laboratory handling practice for faecal microbiota transplantation.}, journal = {Journal of applied microbiology}, volume = {128}, number = {3}, pages = {893-898}, doi = {10.1111/jam.14522}, pmid = {31749279}, issn = {1365-2672}, mesh = {Bacterial Load ; Biological Specimen Banks/standards ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Gastrointestinal Microbiome ; Humans ; Laboratories/*standards ; Specimen Handling/*methods ; Workflow ; }, abstract = {AIMS: Faecal microbiota transplantation (FMT) consists of the infusion of faeces from a healthy donor to the gastrointestinal tract of a recipient patient to treat disease associated with alterations in gut microbiota. The objective of this article was to describe laboratory workflow of an FMT laboratory to provide tips for preparing the faecal suspensions to be infused.<br><br>METHODS AND RESULTS: Twenty-stool solutions obtained from ten donors were prepared using two different protocols: magnet plate emulsion (MPE) and Seward StomacherTM Emulsion (SSE). We evaluated parameters such as preparation time, handiness, and aerobic and anaerobic microbial count. For three donors, we monitored bacterial counts after defrosting at different time-points. MPE requires more time than SSE. In terms of microbial load, both methods showed similar values, with small and statistically differences (P ≤ 0·05) regarding anaerobes in favour of SSE. Frozen aliquots showed the same bacterial load values after defrosting.<br><br>CONCLUSION: Although both methods allow an easy and available preparation of a stool suspension, SSE seems more suitable, particularly for stool banking. Aerobic and anaerobic species are preserved with both protocols; and safety for laboratory operators is guaranteed.<br><br>In recent years, FMT has become a fascinating and interesting subject. Nevertheless, there are no real guidelines describing laboratory facilities and procedures. This paper aims to be a useful and simple guide to increase the number FMT centres as much possible.}, }
@article {pmid31711971, year = {2019}, author = {Seekatz, AM}, title = {Development of an alternative animal model to investigate host-microbe interactions.}, journal = {EBioMedicine}, volume = {50}, number = {}, pages = {7-8}, doi = {10.1016/j.ebiom.2019.10.027}, pmid = {31711971}, issn = {2352-3964}, support = {K01 DK111794/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Inflammatory Bowel Diseases/*therapy ; Rats ; }, }
@article {pmid31144984, year = {2019}, author = {Tashiro, H and Cho, Y and Kasahara, DI and Brand, JD and Bry, L and Yeliseyev, V and Abu-Ali, G and Huttenhower, C and Shore, SA}, title = {Microbiota Contribute to Obesity-related Increases in the Pulmonary Response to Ozone.}, journal = {American journal of respiratory cell and molecular biology}, volume = {61}, number = {6}, pages = {702-712}, pmid = {31144984}, issn = {1535-4989}, support = {P30 ES000002/ES/NIEHS NIH HHS/United States ; R01 ES013307/ES/NIEHS NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; T32 HL007118/HL/NHLBI NIH HHS/United States ; R21 ES024032/ES/NIEHS NIH HHS/United States ; }, mesh = {Airway Resistance ; Animals ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Asthma/etiology/therapy ; Cellulose/administration &amp; dosage ; Dietary Fiber/administration &amp; dosage ; Fecal Microbiota Transplantation ; Female ; Fermentation ; Gastrointestinal Microbiome/drug effects/*physiology ; Germ-Free Life ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity/*complications/genetics/microbiology/physiopathology ; Ozone/*toxicity ; Pectins/administration &amp; dosage/therapeutic use ; Receptors, Leptin/deficiency ; Respiratory Hypersensitivity/chemically induced/diet therapy/*etiology/microbiology ; }, abstract = {Obesity is a risk factor for asthma, especially nonatopic asthma, and attenuates the efficacy of standard asthma therapeutics. Obesity also augments pulmonary responses to ozone, a nonatopic asthma trigger. The purpose of this study was to determine whether obesity-related alterations in gut microbiota contribute to these augmented responses to ozone. Ozone-induced increases in airway responsiveness, a canonical feature of asthma, were greater in obese db/db mice than in lean wild-type control mice. Depletion of gut microbiota with a cocktail of antibiotics attenuated obesity-related increases in the response to ozone, indicating a role for microbiota. Moreover, ozone-induced airway hyperresponsiveness was greater in germ-free mice that had been reconstituted with colonic contents of db/db than in wild-type mice. In addition, compared with dietary supplementation with the nonfermentable fiber cellulose, dietary supplementation with the fermentable fiber pectin attenuated obesity-related increases in the pulmonary response to ozone, likely by reducing ozone-induced release of IL-17A. Our data indicate a role for microbiota in obesity-related increases in the response to an asthma trigger and suggest that microbiome-based therapies such as prebiotics may provide an alternative therapeutic strategy for obese patients with asthma.}, }
@article {pmid31975529, year = {2020}, author = {Groves, HE and Allen, UD}, title = {Winning with poo? Fecal microbiome transplantation as an emerging strategy for the management of recurrent Clostridioides difficile infection in children.}, journal = {Pediatric transplantation}, volume = {24}, number = {1}, pages = {e13651}, doi = {10.1111/petr.13651}, pmid = {31975529}, issn = {1399-3046}, mesh = {Child, Preschool ; *Clostridium Infections ; *Clostridium difficile ; Fecal Microbiota Transplantation ; *Heart Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid31780599, year = {2019}, author = {Tamilarasan, AG and Irving, P and Meadows, CI and Goldenberg, S}, title = {Faecal microbiota transplantation for refractory Clostridiumdifficile infection.}, journal = {BMJ case reports}, volume = {12}, number = {11}, pages = {}, doi = {10.1136/bcr-2019-231027}, pmid = {31780599}, issn = {1757-790X}, mesh = {Aged ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; }, abstract = {Faecal microbiota transplantation (FMT) has become a part of the treatment algorithm for Clostridium difficile infection (CDI), particularly for recurrent infections when antibiotics have diminishing efficacy. Notably, despite a significant proportion of patients suffering from refractory disease, there is a general lack of evidence describing the use of FMT in this patient cohort. We present here a case of successful treatment of refractory CDI in a patient under critical care.}, }
@article {pmid32319703, year = {2020}, author = {Vangoitsenhoven, R and Cresci, GAM}, title = {Role of Microbiome and Antibiotics in Autoimmune Diseases.}, journal = {Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/ncp.10489}, pmid = {32319703}, issn = {1941-2452}, support = {R00AA023266//GAC National Institutes of Health, NIAAA/ ; }, abstract = {The global rise in the incidence of autoimmune diseases has paralleled the widespread use of antibiotics. Recently, the gut microbiome has been shown to be key in the development and maturation of a normal immune system, and a range of microbial disturbances have been associated with the development and activity of several autoimmune diseases. Here, we aim to provide an overview of the mechanistic crosstalk between the human microbiome, the immune system, and antibiotics. The disease-associated microbial gut dysbiosis, the potential role of antibiotics in the development and treatment of autoimmune diseases, and the manipulation of the gut microbiome with prebiotics and probiotics is discussed using 2 key autoimmune diseases as an example: inflammatory bowel disease and type 1 diabetes. Although some data suggest that widespread use of antibiotics may facilitate autoimmunity through gut dysbiosis, there are also data to suggest antibiotics may hold the potential to improve disease activity. Currently, the effect of fecal microbiota transplantation on several autoimmune diseases is being studied in clinical trials, and several preclinical studies are revealing promising results with probiotic and prebiotic therapies.}, }
@article {pmid32319196, year = {2020}, author = {Takashima, S and Tanaka, F and Kawaguchi, Y and Usui, Y and Fujimoto, K and Nadatani, Y and Otani, K and Hosomi, S and Nagami, Y and Kamata, N and Taira, K and Tanigawa, T and Watanabe, T and Imoto, S and Uematsu, S and Fujiwara, Y}, title = {Proton pump inhibitors enhance intestinal permeability via dysbiosis of gut microbiota under stressed conditions in mice.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {}, number = {}, pages = {e13841}, doi = {10.1111/nmo.13841}, pmid = {32319196}, issn = {1365-2982}, support = {//EA Pharma Co., Ltd./ ; //Daiichi Sankyo Corp., Ltd./ ; }, abstract = {BACKGROUND: Intestinal permeability and psychological stress are considered the key mechanism(s) in functional dyspepsia (FD). Although proton pump inhibitors (PPIs) are commonly used for the treatment of FD, the effect of PPIs on intestinal permeability has not been elucidated. This study investigated the effect of PPI on intestinal permeability under stressed conditions.<br><br>METHODS: C57BL/6J mice were subjected to water avoidance stress (WAS) and administered rabeprazole (40 mg/kg) or vehicle treatment (VT). We then evaluated intestinal permeability both in vivo and ex vivo using plasma fluorescein isothiocyanate-dextran and by assessing the paracellular permeability and transepithelial electrical resistance (TEER) in an Ussing chamber, respectively. Furthermore, we evaluated the effect of PPI-treated fecal microbiota transplant (FMT) on intestinal permeability in vivo. Microbiota profiles of donor feces were assessed by 16S rRNA gene analysis using MiSeq and QIIME2.<br><br>KEY RESULTS: In the WAS treatment, PPI significantly enhanced intestinal permeability in vivo compared to that in VT. Moreover, PPI significantly increased paracellular permeability and decreased TEER in the duodenum and jejunum, respectively, compared to those in VT under stressed conditions. Moreover, both vasoactive intestinal peptide (VIP) receptor antagonist and ketotifen significantly reversed the effect of PPI on intestinal permeability. Furthermore, PPI-treated FMT significantly increased the intestinal permeability in vivo compared to that in vehicle-treated FMT. Proton pump inhibitors treatment altered the gut microbiota composition, indicating that PPI induced dysbiosis.<br><br>CONCLUSIONS AND INFERENCES: Under stressed conditions, PPI enhances intestinal permeability via dysbiosis of gut microbiota. Vasoactive intestinal peptide and mast cells are also implicated in the underlying mechanisms.}, }
@article {pmid32318580, year = {2020}, author = {Gerussi, A and Lucà, M and Cristoferi, L and Ronca, V and Mancuso, C and Milani, C and D'Amato, D and O'Donnell, SE and Carbone, M and Invernizzi, P}, title = {New Therapeutic Targets in Autoimmune Cholangiopathies.}, journal = {Frontiers in medicine}, volume = {7}, number = {}, pages = {117}, doi = {10.3389/fmed.2020.00117}, pmid = {32318580}, issn = {2296-858X}, abstract = {Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are autoimmune cholangiopathies characterized by limited treatment options. A more accurate understanding of the several pathways involved in these diseases has fostered the development of novel and promising targeted drugs. For PBC, the characterization of the role of farnesoid X receptor (FXR) and perixosome-proliferator activated receptor (PPAR) has paved the way to several clinical trials including different molecules with choleretic and antinflammatory action. Conversely, different pathogenetic models have been proposed in PSC such as the &quot;leaky gut&quot; hypothesis, a dysbiotic microbiota or a defect in mechanisms protecting against bile acid toxicity. Along these theories, new treatment approaches have been developed, ranging from drugs interfering with trafficking of lymphocytes from the gut to the liver, fecal microbiota transplantation or new biliary acids with possible immunomodulatory potential. Finally, for both diseases, antifibrotic agents are under investigation. In this review, we will illustrate current understanding of molecular mechanisms in PBC and PSC, focusing on actionable biological pathways for which novel treatments are being developed.}, }
@article {pmid32318067, year = {2020}, author = {Zhou, B and Yuan, Y and Zhang, S and Guo, C and Li, X and Li, G and Xiong, W and Zeng, Z}, title = {Intestinal Flora and Disease Mutually Shape the Regional Immune System in the Intestinal Tract.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {575}, doi = {10.3389/fimmu.2020.00575}, pmid = {32318067}, issn = {1664-3224}, abstract = {The intestinal tract is the largest digestive organ in the human body. It is colonized by, and consistently exposed to, a myriad of microorganisms, including bifidobacteria, lactobacillus, Escherichia coli, enterococcus, clostridium perfringens, and pseudomonas. To protect the body from potential pathogens, the intestinal tract has evolved regional immune characteristics. These characteristics are defined by its unique structure, function, and microenvironment, which differ drastically from those of the common central and peripheral immune organs. The intestinal microenvironment created by the intestinal flora and its products significantly affects the immune function of the region. In turn, specific diseases regulate and influence the composition of the intestinal flora. A constant interplay occurs between the intestinal flora and immune system. Further, the intestinal microenvironment can be reconstructed by probiotic use or microbiota transplantation, functioning to recalibrate the immune homeostasis, while also contributing to the treatment or amelioration of diseases. In this review, we summarize the relationship between the intestinal flora and the occurrence and development of diseases as an in-turn effect on intestinal immunity. We also discuss improved immune function as it relates to non-specific and specific immunity. Further, we discuss the proliferation, differentiation and secretion of immune cells, within the intestinal region following remodeling of the microenvironment as a means to ameliorate and treat diseases. Finally, we suggest strategies for improved utilization of intestinal flora.}, }
@article {pmid32317112, year = {2020}, author = {Gryp, T and De Paepe, K and Vanholder, R and Kerckhof, FM and Van Biesen, W and Van de Wiele, T and Verbeke, F and Speeckaert, M and Joossens, M and Couttenye, MM and Vaneechoutte, M and Glorieux, G}, title = {Gut microbiota generation of protein-bound uremic toxins and related metabolites is not altered at different stages of chronic kidney disease.}, journal = {Kidney international}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.kint.2020.01.028}, pmid = {32317112}, issn = {1523-1755}, abstract = {Chronic kidney disease (CKD) is characterized by accumulation of protein-bound uremic toxins such as p-cresyl sulfate, p-cresyl glucuronide, indoxyl sulfate and indole-3-acetic acid, which originate in the gut. Intestinal bacteria metabolize aromatic amino acids into p-cresol and indole, (further conjugated in the colon mucosa and liver) and indole-3-acetic acid. Here we measured fecal, plasma and urine metabolite concentrations; the contribution of gut bacterial generation to plasma protein-bound uremic toxins accumulation; and influx into the gut of circulating protein-bound uremic toxins at different stages of CKD. Feces, blood and urine were collected from 14 control individuals and 141 patients with CKD. Solutes were quantified by ultra-high performance liquid chromatography. To assess the rate of bacterial generation of p-cresol, indole and indole-3-acetic acid, fecal samples were cultured ex vivo. With CKD progression, an increase in protein-bound uremic toxins levels was observed in plasma, whereas the levels of these toxins and their precursors remained the same in feces and urine. Anaerobic culture of fecal samples showed no difference in ex vivo p-cresol, indole and indole-3-acetic acid generation. Therefore, differences in plasma protein-bound uremic toxins levels between different CKD stages cannot be explained by differences in bacterial generation rates in the gut, suggesting retention due to impaired kidney function as the main contributor to their increased plasma levels. Thus, as fractional clearance decreased with the progression of CKD, tubular clearance appeared to be more affected than the glomerular filtration rate, and there was no net increase in protein-bound uremic toxins influx into the gut lumen with increased plasma levels.}, }
@article {pmid32316741, year = {2020}, author = {Li, J and Yang, X and Zhou, X and Cai, J}, title = {The role and mechanism of intestinal flora on blood pressure regulation and hypertension development.}, journal = {Antioxidants &amp; redox signaling}, volume = {}, number = {}, pages = {}, doi = {10.1089/ars.2020.8104}, pmid = {32316741}, issn = {1557-7716}, abstract = {SIGNIFICANCE: Hypertension (HTN) has a complex etiology characterized by genetic and environmental factors. It has become a global health burden leading to cardiovascular diseases and kidney diseases, ultimately progressing to premature death. Accumulating evidence indicated that gut microbiome was associated with metabolic disorders and inflammation, which were closely linked to HTN. Recent Advances: Recent studies using bacterial genomic analysis and fecal microbiota transplantation as well as many lines of seminal evidence demonstrated that aberrant gut microbiome was significantly associated with HTN. The intestinal microbiome of both patients and animals with HTN had decreased bacterial diversity, disordered microbial structure and functions, and altered end products of fermentation. Gut dysbiosis and metabolites of the gut microbiota play an important role in blood pressure control, and are therefore responsible for developing HTN.<br><br>CRITICAL ISSUES: This study aimed to focus on the recent advances in understanding the role played by gut bacteria and the mechanisms underlying the pathological milieu that induced elevated blood pressure and led to HTN pathogenesis. Potential intervention strategies targeting the correction of gut dysbiosis to improve HTN development were summarized.<br><br>FUTURE DIRECTIONS: Larger numbers of fecal transplants from participants with HTN should be carried out to examine the magnitude of blood pressure changes with the replacement of gut microbiome. The proposed mechanisms for gut in regulating blood pressure remain to be verified. Whether intervention strategies using probiotics, dietary interventions, bacteriophages, and fecal transplants are feasible for individuals with HTN remains to be explored.}, }
@article {pmid30789675, year = {2019}, author = {Stern, JM and Urban-Maldonado, M and Usyk, M and Granja, I and Schoenfeld, D and Davies, KP and Agalliu, I and Asplin, J and Burk, R and Suadicani, SO}, title = {Fecal transplant modifies urine chemistry risk factors for urinary stone disease.}, journal = {Physiological reports}, volume = {7}, number = {4}, pages = {e14012}, pmid = {30789675}, issn = {2051-817X}, support = {NIH R21 DK108097-02/NH/NIH HHS/United States ; }, mesh = {Animals ; Calcium/urine ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Absorption ; Gastrointestinal Microbiome ; Male ; Mice ; Mice, Inbred C57BL ; Rats ; Rats, Zucker ; Urinary Calculi/prevention &amp; control/*therapy ; Urine/chemistry/microbiology ; }, abstract = {Urinary stone disease (USD) is a major health concern. There is a need for new treatment modalities. Recently, our group provided evidence for an association between the GMB composition and USD. The accessibility of the Gut Microbiome (GMB) makes it an attractive target for investigation and therefore, in these studies we have evaluated the extent to which the whole gut microbial community in fecal transplants can affect urinary stone risk parameters in an animal model. Fresh fecal pellets were collected from Zucker lean rats, homogenized in PBS (100 mg/mL), filtered through a 70 μm strainer and then orally gavaged into C57BL/6NTac germ-free mice. Twenty-four hours urine collections and GMB analysis were performed over time for 1 month. Kidney and gut tissue were harvested from transplanted mice for western blot analysis of expression levels of the Slc26a6 transporter involved in oxalate balance. Urinary calcium decreased after fecal transplant by 55% (P < 0.001). Urinary oxalate levels were on average 24% lower than baseline levels (P < 0.001). Clostridiaceae family was negatively correlated with urinary oxalate at 4 weeks after transplant (r = -0.83, P < 0.01). There was a 0.6 unit average increase in urinary pH from a baseline of 5.85 (SE ± 0.028) to 6.49 (SE ± 0.04) (P < 0.001) after transplant. There was a concomitant 29% increase in gastrointestinal alkali absorption (P < 0.001) 4-weeks after fecal transplant. Slc26a6 expression increased by 90% in the cecum after transplant. Our results suggest that the gut microbiome may impact metabolism, alters urinary chemistry, and thereby may influence USD; the accessibility of the GMB can potentially be leveraged for therapeutic interventions.}, }
@article {pmid32310042, year = {2020}, author = {De Musis, C and Granata, L and Dallio, M and Miranda, A and Gravina, AG and Romano, M}, title = {Inflammatory bowel diseases: the role of gut microbiota.}, journal = {Current pharmaceutical design}, volume = {}, number = {}, pages = {}, doi = {10.2174/1381612826666200420144128}, pmid = {32310042}, issn = {1873-4286}, abstract = {Inflammatory bowel diseases (IBD) are chronic multifactorial diseases characterized by partially unclear pathogenic mechanisms including changes in intestinal microbiota. Despite the microbiota alteration is well established in IBD patients, as reported by 16RNA sequencing analysis, an important goal is to define if it is just a consequence of the disease progression or a trigger factor of the disease itself. To date gut microbiota composition and gut microbiota-related metabolites seem to affect the host healthy state both by modulating metabolic pathways or acting on the expression of different genes through epigenetic effects. Because of this, it has been suggested that intestinal microbiota might represent a promising therapeutic target for IBD patients. The aim of this review is to summarize both the most recent acquisitions in the field of gut microbiota and its involvement in intestinal inflammation together with the available strategies for the modulation of microbiota, such as prebiotics and/or probiotics administration or fecal microbiota transplantation.}, }
@article {pmid32307472, year = {2020}, author = {Hu, X and Mu, R and Xu, M and Yuan, X and Jiang, P and Guo, J and Cao, Y and Zhang, N and Fu, Y}, title = {Gut microbiota mediate the protective effects on endometritis induced by Staphylococcus aureus in mice.}, journal = {Food &amp; function}, volume = {}, number = {}, pages = {}, doi = {10.1039/c9fo02963j}, pmid = {32307472}, issn = {2042-650X}, abstract = {Endometritis, the inflammation of the endometrial lining caused by bacterial pathogens, is associated with reproductive failure. Recent studies have shown that gut microbiota play an important role in infectious diseases. However, the roles of the gut microbiota in endometritis remain unclear. Here, we assessed the effects and mechanisms of the gut microbiota during endometritis induced by Staphylococcus aureus (S. aureus). A mouse gut microbiota-dysbiosis model was established by a mixture of antibiotics (Abx) and subsequently, a model of endometritis was established by the uterine perfusion of S. aureus. Fecal microbiota transplantation (FMT) was performed to evaluate the relationship between gut microbiota and endometritis. The results showed that the mice with gut microbiota-dysbiosis developed uterine inflammation, while this inflammatory response of the uterus was alleviated in mice with FMT to gut microbiota-dysbiosis. In addition, S. aureus-induced endometritis was greater in severity in the mice with gut dysbiosis as compared to the untreated mice. Moreover, these effects were reversed in mice with FMT to the gut microbiota-dysbiosis. GC-MS analysis demonstrated that the levels of short-chain fatty acids (SCFAs) in the feces of mice with gut microbiota-dysbiosis significantly decreased and pretreatment with sodium butyrate or sodium propionate increased the concentrations of butyrate or propionate in both the circulation and uterine tissues, thereby reducing the severity of endometritis induced by S. aureus. In addition, the increased pathogen load in the uteri of the mice with gut microbiota-dysbiosis was associated with a reduction in the phagocytic ability and responsiveness of neutrophils. In conclusion, the gut microbiota offer a protective effect against S. aureus-induced endometritis by regulating the levels of SCFAs and maintaining the phagocytic ability and responsiveness of neutrophils.}, }
@article {pmid32306706, year = {2020}, author = {Mahajan, R and Midha, V and Singh, A and Mehta, V and Gupta, Y and Kaur, K and Sudhakar, R and Singh Pannu, A and Singh, D and Sood, A}, title = {Incidental benefits after fecal microbiota transplant for ulcerative colitis.}, journal = {Intestinal research}, volume = {}, number = {}, pages = {}, doi = {10.5217/ir.2019.00108}, pmid = {32306706}, issn = {1598-9100}, abstract = {Gut dysbiosis can result in several diseases, including infections (Clostridium difficile infection and infectious gastroenteritis), autoimmune diseases (inflammatory bowel disease, diabetes, and allergic disorders), behavioral disorders and other conditions like metabolic syndrome and functional gastrointestinal disorders. Amongst various therapies targeting gut microbiome, fecal microbiota transplantation (FMT) is becoming a focus in the public media and peer reviewed literature. We have been using FMT for induction of remission in patients with moderate to severe active ulcerative colitis (UC) and also for subsequent maintenance of remission. Four cases reported incidental benefits while being treated with FMT for UC. These included weight loss (n=1), improvement in hair loss (n=1), amelioration of axial arthritis (n=1) and improvement in allergic rhinitis (n=1), thereby suggesting potential clinical applications of FMT in treating extraintestinal diseases associated with gut dysbiosis.}, }
@article {pmid31996833, year = {2020}, author = {Dolgin, E}, title = {Fighting cancer with microbes.}, journal = {Nature}, volume = {577}, number = {7792}, pages = {S16-S18}, doi = {10.1038/d41586-020-00199-x}, pmid = {31996833}, issn = {1476-4687}, mesh = {Animals ; Bacteria/virology ; Bacteriophages/physiology ; Fecal Microbiota Transplantation/trends ; Gastrointestinal Microbiome/*physiology ; Host Microbial Interactions/*physiology ; Humans ; Mice ; Neoplasms/*microbiology/*therapy ; }, }
@article {pmid31996829, year = {2020}, author = {Svoboda, E}, title = {Could the gut microbiome be linked to autism?.}, journal = {Nature}, volume = {577}, number = {7792}, pages = {S14-S15}, doi = {10.1038/d41586-020-00198-y}, pmid = {31996829}, issn = {1476-4687}, mesh = {Animals ; Autistic Disorder/*microbiology/therapy ; Biodiversity ; Fecal Microbiota Transplantation/trends ; Gastrointestinal Microbiome/*physiology ; *Host Microbial Interactions ; Humans ; Mice ; }, }
@article {pmid31898340, year = {2020}, author = {Li, J and Dubois, W and Thovarai, V and Wu, Z and Feng, X and Peat, T and Zhang, S and Sen, SK and Trinchieri, G and Chen, J and Mock, BA and Young, NS}, title = {Attenuation of immune-mediated bone marrow damage in conventionally housed mice.}, journal = {Molecular carcinogenesis}, volume = {59}, number = {2}, pages = {237-245}, doi = {10.1002/mc.23151}, pmid = {31898340}, issn = {1098-2744}, mesh = {Anemia, Aplastic/immunology/pathology/*therapy ; Animals ; Bone Marrow/*immunology/pathology ; Bone Marrow Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome/*immunology ; Hyaluronan Receptors/immunology/metabolism ; Immunologic Memory/immunology ; Lymphocyte Activation/immunology ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Specific Pathogen-Free Organisms ; T-Lymphocytes/*immunology/metabolism/transplantation ; Transplantation Immunology ; Transplantation, Homologous ; }, abstract = {In humans, bone marrow (BM) failure syndromes, both constitutional and acquired, predispose to myeloid malignancies. We have modeled acquired immune aplastic anemia, the paradigmatic disease of these syndromes, in the mouse by infusing lymph node cells from specific pathogen-free (SPF) CD45.1 congenic C57BL/6 (B6) donors into hybrid CByB6F1 recipients housed either in conventional (CVB) or SPF facilities. The severity of BM damage was reduced in CVB recipients; they also had reduced levels of CD44+ CD62L- effector memory T cells, reduced numbers of donor-type CD44+ T cells, and reduced expansion of donor-type CD8 T cells carrying T-cell receptor β-variable regions 07, 11, and 17. Analyses of fecal samples through 16S ribosomal RNA amplicon sequencing revealed greater gut microbial alpha diversity in CVB mice relative to that of SPF mice. Thus, the presence of a broader spectrum of gut microorganisms in CVB-housed CByB6F1 could have primed recipient animal's immune system leading to suppression of allogeneic donor T-cell activation and expansion and attenuation of host BM destruction. These results suggest the potential benefit of diverse gut microbiota in patients receiving BM transplants.}, }
@article {pmid31005929, year = {2019}, author = {Leong, KSW and Jayasinghe, TN and Derraik, JGB and Albert, BB and Chiavaroli, V and Svirskis, DM and Beck, KL and Conlon, CA and Jiang, Y and Schierding, W and Vatanen, T and Holland, DJ and O'Sullivan, JM and Cutfield, WS}, title = {Protocol for the Gut Bugs Trial: a randomised double-blind placebo-controlled trial of gut microbiome transfer for the treatment of obesity in adolescents.}, journal = {BMJ open}, volume = {9}, number = {4}, pages = {e026174}, pmid = {31005929}, issn = {2044-6055}, mesh = {Adolescent ; Adult ; Body Mass Index ; Double-Blind Method ; Dysbiosis/etiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Follow-Up Studies ; *Gastrointestinal Microbiome ; Humans ; Male ; Pediatric Obesity/complications/*therapy ; Quality of Life ; Treatment Outcome ; Young Adult ; }, abstract = {INTRODUCTION: Animal studies showed that germ-free mice inoculated with normal mouse gut bacteria developed obesity, insulin resistance and higher triglyceride levels, despite similar food intake. In humans, an association has been found between obesity and gut microbiome dysbiosis. However, gut microbiome transfer has not been evaluated for the treatment of human obesity. We will examine the effectiveness of gut microbiome transfer using encapsulated material for the treatment of obesity in adolescents.<br><br>METHODS AND ANALYSIS: A two-arm, double-blind, placebo-controlled, randomised clinical trial of a single course of gut microbiome transfer will be conducted in 80 obese [body mass index (BMI) ≥30 kg/m2] adolescents (males and females, aged 14-18 years) in Auckland, New Zealand. Healthy lean donors (males and females, aged 18-28 years) will provide fresh stool samples from which bacteria will be isolated and double encapsulated. Participants (recipients) will be randomised at 1:1 to control (placebo) or treatment (gut microbiome transfer), stratified by sex. Recipients will receive 28 capsules over two consecutive mornings (~14 mL of frozen microbial suspension or saline). Clinical assessments will be performed at baseline, 6, 12 and 26 weeks, and will include: anthropometry, blood pressure, fasting metabolic markers, dietary intake, physical activity levels and health-related quality of life. Insulin sensitivity (Matsuda index), gut microbiota population structure characterised by 16S rRNA amplicon sequencing and body composition (using dual-energy X-ray absorptiometry) will be assessed at baseline, 6, 12 and 26 weeks. 24-hour ambulatory blood pressure monitoring will be performed at baseline and at 6 weeks. The primary outcome is BMI SD scores (SDS) at 6 weeks, with BMI SDS at 12 and 26 weeks as secondary outcomes. Other secondary outcomes include insulin sensitivity, adiposity (total body fat percentage) and gut microbial composition at 6, 12 and 26 weeks. Statistical analysis will be performed on the principle of intention to treat.<br><br>ETHICS AND DISSEMINATION: Ethics approval was provided by the Northern A Health and Disability Ethics Committee (Ministry of Health, New Zealand; 16/NTA/172). The trial results will be published in peer-reviewed journals and presented at international conferences.<br><br>TRIAL REGISTRATION NUMBER: ACTRN12615001351505; Pre-results.}, }
@article {pmid32305646, year = {2020}, author = {Wang, P and Gao, J and Ke, W and Wang, J and Li, D and Liu, R and Jia, Y and Wang, X and Chen, X and Chen, F and Hu, X}, title = {Resveratrol reduces obesity in high-fat diet-fed mice via modulating the structure and metabolic function of the gut microbiota.}, journal = {Free radical biology &amp; medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.freeradbiomed.2020.04.013}, pmid = {32305646}, issn = {1873-4596}, abstract = {Resveratrol (RSV) is a natural polyphenol with anti-obesity effects. However, the mechanisms of anti-obesity remain unclear due to its low bioavailability. Recent evidence demonstrates that gut microbiota plays a key role in obesity. This spurred us to investigate whether the anti-obesity effects of RSV are related to modulations in the gut microbiota and metabolic functions. Here, RSV significantly improved metabolic phenotype in the high-fat diet (HFD)-fed mice. A multi-omics approach was used to systematically profile the microbial signatures at both the phylogenetic and functional levels using 16S rRNA gene sequencing and metagenome. At the phylogenetic level, RSV treatment significantly modulated the gut microbiota composition in HFD-fed mice, characterized with increased Blautia abundance and decreased Desulfovibrio and Lachnospiraceae_NK4A136_group abundance. At the functional level, RSV significantly decreased pathways linked to host metabolic disease and increased pathways involved in the generation of small metabolites. Besides, the fecal microbiota transplantation experiment showed anti-obesity and microbiota-modulating effects similar to those observed in the oral RSV-feeding experiment. Moreover, metabolomic analysis and antibiotic treatment verified that 4-hydroxyphenylacetic acid (4-HPA) and 3-hydroxyphenylpropionic acid (3-HPP) were the two gut metabolites of RSV, which contribute to improving lipid metabolism in vitro. We concluded that the RSV-mediated alteration of gut microbiota and related gut metabolites contributed to prevention of metabolic syndrome in HFD-fed mice.}, }
@article {pmid32300219, year = {2020}, author = {Nazmul Huda, M and Winnike, JH and Crowell, JM and O'Connor, A and Bennett, BJ}, title = {Microbial modulation of host body composition and plasma metabolic profile.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {6545}, doi = {10.1038/s41598-020-63214-1}, pmid = {32300219}, issn = {2045-2322}, abstract = {The gut microbiota is a critical mediator of nutrition and disease risk. Like most complex traits, the microbiome is under genetic regulation and differs between inbred strains of mice. We tested the effect of fecal microbiota transplantation (FMT) on obesity, and plasma glucose. For this study, we collected microbiota from 2 inbred strains of mice which differ in adiposity and glucose tolerance, C57BL/6J and WSB/EiJ. C57BL/6J female mice (n = 18) were first treated with antibiotics for 4 weeks to ablate the microbiota. Following ablation, the mice were transplanted with microbiota from a C57BL/6J or a WSB/EiJ mouse and clinical traits and plasma metabolomic profiles were interrogated at 2- and 4-weeks post-transplantation. Unexpectedly, the mice receiving WSB/EiJ microbiota increased adiposity but decreased plasma glucose. Metabolomic and 16S microbiota profiling indicated broad metabolic changes occurred during and after FMT. Detailed analysis of these interactions demonstrated specific microbiota-host metabolite interactions which may alter disease susceptibility.}, }
@article {pmid32273468, year = {2020}, author = {Bessman, NJ and Mathieu, JRR and Renassia, C and Zhou, L and Fung, TC and Fernandez, KC and Austin, C and Moeller, JB and Zumerle, S and Louis, S and Vaulont, S and Ajami, NJ and Sokol, H and Putzel, GG and Arvedson, T and Sockolow, RE and Lakhal-Littleton, S and Cloonan, SM and Arora, M and Peyssonnaux, C and Sonnenberg, GF}, title = {Dendritic cell-derived hepcidin sequesters iron from the microbiota to promote mucosal healing.}, journal = {Science (New York, N.Y.)}, volume = {368}, number = {6487}, pages = {186-189}, doi = {10.1126/science.aau6481}, pmid = {32273468}, issn = {1095-9203}, support = {R00 HL125899/HL/NHLBI NIH HHS/United States ; R21 CA249274/CA/NCI NIH HHS/United States ; R01 AI123368/AI/NIAID NIH HHS/United States ; F32 AI124517/AI/NIAID NIH HHS/United States ; U01 AI095608/AI/NIAID NIH HHS/United States ; U2C ES030859/ES/NIEHS NIH HHS/United States ; R01 AI143842/AI/NIAID NIH HHS/United States ; R01 AI145989/AI/NIAID NIH HHS/United States ; R00 HD087523/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Cation Transport Proteins/metabolism ; Dendritic Cells/*metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gene Deletion ; Hepcidins/genetics/*metabolism ; Homeostasis ; Intestinal Diseases/*microbiology ; Intestinal Mucosa/*microbiology/*physiology ; Iron/*metabolism ; Mice ; Mice, Mutant Strains ; Phagocytes/metabolism ; }, abstract = {Bleeding and altered iron distribution occur in multiple gastrointestinal diseases, but the importance and regulation of these changes remain unclear. We found that hepcidin, the master regulator of systemic iron homeostasis, is required for tissue repair in the mouse intestine after experimental damage. This effect was independent of hepatocyte-derived hepcidin or systemic iron levels. Rather, we identified conventional dendritic cells (cDCs) as a source of hepcidin that is induced by microbial stimulation in mice, prominent in the inflamed intestine of humans, and essential for tissue repair. cDC-derived hepcidin acted on ferroportin-expressing phagocytes to promote local iron sequestration, which regulated the microbiota and consequently facilitated intestinal repair. Collectively, these results identify a pathway whereby cDC-derived hepcidin promotes mucosal healing in the intestine through means of nutritional immunity.}, }
@article {pmid32298656, year = {2020}, author = {Leonardi, I and Paramsothy, S and Doron, I and Semon, A and Kaakoush, NO and Clemente, JC and Faith, JJ and Borody, TJ and Mitchell, HM and Colombel, JF and Kamm, MA and Iliev, ID}, title = {Fungal Trans-kingdom Dynamics Linked to Responsiveness to Fecal Microbiota Transplantation (FMT) Therapy in Ulcerative Colitis.}, journal = {Cell host &amp; microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2020.03.006}, pmid = {32298656}, issn = {1934-6069}, abstract = {Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been successfully applied to ulcerative colitis. However, only a subset of patients responds to FMT, and there is a pressing need for biomarkers of responsiveness. Fungi (the mycobiota) represent a highly immunologically reactive component of the gut microbiota. We analyzed samples from a large randomized controlled trial of FMT for ulcerative colitis (UC). High Candida abundance pre-FMT was associated with a clinical response, whereas decreased Candida abundance post-FMT was indicative of ameliorated disease severity. High pre-FMT Candida was associated with increased bacterial diversity post-FMT, and the presence of genera was linked to FMT responsiveness. Although we detected elevated anti-Candida antibodies in placebo recipients, this increase was abrogated in FMT recipients. Our data suggest that FMT might reduce Candida to contain pro-inflammatory immunity during intestinal disease and highlight the utility of mycobiota-focused approaches to identify FMT responders prior to therapy initiation.}, }
@article {pmid32297646, year = {2020}, author = {Kilinçarslan, S and Evrensel, A}, title = {The effect of fecal microbiota transplantation on psychiatric symptoms among patients with inflammatory bowel disease: an experimental study.}, journal = {Actas espanolas de psiquiatria}, volume = {48}, number = {1}, pages = {1-7}, pmid = {32297646}, issn = {1578-2735}, abstract = {INTRODUCTION: Over the past decade, evidence that supports the relationship between intestinal microbiota and the brain has been obtained. Ageing, stress, nutrition and medicines can alter the composition of bacteria in the intestinal microbiota. This condition, called dysbiosis, can be repaired through prebiotics, probiotics or fecal microbiota transplantation (FMT). FMT is effective in the treatment of inflammatory bowel diseases (IBD). Information on FMT's use with psychiatric disorders is limited. This study aims to investigate changes in the severity of depression, anxiety and obsession of patients who received FMT for the treatment of inflammatory bowel diseases.<br><br>METHODS: This study was conducted with 10 patients with IBD who underwent FMT between March and September 2017. FMT was performed by an experienced gastroenterologist. The patients completed the Beck Depression Inventory (BDI), Symptom Checklist-90-Revised (SCL-90-R) and Maudsley Obsessive Compulsive Inventory (MOCI) before FMT and again at 1 month after FMT.<br><br>RESULTS: Significant decreases were found in BDI (Z=2.49, p=0.013), SCL-90-R (Z=-2.09, p=0.037) and MOCI (Z=2.08, p=0.037) scores after 1 month of FMT. Although the SCL-90-R anxiety subscale scores decreased, this decrease was not statistically significant (Z=-1.55, p=0.121).<br><br>CONCLUSIONS: The severity of anxiety, depression and obsession in IBD patients decreased after FMT. The decrease in psychiatric symptoms may result from the direct neuropsychiatric effect of FMT (primary effect), but also the improvement of gastrointestinal symptoms (secondary effect). Another possibility is that this result is independent of these two conditions. Therefore, the results of our study are not sufficient to establish a cause-effect relationship. More randomised controlled trials with larger samples from patients with anxiety or depression but without comorbid physical illnesses are needed to generalise these results.}, }
@article {pmid32296975, year = {2020}, author = {Fadda, HM}, title = {The Route to Palatable Fecal Microbiota Transplantation.}, journal = {AAPS PharmSciTech}, volume = {21}, number = {3}, pages = {114}, doi = {10.1208/s12249-020-1637-z}, pmid = {32296975}, issn = {1530-9932}, abstract = {The community of symbiotic microorganisms that reside in our gastrointestinal tract is integral to human health. Fecal microbiota transplantation (FMT) has been shown to be highly effective in treating recurrent Clostridioides difficile infection (rCDI) and is now recommended by medical societies for patients suffering from rCDI who have failed to respond to conventional therapy. The main challenges with FMT are its accessibility, acceptability, lack of standardization, and regulatory complexity, which will be discussed in this review. Access to FMT is being addressed through the development of frozen and lyophilized FMT preparations that can be prepared at stool banks and shipped to the point of care. Both access and patient acceptance would be enhanced by oral FMT capsules, and there is potential to reduce capsule burden by utilizing colonic release capsules, targeting the site of disease. This review compares the efficacy of different FMT routes of administration: capsules, nasal feeding tubes, enemas, and colonoscopic infusions. FMT is considered investigational by the Food and Drug Administration. In effort to improve access to FMT, physicians may perform FMT outside of an investigational new drug application for treating CDI infections not responsive to standard therapies. The majority of FMT studies report only minor adverse effects; however, there is risk of transmission of infections.}, }
@article {pmid32076145, year = {2020}, author = {Lavelle, A and Sokol, H}, title = {Gut microbiota-derived metabolites as key actors in inflammatory bowel disease.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {17}, number = {4}, pages = {223-237}, doi = {10.1038/s41575-019-0258-z}, pmid = {32076145}, issn = {1759-5053}, mesh = {Animals ; Bile Acids and Salts/metabolism ; Fatty Acids, Volatile/physiology ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/metabolism/microbiology ; Humans ; Inflammatory Bowel Diseases/diagnosis/metabolism/*microbiology/therapy ; Metabolomics/methods ; Probiotics/therapeutic use ; Tryptophan/metabolism ; }, abstract = {A key role of the gut microbiota in the establishment and maintenance of health, as well as in the pathogenesis of disease, has been identified over the past two decades. One of the primary modes by which the gut microbiota interacts with the host is by means of metabolites, which are small molecules that are produced as intermediate or end products of microbial metabolism. These metabolites can derive from bacterial metabolism of dietary substrates, modification of host molecules, such as bile acids, or directly from bacteria. Signals from microbial metabolites influence immune maturation, immune homeostasis, host energy metabolism and maintenance of mucosal integrity. Alterations in the composition and function of the microbiota have been described in many studies on IBD. Alterations have also been described in the metabolite profiles of patients with IBD. Furthermore, specific classes of metabolites, notably bile acids, short-chain fatty acids and tryptophan metabolites, have been implicated in the pathogenesis of IBD. This Review aims to define the key classes of microbial-derived metabolites that are altered in IBD, describe the pathophysiological basis of these associations and identify future targets for precision therapeutic modulation.}, }
@article {pmid32291810, year = {2020}, author = {Gallo, A and Cancelli, C and Ceron, E and Covino, M and Capoluongo, E and Pocino, K and Ianiro, G and Cammarota, G and Gasbarrini, A and Montalto, M}, title = {FAECAL CALPROTECTIN MAY PREDICT NEED OF MULTIPLE MICROBIOTA TRANSPLANTATION INFUSIONS IN CLOSTRIDIUM DIFFICILE INFECTION.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.15072}, pmid = {32291810}, issn = {1440-1746}, abstract = {BACKGROUND AND AIM: Faecal microbiota transplantation (FMT) has proven to be very effective in recurrent Clostridium difficile infection (CDI) when compared to standard antibiotic therapy. However, given the lack of validated criteria, decision regarding number and timing of infusions is currently based on the clinician's experience, severity of infection and clinical response. We performed a longitudinal assessment of fecal calprotectin concentration (FCC) in CDI patients undergoing FMT. FCCs were correlated with the need for multiple infusions and with the clinical status of the patient.<br><br>METHODS: FCC measurement was performed just before first procedure (T0) and two (T1) and five (T2) days later. The need for reinfusion was accounted for in the 8 weeks following procedure and clinical status was evaluated at the end of the given period. Both outcomes were correlated with measured FCCs.<br><br>RESULTS: A total of 28 CDI patients undergoing FMT were enrolled. Median FCCs at T0 were significantly higher in patients who needed repeat FMT, 540 μg/g vs patients who underwent single FMT, 290 μg/g (p<0.05). Differences were not significant for FCC at T1 and T2 . Regarding correlation with clinical outcome, median FCC at T0 was found to be lower in responders compared to non-responders with a trend towards statistical significance (p=0.07). Correlation at T1 and T2 was not significant.<br><br>CONCLUSIONS: The use of an easily obtainable parameter such as fecal calprotectin could possibly optimize overall management of FMT procedural framework potentially being able to immediately identify patients who may benefit from repeat infusions.}, }
@article {pmid31850583, year = {2020}, author = {Quigley, EMM}, title = {Commentary: faecal microbiota transplantation-from home brew to holy grail.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {51}, number = {1}, pages = {208-209}, doi = {10.1111/apt.15553}, pmid = {31850583}, issn = {1365-2036}, mesh = {*Clostridium Infections ; Colonoscopy ; *Enterocolitis, Pseudomembranous ; Fecal Microbiota Transplantation ; Humans ; Vancomycin ; }, }
@article {pmid31850561, year = {2020}, author = {Costello, SP and Bryant, RV}, title = {Editorial: faecal microbiota transplantation-the silver bullet for severe and fulminant Clostridioides difficile infection?.}, journal = {Alimentary pharmacology &amp; therapeutics}, volume = {51}, number = {1}, pages = {180-181}, doi = {10.1111/apt.15584}, pmid = {31850561}, issn = {1365-2036}, mesh = {*Clostridium Infections ; *Clostridium difficile ; Critical Illness ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid31784260, year = {2019}, author = {Liu, S and Rezende, RM and Moreira, TG and Tankou, SK and Cox, LM and Wu, M and Song, A and Dhang, FH and Wei, Z and Costamagna, G and Weiner, HL}, title = {Oral Administration of miR-30d from Feces of MS Patients Suppresses MS-like Symptoms in Mice by Expanding Akkermansia muciniphila.}, journal = {Cell host &amp; microbe}, volume = {26}, number = {6}, pages = {779-794.e8}, pmid = {31784260}, issn = {1934-6069}, support = {R01 NS087226/NS/NINDS NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; *Encephalomyelitis, Autoimmune, Experimental/drug therapy/immunology ; *Fecal Microbiota Transplantation ; Feces ; Gastrointestinal Microbiome/immunology ; Host Microbial Interactions ; Humans ; Lactase/metabolism ; Mice ; Mice, Inbred C57BL ; MicroRNAs/metabolism/*therapeutic use ; Multiple Sclerosis/*drug therapy ; T-Lymphocytes, Regulatory/metabolism ; *Verrucomicrobia/growth &amp; development/immunology/metabolism ; }, abstract = {Fecal transfer from healthy donors is being explored as a microbiome modality. MicroRNAs (miRNAs) have been found to affect the microbiome. Multiple sclerosis (MS) patients have been shown to have an altered gut microbiome. Here, we unexpectedly found that transfer of feces harvested at peak disease from the experimental autoimmune encephalomyelitis (EAE) model of MS ameliorates disease in recipients in a miRNA-dependent manner. Specifically, we show that miR-30d is enriched in the feces of peak EAE and untreated MS patients. Synthetic miR-30d given orally ameliorates EAE through expansion of regulatory T cells (Tregs). Mechanistically, miR-30d regulates the expression of a lactase in Akkermansia muciniphila, which increases Akkermansia abundance in the gut. The expanded Akkermansia in turn increases Tregs to suppress EAE symptoms. Our findings report the mechanistic underpinnings of a miRNA-microbiome axis and suggest that the feces of diseased subjects might be enriched with miRNAs with therapeutic properties.}, }
@article {pmid32031511, year = {2020}, author = {Stallmach, A and Steube, A and Grunert, P and Hartmann, M and Biehl, LM and Vehreschild, MJGT}, title = {Fecal Microbiota Transfer.}, journal = {Deutsches Arzteblatt international}, volume = {117}, number = {3}, pages = {31-38}, pmid = {32031511}, issn = {1866-0452}, mesh = {Clostridium Infections/*therapy ; *Clostridium difficile ; *Fecal Microbiota Transplantation ; Germany ; Humans ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transfer (FMT) is increasingly being used in Ger- many, as in other countries, for the treatment of recurrent Clostridioides difficile infection (rCDI). FMT is now being performed both for research and in individual patients outside of clinical trials. No compulsory standards have been established to date for donor screening or for the method of fecal transfer. Given the potential dangers of FMT, this would seem to be urgently necessary.<br><br>METHODS: This review is based on pertinent literature retrieved by a selective search, including the reports of consensus conferences from Germany and abroad.<br><br>RESULTS: Because of its high efficacy, FMT is the treatment of choice for rCDI. It is largely free of adverse side effects, even in immune-deficient patients, as long as comprehensive and repeated donor screening has been carried out, with extensive clinical and microbiological testing and with the use of structured questionnaires. The ingestion of frozen, encapsulated microbiota is just as effective as other modes of delivery for the treatment of rCDI.<br><br>CONCLUSION: Encapsulation of the fecal microbiome (FM) and storage at -20°C is the method of choice, because it can be standardized with the necessary quality controls and it is readily available. Patients with rCDI should undergo FMT by orally ingesting the capsules. There are ongoing research efforts to identify the active e FM. It is not yet clear when the ultimate goal of recombinant production can be achieved.}, }
@article {pmid31147381, year = {2020}, author = {de Groot, P and Scheithauer, T and Bakker, GJ and Prodan, A and Levin, E and Khan, MT and Herrema, H and Ackermans, M and Serlie, MJM and de Brauw, M and Levels, JHM and Sales, A and Gerdes, VE and Ståhlman, M and Schimmel, AWM and Dallinga-Thie, G and Bergman, JJ and Holleman, F and Hoekstra, JBL and Groen, A and Bäckhed, F and Nieuwdorp, M}, title = {Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time.}, journal = {Gut}, volume = {69}, number = {3}, pages = {502-512}, pmid = {31147381}, issn = {1468-3288}, mesh = {Adult ; Aged ; Bile Acids and Salts/analysis ; Chemokine CCL2/blood/genetics ; Energy Metabolism ; Fatty Acids, Volatile/analysis ; *Fecal Microbiota Transplantation ; Feces/chemistry ; *Gastric Bypass ; Gastrointestinal Microbiome ; Gastrointestinal Transit ; Gene Expression ; Glucose/*metabolism ; Humans ; *Insulin Resistance ; Lipolysis ; Male ; Metabolic Syndrome/*metabolism/physiopathology/therapy ; Metabolomics ; Middle Aged ; Subcutaneous Fat/metabolism ; Tissue Donors ; Young Adult ; }, abstract = {OBJECTIVE: Bariatric surgery improves glucose metabolism. Recent data suggest that faecal microbiota transplantation (FMT) using faeces from postbariatric surgery diet-induced obese mice in germ-free mice improves glucose metabolism and intestinal homeostasis. We here investigated whether allogenic FMT using faeces from post-Roux-en-Y gastric bypass donors (RYGB-D) compared with using faeces from metabolic syndrome donors (METS-D) has short-term effects on glucose metabolism, intestinal transit time and adipose tissue inflammation in treatment-naïve, obese, insulin-resistant male subjects.<br><br>DESIGN: Subjects with metabolic syndrome (n=22) received allogenic FMT either from RYGB-D or METS-D. Hepatic and peripheral insulin sensitivity as well as lipolysis were measured at baseline and 2 weeks after FMT by hyperinsulinaemic euglycaemic stable isotope (2H2-glucose and 2H5-glycerol) clamp. Secondary outcome parameters were changes in resting energy expenditure, intestinal transit time, faecal short-chain fatty acids (SCFA) and bile acids, and inflammatory markers in subcutaneous adipose tissue related to intestinal microbiota composition. Faecal SCFA, bile acids, glycaemic control and inflammatory parameters were also evaluated at 8 weeks.<br><br>RESULTS: We observed a significant decrease in insulin sensitivity 2 weeks after allogenic METS-D FMT (median rate of glucose disappearance: from 40.6 to 34.0 µmol/kg/min; p<0.01). Moreover, a trend (p=0.052) towards faster intestinal transit time following RYGB-D FMT was seen. Finally, we observed changes in faecal bile acids (increased lithocholic, deoxycholic and (iso)lithocholic acid after METS-D FMT), inflammatory markers (decreased adipose tissue chemokine ligand 2 (CCL2) gene expression and plasma CCL2 after RYGB-D FMT) and changes in several intestinal microbiota taxa.<br><br>CONCLUSION: Allogenic FMT using METS-D decreases insulin sensitivity in metabolic syndrome recipients when compared with using post-RYGB-D. Further research is needed to delineate the role of donor characteristics in FMT efficacy in human insulin-resistant subjects.<br><br>TRIAL REGISTRATION NUMBER: NTR4327.}, }
@article {pmid32282545, year = {2020}, author = {Li, Q and Zhang, T and Ding, X and Xiang, L and Cui, B and Buch, H and Zhang, F}, title = {Enhancing patient adherence to fecal microbiota transplantation maintains the long-term clinical effects in ulcerative colitis.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MEG.0000000000001725}, pmid = {32282545}, issn = {1473-5687}, abstract = {OBJECTIVES: The way to improve the long-term efficacy of fecal microbiota transplantation (FMT) in ulcerative colitis (UC) remains unclear. This study mainly dedicated to the UC patients' satisfaction with FMT and the importance of patients' adherence to repeated FMT for long-term clinical outcomes.<br><br>METHODS: Patients with UC who underwent FMT at our center from November 2012 to September 2018 were included. We assessed patient satisfaction with efficacy, safety, and reliability of FMT, as well as adherence to the repeated FMT.<br><br>RESULTS: One hundred and seventy-six patients were included in the analysis. The median follow-up duration of the study was 25.5 (interquartile range 13.0-46.5) months. The clinical response rate at 1 week, 1 month, 3 months, and 6 months after FMT was 48.9%, 69.3%, 49.4%, and 32.7%, respectively. 3.4% (6/176) of patients underwent colectomy after FMT during our long-term follow-up. Partial Mayo score at 1-month post-FMT (P < 0.001) was an independent factor of patients' satisfaction. The laboratory preparation process was related to the incidence of adverse events (P < 0.05). 23.8% (29/122) of patients with a good adherence followed our recommendation to undergo the second course of FMT and achieved a longer clinical response compared with the patients with poor adherence (P < 0.001).<br><br>CONCLUSION: Patients' good adherence to repeated FMT is important to maintain long-term clinical benefits achieved from FMT in UC. Registration number: NCT01790061.}, }
@article {pmid32280227, year = {2020}, author = {Liu, S and Guo, R and Liu, F and Yuan, Q and Yu, Y and Ren, F}, title = {Gut Microbiota Regulates Depression-Like Behavior in Rats Through the Neuroendocrine-Immune-Mitochondrial Pathway.}, journal = {Neuropsychiatric disease and treatment}, volume = {16}, number = {}, pages = {859-869}, doi = {10.2147/NDT.S243551}, pmid = {32280227}, issn = {1176-6328}, abstract = {Purpose: Gut microbiota affects various physiological functions in the host and has crucial effects on the nervous system. There is increasing evidence of a correlation between gut microbiota and depression; however, the mechanisms underlying the regulation of depression-like behavior by gut microbiota remain unclear. In this study, we assessed the regulatory mechanism of gut microbiota on depression-like behavior in rats.<br><br>Methods: We transplanted fecal microbiota obtained from patients with depression and healthy individuals into germ-free (GF) rats (n=18) through fecal microbiota transplantation technology. Next, we assessed the affective behavior in the rats using the forced swimming test and a sucrose preference test. We used enzyme-linked immunosorbent assay (ELISA) to determine the hippocampal levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and noradrenaline (NE) and the serum levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-6 (IL-6), interleukin-1 (IL-1), interleukin-1 (IL-4), and interleukin-1 (IL-10). The mitochondrial morphology of small intestinal epithelial cells was observed through transmission electron microscopy.<br><br>Results: Rats that received fecal microbiota from patients with depression (depression microbiota) exhibited depression-like behavior. They presented decreased levels of hippocampal neurotransmitters, serum CORT levels, and anti-inflammatory cytokine levels, as well as increased ACTH, CRH, and serum levels of multiple pro-inflammatory cytokines. Observation of the mitochondria ultrastructure showed damaged mitochondria in the intestinal epithelial cells, significant endoplasmic reticulum expansion, and border aggregation of nuclear chromatin.<br><br>Conclusion: Our findings suggested that the depression-like behaviors induced by the depression microbiota through the neuroendocrine-immune-mitochondrial pathway, which were associated with neuroendocrine disorders, inflammatory responses, and mitochondrial damage.}, }
@article {pmid32107473, year = {2020}, author = {König, J and Brummer, RJ}, title = {Faecal microbiota transplantation in IBS - new evidence for success?.}, journal = {Nature reviews. Gastroenterology &amp; hepatology}, volume = {17}, number = {4}, pages = {199-200}, doi = {10.1038/s41575-020-0282-z}, pmid = {32107473}, issn = {1759-5053}, mesh = {Double-Blind Method ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome ; }, }
@article {pmid31980603, year = {2020}, author = {Yu, M and Malik Tyagi, A and Li, JY and Adams, J and Denning, TL and Weitzmann, MN and Jones, RM and Pacifici, R}, title = {PTH induces bone loss via microbial-dependent expansion of intestinal TNF+ T cells and Th17 cells.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {468}, pmid = {31980603}, issn = {2041-1723}, support = {R01 DK112946/DK/NIDDK NIH HHS/United States ; S10 RR028009/RR/NCRR NIH HHS/United States ; U54 AG062334/AG/NIA NIH HHS/United States ; R01 DK108842/DK/NIDDK NIH HHS/United States ; R01 AR068157/AR/NIAMS NIH HHS/United States ; R01 AR070091/AR/NIAMS NIH HHS/United States ; I01 BX000105/BX/BLRD VA/United States ; R01 DK098391/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*immunology ; Germ-Free Life ; Gram-Positive Endospore-Forming Rods/immunology ; Hyperparathyroidism, Primary/complications/immunology/microbiology ; Intestines/immunology/microbiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Osteoporosis/*etiology/immunology/microbiology ; Parathyroid Hormone/*immunology ; T-Lymphocyte Subsets/*immunology ; Th17 Cells/*immunology ; Tumor Necrosis Factor-alpha/immunology ; }, abstract = {Bone loss is a frequent but not universal complication of hyperparathyroidism. Using antibiotic-treated or germ-free mice, we show that parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched by the Th17 cell-inducing taxa segmented filamentous bacteria (SFB). SFB+ microbiota enabled PTH to expand intestinal TNF+ T and Th17 cells and increase their S1P-receptor-1 mediated egress from the intestine and recruitment to the bone marrow (BM) that causes bone loss. CXCR3-mediated TNF+ T cell homing to the BM upregulated the Th17 chemoattractant CCL20, which recruited Th17 cells to the BM. This study reveals mechanisms for microbiota-mediated gut-bone crosstalk in mice models of hyperparathyroidism that may help predict its clinical course. Targeting the gut microbiota or T cell migration may represent therapeutic strategies for hyperparathyroidism.}, }
@article {pmid31907459, year = {2020}, author = {Zhai, B and Ola, M and Rolling, T and Tosini, NL and Joshowitz, S and Littmann, ER and Amoretti, LA and Fontana, E and Wright, RJ and Miranda, E and Veelken, CA and Morjaria, SM and Peled, JU and van den Brink, MRM and Babady, NE and Butler, G and Taur, Y and Hohl, TM}, title = {High-resolution mycobiota analysis reveals dynamic intestinal translocation preceding invasive candidiasis.}, journal = {Nature medicine}, volume = {26}, number = {1}, pages = {59-64}, pmid = {31907459}, issn = {1546-170X}, support = {R01 AI139632/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI093808/AI/NIAID NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; R01 AI137269/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/isolation &amp; purification ; Candida/pathogenicity ; Candidiasis, Invasive/*microbiology ; Cross Infection/blood/microbiology ; Feces/microbiology ; Hematopoietic Stem Cell Transplantation ; Humans ; Intestines/*microbiology ; *Mycobiome ; Species Specificity ; Transplantation, Homologous ; }, abstract = {The intestinal microbiota is a complex community of bacteria, archaea, viruses, protists and fungi1,2. Although the composition of bacterial constituents has been linked to immune homeostasis and infectious susceptibility3-7, the role of non-bacterial constituents and cross-kingdom microbial interactions in these processes is poorly understood2,8. Fungi represent a major cause of infectious morbidity and mortality in immunocompromised individuals, although the relationship of intestinal fungi (that is, the mycobiota) with fungal bloodstream infections remains undefined9. We integrated an optimized bioinformatics pipeline with high-resolution mycobiota sequencing and comparative genomic analyses of fecal and blood specimens from recipients of allogeneic hematopoietic cell transplant. Patients with Candida bloodstream infection experienced a prior marked intestinal expansion of pathogenic Candida species; this expansion consisted of a complex dynamic between multiple species and subspecies with a stochastic translocation pattern into the bloodstream. The intestinal expansion of pathogenic Candida spp. was associated with a substantial loss in bacterial burden and diversity, particularly in the anaerobes. Thus, simultaneous analysis of intestinal fungi and bacteria identifies dysbiosis states across kingdoms that may promote fungal translocation and facilitate invasive disease. These findings support microbiota-driven approaches to identify patients at risk of fungal bloodstream infections for pre-emptive therapeutic intervention.}, }
@article {pmid31668180, year = {2019}, author = {Pironi, L and Sasdelli, AS}, title = {Management of the Patient with Chronic Intestinal Pseudo-Obstruction and Intestinal Failure.}, journal = {Gastroenterology clinics of North America}, volume = {48}, number = {4}, pages = {513-524}, doi = {10.1016/j.gtc.2019.08.005}, pmid = {31668180}, issn = {1558-1942}, mesh = {Chronic Disease ; Fecal Microbiota Transplantation ; Gastrointestinal Agents/therapeutic use ; Hematopoietic Stem Cell Transplantation ; Humans ; Intestinal Pseudo-Obstruction/classification/*diagnosis/epidemiology/*therapy ; Intestines/transplantation ; Liver Transplantation ; Malabsorption Syndromes/etiology/*therapy ; Parenteral Nutrition, Home ; Trace Elements/administration &amp; dosage ; Vitamins/administration &amp; dosage ; }, abstract = {Chronic intestinal pseudo-obstruction (CIPO) is a severe form of intestinal dysmotility disorder, characterized by the impairment of gastrointestinal propulsion of the gut content in the absence of fixed occluding lesions. CIPO is a rare disease that can develop in both children and adults. CIPO is classified as primary/idiopathic, when no underlying disorder is demonstrated, or secondary, when related to systemic diseases. Diagnosis relies on the finding of chronic/recurrent obstructive type symptoms with radiological features of dilated intestine with air/fluid levels without any lumen occluding lesion. Therapy is based on nutrition, pharmacologic and surgical intervention and requires a multidisciplinary approach.}, }
@article {pmid32279172, year = {2020}, author = {Chauhan, A and Kumar, R and Sharma, S and Mahanta, M and Vayuuru, SK and Nayak, B and Kumar, S and Shalimar, }, title = {Fecal Microbiota Transplantation in Hepatitis B e Antigen-Positive Chronic Hepatitis B Patients: A Pilot Study.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-020-06246-x}, pmid = {32279172}, issn = {1573-2568}, abstract = {BACKGROUND: Intestinal flora plays a critical role in immunity against hepatitis B virus (HBV). Fecal Microbiota Transplantation (FMT) may be a potential immunomodulatory therapy in patients with chronic hepatitis B (CHB).<br><br>AIM: We aimed to study role of FMT in hepatitis B e antigen (HBeAg)-positive CHB patients in terms of its effect on HBeAg, HBsAg, and HBV DNA.<br><br>METHODS: HBeAg-positive patients despite being on antiviral treatment for > 1 year were given six cycles of FMT via gastroscope (nasoduodenal route) at 4 weekly intervals along with antiviral therapy. Twelve out of 14 included patients in FMT arm completed six cycles. Another 15 HBeAg-positive patients who were on oral antivirals for > 1 year were taken as control-antiviral therapy (AVT) arm. Per-protocol analysis was done.<br><br>RESULTS: The median (interquartile range) age in the FMT and AVT arm were 29 (25-35) and 29(24-38), respectively (P = 0.794). The median (interquartile range) duration of AVT prior to inclusion in the study was 80 (52-104) and 76 (52-114) months in FMT and AVT arm, respectively (P = 0.884). In the FMT arm, 16.7% (2/12) patients had HBeAg clearance in comparison to none in the AVT arm (P = 0.188). None of the patients in either arm had HBsAg loss. The FMT was tolerated well, 42.8% (6/14) patients reported one or more minor adverse events.<br><br>CONCLUSIONS: In this non-randomized pilot study, FMT appears to be safe and potentially effective in terms of viral suppression and HBeAg clearance in patients with HBeAg-positive CHB. Further randomized controlled trials are needed in order to obtain robust conclusions.}, }
@article {pmid32278875, year = {2020}, author = {Ricciuto, A and Sherman, PM and Laxer, RM}, title = {Gut microbiota in chronic inflammatory disorders: A focus on pediatric inflammatory bowel diseases and juvenile idiopathic arthritis.}, journal = {Clinical immunology (Orlando, Fla.)}, volume = {}, number = {}, pages = {108415}, doi = {10.1016/j.clim.2020.108415}, pmid = {32278875}, issn = {1521-7035}, abstract = {The gut microbiota is integral to human health, including maintaining the delicate balance between tolerance and protection against potentially harmful pathogens. A growing body of evidence implicates the intestinal microbiome in immune-mediated inflammatory disorders; these data span the spectrum from genetic and environmental disease risk factors, to animal studies (particularly germ-free and gnotobiotic models) and human studies, including evidence of dysbiosis in diseased individuals compared to healthy populations. In this review, we summarize both animal and human data supporting a link between the gut microbiota and inflammatory bowel diseases (IBD) and systemic inflammatory arthritis, as models for chronic inflammatory disorders, while offering a pediatric focus (pediatric IBD and juvenile idiopathic arthritis). We discuss relevant mechanisms related to the crosstalk between the gut microbiota and the innate and adaptive immune system. We close with a brief discussion of emerging microbe-altering interventions, including fecal microbial transplantation and its immunologic effects.}, }
@article {pmid32277534, year = {2020}, author = {Meng, X and Zhang, G and Cao, H and Yu, D and Fang, X and de Vos, WM and Wu, H}, title = {Gut Dysbacteriosis and Intestinal Disease: Mechanism and Treatment.}, journal = {Journal of applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jam.14661}, pmid = {32277534}, issn = {1365-2672}, abstract = {The gut microbiome functions like an endocrine organ, generating bioactive metabolites, enzymes or small molecules that can impact host physiology. Gut dysbacteriosis is associated with many intestinal diseases including (but not limited to) IBD, PSC-IBD, IBS, chronic constipation, osmotic diarrhea and colorectal cancer. The potential pathogenic mechanism of gut dysbacteriosis associated with intestinal diseases includes the alteration of composition of gut microbiota as well as the gut microbiota-derived signaling molecules. The many correlations between the latter and the susceptibility for intestinal diseases has placed a spotlight on the gut microbiome as a potential novel target for therapeutics. Currently, fecal microbial transplantation, dietary interventions, use of probiotics, prebiotics and drugs are the major therapeutic tools utilized to impact dysbacteriosis and associated intestinal diseases. In this review, we systematically summarized the role of intestinal microbiome in the occurrence and development of intestinal diseases. The potential mechanism of the complex interplay between gut dysbacteriosis and intestinal diseases, and the treatment methods are also highlighted.}, }
@article {pmid32276499, year = {2020}, author = {Fond, GB and Lagier, JC and Honore, S and Lancon, C and Korchia, T and Verville, PS and Llorca, PM and Auquier, P and Guedj, E and Boyer, L}, title = {Microbiota-Orientated Treatments for Major Depression and Schizophrenia.}, journal = {Nutrients}, volume = {12}, number = {4}, pages = {}, doi = {10.3390/nu12041024}, pmid = {32276499}, issn = {2072-6643}, abstract = {BACKGROUND AND SIGNIFICANCE: There is a need to develop new hypothesis-driven treatment for both both major depression (MD) and schizophrenia in which the risk of depression is 5 times higher than the general population. Major depression has been also associated with poor illness outcomes including pain, metabolic disturbances, and less adherence. Conventional antidepressants are partly effective, and 44% of the subjects remain unremitted under treatment. Improving MD treatment efficacy is thus needed to improve the SZ prognosis. Microbiota-orientated treatments are currently one of the most promising tracks.<br><br>METHOD: This work is a systematic review synthetizing data of arguments to develop microbiota-orientated treatments (including fecal microbiota transplantation (FMT)) in major depression and schizophrenia.<br><br>RESULTS: The effectiveness of probiotic administration in MD constitutes a strong evidence for developing microbiota-orientated treatments. Probiotics have yielded medium-to-large significant effects on depressive symptoms, but it is still unclear if the effect is maintained following probiotic discontinuation. Several factors may limit MD improvement when using probiotics, including the small number of bacterial strains administered in probiotic complementary agents, as well as the presence of a disturbed gut microbiota that probably limits the probiotics' impact. FMT is a safe technique enabling to improve microbiota in several gut disorders. The benefit/risk ratio of FMT has been discussed and has been recently improved by capsule administration.<br><br>CONCLUSION: Cleaning up the gut microbiota by transplanting a totally new human gut microbiota in one shot, which is referred to as FMT, is likely to strongly improve the efficacy of microbiota-orientated treatments in MD and schizophrenia and maintain the effect over time. This hypothesis should be tested in future clinical trials.}, }
@article {pmid32275059, year = {2019}, author = {Revolinski, S and Munoz-Price, LS}, title = {Fecal Microbiota Transplantation for Clostridioides difficile Infection in Immunocompromised Hosts.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciz689}, pmid = {32275059}, issn = {1537-6591}, }
@article {pmid32272276, year = {2020}, author = {Liu, C and Cheng, L and Ji, L and Li, F and Zhan, Y and Wu, B and Ke, Y and Chen, P and Hua, F and Yuan, L and Min, Z and Sun, L and Chen, H and Cheng, Y}, title = {Intestinal microbiota dysbiosis play a role in pathogenesis of patients with primary immune thrombocytopenia.}, journal = {Thrombosis research}, volume = {190}, number = {}, pages = {11-19}, doi = {10.1016/j.thromres.2020.03.012}, pmid = {32272276}, issn = {1879-2472}, abstract = {BACKGROUND: The intestinal microbiota is essential for the maintenance of the physiology of immune homeostasis. Dysbiosis has been described in some autoimmune diseases, however its role is still elusive in primary immune thrombocytopenia (ITP), which is one kind of autoimmune diseases. This study aimed to characterize the phylogenetic diversity of the fecal microbiota and its relationship with the platelet activation status in patients with ITP.<br><br>METHODS: The platelet activation status was assessed by 2 platelet markers, PAC-1 (antibody that recognizes the activated GPIIb/IIIa complex) and CD62p (Platelet surface P-selectin) by flow cytometry. Total DNA was extracted from fecal samples of ITP patients and healthy controls (HC). Sequencing the V4 hypervariable region of bacterial 16S rRNA genes was used to identify the changes in phylogenetic diversity and composition of the intestinal flora. The obtained sequencing reads were assigned to operational taxonomic units (OTUs, 97% sequence identity) and taxonomically classified to assess composition and diversity.<br><br>RESULTS: The percentage of PAC-1+ platelets in ITP patients was higher than that in control group (p < 0.001), The percentage of CD62p+ and PAC-1+CD62p+ platelets in ITP patients both higher than those in control group (p < 0.001). At the phylum level, eight different phyla were identified in ITP individuals, with a majority of Bacteroidetes (45.96%) and Firmicutes (38.59%), followed by Proteobacteria (11.43%), Fusobacteria(1.29%), and Actinobacteria (1.22%). While in the Healthy volunteers, ten phyla were detected, with a predominance of Firmicutes (50.92%) and Bacteroidetes (34.26%), came before Proteobacteria (13.60%), and Actinobacteria (0.90%). The gut microbiota was skewed in ITP, with an increased proportion of Proteobacteria, Bacteroidetes and Bacteroidetes/Firmicutes ratio, a decreased proportion of Firmicutes compared with HC. Disease specific alterations in diversity was also identified, especially the potential markers (Anaerorhabdus, sutterella, Peptostreptococcaceae, Clostridium_XI and carnobacteriaceae, p < 0.05) for ITP.<br><br>CONCLUSIONS: The results suggested that the distinct microbiota dysbiosis in ITP characterized by alterations in biodiversity and composition, which could provide insights for diet therapy and fecal microbiota transplantation treatment to cure ITP. There might be somehow compensatory enhancement of platelet activation in ITP patients. And there is associate between platelet activation and intestinal microbiota in patients with ITP.}, }
@article {pmid31559564, year = {2019}, author = {Li, J and Wei, H}, title = {Establishment of an efficient germ-free animal system to support functional microbiome research.}, journal = {Science China. Life sciences}, volume = {62}, number = {10}, pages = {1400-1403}, doi = {10.1007/s11427-019-9832-9}, pmid = {31559564}, issn = {1869-1889}, mesh = {Animals ; Anti-Bacterial Agents/metabolism ; Bacteria/metabolism ; Fecal Microbiota Transplantation ; Food/adverse effects ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; *Microbiota ; *Models, Animal ; Stomach Diseases/metabolism ; }, }
@article {pmid32266849, year = {2020}, author = {Boem, F and Nannini, G and Amedei, A}, title = {Not just 'immunity': how the microbiota can reshape our approach to cancer immunotherapy.}, journal = {Immunotherapy}, volume = {}, number = {}, pages = {}, doi = {10.2217/imt-2019-0192}, pmid = {32266849}, issn = {1750-7448}, abstract = {Cancer immunotherapy refers to a set of approaches aiming at enhancing the immune system to fight cancer growth and spread. This variety of therapeutic approaches, especially those inhibiting immune checkpoints, have shown very promising results. Nevertheless, patients may respond differently to treatments and the efficacy of immunotherapy seems to be dependent on several factors that go beyond the molecular targeting of immune cells modulation. Here, we review how the activity of gut microbiota appears to be crucial in determining the effectiveness of some immunotherapeutic treatments, fostering or impeding the conditions under which treatments can work or not. Moreover, we discuss how these findings suggest not only extending the range of immunotherapeutic approaches but also reshaping our understanding of immunotherapy itself.}, }
@article {pmid32266848, year = {2020}, author = {Voth, E and Khanna, S}, title = {Fecal microbiota transplantation for treatment of patients with recurrent Clostridioides difficile infection.}, journal = {Expert review of anti-infective therapy}, volume = {}, number = {}, pages = {}, doi = {10.1080/14787210.2020.1752192}, pmid = {32266848}, issn = {1744-8336}, abstract = {Introduction: Recurrent Clostridiodes difficile infection (rCDI) is a growing public health burden, and is associated with poor patient outcomes. Fecal microbiota transplantation (FMT) is a novel therapy with an aim to restore the disrupted microbiota with demonstrated success in management of rCDI and a favorable safety profile.Areas covered: This review includes a comprehensive overview of a search of the literature including epidemiology of rCDI, basics of the gut microbiome, antibiotic therapy for rCDI along with rationale for, safety and efficacy of FMT for rCDI.Expert opinion: Patients exposed to risk factors, such as antimicrobial agents, are at risk for disruption of the gut microbiome resulting in reduction of microbial diversity and dysbiosis. Dysbiotic microbiota predispose to primary and rCDI. Strategies to improve the current and future management of rCDI are under clinical investigation, including narrow spectrum antibiotics, monoclonal antibodies, and FMT, which has shown a high success rate for rCDI. Further investigation is needed to determine optimal standardization of the methodological components of FMT including donor screening, stool preparation, storage and instillation, and patient follow-up. Newer methods of microbiota replacement therapies including enema- and capsule-based therapies are under investigation.}, }
@article {pmid32266160, year = {2020}, author = {Vendrik, KEW and Ooijevaar, RE and de Jong, PRC and Laman, JD and van Oosten, BW and van Hilten, JJ and Ducarmon, QR and Keller, JJ and Kuijper, EJ and Contarino, MF}, title = {Fecal Microbiota Transplantation in Neurological Disorders.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {98}, doi = {10.3389/fcimb.2020.00098}, pmid = {32266160}, issn = {2235-2988}, abstract = {Background: Several studies suggested an important role of the gut microbiota in the pathophysiology of neurological disorders, implying that alteration of the gut microbiota might serve as a treatment strategy. Fecal microbiota transplantation (FMT) is currently the most effective gut microbiota intervention and an accepted treatment for recurrent Clostridioides difficile infections. To evaluate indications of FMT for patients with neurological disorders, we summarized the available literature on FMT. In addition, we provide suggestions for future directions. Methods: In July 2019, five main databases were searched for studies and case descriptions on FMT in neurological disorders in humans or animal models. In addition, the ClinicalTrials.gov website was consulted for registered planned and ongoing trials. Results: Of 541 identified studies, 34 were included in the analysis. Clinical trials with FMT have been performed in patients with autism spectrum disorder and showed beneficial effects on neurological symptoms. For multiple sclerosis and Parkinson's disease, several animal studies suggested a positive effect of FMT, supported by some human case reports. For epilepsy, Tourette syndrome, and diabetic neuropathy some studies suggested a beneficial effect of FMT, but evidence was restricted to case reports and limited numbers of animal studies. For stroke, Alzheimer's disease and Guillain-Barré syndrome only studies with animal models were identified. These studies suggested a potential beneficial effect of healthy donor FMT. In contrast, one study with an animal model for stroke showed increased mortality after FMT. For Guillain-Barré only one study was identified. Whether positive findings from animal studies can be confirmed in the treatment of human diseases awaits to be seen. Several trials with FMT as treatment for the above mentioned neurological disorders are planned or ongoing, as well as for amyotrophic lateral sclerosis. Conclusions: Preliminary literature suggests that FMT may be a promising treatment option for several neurological disorders. However, available evidence is still scanty and some contrasting results were observed. A limited number of studies in humans have been performed or are ongoing, while for some disorders only animal experiments have been conducted. Large double-blinded randomized controlled trials are needed to further elucidate the effect of FMT in neurological disorders.}, }
@article {pmid31940312, year = {2020}, author = {Schmidt, EKA and Torres-Espin, A and Raposo, PJF and Madsen, KL and Kigerl, KA and Popovich, PG and Fenrich, KK and Fouad, K}, title = {Fecal transplant prevents gut dysbiosis and anxiety-like behaviour after spinal cord injury in rats.}, journal = {PloS one}, volume = {15}, number = {1}, pages = {e0226128}, pmid = {31940312}, issn = {1932-6203}, support = {MOP 119281//CIHR/Canada ; }, mesh = {Animals ; Anxiety/*complications/*prevention &amp; control ; *Behavior, Animal ; Dysbiosis/*complications/microbiology/*prevention &amp; control ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Maze Learning ; Rats ; Recovery of Function ; Spinal Cord Injuries/*complications/microbiology/physiopathology/psychology ; }, abstract = {Secondary manifestations of spinal cord injury beyond motor and sensory dysfunction can negatively affect a person's quality of life. Spinal cord injury is associated with an increased incidence of depression and anxiety; however, the mechanisms of this relationship are currently not well understood. Human and animal studies suggest that changes in the composition of the intestinal microbiota (dysbiosis) are associated with mood disorders. The objective of the current study is to establish a model of anxiety following a cervical contusion spinal cord injury in rats and to determine whether the microbiota play a role in the observed behavioural changes. We found that spinal cord injury caused dysbiosis and increased symptoms of anxiety-like behaviour. Treatment with a fecal transplant prevented both spinal cord injury-induced dysbiosis as well as the development of anxiety-like behaviour. These results indicate that an incomplete unilateral cervical spinal cord injury can cause affective disorders and intestinal dysbiosis, and that both can be prevented by treatment with fecal transplant therapy.}, }
@article {pmid31857577, year = {2019}, author = {Cao, Z and Wang, X and Pang, Y and Cheng, S and Liu, J}, title = {Biointerfacial self-assembly generates lipid membrane coated bacteria for enhanced oral delivery and treatment.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {5783}, pmid = {31857577}, issn = {2041-1723}, mesh = {Administration, Oral ; Animals ; Colitis/chemically induced/microbiology/*therapy ; Colon/microbiology/pathology ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Drug Compounding/methods ; Drug Delivery Systems/*methods ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa/microbiology/pathology ; *Membrane Lipids ; Mice ; Probiotics/*administration &amp; dosage ; Proof of Concept Study ; }, abstract = {The gut microbiota represents a huge community of microorganisms that play essential roles in immune modulation and homeostasis maintenance. Microbiota transplantation is an important approach to prevent and treat disease as it can inhibit pathogen colonization and positively modulate bacterial composition. However, the development of oral bacterial therapeutics has been restricted by low bioavailability and limited retention in the gastrointestinal tract. Here, we report a simple yet highly efficient method to coat gut microbes via biointerfacial supramolecular self-assembly. Coating can be performed within 15 min by simply vortexing with biocompatible lipids. Bacteria coated with an extra self-assembled lipid membrane exhibit significantly improved survival against environmental assaults and almost unchanged viability and bioactivity. We demonstrate their enhanced efficacies in oral delivery and treatment using two murine models of colitis. We suggest that biointerfacial supramolecular self-assembly may provide a unique platform to generate advanced bacterial therapeutics for the treatment of various diseases.}, }
@article {pmid31469291, year = {2019}, author = {Ahmad, AF and Dwivedi, G and O'Gara, F and Caparros-Martin, J and Ward, NC}, title = {The gut microbiome and cardiovascular disease: current knowledge and clinical potential.}, journal = {American journal of physiology. Heart and circulatory physiology}, volume = {317}, number = {5}, pages = {H923-H938}, doi = {10.1152/ajpheart.00376.2019}, pmid = {31469291}, issn = {1522-1539}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Arteries/metabolism/*microbiology/pathology ; Atherosclerosis/metabolism/*microbiology/pathology/therapy ; Bacteria/*metabolism ; Diet, Healthy ; Dietary Supplements ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Intestines/*microbiology ; Plaque, Atherosclerotic ; Signal Transduction ; }, abstract = {Cardiovascular disease (CVD) is the leading cause of death worldwide. The human body is populated by a diverse community of microbes, dominated by bacteria, but also including viruses and fungi. The largest and most complex of these communities is located in the gastrointestinal system and, with its associated genome, is known as the gut microbiome. Gut microbiome perturbations and related dysbiosis have been implicated in the progression and pathogenesis of CVD, including atherosclerosis, hypertension, and heart failure. Although there have been advances in the characterization and analysis of the gut microbiota and associated bacterial metabolites, the exact mechanisms through which they exert their action are not well understood. This review will focus on the role of the gut microbiome and associated functional components in the development and progression of atherosclerosis. Potential treatments to alter the gut microbiome to prevent or treat atherosclerosis and CVD are also discussed.}, }
@article {pmid30836147, year = {2019}, author = {Viennois, E and Gewirtz, AT and Chassaing, B}, title = {Chronic Inflammatory Diseases: Are We Ready for Microbiota-based Dietary Intervention?.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {8}, number = {1}, pages = {61-71}, pmid = {30836147}, issn = {2352-345X}, support = {R01 DK083890/DK/NIDDK NIH HHS/United States ; R01 DK099071/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Dysbiosis/*diet therapy ; Emulsifying Agents/pharmacology/therapeutic use ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Humans ; Inflammation/*diet therapy/microbiology ; }, abstract = {The last 15 years have witnessed the emergence of a new field of research that focuses on the roles played by the intestinal microbiota in health and disease. This research field has produced accumulating evidence indicating that dysregulation of host-microbiota interactions contributes to a range of chronic inflammatory diseases, including inflammatory bowel diseases, colorectal cancer, and metabolic syndrome. Although dysregulation of the microbiota can take complex forms, in some cases, specific bacterial species that can drive specific clinical outcomes have been identified. Among the numerous factors influencing the intestinal microbiota composition, diet is a central actor, wherein numerous dietary factors can beneficially or detrimentally impact the host/microbiota relationship. This review will highlight recent literature that has advanced understanding of microbiota-diet-disease interplay, with a central focus on the following question: Are we ready to use intestinal microbiota composition-based personalized dietary interventions to treat chronic inflammatory diseases?}, }
@article {pmid30681907, year = {2019}, author = {Morris, DJ and Brem, AS}, title = {Role of gut metabolism of adrenal corticosteroids and hypertension: clues gut-cleansing antibiotics give us.}, journal = {Physiological genomics}, volume = {51}, number = {3}, pages = {83-89}, doi = {10.1152/physiolgenomics.00115.2018}, pmid = {30681907}, issn = {1531-2267}, mesh = {11-beta-Hydroxysteroid Dehydrogenase Type 1/antagonists &amp; inhibitors/metabolism ; 11-beta-Hydroxysteroid Dehydrogenase Type 2/antagonists &amp; inhibitors/metabolism ; Animals ; Anti-Bacterial Agents/*therapeutic use ; Blood Pressure/drug effects ; Corticosterone/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*physiology ; Glucocorticoids/*metabolism ; Humans ; Hydrocortisone/metabolism ; Hypertension/*drug therapy/*microbiology ; Intestinal Mucosa/drug effects/*metabolism ; Mice ; Rats ; }, abstract = {Intestinal bacteria can metabolize sterols, bile acids, steroid hormones, dietary proteins, fiber, foodstuffs, and short chain fatty acids. The metabolic products generated by some of these intestinal bacteria have been linked to a number of systemic diseases including obesity with Type 2 diabetes mellitus, some forms of inflammation, and more recently, systemic hypertension. In this review, we primarily focus on the potential role selected gut bacteria play in metabolizing the endogenous glucocorticoids corticosterone and cortisol. Those generated steroid metabolites, when reabsorbed in the intestine back into the circulation, produce biological effects most notably as inhibitors of 11β-hydroxysteroid dehydrogenase (11β-HSD) types 1 and 2. Inhibition of the dehydrogenase actions of 11β-HSD, particularly in kidney and vascular tissue, allows both corticosterone and cortisol the ability to bind to and activate mineralocorticoid receptors with attended changes in sodium handling and vascular resistance leading to increases in blood pressure. In several animal models of hypertension, administration of gut-cleansing antibiotics results in transient resolution of hypertension and transfer of intestinal contents from a hypertensive animal to a normotensive animal produces hypertension in the recipient. Moreover, fecal samples from hypertensive humans transplanted into germ-free mice resulted in hypertension in the recipient mice. Thus, it appears that the intestinal microbiome may not just be an innocent bystander but certain perturbations in the type and number of bacteria may directly or indirectly affect hypertension and other diseases.}, }
@article {pmid32256746, year = {2020}, author = {Chen, HT and Huang, HL and Xu, HM and Luo, QL and He, J and Li, YQ and Zhou, YL and Nie, YQ and Zhou, YJ}, title = {Fecal microbiota transplantation ameliorates active ulcerative colitis.}, journal = {Experimental and therapeutic medicine}, volume = {19}, number = {4}, pages = {2650-2660}, doi = {10.3892/etm.2020.8512}, pmid = {32256746}, issn = {1792-0981}, abstract = {Ulcerative colitis (UC) is a complex chronic pathological condition of the gut in which microbiota targeted treatment, such as fecal microbiota transplantation (FMT), has shown an encouraging effect. The aim of the present study was to investigate the efficacy and safety of FMT in patients with mild or moderate UC. A single-center, open-label study was designed, including 47 patients with mild or moderate active UC who received three treatments of fresh FMT via colonic transendoscopic enteral tubing within 1 week. The inflammatory bowel disease questionnaire, partial Mayo scores, colonoscopy, erythrocyte sedimentation rate, C-reactive protein level and procalcitoin values were used to assess the efficacy of FMT and alteration in gut microbiota was detected by 16S ribosomal RNA-sequencing. Before FMT, microbiota Faecalibacterium prausnitzii (F. prausnitzii) levels were significantly decreased in patients with UC compared with healthy donors (P<0.01). At 4 weeks post-FMT, F. prausnitzii levels were significantly increased (P<0.05), and the Mayo score was significantly decreased (1.91±1.07 at baseline vs. 4.02±1.47 at week 4; P<0.001) in patients with UC compared with healthy donors. Steroid-free clinical responses were reported in 37 patients (84.1%), and steroid-free clinical remission was achieved in 31 patients (70.5%) at week 4 post-FMT, however, steroid-free remission was not achieved in any patient. No adverse events were reported in 41 (93.2%) patients after FMT or during the 12-week follow-up. Shannon's diversity index and Chao1 estimator were also improved in patients with UC receiving FMT. In conclusion, the results of the present study suggested that FMT resulted in clinical remission in patients with mild to moderate UC, and that the remission may be associated with significant alterations to the intestinal microbiota of patients with UC. Furthermore, F. prausnitzii may serve as a diagnostic and therapeutic biomarker for the use of FMT in UC.}, }
@article {pmid32255522, year = {2020}, author = {Du, HX and Liu, Y and Zhang, LG and Zhan, CS and Chen, J and Zhang, M and Chen, XG and Zhang, L and Liang, CZ}, title = {Abnormal gut microbiota composition is associated with experimental autoimmune prostatitis-induced depressive-like behaviors in mice.}, journal = {The Prostate}, volume = {}, number = {}, pages = {}, doi = {10.1002/pros.23978}, pmid = {32255522}, issn = {1097-0045}, support = {81470986//National Natural Science Foundation of China/ ; 81630019//National Natural Science Foundation of China/ ; 81870519//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Depressive symptoms are found in approximately 78% of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients, but the pathological mechanisms remain unknown. Increasing evidence suggests that abnormal gut microbiota may play an important role in depression. Thus, we aimed to investigate whether gut microbiota contributes to CP/CPPS-associated depression by using a mouse model of experimental autoimmune prostatitis (EAP).<br><br>METHODS: Male nonobese diabetic mice were immunized twice by subcutaneous injection of prostate antigen and adjuvant. Behavioral tests consisted of an open field test, sucrose preference test, forced swimming tests, and tail suspension test was used to confirm the depression-like symptoms that were induced by EAP. Then, fecal samples were collected, and 16S ribosomal RNA gene sequencing was performed to detect differences in gut microbiota composition between control and EAP group. Additionally, fecal bacteria from the control and EAP mice were transplanted into antibiotics-induced pseudo-germ-free mice to investigate the effects on host behaviors and the composition of gut bacteria.<br><br>RESULTS: EAP was successfully established and exhibited depressive-like behaviors in mice. The 16S rRNA analysis of fecal samples indicated the abnormal composition of gut microbiota in the EAP mice compared to the control mice. In the fecal microbiota transplant study, antibiotics-treated pseudo-germ-free mice presented depressive states as compared to naïve mice. Fecal bacteria transplant from EAP mice, but not from control mice, into the pseudo-germ-free mice, significantly exaggerated host depression-like behaviors. Moreover, fecal bacteria transplants from control and EAP mice induced distinct alterations in α-diversity and β-diversity indices. In all, 24 bacteria at six phylogenetic levels were remarkably changed by the fecal bacteria transplantation.<br><br>CONCLUSIONS: Abnormal gut microbiota composition after EAP induction may contribute to the development of depression in mice. A therapeutic strategy that targets gut microbiota may provide an alternative treatment for alleviating this condition.}, }
@article {pmid32253791, year = {2020}, author = {Hughes, KR and Schofield, Z and Dalby, MJ and Caim, S and Chalklen, L and Bernuzzi, F and Alcon-Giner, C and Le Gall, G and Watson, AJM and Hall, LJ}, title = {The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {}, number = {}, pages = {}, doi = {10.1096/fj.202000042R}, pmid = {32253791}, issn = {1530-6860}, support = {100974/C/13/Z//Wellcome Trust (Wellcome)/ ; BB/J004529/1//Biotechnology and Biological Sciences Research Council (BBSRC)/ ; BB/R012490/1//Biotechnology and Biological Sciences Research Council (BBSRC)/ ; }, abstract = {The early life gut microbiota plays a crucial role in regulating and maintaining the intestinal barrier, with disturbances in these communities linked to dysregulated renewal and replenishment of intestinal epithelial cells. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period, and which host and microbial factors mediate these responses. Surprisingly, neonatal mice (Day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of liposaccharide (LPS), with Day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses. When we profiled microbiota and metabolites, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia, and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes, and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Antibiotic treatment of neonates restored LPS-induced small intestinal cell shedding, whereas adult fecal microbiota transplant alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlights areas for further investigation.}, }
@article {pmid32251667, year = {2020}, author = {Pickert, G and Wirtz, S and Matzner, J and Ashfaq-Khan, M and Heck, R and Rosigkeit, S and Thies, D and Surabattula, R and Ehmann, D and Wehkamp, J and Aslam, M and He, G and Weigert, A and Foerster, F and Klotz, L and Frick, JS and Becker, C and Bockamp, E and Schuppan, D}, title = {Wheat Consumption Aggravates Colitis in Mice via Amylase Trypsin Inhibitor-mediated Dysbiosis.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2020.03.064}, pmid = {32251667}, issn = {1528-0012}, abstract = {BACKGROUND &amp; AIMS: Wheat has become the world´s major staple and its consumption correlates with prevalence of non-communicable disorders such as inflammatory bowel diseases. Amylase trypsin inhibitors (ATIs), a component of wheat, activate the intestine's innate immune response via toll-like receptor 4 (TLR4). We investigated the effects of wheat and ATIs on severity of colitis and fecal microbiota in mice.<br><br>METHODS: C57BL/6 wildtype and Tlr4-/- mice were fed wheat- or ATI-containing diets or a wheat-free (control) diet and then given dextran sodium sulfate to induce colitis; we also studied Il10-/- mice, which develop spontaneous colitis. Changes in fecal bacteria were assessed by taxa-specific quantitative PCR and 16S ribosomal RNA metagenomic sequencing. Feces were collected from mice on wheat-containing, ATI-containing, control diets and transplanted to intestines of mice with and without colitis on control or on ATI-containing diets. Intestinal tissues were collected and analyzed by histology, immunohistochemistry and flow cytometry. Bacteria with reported immunomodulatory effects were incubated with ATIs and analyzed in radial diffusion assays.<br><br>RESULTS: The wheat- or ATI-containing diets equally increased inflammation in intestinal tissues of C57BL/6 mice with colitis, compared with mice on control diets. The ATI-containing diet promoted expansion of taxa associated with development of colitis comparable to the wheat-containing diet. ATIs inhibited proliferation of specific human commensal bacteria in radial diffusion assays. Transplantation of microbiota from feces of mice fed the wheat- or ATI-containing diets to intestines of mice on control diets increased the severity of colitis in these mice. The ATI-containing diet did not increase the severity of colitis in Tlr4-/- mice.<br><br>CONCLUSIONS: Consumption of wheat or wheat-ATIs increases intestinal inflammation in mice with colitis, via TLR4, and alters their fecal microbiota. Wheat-based, ATI-containing diets therefore activate TLR4 signaling and promote intestinal dysbiosis.}, }
@article {pmid32250972, year = {2020}, author = {Mennini, M and Fierro, V and Di Nardo, G and Pecora, V and Fiocchi, A}, title = {Microbiota in non-IgE-mediated food allergy.}, journal = {Current opinion in allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1097/ACI.0000000000000644}, pmid = {32250972}, issn = {1473-6322}, abstract = {PURPOSE OF REVIEW: To perform a nonsystematic review of the literature on the microbiota in the different types of non-IgE-mediated food allergy.<br><br>RECENT FINDINGS: The commonest non-IgE-mediated disorders managed by allergists include: eosinophilic esophagitis, food protein-induced enteropathy, food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis. The review of the literature describes how at phylum level we observe an increase of Proteobacteria in eosinophilic esophagitis esophageal microbiota and in food protein-induced enterocolitis syndrome, and food protein-induced allergic proctocolitis gut microbiota, while we observe an increase of Bacteroidetes in healthy controls. Several studies endorse the concept that a bloom of Proteobacteria in the gut reflects dysbiosis or an unstable gut microbial community structure. In several studies, the type of diet, the use of probiotics and in a single experience the use of fecal microbiota transplantation has produced significant variations of the microbiota.<br><br>SUMMARY: Genetic factors alone cannot account for the rapid rise in food allergy prevalence and the microbiome might be contributing to allergy risk. Our review showed that common features of the pathological microbiota among different types of non-IgE-mediated food allergy can be identified. These evidences suggest a possible role of the microbiota in the pathogenesis and non-IgE-mediated food allergies and the need to understand the effects of its modulation on the disorders themselves.}, }
@article {pmid32245531, year = {2020}, author = {Weir, V and Reddy, KR}, title = {Nonpharmacologic Management of Hepatic Encephalopathy: An Update.}, journal = {Clinics in liver disease}, volume = {24}, number = {2}, pages = {243-261}, doi = {10.1016/j.cld.2020.01.003}, pmid = {32245531}, issn = {1557-8224}, abstract = {Research increasingly shows that the gut-liver-brain axis is a crucial component in the pathophysiology of hepatic encephalopathy (HE). Due to the limitations of current standard-of-care medications, non-pharmacological treatments that target gut dysbiosis, including probiotics, nutritional management, and fecal microbiota transplants, are being considered as alternative and adjunct therapies. Meta-analyses note that probiotics could offer benefits in HE treatment, but have not shown superiority over lactulose. Emerging literature suggests that fecal microbiota transplants could offer a novel strategy to treat gut dysbiosis and favorably impact HE. Finally, liver support devices and liver transplantation could offer a last-resort treatment option for persistent HE.}, }
@article {pmid32245530, year = {2020}, author = {Mahpour, NY and Pioppo-Phelan, L and Reja, M and Tawadros, A and Rustgi, VK}, title = {Pharmacologic Management of Hepatic Encephalopathy.}, journal = {Clinics in liver disease}, volume = {24}, number = {2}, pages = {231-242}, doi = {10.1016/j.cld.2020.01.005}, pmid = {32245530}, issn = {1557-8224}, abstract = {Pharmacologic management of hepatic encephalopathy includes a broad range of therapies. This article covers the specific mainstays of therapies, such as antimicrobials and laxatives, with an established evidence base. This article also covers newer modalities of therapies, such as fecal microbiota transplant, probiotics, bioartificial support systems, small molecular therapies such as l-ornithine l-aspartate, branched chain amino acids, l-carnitine, zinc, and other forms of therapy currently under review.}, }
@article {pmid32243284, year = {2020}, author = {Kumar, AR}, title = {Continuing Medical Education Questions: April 2020: Understanding the Scope of Do-It-Yourself Fecal Microbiota Transplant.}, journal = {The American journal of gastroenterology}, volume = {115}, number = {4}, pages = {505}, doi = {10.14309/ajg.0000000000000593}, pmid = {32243284}, issn = {1572-0241}, }
@article {pmid31648984, year = {2019}, author = {Ma, Y and Chen, H}, title = {Faecal microbiota transplantation, a promising way to treat colorectal cancer.}, journal = {EBioMedicine}, volume = {49}, number = {}, pages = {13-14}, pmid = {31648984}, issn = {2352-3964}, mesh = {Colorectal Neoplasms/diagnosis/*therapy ; *Fecal Microbiota Transplantation/methods ; Humans ; Treatment Outcome ; }, }
@article {pmid32239720, year = {2020}, author = {Eltokhi, A and Janmaat, IE and Genedi, M and Haarman, BCM and Sommer, IEC}, title = {Dysregulation of synaptic pruning as a possible link between intestinal microbiota dysbiosis and neuropsychiatric disorders.}, journal = {Journal of neuroscience research}, volume = {}, number = {}, pages = {}, doi = {10.1002/jnr.24616}, pmid = {32239720}, issn = {1097-4547}, support = {//The Stanley Medical Research Institute and ZonMW/ ; }, abstract = {The prenatal and early postnatal stages represent a critical time window for human brain development. Interestingly, this window partly overlaps with the maturation of the intestinal flora (microbiota) that play a critical role in the bidirectional communication between the central and the enteric nervous systems (microbiota-gut-brain axis). The microbial composition has important influences on general health and the development of several organ systems, such as the gastrointestinal tract, the immune system, and also the brain. Clinical studies have shown that microbiota alterations are associated with a wide range of neuropsychiatric disorders including autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, and bipolar disorder. In this review, we dissect the link between these neuropsychiatric disorders and the intestinal microbiota by focusing on their effect on synaptic pruning, a vital process in the maturation and establishing efficient functioning of the brain. We discuss in detail how synaptic pruning is dysregulated differently in the aforementioned neuropsychiatric disorders and how it can be influenced by dysbiosis and/or changes in the intestinal microbiota composition. We also review that the improvement in the intestinal microbiota composition by a change in diet, probiotics, prebiotics, or fecal microbiota transplantation may play a role in improving neuropsychiatric functioning, which can be at least partly explained via the optimization of synaptic pruning and neuronal connections. Altogether, the demonstration of the microbiota's influence on brain function via microglial-induced synaptic pruning addresses the possibility that the manipulation of microbiota-immune crosstalk represents a promising strategy for treating neuropsychiatric disorders.}, }
@article {pmid32235826, year = {2020}, author = {Zhu, F and Ju, Y and Wang, W and Wang, Q and Guo, R 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 Feng, J 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 = {Metagenome-wide association of gut microbiome features for schizophrenia.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {1612}, doi = {10.1038/s41467-020-15457-9}, pmid = {32235826}, issn = {2041-1723}, abstract = {Evidence is mounting that the gut-brain axis plays an important role in mental diseases fueling mechanistic investigations to provide a basis for future targeted interventions. However, shotgun metagenomic data from treatment-naïve patients are scarce hampering comprehensive analyses of the complex interaction between the gut microbiota and the brain. Here we explore the fecal microbiome based on 90 medication-free schizophrenia patients and 81 controls and identify a microbial species classifier distinguishing patients from controls with an area under the receiver operating characteristic curve (AUC) of 0.896, and replicate the microbiome-based disease classifier in 45 patients and 45 controls (AUC = 0.765). Functional potentials associated with schizophrenia include differences in short-chain fatty acids synthesis, tryptophan metabolism, and synthesis/degradation of neurotransmitters. Transplantation of a schizophrenia-enriched bacterium, Streptococcus vestibularis, appear to induces deficits in social behaviors, and alters neurotransmitter levels in peripheral tissues in recipient mice. Our findings provide new leads for further investigations in cohort studies and animal models.}, }
@article {pmid32234317, year = {2020}, author = {Liu, J and Miyake, H and Zhu, H and Li, B and Alganabi, M and Lee, C and Pierro, A}, title = {Fecal microbiota transplantation by enema reduces intestinal injury in experimental necrotizing enterocolitis.}, journal = {Journal of pediatric surgery}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jpedsurg.2020.02.035}, pmid = {32234317}, issn = {1531-5037}, abstract = {PURPOSE: Necrotizing Enterocolitis (NEC) is a devastating neonatal disease with a high mortality rate. Fecal Microbiota Transplantation (FMT) has been used to treat a variety of gastrointestinal diseases. We aimed to investigate the role of FMT in NEC.<br><br>METHODS: NEC was induced by hypoxia, LPS, and hyperosmolar gavage feeding between postnatal days P5 and P9 (n = 8). Breastfed mice were used as control (n = 7). FMT (30 μl/g) was administered by gavage or enema at P6 during NEC induction. Distal ileum was harvested on P9. Disease severity was evaluated by H&amp;E staining. Gene expression of inflammatory markers IL6 and TNFa was measured. Expression of intestinal barrier function was investigated by measuring Claudin-7. Microbiota composition in ileum and colon was analyzed by quantitative PCR.<br><br>RESULTS: FMT by gavage further increased terminal ileum inflammation and did not improve the histological damage owing to experimental NEC. Conversely, FMT by enema decreased intestinal inflammation and improved histology of the NEC-like injury in the ileum. In addition, compared with NEC alone, FMT by enema increased Claudin-7 expression indicating an improvement in barrier function. These beneficial effects occurred despite no change in microbiota.<br><br>CONCLUSION: Our results show that FMT by enema may be an effective strategy to reduce NEC progression as it attenuates intestinal inflammation and enhances intestinal barrier function. FMT by enema is a potential novel treatment for NEC.<br><br>LEVEL OF EVIDENCE: Level IV, Evidence from well-designed case-control or cohort studies.}, }
@article {pmid32233326, year = {2019}, author = {Trang-Poisson, C}, title = {[Fecal transplantation].}, journal = {La Revue du praticien}, volume = {69}, number = {7}, pages = {792-793}, pmid = {32233326}, issn = {2101-017X}, }
@article {pmid32233325, year = {2019}, author = {Barbut, F and Couturier, J}, title = {[Interactions between intestinal microbiota and Clostridioides difficile].}, journal = {La Revue du praticien}, volume = {69}, number = {7}, pages = {784-791}, pmid = {32233325}, issn = {2101-017X}, abstract = {Interactions between intestinal microbiota and clostridioides difficile. Clostridioides difficile is a spore-forming anaerobic Gram-positive bacillus that is responsible for diarrhea and post-antibiotic colitis. Approximately 20,000 inpatients are infected by C. difficile in France per year. This bacterium is recognized as an emerging pathogen responsible for community-acquired diarrhea. Antibiotic therapy is the main risk factor for C. difficile infection (CDI) because it leads to intestinal dysbiosis and loss of &quot;colonization resistance&quot;. C. difficile from endogenous or exogenous origin can then establish, multiply and produce its two toxins causing enterocyte lesions and a significant inflammatory reaction. The loss of colonization resistance has been associated with the loss of microbial diversity, particularly of some taxa that play a protective role. These variations of bacterial communities lead to changes in functions that can be explored by metabolomic or metagenomic approaches. Data from these experiments led to mechanistic assumptions about resistance or susceptibility to CDI. Microbiota studies have also pushed physicians to develop therapeutic approaches based on biotherapies. These therapies aim at repopulating the colon by a healthy microbiota either by fecal microbiota transplantation or by the administration of strains and cocktails of strains to restore the colonization resistance effect.}, }
@article {pmid32230951, year = {2020}, author = {Hiippala, K and Kainulainen, V and Suutarinen, M and Heini, T and Bowers, JR and Jasso-Selles, D and Lemmer, D and Valentine, M and Barnes, R and Engelthaler, DM and Satokari, R}, title = {Isolation of Anti-Inflammatory and Epithelium Reinforcing Bacteroides and Parabacteroides Spp. from A Healthy Fecal Donor.}, journal = {Nutrients}, volume = {12}, number = {4}, pages = {}, doi = {10.3390/nu12040935}, pmid = {32230951}, issn = {2072-6643}, support = {304490//Academy of Finland/ ; 323156//Academy of Finland/ ; 285632//Academy of Finland/ ; Reetta Satokari//Sigrid Juséliuksen Säätiö/ ; }, abstract = {Altered intestinal microbiota is associated with systemic and intestinal diseases, such as inflammatory bowel disease (IBD). Dysbiotic microbiota with enhanced proinflammatory capacity is characterized by depletion of anaerobic commensals, increased proportion of facultatively anaerobic bacteria, as well as reduced diversity and stability. In this study, we developed a high-throughput in vitro screening assay to isolate intestinal commensal bacteria with anti-inflammatory capacity from a healthy fecal microbiota transplantation donor. Freshly isolated gut bacteria were screened for their capacity to attenuate Escherichia coli lipopolysaccharide (LPS)-induced interleukin 8 (IL-8) release from HT-29 cells. The screen yielded a number of Bacteroides and Parabacteroides isolates, which were identified as P.distasonis, B.caccae, B. intestinalis, B.uniformis, B. fragilis, B.vulgatus and B.ovatus using whole genome sequencing. We observed that a cell-cell contact with the epithelium was not necessary to alleviate in vitro inflammation as spent culture media from the isolates were also effective and the anti-inflammatory action did not correlate with the enterocyte adherence capacity of the isolates. The anti-inflammatory isolates also exerted enterocyte monolayer reinforcing action and lacked essential genes to synthetize hexa-acylated, proinflammatory lipid A, part of LPS. Yet, the anti-inflammatory effector molecules remain to be identified. The Bacteroides strains isolated and characterized in this study have potential to be used as so-called next-generation probiotics.}, }
@article {pmid32228321, year = {2020}, author = {Morissette, A and Kropp, C and Songpadith, JP and Junges Moreira, R and Costa, J and Mariné Casadó, R and Pilon, G and Varin, TV and Dudonné, S and Boutekrabt, L and St-Pierre, P and Levy, E and Roy, D and Desjardins, Y and Raymond, F and Houde, VP and Marette, A}, title = {Blueberry proanthocyanidins and anthocyanins improve metabolic health through a gut microbiota-dependent mechanism in diet-induced obese mice.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpendo.00560.2019}, pmid = {32228321}, issn = {1522-1555}, abstract = {Blueberry consumption can prevent obesity-linked metabolic diseases and it has been proposed that its polyphenol content may contribute to these effects. Polyphenols have been shown to favourably impact metabolic health, but the role of specific polyphenol classes, and whether the gut microbiota is linked to these effects remains unclear. We aimed to evaluate the impact of whole blueberry and blueberry polyphenols against the development of obesity and insulin resistance, and to determine the potential role of gut microbes in these effects by using fecal microbiota transplantation (FMT). Seventy C57BL/6 male mice were assigned to one of the following diets for 12 weeks: balanced diet (Chow), high-fat high-sucrose (HFHS) diet, or HFHS supplemented with whole blueberry powder (BB), anthocyanidin (ANT) or proanthocyanidin (PAC)-rich extracts. After 8 weeks, mice were housed in metabolic cages and an oral glucose tolerance test (oGTT) was performed. Sixty germ-free mice fed HFHS diet received FMT from one of the above groups bi-weekly for 8 weeks, followed by an oGTT. PAC-treated mice were leaner than HFHS controls although they had the same energy intake and were more physically active. This observation was reproduced in germ-free mice receiving FMT from PAC-treated mice. PAC and ANT-treated mice showed improved insulin responses during oGTT, and this finding was also reproduced in germ-free mice following FMT. These results show that blueberry PAC and ANT polyphenols can reduce diet-induced body weight and improve insulin sensitivity, and that at least part of these beneficial effects are explained by modulation of the gut microbiota.}, }
@article {pmid31948404, year = {2020}, author = {Kachlíková, M and Sabaka, P and Koščálová, A and Bendžala, M and Dovalová, Z and Stankovič, I}, title = {Comorbid status and the faecal microbial transplantation failure in treatment of recurrent Clostridioides difficile infection - pilot prospective observational cohort study.}, journal = {BMC infectious diseases}, volume = {20}, number = {1}, pages = {52}, pmid = {31948404}, issn = {1471-2334}, mesh = {Aged ; Clostridium Infections/epidemiology/microbiology/*therapy ; Cohort Studies ; Comorbidity ; Diarrhea/etiology ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Recurrence ; Risk Factors ; Treatment Failure ; }, abstract = {BACKGROUND: Faecal microbial transplantation (FMT) is currently the most effective treatment of recurrent Clostridioides difficile infection (CDI). However, up to 20% of patients experience further recurrences after single FMT. The mechanisms that lead to FMT failure and its risk factors are poorly understood. Comorbidity is one of the risk factors of the failure of standard antibiotic therapy of recurrent CDI. It is not known if comorbidity is also associated with the risk of FMT failure.<br><br>METHODS: We conducted a prospective observational cohort study in order to elucidate if comorbid status is associated with FMT failure. Patients with microbiologically proven recurrent CDI were recruited and underwent FMT via retention enema. Patients were followed up for 12 weeks after FMT for signs and symptoms of CDI recurrence. Single FMT failure was defined as recurrence of diarrhoea and a positive stool test for the presence of C. difficile antigen or toxin at any time point during the 12 weeks of follow-up. We assessed the association of single FMT failure with possible manageable and unmanageable risk factors. As a surrogate of comorbid status, we used Charlson Comorbidity Index (CCI) ≥ 7.<br><br>RESULTS: A total of 60 patients that underwent single FMT (34 women, 26 men) were included in the study. Overall, 15 patients (25%) experienced single FMT failure. 24 patients (40%) had CCI ≥ 7, and 45.0% patients with CCI ≥ 7 experienced failure of single FMT. Patients who experienced single FMT failure had a significantly higher CCI and significantly lower albumin concentration as compared to patients who experienced single FMT success. There was no difference in age, C-reactive protein concentration, leukocyte count and time from FMT to first defecation. In multivariate analysis, CCI ≥ 7 was positively associated with the failure of single FMT. Analysis was controlled for sex, age, time from FMT to first defecation, concomitant PPI therapy, severe CDI, hospital-acquired infection and albumin concentration.<br><br>CONCLUSIONS: Comorbid status surrogated by CCI is positively associated with the failure of single FMT in the treatment of recurrent CDI.}, }
@article {pmid31455805, year = {2019}, author = {Bo, TB and Zhang, XY and Wen, J and Deng, K and Qin, XW and Wang, DH}, title = {The microbiota-gut-brain interaction in regulating host metabolic adaptation to cold in male Brandt's voles (Lasiopodomys brandtii).}, journal = {The ISME journal}, volume = {13}, number = {12}, pages = {3037-3053}, pmid = {31455805}, issn = {1751-7370}, mesh = {Acclimatization ; Adaptation, Physiological ; Animals ; Arvicolinae/*microbiology/*physiology ; Bacteria/genetics/isolation &amp; purification/metabolism ; Brain/*metabolism ; Cecum/metabolism/microbiology ; Cold Temperature ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Ghrelin/metabolism ; Male ; Neurotransmitter Agents/metabolism ; Norepinephrine/metabolism ; Thermogenesis ; }, abstract = {Gut microbiota play a critical role in orchestrating metabolic homeostasis of the host. However, the crosstalk between host and microbial symbionts in small mammals are rarely illustrated. We used male Brandt's voles (Lasiopodomys brandtii) to test the hypothesis that gut microbiota and host neurotransmitters, such as norepinephrine (NE), interact to regulate energetics and thermogenesis during cold acclimation. We found that increases in food intake and thermogenesis were associated with increased monoamine neurotransmitters, ghrelin, short-chain fatty acids, and altered cecal microbiota during cold acclimation. Further, our pair-fed study showed that cold temperature can alter the cecal microbiota independently of overfeeding. Using cecal microbiota transplant along with β3-adrenoceptor antagonism and PKA inhibition, we confirmed that transplant of cold-acclimated microbiota increased thermogenesis through activation of cAMP-PKA-pCREB signaling. In addition, NE manipulation induced a long-term alteration in gut microbiota structure. These data demonstrate that gut microbiota-NE crosstalk via cAMP signaling regulates energetics and thermogenesis during cold acclimation in male Brandt's voles.}, }
@article {pmid32222124, year = {2020}, author = {Dale, HF and Lied, GA}, title = {Gut microbiota and therapeutic approaches for dysbiosis in irritable bowel syndrome: Recent developments and future perspectives.}, journal = {Turkish journal of medical sciences}, volume = {}, number = {}, pages = {}, doi = {10.3906/sag-2002-57}, pmid = {32222124}, issn = {1303-6165}, abstract = {Increased knowledge regarding the implications of gut microbiota in irritable bowel syndrome (IBS), suggest that a disturbed intestinal microenvironment (dysbiosis) might promote the development and maintenance of IBS symptoms and effects several pathways in the pathology of this multifactorial disease. Accordingly, manipulation of the gut microbiota in order to improve IBS symptoms has the last decade evolved as a novel treatment strategy. Several different approaches have been investigated in order to improve the gut microbiota composition. Dietary modifications including supplementation with fibers, prebiotics and probiotics are shown to improve symptoms and composition of gut microbiota in IBS, however the exact probiotic mixture beneficial for each individual remains to be identified. The use of antibiotics still needs confirmation, although promising results have been reported with use of rifaximin. Fecal microbiota transplantation (FMT) has recently gained a lot of attention, and several placebo-controlled trials investigating FMT pose promising results regarding symptom reduction and gut microbiota manipulation in IBS. However, more data regarding long-term effects is needed before FMT can be integrated as a customised treatment for IBS in the clinical routine.}, }
@article {pmid32218321, year = {2020}, author = {Polimeno, L and Barone, M and Mosca, A and Viggiani, MT and Joukar, F and Mansour-Ghanaei, F and Mavaddati, S and Daniele, A and Debellis, L and Bilancia, M and Santacroce, L and Di Leo, A}, title = {Soy Metabolism by Gut Microbiota from Patients with Precancerous Intestinal Lesions.}, journal = {Microorganisms}, volume = {8}, number = {4}, pages = {}, doi = {10.3390/microorganisms8040469}, pmid = {32218321}, issn = {2076-2607}, support = {PON-BIOMIS 2018 (Project: Costituzione della Biobanca del Microbiota intestinale e salivare umano: dalla disbiosi alla simbiosi).//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) requires the presence of a variety of factors predisposing a tumorigenic milieu. Excluding familial clustering and hereditary CRC syndromes, the development of sporadic CRC from precancerous lesions is influenced by tissue inflammation, modulation of intestinal immunity, hormones, dietary habits and gut microbiota composition. As concerning the last two aspects, the intestinal presence of equol, the most biologically active metabolite of the soy isoflavone daidzein and the presence of a genetic determinant of gut microbiota able to metabolize daidzein, seem to lower the CRC risk. It has been hypothesized that the anaerobic microorganisms of the Bacteroides genus play a role in equol production.<br><br>AIM: To evaluate the presence of (i) anaerobic gut microbiota and (ii) the urinary levels of soy isoflavones (daidzein, genistein and equol) in patients with and without precancerous lesions, challenged with a daidzein-rich soy extract.<br><br>METHODS: Consecutive subjects undergoing colonoscopy participated to the study. Feces were collected from all patients one week before colonoscopy for gut microbiota studies. After the endoscopy examination and the histological evaluation, 40 subjects, 20 with sporadic colorectal adenomas (SCA/P group) and 20 without proliferative lesions (control group) were enrolled for the study. Urine levels of soy isoflavones daidzein, genistein and their metabolite equol, were determined by high performance liquid chromatographic (HPLC) analysis and gut microbiota analysis was performed by Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) procedure.<br><br>RESULTS: Seventeen different bacterial species were identified in the fecal samples of the forty subjects participating to the study. Ten bacterial species resulted anaerobic Gram-negative bacteria, all belonging to the Bacteroides genus. A significant difference of bacteria species was evidenced in the fecal samples of the two groups of subjects. Particularly important was the evidence of Parabacteroidesdistasonis, Clostridiumclostridioforme and Pediococcuspentasaceus only in control fecal samples, such as the presence of Bacteroides fragilis and Prevotellamelaningenica only in SCA/P fecal samples. Concerning the soy isoflavones levels, no statistically significant differences were revealed in the genistein and daidzein urinary levels between the two groups of subjects. On the contrary, urinary equol levels were undetectable in ten SCA/P subjects and in two controls; moreover, when present, the levels of urinary equol were significantly lower in SCA/P subjects compared to controls (0.24 ± 0.27 mg/24 hrs vs. 21.25 ± 4.3 mg/24 hrs, respectively, p = 1.12 × 10-6).<br><br>CONCLUSIONS: Our results suggest that the presence of anaerobic Bacteroides in the colon, and the production of equol from soy, could determine a milieu able to contrast the development of colonic mucosa proliferative lesions.}, }
@article {pmid32215122, year = {2020}, author = {Kukla, M and Adrych, K and Dobrowolska, A and Mach, T and Reguła, J and Rydzewska, G}, title = {Guidelines for Clostridium difficile infection in adults.}, journal = {Przeglad gastroenterologiczny}, volume = {15}, number = {1}, pages = {1-21}, doi = {10.5114/pg.2020.93629}, pmid = {32215122}, issn = {1895-5770}, abstract = {Clostridium difficile infection (CDI) has become a serious medical and epidemiological problem, especially in well developed countries. There has been evident increase in incidence and severity of CDI. Prevention, proper diagnosis and effective treatment are necessary to reduce the risk for the patients, deplete the spreading of infection and diminish the probability of recurrent infection. Antibiotics are the fundamental treatment of CDI. In patients who had recurrent CDI fecal microbiota transplantation seems to be promising and efficient strategy. These guidelines systematize existing data and include recent changes implemented in the management of CDI.}, }
@article {pmid32207794, year = {2020}, author = {Slomski, A}, title = {&quot;Superdonor&quot; Fecal Microbiota Transplant Effective for IBS.}, journal = {JAMA}, volume = {323}, number = {12}, pages = {1124}, doi = {10.1001/jama.2020.2812}, pmid = {32207794}, issn = {1538-3598}, }
@article {pmid32204538, year = {2020}, author = {Tsai, MC and Liu, YY and Lin, CC and Wang, CC and Wu, YJ and Yong, CC and Chen, KD and Chuah, SK and Yao, CC and Huang, PY and Chen, CH and Hu, TH and Chen, CL}, title = {Gut Microbiota Dysbiosis in Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study in Taiwan.}, journal = {Nutrients}, volume = {12}, number = {3}, pages = {}, doi = {10.3390/nu12030820}, pmid = {32204538}, issn = {2072-6643}, support = {CMRPG8H1111//Kaohsiung Chang Gung Memorial Hospital/ ; CMRPG8J1571//Kaohsiung Chang Gung Memorial Hospital/ ; CMRPG8K0661//Kaohsiung Chang Gung Memorial Hospital/ ; }, abstract = {The gut microbiota plays a role in nonalcoholic fatty liver disease (NAFLD), but data about gut dysbiosis in Asians with NAFLD remains scarce. We analyzed the differences in fecal microbiota between adults with and without NAFLD. This cross-sectional study examined adults with histology-proven NAFLD (25 nonalcoholic fatty liver (NAFL) patients, 25 nonalcoholic steatohepatitis (NASH) patients, and 25 living liver donors (healthy controls)). The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples. The NAFL and NASH groups showed lower total bacterial diversity and richness than the controls. NAFLD patients had higher levels of the phylum Bacteroidetes and lower levels of Firmicutes than controls. The genus RuminococcaceaeUCG-010, family Ruminococcaceae, order Clostridiales, and class Clostridia were less abundant in patients with NAFL or NASH than healthy individuals. The lipopolysaccharide biosynthesis pathway was differentially enriched in the NASH group. This study examined the largest number of Asian patients with biopsy-proven NAFL and NASH in terms of dysbiosis of the gut microbiota in NAFLD patients. NAFLD patients had higher levels of Bacteroidetes and lower levels of Firmicutes. These results are different from research from western countries and could provide different targets for therapies by region.}, }
@article {pmid32203111, year = {2020}, author = {Hui, S and Liu, Y and Huang, L and Zheng, L and Zhou, M and Lang, H and Wang, X and Yi, L and Mi, M}, title = {Resveratrol enhances brown adipose tissue activity and white adipose tissue browning in part by regulating bile acid metabolism via gut microbiota remodeling.}, journal = {International journal of obesity (2005)}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41366-020-0566-y}, pmid = {32203111}, issn = {1476-5497}, abstract = {OBJECTIVE: Current evidence has linked dietary resveratrol (RSV) intake to the activation of brown adipose tissue (BAT) and induction of white adipose tissue (WAT) browning, which may be a potential means of improving glucose homeostasis. However, the underlying mechanisms remain unclear.<br><br>METHODS: A diet containing RSV was fed to db/db mice for 10 weeks, following which the body weight, adipose tissue accumulation, bile acid (BA) profiles, and markers of BA metabolism were analyzed. Oral glucose tolerance testing, immunohistochemistry, and gut microbiota sequencing were also performed.<br><br>RESULTS: RSV intervention improved glucose homeostasis in db/db mice, which was linked to the enhanced BAT activity and WAT browning. Moreover, RSV-treated mice exhibited altered plasma and fecal BA compositions and significant remodeling of the gut microbiota, the latter confirmed by a higher level of lithocholic acid (LCA) in the plasma and feces. LCA was identified to be the agonist of Takeda G-protein coupled receptor 5 (TGR5), which mediated the BAT activation and WAT browning by upregulating uncoupling protein 1 (UCP1) expression. Furthermore, depletion of the gut microbiota using antibiotics partially abolished the beneficial effects of RSV against glucose intolerance. Finally, microbiota transplantation experiments demonstrated that the RSV-induced beneficial effects were transferable, indicating that these effects were largely dependent on the gut microbiota.<br><br>CONCLUSIONS: These data indicate that RSV administration improves glucose homeostasis by enhancing BAT activation and WAT browning, a mechanism that might partially be mediated by the gut microbiota-BA-TGR5/UCP1 pathway.}, }
@article {pmid32200611, year = {2020}, author = {Zybura, J and Dyla, A and Mielnicki, W}, title = {Fecal microbiota transplantation is feasible even in critically ill patients with toxic megacolon due to Clostridium difficile infection.}, journal = {Anaesthesiology intensive therapy}, volume = {}, number = {}, pages = {}, doi = {10.5114/ait.2020.93712}, pmid = {32200611}, issn = {1731-2531}, }
@article {pmid32197802, year = {2020}, author = {Khoruts, A and Bajaj, JS}, title = {Intestinal microbiota transplantation: Naming a new paradigm.}, journal = {Journal of hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhep.2020.02.014}, pmid = {32197802}, issn = {1600-0641}, }
@article {pmid32192627, year = {2020}, author = {Ianiro, G and Mullish, BH and Kelly, CR and Sokol, H and Kassam, Z and Ng, S and Fischer, M and Allegretti, JR and Masucci, L and Zhang, F and Keller, J and Sanguinetti, M and Costello, SP and Tilg, H and Gasbarrini, A and Cammarota, G}, title = {Screening of faecal microbiota transplant donors during the COVID-19 outbreak: suggestions for urgent updates from an international expert panel.}, journal = {The lancet. Gastroenterology &amp; hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/S2468-1253(20)30082-0}, pmid = {32192627}, issn = {2468-1253}, }
@article {pmid31628021, year = {2019}, author = {Lleal, M and Sarrabayrouse, G and Willamil, J and Santiago, A and Pozuelo, M and Manichanh, C}, title = {A single faecal microbiota transplantation modulates the microbiome and improves clinical manifestations in a rat model of colitis.}, journal = {EBioMedicine}, volume = {48}, number = {}, pages = {630-641}, pmid = {31628021}, issn = {2352-3964}, mesh = {Animals ; Biodiversity ; Biomarkers ; Biopsy ; Colitis/*etiology/pathology/*therapy ; Disease Models, Animal ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/etiology/pathology/therapy ; Intestinal Mucosa/metabolism/microbiology/pathology ; Male ; Mice ; *Microbial Interactions ; Rats ; Treatment Outcome ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is a novel potential therapy for inflammatory bowel diseases, but it is poorly characterised.<br><br>METHODS: We evaluated the performance of the mouse and rat as a pre-clinical model for human microbiota engraftment. We then characterised the effect of a single human stool transfer (HST) on a humanised model of DSS-induced colitis. Colonic and faecal microbial communities were analysed using the 16S rRNA approach and clinical manifestations were assessed in a longitudinal setting.<br><br>FINDINGS: The microbial community of rats showed greater similarity to that of humans, while the microbiome of mice showed less similarity to that of humans. Moreover, rats captured more human microbial species than mice after a single HST. Using the rat model, we showed that HST compensated faecal dysbiosis by restoring alpha-diversity and by increasing the relative abundance of health-related microbial genera. To some extent, HST also modulated the microbial composition of colonic tissue. These faecal and colonic microbial communities alterations led to a relative restoration of colon length, and a significant decrease in both epithelium damage and disease severity. Remarkably, stopping inflammation by removing DSS before HST caused a faster and greater recovery of both microbiome and clinical manifestation features.<br><br>INTERPRETATION: Our results indicate that the rat outperforms the mouse as a model for human microbiota engraftment and show that the efficacy of HST can be enhanced when inflammation stimulation is withdrawn. Finally, our findings support a new therapeutic strategy based on the use FMT combined with anti-inflammatory drugs.}, }
@article {pmid32185143, year = {2020}, author = {Dorsaz, S and Charretier, Y and Girard, M and Gaïa, N and Leo, S and Schrenzel, J and Harbarth, S and Huttner, B and Lazarevic, V}, title = {Changes in Microbiota Profiles After Prolonged Frozen Storage of Stool Suspensions.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {77}, doi = {10.3389/fcimb.2020.00077}, pmid = {32185143}, issn = {2235-2988}, abstract = {Introduction: Fecal microbiota transplantation (FMT) is recommended as safe and effective treatment for recurrent Clostridioides difficile infections. Freezing the FMT preparation simplifies the process, allowing a single stool sample to be used for multiple receivers and over an extended period of time. We aimed to assess the effect of long-term frozen storage on bacterial taxonomic profiles of a stool suspension prepared for FMT. Methods: DNA was extracted from a stool suspension before freezing and sequentially during the 18-month storage period at -80°C. Two different protocols were used for DNA extraction. The first relied on a classical mechanical and chemical cell disruption to extract both intra- and extracellular DNA; the second included specific pre-treatments aimed at removing free DNA and DNA from human and damaged bacterial cells. Taxonomic profiling of bacterial communities was performed by sequencing of V3-V4 16S rRNA gene amplicons. Results: Microbiota profiles obtained by whole DNA extraction procedure remained relatively stable during frozen storage. When DNA extraction procedure included specific pre-treatments, microbiota similarity between fresh and frozen samples progressively decreased with longer frozen storage times; notably, the abundance of Bacteroidetes decreased in a storage duration-dependent manner. The abundance of Firmicutes, the main butyrate producers in the colon, were not much affected by frozen storage for up to 1 year. Conclusion: Our data show that metataxonomic analysis of frozen stool suspensions subjected to specific pre-treatments prior to DNA extractions might provide an interesting indication of bacterial resistance to stress conditions and thus of chances of survival in FMT recipients.}, }
@article {pmid32185104, year = {2020}, author = {Liu, X and Lv, Q and Ren, H and Gao, L and Zhao, P and Yang, X and Yang, G and Xu, D and Wang, G and Yang, W and Wang, P and Wang, Z and Xing, S}, title = {The altered gut microbiota of high-purine-induced hyperuricemia rats and its correlation with hyperuricemia.}, journal = {PeerJ}, volume = {8}, number = {}, pages = {e8664}, doi = {10.7717/peerj.8664}, pmid = {32185104}, issn = {2167-8359}, abstract = {Some studies on the hyperuricemia (HUA) have focused on intestinal bacteria. To better understand the correlation between gut microbiota and HUA, we established a HUA rat model with high-purine diet, and used 16S rRNA genes sequencing to analyze gut microbiota changes in HUA rats. To analyze the potential role played by gut microbiota in HUA, we altered the gut microbiota of HUA rats with antibiotics, and compared the degree of uric acid elevation between HUA and antibiotic-fed HUA rats (Ab+HUA). Finally, we established a recipient rat model, in which we transplanted fecal microbiota of HUA and normal rats into recipient rats. Three weeks later, we compared the uric acid content of recipient rats. As a result, the diversity and abundance of the gut microbiota had changed in HUA rats. The Ab-fed HUA rats had significantly lower uric acid content compared to the HUA rats, and gut microbiota from HUA rats increased uric acid content of recipient rats. The genera Vallitalea, Christensenella and Insolitispirillum may associate with HUA. Our findings highlight the association between gut microbiota and HUA, and the potential role played by gut microbiota in HUA. We hope that this finding will promote the isolation and culture of HUA-related bacteria and orient HUA-related studies from being correlational to mechanistic. These steps will therefore make it possible for us to treat HUA using gut microbiota as the target.}, }
@article {pmid32182248, year = {2020}, author = {Dang, X and Xu, M and Liu, D and Zhou, D and Yang, W}, title = {Assessing the efficacy and safety of fecal microbiota transplantation and probiotic VSL#3 for active ulcerative colitis: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {15}, number = {3}, pages = {e0228846}, doi = {10.1371/journal.pone.0228846}, pmid = {32182248}, issn = {1932-6203}, abstract = {BACKGROUND: Fecal microbiota transplantation is an effective treatment for many gastrointestinal diseases, such as Clostridium difficile infection and inflammatory bowel disease, especially ulcerative colitis. Changes in colonic microflora may play an important role in the pathogenesis of ulcerative colitis, and improvements in the intestinal microflora may relieve the disease. Fecal bacterial transplants and oral probiotics are becoming important ways to relieve active ulcerative colitis.<br><br>PURPOSE: This systematic review with meta-analysis compared the efficacy and safety of basic treatment combined with fecal microbiota transplantation or mixed probiotics therapy in relieving mild to moderate ulcerative colitis.<br><br>METHODS: The PubMed, Embase, and Cochrane libraries (updated September 2019) were searched to identify randomized, placebo-controlled, or head-to-head trials assessing fecal microbiota transplantation or probiotic VSL#3 as induction therapy in active ulcerative colitis. We analyze data using the R program to obtain evidence of direct comparison and to generate intermediate variables for indirect treatment comparisons.<br><br>RESULTS: Seven randomized, double-blind, placebo-controlled trials were used as the sources of the induction data. All treatments were superior to placebo. In terms of clinical remission and clinical response to active ulcerative colitis, direct comparisons showed fecal microbiota transplantation (OR = 3.47, 95% CI = 1.93-6.25) (OR = 2.48, 95% CI = 1.18-5.21) and mixed probiotics VSL#3 (OR = 2.40, 95% CI = 1.49-3.88) (OR = 3.09, 95% CI = 1.53-6.25) to have better effects than the placebo. Indirect comparison showed fecal microbiota transplantation and probiotic VSL#3 did not reach statistical significance either in clinical remission (RR = 1.20, 95% CI = 0.70-2.06) or clinical response (RR = 0.95, 95% CI = 0.62-1.45). In terms of safety, fecal microbiota transplantation (OR = 1.15, 95% CI = 0.51-2.61) and VSL #3 (OR = 0.90, 95% CI = 0.33-2.49) showed no statistically significant increase in adverse events compared with the control group. In terms of serious adverse events, there was no statistical difference between the fecal microbiota transplantation group and the control group (OR = 1.29, 95% CI = 0.46-3.57). The probiotics VSL#3 seems more safer than fecal microbiota transplantation, because serious adverse events were not reported in the VSL#3 articles.<br><br>CONCLUSIONS: Fecal microbiota transplantation or mixed probiotics VSL#3 achieved good results in clinical remission and clinical response in active ulcerative colitis, and there was no increased risk of adverse reactions. There was no statistical difference between the therapeutic effect of fecal microbiota transplantation and that of mixed probiotics VSL#3. However, the use of fecal microbiota transplantation and probiotics still has many unresolved problems in clinical applications, and more randomized controlled trials are required to confirm its efficacy.}, }
@article {pmid32179403, year = {2020}, author = {Ávila, PRM and Michels, M and Vuolo, F and Bilésimo, R and Burger, H and Milioli, MVM and Sonai, B and Borges, H and Carneiro, C and Abatti, M and Santana, IVV and Michelon, C and Dal-Pizzol, F}, title = {Protective effects of fecal microbiota transplantation in sepsis are independent of the modulation of the intestinal flora.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {73}, number = {}, pages = {110727}, doi = {10.1016/j.nut.2020.110727}, pmid = {32179403}, issn = {1873-1244}, abstract = {OBJECTIVE: The aim of this study was to investigate the protective effects of probiotics and fecal transplantation on inflammatory and oxidative parameters in the intestines of two rat models of sepsis.<br><br>METHODS: Rats were treated with prebiotics, probiotics, or symbiotics and exposed to lipopolysaccharide (LPS) or zymosan after 15 d to induce endotoxemia. Oxidative damage and inflammation were analyzed, and histologic examination of the intestinal tissue was performed. Fecal microbiota transplantation (FMT) was carried out in LPS- and zymosan-induced rat models of sepsis.<br><br>RESULTS: Supplementation with symbiotics for 15 d effectively reduced the inflammatory parameters compared with supplementation for 7 d. Probiotics, prebiotics, and symbiotics exerted different effects on the evaluated parameters. In general, Lactobacillus rhamnosus and L. casei exerted better local protective effects. Evaluation of the role of the intestinal microbiota through FMT revealed its protective effects irrespective of the previous treatment with probiotics.<br><br>CONCLUSION: Probiotic strains significantly differ among themselves and exert different effects on the host's health. Symbiotics and FMT could offer additional immunomodulatory benefits to drug therapy, thus serving as a new therapeutic alternative in pediatric patients with sepsis.}, }
@article {pmid32176868, year = {2020}, author = {Chen, Y and Zhang, S and Zeng, B and Zhao, J and Yang, M and Zhang, M and Li, Y and Ni, Q and Wu,  and Li, Y}, title = {Transplant of microbiota from long-living people to mice reduces aging-related indices and transfers beneficial bacteria.}, journal = {Aging}, volume = {12}, number = {}, pages = {}, doi = {10.18632/aging.102872}, pmid = {32176868}, issn = {1945-4589}, abstract = {A close relationship between age and gut microbiota exists in invertebrates and vertebrates, including humans. Long-living people are a model for studying healthy aging; they also have a distinctive microbiota structure. The relationship between the microbiota of long-living people and aging phenotype remains largely unknown. Herein, the feces of long-living people were transplanted into mice, which were then examined for aging-related indices and beneficial bacteria. Mice transplanted with fecal matter from long-living people (L group) had greater α diversity, more probiotic genera (Lactobacillus and Bifidobacterium), and short-chain fatty acid producing genera (Roseburia, Faecalibacterium, Ruminococcus, Coprococcus) than the control group. L group mice also accumulated less lipofuscin and β-galactosidase and had longer intestinal villi. This study indicates the effects that the gut microbiota from long-living people have on healthy aging.}, }
@article {pmid32170542, year = {2020}, author = {Tamez-Torres, KM and Ponce-de-Leon, A and Torres-Gonzalez, P and Perez-Garcia, E and Torres-Veintimilla, E and Valle, MB and Sifuentes-Osornio, J}, title = {High prevalence of MDR gram-negative bacteria in feces of healthy blood donors in Mexico.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10096-020-03858-z}, pmid = {32170542}, issn = {1435-4373}, support = {289673//Consejo Nacional de Ciencia y Tecnología/ ; }, abstract = {During the initial stage of a study to recruit universal intestinal microbiota donors in Mexico City, we found multiple &quot;healthy&quot; subjects that colonized with MDRO (Multidrug-resistant organisms). We aimed to describe clinical and demographic characteristics of these individuals. This was a prospective observational study. Participants were consecutively recruited among blood donors. A fecal sample was collected from each subject and analyzed at the same day in search of MDRO through chromographic culture media and, if growth observed, later confirmed by MALDI-TOF and susceptibility testing in Vitek 2 system. From July 2018 to March 2019, 85 individuals were screened for fecal colonization. Median age was 35 years (IQR 27-46 years), and 48/85 (56.4%) were males. Seventy-two (84.7%) subjects harbored at least one MDRO. ESBL-producing microorganisms were found in 72/85 (84.3%) subjects, and E. coli was the most frequent (63/85, 74.1%). Four samples (2 E. coli, 2 P. aeruginosa, 2.4% each) harbored carbapenem-resistant Enterobacteriaceae (CRE), together with an ESBL-producing microorganism. Antibiotic use (p = 0.06) and PPIs or H2-blockers intake (p = 0.03) were more common in the colonized subjects during the previous 6-month period. We report a high incidence of enteric colonization of healthy subjects with MDRO, a condition that may be related to antibiotics or PPIs/H2-blockers consumption. This surprisingly high MDRO colonization rate in potential FMT donors emphasizes the need for careful screening of donors to avoid possible transmission to FMT recipients.}, }
@article {pmid32170474, year = {2020}, author = {Allegretti, JR and Mehta, SR and Kassam, Z and Kelly, CR and Kao, D and Xu, H and Fischer, M}, title = {Risk Factors that Predict the Failure of Multiple Fecal Microbiota Transplantations for Clostridioides difficile Infection.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-020-06198-2}, pmid = {32170474}, issn = {1573-2568}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (CDI); however, a small percentage of patients fail to achieve cure even after two FMTs. This high-risk cohort remains poorly understood.<br><br>METHODS: We performed a multicenter, multinational retrospective review of patients that underwent at least one FMT for a CDI indication at four academic FMT referrals. Patients' data including CDI, FMT, and FMT variables were assessed. The primary outcome was FMT failure after a second FMT defined as persistent diarrhea and positive laboratory test for C. difficile (PCR or toxin) despite a second FMT within 8 weeks of the first FMT. A multivariable logistic regression model was performed to determine predictors of second FMT failure.<br><br>RESULTS: A total of 540 patients received at least one FMT during the study period, of which 432 patients had success following the first FMT, 108 had documented failure (25%). Among those who failed the first FMT, 63 patients received a second FMT, of which 36 achieved cure, and 24 had documented failure after the second FMT. Patients that failed the first FMT but did not receive a second FMT and those lost to follow-up were excluded leaving 492 patients included in the analysis. The second FMT failure rate was 4.8% (24/492). Risk factors for second FMT failure identified by multivariable logistic regression included: inpatient status (OR 7.01, 95% CI: 2.37-20.78), the presence of pseudomembranes (OR 3.53, 95% CI: 1.1-11.33), and immunocompromised state (OR 3.56, 95% CI: 1.45-8.72) at the time of first FMT.<br><br>CONCLUSION: This study identifies clinically relevant risk factors predictive of failing a second FMT. Clinicians can use these variables to help identify high-risk patients and provide a better-informed consent regarding the possibility of needing multiple FMTs.}, }
@article {pmid32169506, year = {2020}, author = {Li, Y and Su, X and Gao, Y and Lv, C and Gao, Z and Liu, Y and Wang, Y and Li, S and Wang, Z}, title = {The potential role of the gut microbiota in modulating renal function in experimental diabetic nephropathy murine models established in same environment.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {}, number = {}, pages = {165764}, doi = {10.1016/j.bbadis.2020.165764}, pmid = {32169506}, issn = {1879-260X}, abstract = {Recent studies have shown that laboratory murine autoimmunity models under the same environment display different outcomes. We established diabetic nephropathy model mice under the same environment using the classic streptozotocin method. Renal dysfunction was different among the mice. Proteinuria was more significant in the severe proteinuria group (SP) than in the mild proteinuria group (MP). We hypothesized a role for the gut microbiota in the outcome and reproducibility of induced DN models. 16S rDNA gene sequencing technology was used to analyze the differences in the gut microbiota between the two groups. Here, through fecal microbiota transplantation (FMT) and gas chromatography mass spectrometry (GC-MS), we verified the role of the gut microbiota and its short-chain fatty acid (SCFA) generation in DN mouse renal dysfunction. In the SP group, there was a reduced abundance of Firmicutes (P < 0.0001), and the dominant genus Allobaculum [linear discriminant analysis (LDA) >3, P < 0.05] was positively correlated with body weight (Rho = 0.767, P < 0.01) and blood glucose content (Rho = 0.648, P < 0.05), while the dominant genus Anaerosporobacter (LDA > 3, P < 0.05) was positively correlated with 24-hour urinary protein content (Rho = 0.773, P < 0.01). In the MP group, the dominant genus Blautia (LDA > 3, P < 0.05) was negatively correlated with 24-hour urinary protein content (Rho = -0.829, P < 0.05). The results indicated that Allobaculum and Anaerosporobacter may worsen renal function, while Blautia may be a protective factor in DN. These findings suggested that the gut microbiota may contribute to the heterogeneity of the induced response since we observed potential disease-associated microbial taxonomies and correlations with DN.}, }
@article {pmid32168885, year = {2020}, author = {Jo, YJ and Tagele, SB and Pham, HQ and Jung, Y and Ibal, JC and Choi, S and Kang, GU and Park, S and Kang, Y and Kim, S and Koh, H and Shin, JH}, title = {In Situ Profiling of the Three Dominant Phyla Within the Human Gut Using TaqMan PCR for Pre-Hospital Diagnosis of Gut Dysbiosis.}, journal = {International journal of molecular sciences}, volume = {21}, number = {6}, pages = {}, doi = {10.3390/ijms21061916}, pmid = {32168885}, issn = {1422-0067}, support = {2018M3A9H3025030//National Research Foundation, Korea/ ; 918010-4//Strategic Initiative for Microbiomes in Agriculture and Food, Korea/ ; }, abstract = {A microbial imbalance called dysbiosis leads to inflammatory bowel disease (IBD), which can include ulcerative colitis (UC). Fecal microbiota transplantation (FMT), a novel therapy, has recently been successful in treating gut dysbiosis in UC patients. For the FMT technique to be successful, the gut microbiota of both the healthy donors and UC patients must be characterized. For decades, next-generation sequencing (NGS) has been used to analyze gut microbiota. Despite the popularity of NGS, the cost and time constraints make it difficult to use in emergency services and activities related to the periodic monitoring of microbiota profile alterations. Hence, in this study, we developed a multiplex TaqMan qPCR assay (MTq-PCR) with novel probes to simultaneously determine the relative proportions of the three dominant microbial phyla in the human gut: Bacteroidetes, Firmicutes, and Proteobacteria. The relative proportions of the three phyla in fecal samples of either healthy volunteers or UC patients were similar when assessed NGS and the MTq-PCR. Thus, our MTq-PCR assay could be a practical microbiota profiling alternative for diagnosing and monitoring gut dysbiosis in UC patients during emergency situations, and it could have a role in screening stool from potential FMT donors.}, }
@article {pmid32167008, year = {2020}, author = {Yu, L and Wang, L and Yi, H and Wu, X}, title = {Beneficial effects of LRP6-CRISPR on prevention of alcohol-related liver injury surpassed fecal microbiota transplant in a rat model.}, journal = {Gut microbes}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/19490976.2020.1736457}, pmid = {32167008}, issn = {1949-0984}, abstract = {Alcohol intake can modify gut microbiota composition, increase gut permeability, and promote liver fibrogenesis. LRP6 is a signal transmembrane protein and a co-receptor for the canonical Wnt signaling pathway. This study compared the curative effect of LRP6-CRISPR on alcohol-related liver injury with that of traditional fecal microbiota transplant (FMT) and investigated the alteration of the gut microbiome following the treatment. A rat model of alcohol-related liver injury was established and injected with lentiviral vectors expressing LRP6-CRISPR or administered with fecal filtrate from healthy rats, with healthy rat served as the control. Liver tissues of rats were examined by HE staining, Sirius staining, and Oil red O staining, respectively. The expression of LRP6 and fibrosis biomarkers were tested by PCR. The fecal sample of rats was collected and examined by 16S rRNA sequencing. Our data indicated that LRP6-CRISPR was more efficient in the prevention of alcohol-related liver injury than FMT. Microbiome analysis showed that alcohol-related liver injury related to gut microbiota dysbiosis, while treatment with LRP6-CRISPR or FMT increased gut microflora diversity and improved gut symbiosis. Further, bacteria specific to the disease stages were identified. Genera Romboutsia, Escherichia-Shigella, Pseudomonas, Turicibacter, and Helicobacter were prevalent in the intestine of rats with alcohol-related liver injury, while the domination of Lactobacillus was found in rats treated with LRP6-CRISPR or FMT. Besides, Lactobacillus and genera belonging to family Lachnospiraceae, Bacteroidales S24-7 group, and Ruminococcaceae were enriched in healthy rats. LRP6-CRISPR and FMT have beneficial effects on the prevention of alcohol-related liver injury, and correspondently, both treatments altered the disrupted gut microflora to a healthy one.}, }
@article {pmid32166622, year = {2020}, author = {Ramai, D and Zakhia, K and Fields, PJ and Ofosu, A and Patel, G and Shahnazarian, V and Lai, JK and Dhaliwal, A and Reddy, M and Chang, S}, title = {Fecal Microbiota Transplantation (FMT) with Colonoscopy Is Superior to Enema and Nasogastric Tube While Comparable to Capsule for the Treatment of Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-020-06185-7}, pmid = {32166622}, issn = {1573-2568}, abstract = {BACKGROUND: Several routes of fecal microbiota transplantation (FMT) administration are available for treating recurrent Clostridioides difficile infections (CDI), the most recent of which are capsules.<br><br>AIM: To assess the efficacy of colonoscopy, capsule, enema, and nasogastric tube (NGT) FMT for the treatment of recurrent CDI.<br><br>METHODS: We reported clinical outcomes of colonoscopy, capsule, enema, and NGT FMT for the treatment of recurrent CDI according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. During January 2000 to January 2018, three databases were searched: PubMed, EMBASE, and CINAHL. Primary outcome was overall cure rate which was assessed using a random effects model; secondary outcomes included adverse effects as well as subgroup analyses comparing donor relationship, sample preparation, and study design.<br><br>RESULTS: Twenty-six studies (1309 patients) were included in the study. FMT was administered using colonoscopy in 16 studies (483 patients), NGT in five studies (149 patients), enema in four studies (360 patients), and capsules in four studies (301 patients). The random effects of pooled FMT cure rates were colonoscopy 94.8% (CI 92.4-96.8%; I2 15.6%), capsule 92.1% (CI 88.6-95.0%; I2 7.1%), enema 87.2% (CI 83.4-90.5%; I2 0%), and NGT/NDT 78.1% (CI 71.6-84.1%; I2 0%). On subgroup analysis of colonoscopy FMT, sample preparation methods had comparable cure rates: fresh 94.9% compared to 94.5%. Similarly, cure rates were unaffected by donor relationship: mixed 94.5% compared to unrelated donor 95.7%.<br><br>CONCLUSION: CDI cure rates with FMT performed with colonoscopy are superior to enema and NGT FMT, while those with FMT with colonoscopy and capsule are comparable.}, }
@article {pmid32158569, year = {2020}, author = {AlQahtani, H and Baloch, S and Tabb, D}, title = {Treatment of Recurrent Clostridium difficile Infection in an Immunocompromised Patient with Severe Neutropenia Not Responding to Standard Therapy.}, journal = {Case reports in infectious diseases}, volume = {2020}, number = {}, pages = {3089023}, doi = {10.1155/2020/3089023}, pmid = {32158569}, issn = {2090-6625}, abstract = {One of the most effective strategies in reducing the risk of Clostridium difficile infection (CDI) recurrence is fecal microbiota transplantation (FMT). However, several adverse events have been reported post FMT, and data on the efficacy and safety of FMT in immunocompromised patients with hematological malignancies are rare. This report presents FMT treatment for refractory CDI in a severely immunocompromised patient. A 69-year-old female presented to the emergency department complaining of foul smelling, intractable, watery diarrhea and generalized abdominal pain. She was recently diagnosed with high-risk myelodysplastic Syndrome (MDS) requiring daily blood transfusions and reported multiple CDI episodes in the past treated successfully with metronidazole and vancomycin as mono- or combotherapy. During this admission, treatment with oral vancomycin (high dose) and intravenous metronidazole was unsuccessful, so FMT was administered. The patient recovered well despite an absolute neutrophil count (ANC) < 0.25 × 109/L, and chemotherapy was initiated soon after. FMT was successful and safe in this patient, with no relapse and adverse events seen in 8 weeks of follow-up via phone calls and office visits.}, }
@article {pmid32156514, year = {2020}, author = {Ren, K}, title = {Commentary on Ma et al. Resveratrol brings back happy bug's harmony.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2020.03.005}, pmid = {32156514}, issn = {1090-2139}, }
@article {pmid32155205, year = {2020}, author = {McKinney, CA and Oliveira, BCM and Bedenice, D and Paradis, MR and Mazan, M and Sage, S and Sanchez, A and Widmer, G}, title = {The fecal microbiota of healthy donor horses and geriatric recipients undergoing fecal microbial transplantation for the treatment of diarrhea.}, journal = {PloS one}, volume = {15}, number = {3}, pages = {e0230148}, doi = {10.1371/journal.pone.0230148}, pmid = {32155205}, issn = {1932-6203}, abstract = {BACKGROUND AND AIMS: Fecal microbial transplantation (FMT), a treatment for certain gastrointestinal conditions associated with dysbiosis in people, is also empirically employed in horses with colitis. This study used microbiota high-throughput sequencing to compare the fecal microbial profile of healthy horses to that of geriatric microbial transplant recipients experiencing diarrhea and tested whether FMT restores microbiota diversity.<br><br>METHODS: To evaluate the effect of environment and donor characteristics on the intestinal microbiota, fecal samples were collected per rectum from 15 healthy young-adult (2-12 years) and 15 geriatric (≥20 years) horses. Additionally, FMT was performed for 3 consecutive days in 5 geriatric horses with diarrhea using feces from the same healthy donor. Fecal samples were collected from both donor and recipient prior to each FMT and from recipients 24 hours following the last FMT. The profile of the fecal bacterial microbiota was compared using 16S amplicon sequencing.<br><br>RESULTS AND CONCLUSIONS: In contrast to diet and farm location, age did not significantly affect the healthy equine fecal microbiota, indicating that both healthy geriatric and young-adult horses may serve as FMT donors. The fecal microbiota of horses with diarrhea was significantly more variable in terms of β-diversity than that of healthy horses. An inverse correlation between diarrhea score and relative abundance of Verrucomicrobia was identified in surviving FMT recipients. At study completion, the fecal microbiota of horses which responded to FMT had a higher α-diversity than prior to treatment and was phylogenetically more similar to that of the donor.}, }
@article {pmid32154322, year = {2020}, author = {Keen, EC and Tasoff, P and Hink, T and Reske, KA and Burnham, CD and Dantas, G and Kwon, JH and Dubberke, ER}, title = {Microbiome Restoration by RBX2660 Does Not Preclude Recurrence of Multidrug-Resistant Urinary Tract Infection Following Subsequent Antibiotic Exposure: A Case Report.}, journal = {Open forum infectious diseases}, volume = {7}, number = {3}, pages = {ofaa042}, doi = {10.1093/ofid/ofaa042}, pmid = {32154322}, issn = {2328-8957}, abstract = {A 62-year-old woman received RBX2660, an investigational microbiome restoration therapeutic, for recurrent multidrug-resistant (MDR) urinary tract infection (UTI). RBX2660 increased gut microbiome diversity but did not eliminate uropathogen carriage, and MDR UTI recurred after subsequent antibiotic exposure. Thus, restoration of microbiome diversity does not preclude disease recurrence by residual MDR pathogens.}, }
@article {pmid31273923, year = {2019}, author = {Durgan, DJ}, title = {Evidence for a gut-immune-vascular axis in the development of hypertension.}, journal = {Acta physiologica (Oxford, England)}, volume = {227}, number = {1}, pages = {e13338}, doi = {10.1111/apha.13338}, pmid = {31273923}, issn = {1748-1716}, mesh = {Animals ; Blood Pressure ; *Fecal Microbiota Transplantation ; *Hypertension ; Immune System ; Rats ; }, }
@article {pmid32150549, year = {2020}, author = {Yu, EW and Gao, L and Stastka, P and Cheney, MC and Mahabamunuge, J and Torres Soto, M and Ford, CB and Bryant, JA and Henn, MR and Hohmann, EL}, title = {Fecal microbiota transplantation for the improvement of metabolism in obesity: The FMT-TRIM double-blind placebo-controlled pilot trial.}, journal = {PLoS medicine}, volume = {17}, number = {3}, pages = {e1003051}, doi = {10.1371/journal.pmed.1003051}, pmid = {32150549}, issn = {1549-1676}, abstract = {BACKGROUND: There is intense interest about whether modulating gut microbiota can impact systemic metabolism. We investigated the safety of weekly oral fecal microbiota transplantation (FMT) capsules from healthy lean donors and their ability to alter gut microbiota and improve metabolic outcomes in patients with obesity.<br><br>METHODS AND FINDINGS: FMT-TRIM was a 12-week double-blind randomized placebo-controlled pilot trial of oral FMT capsules performed at a single US academic medical center. Between August 2016 and April 2018, we randomized 24 adults with obesity and mild-moderate insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] between 2.0 and 8.0) to weekly healthy lean donor FMT versus placebo capsules for 6 weeks. The primary outcome, assessed by intention to treat, was change in insulin sensitivity between 0 and 6 weeks as measured by hyperinsulinemic euglycemic clamps. Additional metabolic parameters were evaluated at 0, 6, and 12 weeks, including HbA1c, body weight, body composition by dual-energy X-ray absorptiometry, and resting energy expenditure by indirect calorimetry. Fecal samples were serially collected and evaluated via 16S V4 rRNA sequencing. Our study population was 71% female, with an average baseline BMI of 38.8 ± 6.7 kg/m2 and 41.3 ± 5.1 kg/m2 in the FMT and placebo groups, respectively. There were no statistically significant improvements in insulin sensitivity in the FMT group compared to the placebo group (+5% ± 12% in FMT group versus -3% ± 32% in placebo group, mean difference 9%, 95% CI -5% to 28%, p = 0.16). There were no statistically significant differences between groups for most of the other secondary metabolic outcomes, including HOMA-IR (mean difference 0.2, 95% CI -0.9 to 0.9, p = 0.96) and body composition (lean mass mean difference -0.1 kg, 95% CI -1.9 to 1.6 kg, p = 0.87; fat mass mean difference 1.2 kg, 95% CI -0.6 to 3.0 kg, p = 0.18), over the 12-week study. We observed variable engraftment of donor bacterial groups among FMT recipients, which persisted throughout the 12-week study. There were no significant differences in adverse events (AEs) (10 versus 5, p = 0.09), and no serious AEs related to FMT. Limitations of this pilot study are the small sample size, inclusion of participants with relatively mild insulin resistance, and lack of concurrent dietary intervention.<br><br>CONCLUSIONS: Weekly administration of FMT capsules in adults with obesity results in gut microbiota engraftment in most recipients for at least 12 weeks. Despite engraftment, we did not observe clinically significant metabolic effects during the study.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov NCT02530385.}, }
@article {pmid32148376, year = {2020}, author = {Gupta, A and Saha, S and Khanna, S}, title = {Therapies to modulate gut microbiota: Past, present and future.}, journal = {World journal of gastroenterology}, volume = {26}, number = {8}, pages = {777-788}, doi = {10.3748/wjg.v26.i8.777}, pmid = {32148376}, issn = {2219-2840}, abstract = {The human gut microbiota comprises of a complex and diverse array of microorganisms, and over the years the interaction between human diseases and the gut microbiota has become a subject of growing interest. Disturbed microbial milieu in the gastrointestinal tract is central to the pathogenesis of several diseases including antibiotic-associated diarrhea and Clostridioides difficile infection (CDI). Manipulation of this microbial milieu to restore balance by microbial replacement therapies has proven to be a safe and effective treatment for recurrent CDI. There is considerable heterogeneity in various aspects of stool processing and administration for fecal microbiota transplantation (FMT) across different centers globally, and standardized microbioal replacement therapies offer an attractive alternative. The adverse effects associated with FMT are usually mild. However, there is paucity of data on long term safety of FMT and there is a need for further studies in this regard. With our increasing understanding of the host-microbiome interaction, there is immense potential for microbial replacement therapies to emerge as a treatment option for several diseases. The role of microbioal replacement therapies in diseases other than CDI is being extensively studied in ongoing clinical trials and it may be a potential treatment option for inflammatory bowel disease, irritable bowel syndrome, obesity, multidrug resistant infections, and neuropsychiatric illnesses. Fecal microbiota transplantation for non-CDI disease states should currently be limited only to research settings.}, }
@article {pmid32146836, year = {2020}, author = {Giuffrè, M and Campigotto, M and Campisciano, G and Comar, M and Crocè, LS}, title = {A Story of Liver and Gut Microbes: How Does the Intestinal Flora Affect Liver Disease? A Review of the Literature.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpgi.00161.2019}, pmid = {32146836}, issn = {1522-1547}, abstract = {Each individual is endowed with a unique gut microbiota (GM) footprint, which mediates numerous host-related physiological functions such as nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against microbial pathogens. The rapid scientific interest in GM has recognized its central role in the pathophysiology of many intestinal and extra-intestinal conditions. Given the close relationship between the gastro-intestinal tract and the liver, many pathological processes have been investigated in the light of a microbial-centered hypothesis of hepatic damage. In this review, we want to introduce to neophytes the vast world of gut microbes - including prevalent bacterial distribution in healthy individuals, how the microbiota is commonly analyzed, and the current knowledge on the role of GM in liver diseases pathophysiology. Besides, we highlight the potentials and downsides of GM-based therapy.}, }
@article {pmid32132347, year = {2020}, author = {Zhang, F and Zhai, M and Wu, Q and Jia, X and Wang, Y and Wang, N}, title = {Protective effect of Tong-Qiao-Huo-Xue Decoction on inflammatory injury caused by intestinal microbial disorders in stroke rats.}, journal = {Biological &amp; pharmaceutical bulletin}, volume = {}, number = {}, pages = {}, doi = {10.1248/bpb.b19-00847}, pmid = {32132347}, issn = {1347-5215}, abstract = {Tong-Qiao-Huo-Xue Decoction (TQHXD) is a classic traditional Chinese medicine prescription for treating cerebral ischemia. The purpose of this study was to investigate the effect of TQHXD on intervening inflammatory response of ischemic stroke by regulating intestinal flora and repairing the intestinal barrier. A rat model of cerebral ischemia was established using middle cerebral artery occlusion (MCAO) and behavioral scores were performed. Additionally, the high throughput 16S rDNA sequence of intestinal bacteria in fecal samples of rat was also carried out. Our results showed that TQHXD could change the main components of intestinal flora in stroke rats, and reduced the excessive increase of Bacteroidetes, and also regulated the abnormal changes of abundance of some flora as well. In addition, the intestinal epithelial barrier was damaged after stroke, allowing bacterial metabolites to enter the blood, while TQHXD had an improved effect on this phenomenon. Meanwhile, pathological changes in the brain tissue and infarct volume was also alleviated by TQHXD. Due to the disorder of the intestinal flora and the destruction of the barrier, the peripheral immune imbalance caused an inflammatory reaction. TQHXD improved the imbalance of T cells, and inhibited the inflammatory response. Finally, the therapeutic transplantation of fecal microbiota also improved the outcome of stroke in rats. Our presented results suggest that TQHXD may improve the gut microbiota disorder and its induced inflammatory response after stroke, which could be a new target and mechanism for the treatment of stroke.}, }
@article {pmid32130695, year = {2020}, author = {Baffy, G}, title = {Gut Microbiota and Cancer of the Host: Colliding Interests.}, journal = {Advances in experimental medicine and biology}, volume = {1219}, number = {}, pages = {93-107}, doi = {10.1007/978-3-030-34025-4_5}, pmid = {32130695}, issn = {0065-2598}, abstract = {Cancer develops in multicellular organisms from cells that ignore the rules of cooperation and escape the mechanisms of anti-cancer surveillance. Tumorigenesis is jointly encountered by the host and microbiota, a vast collection of microorganisms that live on the external and internal epithelial surfaces of the body. The largest community of human microbiota resides in the gastrointestinal tract where commensal, symbiotic and pathogenic microorganisms interact with the intestinal barrier and gut mucosal lymphoid tissue, creating a tumor microenvironment in which cancer cells thrive or perish. Aberrant composition and function of the gut microbiota (dysbiosis) has been associated with tumorigenesis by inducing inflammation, promoting cell growth and proliferation, weakening immunosurveillance, and altering food and drug metabolism or other biochemical functions of the host. However, recent research has also identified several mechanisms through which gut microbiota support the host in the fight against cancer. These mechanisms include the use of antigenic mimicry, biotransformation of chemotherapeutic agents, and other mechanisms to boost anti-cancer immune responses and improve the efficacy of cancer immunotherapy. Further research in this rapidly advancing field is expected to identify additional microbial metabolites with tumor suppressing properties, map the complex interactions of host-microbe 'transkingdom network' with cancer cells, and elucidate cellular and molecular pathways underlying the impact of specific intestinal microbial configurations on immune checkpoint inhibitor therapy.}, }
@article {pmid32126303, year = {2020}, author = {Ebrahimzadeh Leylabadlo, H and Sanaie, S and Sadeghpour Heravi, F and Ahmadian, Z and Ghotaslou, R}, title = {From role of gut microbiota to microbial-based therapies in type 2-diabetes.}, journal = {Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases}, volume = {81}, number = {}, pages = {104268}, doi = {10.1016/j.meegid.2020.104268}, pmid = {32126303}, issn = {1567-7257}, abstract = {The incidence of type 2 diabetes mellitus (T2DM) has increased dramatically at an alarming level around the world.T2DM is associated with changeable risk factors in lifestyle as well as genetic and family associated risk factors. More importantly, imbalanced or impaired gut microbial distribution (dysbiosis) has been reported as a contributing risk factor in insulin resistance progression in T2DM. Dysbiosis may restructure the metabolic and functional pathways in the intestine which are involved in the development of T2DM. However, several studies have indicated the constructive and helpful effect of prebiotics, probiotics, and fecal microbiota transplantation (FMT) on the improvement of gut microbiota (GM) and accordingly host metabolism. In this review, the association between GM and T2DM have been evaluated and the role of prebiotics, probiotics and FMT, as potential therapeutic approaches have been discussed. Relevant studies were obtained randomly from online databases such as PubMed/Medline and ISI Web of Science.}, }
@article {pmid32117913, year = {2020}, author = {Adamberg, K and Raba, G and Adamberg, S}, title = {Use of Changestat for Growth Rate Studies of Gut Microbiota.}, journal = {Frontiers in bioengineering and biotechnology}, volume = {8}, number = {}, pages = {24}, pmid = {32117913}, issn = {2296-4185}, abstract = {Human colon microbiota, composed of hundreds of different species, is closely associated with several health conditions. Controlled in vitro cultivation and up-to-date analytical methods make possible the systematic evaluation of the underlying mechanisms of complex interactions between the members of microbial consortia. Information on reproducing fecal microbial consortia can be used for various clinical and biotechnological applications. In this study, chemostat and changestat cultures were used to elucidate the effects of the physiologically relevant range of dilution rates on the growth and metabolism of adult fecal microbiota. The dilution rate was kept either at D = 0.05 or D = 0.2 1/h in chemostat cultures, while gradually changing from 0.05 to 0.2 1/h in the A-stat and from 0.2 to 0.05 1/h in the De-stat. Apple pectin as a substrate was used in the chemostat experiments and apple pectin or birch xylan in the changestat experiments, in the presence of porcine mucin in all cases. The analyses were comprised of HPLC for organic acids, UPLC for amino acids, GC for gas composition, 16S-rDNA sequencing for microbial composition, and growth parameter calculations. It was shown that the abundance of most bacterial taxa was determined by the dilution rate on both substrates. Bacteroides ovatus, Bacteroides vulgatus, and Faecalibacterium were prevalent within the whole range of dilution rates. Akkermansia muciniphila and Ruminococcaceae UCG-013 were significantly enriched at D = 0.05 1/h, while Bacteroides caccae, Lachnospiraceae unclassified and Escherichia coli clearly preferred D = 0.2 1/h. In the chemostat cultures, the production of organic acids and gases from pectin was related to the dilution rate. The ratio of acetate, propionate and butyrate was 5:2:1 (D = 0.05 1/h) and 14:2:1 (D = 0.2 1/h). It was shown that the growth rate-related characteristics of the fecal microbiota were concise in both directions between D = 0.05 and 0.2 1/h. Reproducible adaptation of the fecal microbiota was shown in the continuous culture with a changing dilution rate: changestat. Consortia cultivation is a promising approach for research purposes and several biotechnological applications, including the production of multi-strain probiotics and fecal transplantation mixtures.}, }
@article {pmid32117102, year = {2020}, author = {Tsigalou, C and Konstantinidis, T and Stavropoulou, E and Bezirtzoglou, EE and Tsakris, A}, title = {Potential Elimination of Human Gut Resistome by Exploiting the Benefits of Functional Foods.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {50}, pmid = {32117102}, issn = {1664-302X}, abstract = {Recent advances in technology over the last decades have strived to elucidate the diverse and abundant ecosystem of the human microbiome. The intestinal microbiota represents a densely inhabited environment that offers a plethora of beneficial effects to the host's wellbeing. On the other hand, it can serve as a potential reservoir of Multi-Drug Resistant (MDR) bacteria and their antibiotic-resistant genes (ARgenes), which comprise the &quot;gut resistome.&quot; ARgenes, like antibiotics, have been omnipresent in the environment for billions of years. In the context of the gut microbiome, these genes may conflate into exogenous MDR or emerge in commensals due to mutations or gene transfers. It is currently generally accepted that Antimicrobial Resistance (AMR) poses a serious threat to public health worldwide. It is of paramount importance that researchers focus on, amongst other parameters, elaborating strategies to manage the gut resistome, particularly focusing on the diminution of AMR. Potential interventions in the gut microbiome field by Fecal Microbiota Transplant (FMT) or functional foods are newly emerged candidates for the uprooting of MDR strains and restoring dysbiosis and resilience. Probiotic nutrition is thought to diminish gut colonization from pathobionts. Yet only a few studies have explored the effects of antibiotics use on the reservoir of AR genes and the demanding time for return to normal by gut microbiota-targeted strategies. Regular administration of probiotic bacteria has recently been linked to restoration of the gut ecosystem and decrease of the gut resistome and AR genes carriers. This review summarizes the latest information about the intestinal resistome and the intriguing methods of fighting against AMR through probiotic-based methods and gut microbial shifts that have been proposed. This study contains some key messages: (1) AMR currently poses a lethal threat to global health, and it is pivotal for the scientific community to do its utmost in fighting against it; (2) human gut microbiome research, within the last decade especially, seems to be preoccupied with the interface of numerous diseases and identifying a potential target for a variety of interventions; (3) the gut resistome, comprised of AR genesis, presents very early on in life and is prone to shifts due to the use of antibiotics or dietary supplements; and (4) future strategies involving functional foods seem promising for the battle against AMR through intestinal resistome diminution.}, }
@article {pmid32115244, year = {2020}, author = {Neff, AS}, title = {Technical and Theoretic Limitations of the Experimental Evidence Supporting a Gut Bacterial Etiology in Mental Illness.}, journal = {Clinical therapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.clinthera.2020.02.002}, pmid = {32115244}, issn = {1879-114X}, abstract = {The impact of gut bacteria on the brain and behavior has become the subject of intense research. The brain is sensitive to biochemical and physiologic changes in the body, for example, changes in blood oxygenation or nutritional status. The collection of microorganisms residing within the digestive tract (the gut microbiome) is increasingly considered a major contributor to human physiology. These 2 considerations have led to the hypothesis that human psychology, including complex constructs like emotion and mental illness, could be influenced by the composition or function of gut bacteria. Five lines of evidence have been used to support the concept, including human correlational research, probiotic supplementation, antibiotic use, germ-free animal research, and fecal transplantation. Results from these experiments do not provide substantial support for the theory that complex human psychology is under the influence of gut bacteria. Placebo-controlled interventional research in humans, in particular fecal microbiota transplantation, will be required before a stronger conclusion can be reached. (Clin Ther. 2020;42:XXX-XXX) © 2020 Elsevier Inc.}, }
@article {pmid32114770, year = {2020}, author = {Jiménez-Avalos, JA and Arrevillaga-Boni, G and González-López, L and García-Carvajal, ZY and González-Avila, M}, title = {Classical methods and perspectives for manipulating the human gut microbial ecosystem.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-25}, doi = {10.1080/10408398.2020.1724075}, pmid = {32114770}, issn = {1549-7852}, abstract = {A healthy Human Gut Microbial Ecosystem (HGME) is a necessary condition for maintaining the orderly function of the whole body. Major alterations in the normal gut microbial composition, activity and functionality (dysbiosis) by an environmental or host-related disruptive event, can compromise metabolic, inflammatory, and neurological processes, causing disorders such as obesity, inflammatory bowel disease, colorectal cancer, and depressive episodes. The restore or the maintaining of the homeostatic balance of Gut Microbiota (GM) populations (eubiosis) is possible through diet, the use of probiotics, prebiotics, antibiotics, and even Fecal Microbiota Transplantation (FMT). Although these &quot;classic methods&quot; represent an effective and accepted way to modulate GM, the complexity of HGME requires new approaches to control it in a more appropriate way. Among the most promising emergent strategies for modulating GM are the use of engineered nanomaterials (metallic nanoparticles (NP), polymeric-NP, quantum dots, micelles, dendrimers, and liposomes); phagotherapy (i.e., phages linked with the CRISPR/Cas9 system), and the use of antimicrobial peptides, non-antibiotic drugs, vaccines, and immunoglobulins. Here we review the current state of development, implications, advantages, disadvantages, and perspectives of the different approaches for manipulating HGME.}, }
@article {pmid32109968, year = {2020}, author = {Zhao, X and Jiang, Y and Xi, H and Chen, L and Feng, X}, title = {Exploration of the Relationship Between Gut Microbiota and Polycystic Ovary Syndrome (PCOS): a Review.}, journal = {Geburtshilfe und Frauenheilkunde}, volume = {80}, number = {2}, pages = {161-171}, pmid = {32109968}, issn = {0016-5751}, abstract = {Polycystic ovary syndrome (PCOS) is an endocrine and metabolic syndrome (MS) with a complex etiology, and its pathogenesis is not yet clear. In recent years, the correlation between gut microbiota (GM) and metabolic disease has become a hot topic in research, leading to a number of new ideas about the etiology and pathological mechanisms of PCOS. The literature shows that GM can cause insulin resistance, hyperandrogenism, chronic inflammation and metabolic syndrome (obesity, diabetes) and may contribute to the development of PCOS by influencing energy absorption, the pathways of short chain fatty acids (SCFA), lipopolysaccharides, choline and bile acids, intestinal permeability and the brain-gut axis. As part of the treatment of PCOS, fecal microbiota transplantation, supplementation with prebiotics and traditional Chinese medicine can be used to regulate GM and treat disorders. This article reviews possible mechanisms and treatment options for PCOS, based on methods which target the GM, and offers new ideas for the treatment of PCOS.}, }
@article {pmid32107336, year = {2020}, author = {Merli, P and Putignani, L and Ruggeri, A and Del Chierico, F and Gargiullo, L and Galaverna, F and Gaspari, S and Pagliara, D and Russo, A and Pane, S and Strocchio, L and Algeri, M and Rea, F and Romeo, EF and Bernaschi, P and Onetti Muda, A and Dallapiccola, B and Locatelli, F}, title = {Decolonization of multi-drug resistant bacteria by fecal microbiota transplantation in five pediatric patients before allogeneic hematopoietic stem cell transplantation: gut microbiota profiling, infectious and clinical outcomes.}, journal = {Haematologica}, volume = {}, number = {}, pages = {}, doi = {10.3324/haematol.2019.244210}, pmid = {32107336}, issn = {1592-8721}, }
@article {pmid32106123, year = {2020}, author = {Yan, PG and Li, JN}, title = {Advances in the understanding of the intestinal micro-environment and inflammatory bowel disease.}, journal = {Chinese medical journal}, volume = {}, number = {}, pages = {}, doi = {10.1097/CM9.0000000000000718}, pmid = {32106123}, issn = {2542-5641}, abstract = {The human gastrointestinal tract accommodates an entire micro-environment for divergent physiologic processes, the dysbiosis of this micro-ecology has a strong inter-action with the pathogenesis of inflammatory bowel disease (IBD). In the past few years, with the advances in the understanding of microbiome, its metabolites and further application of next generation sequencing, analysis of dynamic alteration of gut micro-environment was realized, which provides numerous information beyond simple microbiota structure or metabolites differences under chronic colitis status. The subsequent intervention strategies targeting the modulation of intestinal micro-environment have been explored as a potential therapy. In this review, we will summarize the recent knowledge about multi-dimensional dysbiosis, the inter-action between fungus and bacteria under inflamed mucosa, and the clinical application of probiotics and fecal microbiota transplantation as a promising therapeutic approach in IBD.}, }
@article {pmid32104162, year = {2020}, author = {Cheng, YW and Fischer, M}, title = {Fecal Microbiota Transplantation: Redefining Surgical Management of Refractory Clostridium difficile Infection.}, journal = {Clinics in colon and rectal surgery}, volume = {33}, number = {2}, pages = {92-97}, pmid = {32104162}, issn = {1531-0043}, abstract = {Fecal microbiota transplantation (FMT) is the process of transplanting stool from a healthy donor into the gut of a diseased individual for therapeutic purposes. It has a clearly defined role in the treatment of recurrent Clostridium difficile (reclassified as &quot; Clostridioides difficile &quot;) infection (CDI), with cure rates over 90% and decreased rates of subsequent recurrence compared with anti-CDI antibiotics. There is emerging evidence that FMT is also effective in the treatment of severe and fulminant CDI, with associated decreases in mortality and colectomy rates compared with standard antibiotic therapy. FMT shows promise as salvage therapy for critically-ill CDI patients refractory to maximum medical therapy and not deemed to be surgical candidates. FMT should be considered early in the course of severe CDI and should be delivered immediately in patients with signs of refractory CDI. Expansion of FMT's use along the spectrum of CDI severity has potential to decrease associated rates of mortality and colectomy.}, }
@article {pmid32101664, year = {2020}, author = {Peled, JU and Gomes, ALC and Devlin, SM and Littmann, ER and Taur, Y and Sung, AD and Weber, D and Hashimoto, D and Slingerland, AE and Slingerland, JB and Maloy, M and Clurman, AG and Stein-Thoeringer, CK and Markey, KA and Docampo, MD and Burgos da Silva, M and Khan, N and Gessner, A and Messina, JA and Romero, K and Lew, MV and Bush, A and Bohannon, L and Brereton, DG and Fontana, E and Amoretti, LA and Wright, RJ and Armijo, GK and Shono, Y and Sanchez-Escamilla, M and Castillo Flores, N and Alarcon Tomas, A and Lin, RJ and Yáñez San Segundo, L and Shah, GL and Cho, C and Scordo, M and Politikos, I and Hayasaka, K and Hasegawa, Y and Gyurkocza, B and Ponce, DM and Barker, JN and Perales, MA and Giralt, SA and Jenq, RR and Teshima, T and Chao, NJ and Holler, E and Xavier, JB and Pamer, EG and van den Brink, MRM}, title = {Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation.}, journal = {The New England journal of medicine}, volume = {382}, number = {9}, pages = {822-834}, doi = {10.1056/NEJMoa1900623}, pmid = {32101664}, issn = {1533-4406}, support = {2016-013/US/United States/United States ; 17H04206//Japan Society for the Promotion of Science/International ; 17K09945//Japan Society for the Promotion of Science/International ; KL2 TR001115-03/TR/NCATS NIH HHS/United States ; R01 AI032135/NH/NIH HHS/United States ; 1R01CA228308-01/CA/NCI NIH HHS/United States ; 1R01CA228358-01/CA/NCI NIH HHS/United States ; P01-CA023766 (Project 4)/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01-HL125571/CA/NCI NIH HHS/United States ; R01CA203950-01/CA/NCI NIH HHS/United States ; U01 AI124275/CA/NCI NIH HHS/United States ; 1R01HL124112-01A/HL/NHLBI NIH HHS/United States ; K08HL143189-01A1/HL/NHLBI NIH HHS/United States ; R01-HL123340/HL/NHLBI NIH HHS/United States ; R01-HL125571/HL/NHLBI NIH HHS/United States ; 2P30AG028716-11/AG/NIA NIH HHS/United States ; P01-AG052359 (Project 2)/AG/NIA NIH HHS/United States ; AI095706//National Institute of Allergy and Infectious Diseases/International ; R01 AI137269-01//National Institute of Allergy and Infectious Diseases/International ; U01 AI124275/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Relationships between microbiota composition and clinical outcomes after allogeneic hematopoietic-cell transplantation have been described in single-center studies. Geographic variations in the composition of human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable.<br><br>METHODS: The microbiota composition of fecal samples obtained from patients who were undergoing allogeneic hematopoietic-cell transplantation at four centers was profiled by means of 16S ribosomal RNA gene sequencing. In an observational study, we examined associations between microbiota diversity and mortality using Cox proportional-hazards analysis. For stratification of the cohorts into higher- and lower-diversity groups, the median diversity value that was observed at the study center in New York was used. In the analysis of independent cohorts, the New York center was cohort 1, and three centers in Germany, Japan, and North Carolina composed cohort 2. Cohort 1 and subgroups within it were analyzed for additional outcomes, including transplantation-related death.<br><br>RESULTS: We profiled 8767 fecal samples obtained from 1362 patients undergoing allogeneic hematopoietic-cell transplantation at the four centers. We observed patterns of microbiota disruption characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota was associated with a lower risk of death in independent cohorts (cohort 1: 104 deaths among 354 patients in the higher-diversity group vs. 136 deaths among 350 patients in the lower-diversity group; adjusted hazard ratio, 0.71; 95% confidence interval [CI], 0.55 to 0.92; cohort 2: 18 deaths among 87 patients in the higher-diversity group vs. 35 deaths among 92 patients in the lower-diversity group; adjusted hazard ratio, 0.49; 95% CI, 0.27 to 0.90). Subgroup analyses identified an association between lower intestinal diversity and higher risks of transplantation-related death and death attributable to graft-versus-host disease. Baseline samples obtained before transplantation already showed evidence of microbiome disruption, and lower diversity before transplantation was associated with poor survival.<br><br>CONCLUSIONS: Patterns of microbiota disruption during allogeneic hematopoietic-cell transplantation were similar across transplantation centers and geographic locations; patterns were characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota at the time of neutrophil engraftment was associated with lower mortality. (Funded by the National Cancer Institute and others.).}, }
@article {pmid32100127, year = {2020}, author = {Chen, K and Fu, Y and Wang, Y and Liao, L and Xu, H and Zhang, A and Zhang, J and Fan, L and Ren, J and Fang, B}, title = {Therapeutic Effects of the In Vitro Cultured Human Gut Microbiota as Transplants on Altering Gut Microbiota and Improving Symptoms Associated with Autism Spectrum Disorder.}, journal = {Microbial ecology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00248-020-01494-w}, pmid = {32100127}, issn = {1432-184X}, support = {81770558//National Natural Science Foundation of China/ ; 3502Z20149031//Xiamen Joint Projects for Major Diseases/ ; }, abstract = {Autism spectrum disorder (ASD) is a brain-based neurodevelopmental disorder characterized by behavioral abnormalities. Accumulating studies show that the gut microbiota plays a vital role in the pathogenesis of ASD, and gut microbiota transplantation (GMT) is a promising technique for the treatment of ASD. In clinical applications of GMT, it is challenging to obtain effective transplants because of the high costs of donor selection and heterogeneity of donors' gut microbiota, which can cause different clinical responses. In vitro batch culture is a fast, easy-to-operate, and repeatable method to culture gut microbiota. Thus, the present study investigates the feasibility of treating ASD with in vitro cultured gut microbiota as transplants. We cultured gut microbiota via the in vitro batch culture method and performed GMT in the maternal immune activation (MIA)-induced ASD mouse model with original donor microbiota and in vitro cultured microbiota. Open field, three-chamber social, marble burying, and self-grooming tests were used for behavioral improvement assessment. Serum levels of chemokines were detected. Microbial total DNA was extracted from mouse fecal samples, and 16S rDNA was sequenced using Illumina. Our results showed that GMT treatment with original and cultured donor gut microbiota significantly ameliorated anxiety-like and repetitive behaviors and improved serum levels of chemokines including GRO-α (CXCL1), MIP-1α (CCL3), MCP-3 (CCL7), RANTES (CCL5), and Eotaxin (CCL11) in ASD mice. Meanwhile, the gut microbial communities of the two groups that received GMT treatment were changed compared with the ASD mice groups. In the group treated with in vitro cultured donor gut microbiota, there was a significant decrease in the relative abundance of key differential taxa, including S24-7, Clostridiaceae, Prevotella_other, and Candidatus Arthromitus. The relative abundance of these taxa reached close to the level of healthy mice. Prevotella_other also decreased in the group treated with original donor gut microbiota, with a significant increase in Ruminococcaceae and Oscillospira. The present study demonstrated that GMT with in vitro cultured microbiota also improved behavioral abnormalities and chemokine disorders in an ASD mouse model compared with GMT with original donor gut microbiota. In addition, it significantly modified several key differential taxa in gut microbial composition.}, }
@article {pmid32099702, year = {2020}, author = {Ueckermann, V and Hoosien, E and De Villiers, N and Geldenhuys, J}, title = {Fecal Microbial Transplantation for the Treatment of Persistent Multidrug-Resistant Klebsiella pneumoniae Infection in a Critically Ill Patient.}, journal = {Case reports in infectious diseases}, volume = {2020}, number = {}, pages = {8462659}, pmid = {32099702}, issn = {2090-6625}, abstract = {Dysbiosis of the microbiome is a common finding in critically ill patients, who receive broad-spectrum antibiotics and various forms of organ support. Multidrug-resistant (MDR) organisms are a growing threat in all areas of medicine, but most markedly in the critically ill, where there is both loss of host defences and widespread use of broad spectrum antibiotics. We present a case of a critically ill patient with persistent MDR Klebsiella pneumoniae infection, successfully treated with fecal microbiota transplantation (FMT), using stool of a rigorously-screened, healthy donor. FMT for Clostridium difficile colitis has been well described in the literature and is an established therapy for recurrent infections with Clostridium difficile. The use of FMT for other multidrug-resistant organisms is less frequently described, particularly in the context of critically ill patients. In our case, we have culture-documented clearance of the MDR Klebsiella pneumoniae form a patient of FMT.}, }
@article {pmid32089675, year = {2020}, author = {Mazzawi, T and Eikrem, Ø and Lied, GA and Hausken, T}, title = {Abnormal Uroguanylin Immunoreactive Cells Density in the Duodenum of Patients with Diarrhea-Predominant Irritable Bowel Syndrome Changes following Fecal Microbiota Transplantation.}, journal = {Gastroenterology research and practice}, volume = {2020}, number = {}, pages = {3520686}, pmid = {32089675}, issn = {1687-6121}, abstract = {Altered densities of enteroendocrine cells play an important role in patients with irritable bowel syndrome (IBS). Uroguanylin activates guanylate cyclase-C to regulate intestinal electrolyte and water transport. Aim. To quantify uroguanylin immunoreactive cells density in the duodenum of diarrhea-predominant IBS (IBS-D) patients compared to controls and to investigate the effect of fecal microbiota transplantation (FMT) on these cell densities. Method. Twelve patients with IBS-D according to Rome III criteria were included. The cause was identified as post infectious (PI, n = 6) or idiopathic (n = 6). They completed the IBS-symptom questionnaire before and 3 weeks after FMT. Thirty grams of fresh feces donated from healthy relatives were diluted with 60 ml normal saline and instilled via endoscope into the duodenum. Biopsies were taken from the patients' duodenum before and 3 weeks after FMT. Duodenal biopsies taken from eight healthy controls were also included. The biopsies were immunostained for uroguanylin and quantified using computerized image analysis. Results. Uroguanylin immunoreactive cells were found both in duodenal villi and crypts in both controls and IBS-D patients. The densities of uroguanylin immunoreactive cells were significantly lower in the villi (P < 0.0001) and higher in the crypts (P < 0.0001) for the patients than the controls. Following FMT, the densities of uroguanylin immunoreactive cells for the total group and idiopathic subgroup decreased significantly in the duodenal crypts (P = 0.049 and 0.04, respectively) but not in the villi. No significant changes were shown in the PI-IBS subgroups. The cells density in only the crypts correlated with diarrhea (r = 0.97, P = 0.001) and bloating (r = -0.91, P = 0.01) in the PI-IBS subgroup before FMT and with abdominal pain (r = 0.63, P = 0.03) in the total group of IBS-D patients after FMT. Conclusion. Altered uroguanylin immunoreactive cells density was found in IBS-D patients compared to controls. Changes in these cells density following FMT correlated with IBS symptoms (diarrhea, bloating, and abdominal pain).}, }
@article {pmid32089055, year = {2020}, author = {Chen, EB and Shapiro, KE and Wun, K and Kuntz, T and Theriault, BR and Nooromid, MJ and Leone, VA and Harris, KG and Jiang, Q and Spedale, M and Xiong, L and Gilbert, JA and Chang, EB and Ho, KJ}, title = {Microbial Colonization of Germ-Free Mice Restores Neointimal Hyperplasia Development After Arterial Injury.}, journal = {Journal of the American Heart Association}, volume = {9}, number = {5}, pages = {e013496}, doi = {10.1161/JAHA.119.013496}, pmid = {32089055}, issn = {2047-9980}, abstract = {Background The potential role of the gut microbiome in cardiovascular diseases is increasingly evident. Arterial restenosis attributable to neointimal hyperplasia after cardiovascular procedures such as balloon angioplasty, stenting, and bypass surgery is a common cause of treatment failure, yet whether gut microbiota participate in the development of neointimal hyperplasia remains largely unknown. Methods and Results We performed fecal microbial transplantation from conventionally raised male C57BL/6 mice to age-, sex-, and strain-matched germ-free mice. Five weeks after inoculation, all mice underwent unilateral carotid ligation. Neointimal hyperplasia development was quantified after 4 weeks. Conventionally raised and germ-free cohorts served as comparison groups. Conclusions Germ-free mice have significantly attenuated neointimal hyperplasia development compared with conventionally raised mice. The arterial remodeling response is restored by fecal transplantation. Our results describe a causative role of gut microbiota in contributing to the pathogenesis of neointimal hyperplasia.}, }
@article {pmid32083498, year = {2020}, author = {Lopetuso, LR and Ianiro, G and Allegretti, JR and Bibbò, S and Gasbarrini, A and Scaldaferri, F and Cammarota, G}, title = {Fecal transplantation for ulcerative colitis: current evidence and future applications.}, journal = {Expert opinion on biological therapy}, volume = {20}, number = {4}, pages = {343-351}, doi = {10.1080/14712598.2020.1733964}, pmid = {32083498}, issn = {1744-7682}, abstract = {Introduction: Established evidence suggests that gut microbiota plays a role in ulcerative colitis (UC). Fecal microbiota transplantation (FMT) is clearly recognized as a highly effective treatment for patients with recurrent Clostridium difficile infection and has been investigated also in patients with UC, with promising results.Areas covered: Literature review was performed to select publications concerning current evidence on the role of gut microbiota in the pathogenesis of UC, and on the effectiveness of FMT in this disorder.Expert opinion: The randomized controlled trials published investigating the use of FMT suggested a potential role for FMT in the treatment of mild to moderate UC. However, given several unanswered questions regarding donor selection, dose, route of administration and duration of therapy, this is not yet recommended as a viable therapy option. FMT has allowed for more in depth investigation with regards to the role the gut microbiota may be playing in UC. This knowledge is critical to identifying where FMT may appropriately fit in the UC treatment paradigm. As our understanding of the role the microbiome plays in this chronic disease, FMT, and then eventually defined microbes, will hopefully serve in a complementary role to conventional IBD therapies.}, }
@article {pmid32079318, year = {2020}, author = {Pilmis, B and Le Monnier, A and Zahar, JR}, title = {Gut Microbiota, Antibiotic Therapy and Antimicrobial Resistance: A Narrative Review.}, journal = {Microorganisms}, volume = {8}, number = {2}, pages = {}, doi = {10.3390/microorganisms8020269}, pmid = {32079318}, issn = {2076-2607}, abstract = {Antimicrobial resistance is a major concern. Epidemiological studies have demonstrated direct relationships between antibiotic consumption and emergence/dissemination of resistant strains. Within the last decade, authors confounded spectrum activity and ecological effects and did not take into account several other factors playing important roles, such as impact on anaerobic flora, biliary elimination and sub-inhibitory concentration. The ecological impact of antibiotics on the gut microbiota by direct or indirect mechanisms reflects the breaking of the resistance barrier to colonization. To limit the impact of antibiotic therapy on gut microbiota, consideration of the spectrum of activity and route of elimination must be integrated into the decision. Various strategies to prevent (antimicrobial stewardship, action on residual antibiotics at colonic level) or cure dysbiosis (prebiotic, probiotic and fecal microbiota transplantation) have been introduced or are currently being developed.}, }
@article {pmid32078714, year = {2020}, author = {Luo, Y and Tixier, EN and Grinspan, AM}, title = {Fecal Microbiota Transplantation for Clostridioides difficile in High-Risk Older Adults Is Associated with Early Recurrence.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-020-06147-z}, pmid = {32078714}, issn = {1573-2568}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridioides difficile infection (CDI). CDI disproportionately affects the elderly; however, there is a paucity of data on FMT effectiveness in older adults, especially subpopulations at highest risk for CDI-related morbidity and mortality.<br><br>AIM: To assess the efficacy and safety of FMT for CDI in older adults.<br><br>METHODS: A retrospective, long-term follow-up study was performed. The high-risk subpopulation included patients who were immunocompromised, patients with inflammatory bowel disease, and patients presenting with severe or fulminant colitis. Outcome measures included primary cure rates, early (< 12 weeks) and late (> 12 weeks) recurrence rates, adverse events, and subgroup analysis of higher-risk populations.<br><br>RESULTS: Our cohort included 75 patients (72% female) with a mean age of 76.4 and Charlson comorbidity index score of 5.4. There were 34 patients in our higher-risk subpopulation as defined above with an adjusted recurrence rate of 32.1%. FMT was performed for severe or fulminant disease in 30.6% of patients with a 3-month survival rate of 73.9%. Overall, the adjusted primary cure rate was 67.2% and the adjusted CDI recurrence was 29.9% in our cohort (90% of recurrences occurred early). Most adverse events in our study were rehospitalizations for recurrent CDI.<br><br>CONCLUSION: Compared with previous studies of FMT efficacy, our cohort had a lower primary cure rate and higher CDI recurrence rate than previously reported, likely driven by our higher-risk subpopulations. Nevertheless, FMT should be considered early to prevent progression of CDI severity and recurrence, especially in patients who present with severe and fulminant disease.}, }
@article {pmid32078445, year = {2020}, author = {Yan, X and Jin, J and Su, X and Yin, X and Gao, J and Wang, X and Zhang, S and Bu, P and Wang, M and Zhang, Y and Wang, Z and Zhang, Q}, title = {Intestinal Flora Modulates Blood Pressure by Regulating the Synthesis of Intestinal-Derived Corticosterone in High Salt-Induced Hypertension.}, journal = {Circulation research}, volume = {}, number = {}, pages = {}, doi = {10.1161/CIRCRESAHA.119.316394}, pmid = {32078445}, issn = {1524-4571}, abstract = {Rationale: High-salt diet (HSD) is one of the most important risk factors for hypertension. Intestinal flora has been reported to be associated with high salt-induced hypertension (hSIH). However, the detailed roles of intestinal flora in hSIH pathogenesis have not yet been fully elucidated. Objective: To reveal the roles and mechanisms of intestinal flora in hSIH development. Methods and Results: The above-mentioned issues were investigated using various techniques including 16S rRNA gene sequencing, untargeted metabolomics, selective bacterial culture and fecal microbiota transplantation (FMT). We found that HSD induced hypertension in Wistar rats. The fecal microbiota of healthy rats could dramatically lower blood pressure (BP) of hypertensive rats, while the fecal microbiota of hSIH rats had opposite effects. The composition, metabolism and interrelationship of intestinal flora in hSIH rats were considerably reshaped, including the increased corticosterone level and reduced Bacteroides and arachidonic acid (AA) levels, which tightly correlated with BP. The serum corticosterone level was also significantly increased in rats with hSIH. Furthermore, the above abnormalities were confirmed in patients with hypertension. The intestinal Bacteroides fragilis (B. fragilis) could inhibit the production of intestinal-derived corticosterone induced by HSD through its metabolite AA. Conclusions: hSIH could be transferred by FMT, indicating the pivotal roles of intestinal flora in hSIH development. HSD reduced the levels of B. fragilis and AA in the intestine, which increased intestinal-derived corticosterone production and corticosterone levels in serum and intestine, thereby promoting BP elevation. This study revealed a novel mechanism different from inflammation/immunity by which intestinal flora regulated BP, namely intestinal flora could modulate BP by affecting steroid hormone levels. These findings enriched the understanding of the function of intestinal flora and its effects on hypertension.}, }
@article {pmid32068018, year = {2020}, author = {Liu, X and Liu, Y and Chen, X and Wang, C and Chen, X and Liu, W and Huang, K and Chen, H and Yang, J}, title = {Multi-walled carbon nanotubes exacerbate doxorubicin-induced cardiotoxicity by altering gut microbiota and pulmonary and colonic macrophage phenotype in mice.}, journal = {Toxicology}, volume = {435}, number = {}, pages = {152410}, doi = {10.1016/j.tox.2020.152410}, pmid = {32068018}, issn = {1879-3185}, abstract = {Epidemiologic studies show that the levels of air pollutants and particulate matter are positively associated with the morbidity and mortality of cardiovascular diseases. Here we demonstrate that the intratracheal instillation of multi-walled carbon nanotubes (MWCNTs), a standard fine particle, exacerbate doxorubicin (DOX)-induced cardiotoxicity in mice through altering gut microbiota and pulmonary and colonic macrophage phenotype. MWCNTs (25 μg/kg per day, 5 days a week for 3 weeks) promoted cardiotoxicity and apoptosis in the DOX (2 mg/kg, twice a week for 5 weeks)-treated C57BL/6 mice. MWCNTs exaggerated DOX-induced gut microbiota dysbiosis characterized by the increased abundances of Helicobacteraceae and Coriobacteriaceae. In addition, MWCNTs promoted DOX-induced M1-like polarization of colonic macrophages with an increase in TNF-α, IL-1β and CC chemokine ligand 2 in peripheral blood. Importantly, treatment with the antibiotics attenuated MWCNTs plus DOX-induced apoptosis of cardiomyocytes and M1-like polarization of colonic macrophages. The fecal microbiota transplantation demonstrated that MWCNTs exaggerated DOX-induced cardiotoxicity with M1-like polarization of colonic macrophages. The conditioned medium from MWCNTs-treated pulmonary macrophages promoted DOX-induced gut microbiota dysbiosis and colonic macrophage polarization. Furthermore, the co-culture of macrophages and fecal bacteria promoted M1-like macrophage polarization and their production of TNF-α and IL-1β, and thereby exacerbated the effects of MWCNTs. Moreover, IL-1β and TNF-α blockade, either alone or in combination attenuated MWCNTs-exacerbated cardiotoxicity. In summary, MWCNTs exacerbate DOX-induced cardiotoxicity in mice through gut microbiota and pulmonary and colonic macrophage interaction. Our findings identify a novel mechanism of action of inhaled particle-driven cardiotoxicity.}, }
@article {pmid32066679, year = {2020}, author = {Xiao, J and Wang, T and Xu, Y and Gu, X and Li, D and Niu, K and Wang, T and Zhao, J and Zhou, R and Wang, HL}, title = {Long-term probiotic intervention mitigates memory dysfunction through a novel H3K27me3-based mechanism in lead-exposed rats.}, journal = {Translational psychiatry}, volume = {10}, number = {1}, pages = {25}, pmid = {32066679}, issn = {2158-3188}, support = {31401671//National Science Foundation of China | Young Scientists Fund/ ; 81773475, 21477031//National Science Foundation of China | Major Research Plan/ ; }, abstract = {Chronic lead exposure is associated with the development of neurodegenerative diseases, characterized by the long-term memory decline. However, whether this pathogenesis could be prevented through adjusting gut microbiota is not yet understood. To address the issue, pregnant rats and their female offspring were treated with lead (125 ppm) or separately the extra probiotics (1010 organisms/rat/day) till adulthood. For results, memory dysfunction was alleviated by the treatment of multispecies probiotics. Meanwhile, the gut microbiota composition was partially normalized against lead-exposed rats, which in turn mediated the memory repairment via fecal transplantation trials. In the molecular aspect, the decreased H3K27me3 (trimethylation of histone H3 Lys 27) in the adult hippocampus was restored with probiotic intervention, an epigenetic event mediated by EZH2 (enhancer of zeste homolog 2) at early developmental stage. In a neural cellular model, EZH2 overexpression showed the similar rescue effect with probiotics, whereas its blockade led to the neural re-damages. Regarding the gut-brain inflammatory mediators, the disrupted IL-6 (interleukin 6) expression was resumed by probiotic treatment. Intraperitoneal injection of tocilizumab, an IL-6 receptor antagonist, upregulated the hippocampal EZH2 level and consequently alleviated the memory injuries. In conclusion, reshaping gut microbiota could mitigate memory dysfunction caused by chronic lead exposure, wherein the inflammation-hippocampal epigenetic pathway of IL-6-EZH2-H3K27me3, was first proposed to mediate the studied gut-brain communication. These findings provided insight with epigenetic mechanisms underlying a unique gut-brain interaction, shedding light on the safe and non-invasive treatment of neurodegenerative disorders with environmental etiology.}, }
@article {pmid32063856, year = {2019}, author = {Wu, H and Rao, Q and Ma, GC and Yu, XH and Zhang, CE and Ma, ZJ}, title = {Effect of Triptolide on Dextran Sodium Sulfate-Induced Ulcerative Colitis and Gut Microbiota in Mice.}, journal = {Frontiers in pharmacology}, volume = {10}, number = {}, pages = {1652}, pmid = {32063856}, issn = {1663-9812}, abstract = {Triptolide is beneficial for the treatment of ulcerative colitis (UC), which is closely related to the gut microbiota. However, whether the therapeutic effects of triptolide involve the regulation of the gut microbiota is still unclear. In the present study, animal models of UC mice induced by dextran sodium sulfate (DSS) were established, the changes of gut microbiota in mice were detected by high-throughput sequencing. The effects of triptolide on DSS-induced UC mouse and its gut microbiota were studied. As a result, we found that triptolide exerted anti-inflammatory and therapeutic effects on UC mice. Sequencing results for the gut microbiota showed that the composition of the gut microbiota from DSS group was disordered as compared with that from the control group, consistent with a decrease in the abundance of flora. Triptolide treatment accelerated the recovery of the population of the gut microbiota and significantly improved the microbial diversity. At the phylum level, the population of Bacteroidetes decreased and that of Firmicutes increased. At the genus level, Bacteroides and Lachnospiraceae counts decreased. Thus, triptolide could regulate the composition of the gut microbiota, accelerate the recovery of microbiota, and exert good therapeutic effects in UC mice. Our results also revealed that fecal transplantation from triptolide-treated mice could relieve UC. This study provides a reference for the rational use of triptolide for the treatment of UC.}, }
@article {pmid32057278, year = {2020}, author = {Cheng, YW and Fischer, M}, title = {Clinical management of severe, fulminant, and refractory Clostridioides difficile infection.}, journal = {Expert review of anti-infective therapy}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/14787210.2020.1730814}, pmid = {32057278}, issn = {1744-8336}, abstract = {Introduction: Up to 15% of hospitalized patients with Clostridioides difficile infection (CDI) develop severe CDI (SCDI) or Fulminant CDI (FCDI). Due to high rates of mortality in medically-refractory CDI cases, 30% of patients with severe infection historically require surgical intervention. However, colectomy itself is an imperfect solution because it is difficult to predict who will fail medical therapy, patients with SCDI are more likely to have underlying medical conditions that make them poor surgical candidates, and post-surgical mortality still approaches 30-50%.Areas covered: This review will serve as a clinically-based review of severe and fulminant CDI management including discussion of models to predict severe infection, emerging treatments, novel targets for therapy, and innovations in surgical management.Expert opinion: Among the most promising studies to emerge in the last decade have involved fecal microbiota transplantation (FMT), which is already recommended by multiple society guidelines for recurrent CDI (RCDI). In the case of SCDI/FCDI, multiple studies have safely and successfully utilized FMT to produce rates of cure in the 70-90% range. Additionally, patients who have FCDI refractory to medical therapy and are poor candidates for colectomy may benefit from FMT as salvage therapy.}, }
@article {pmid32056091, year = {2020}, author = {Saurman, V and Margolis, KG and Luna, RA}, title = {Autism Spectrum Disorder as a Brain-Gut-Microbiome Axis Disorder.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {818-828}, pmid = {32056091}, issn = {1573-2568}, abstract = {While there are numerous medical comorbidities associated with ASD, gastrointestinal (GI) issues have a significant impact on quality of life for these individuals. Recent findings continue to support the relationship between the gut microbiome and both GI symptoms and behavior, but the heterogeneity within the autism spectrum requires in-depth clinical characterization of these clinical cohorts. Large, diverse, well-controlled studies in this area of research are still needed. Although there is still much to discover about the brain-gut-microbiome axis in ASD, microbially mediated therapies, specifically probiotics and fecal microbiota transplantation have shown promise in the treatment of GI symptoms in ASD, with potential benefit to the core behavioral symptoms of ASD as well. Future research and clinical trials must increasingly consider complex phenotypes in ASD in stratification of large datasets as well as in design of inclusion criteria for individual therapeutic interventions.}, }
@article {pmid32055962, year = {2020}, author = {Shin, JH and Lee, YK and Shon, WJ and Kim, B and Jeon, CO and Cho, JY and Morse, HC and Choi, EY and Shin, DM}, title = {Gut microorganisms and their metabolites modulate the severity of acute colitis in a tryptophan metabolism-dependent manner.}, journal = {European journal of nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00394-020-02194-4}, pmid = {32055962}, issn = {1436-6215}, support = {HI16C0047//Ministry of Health and Welfare/ ; }, abstract = {PURPOSE: Growing evidence shows that nutrient metabolism affects inflammatory bowel diseases (IBD) development. Previously, we showed that deficiency of indoleamine 2,3-dioxygenase 1 (Ido1), a tryptophan-catabolizing enzyme, reduced the severity of dextran sulfate sodium (DSS)-induced colitis in mice. However, the roles played by intestinal microbiota in generating the differences in disease progression between Ido1+/+ and Ido1-/- mice are unknown. Therefore, we aimed to investigate the interactions between the intestinal microbiome and host IDO1 in governing intestinal inflammatory responses.<br><br>METHODS: Microbial 16s rRNA sequencing was conducted in Ido1+/+ and Ido1-/- mice after DSS treatment. Bacteria-derived tryptophan metabolites were measured in urine. Transcriptome analysis revealed the effects of the metabolite and IDO1 expression in HCT116 cells. Colitis severity of Ido1+/+ was compared to Ido1-/- mice following fecal microbiota transplantation (FMT).<br><br>RESULTS: Microbiome analysis through 16S-rRNA gene sequencing showed that IDO1 deficiency increased intestinal bacteria that use tryptophan preferentially to produce indolic compounds. Urinary excretion of 3-indoxyl sulfate, a metabolized form of gut bacteria-derived indole, was significantly higher in Ido1-/- than in Ido1+/+ mice. Transcriptome analysis showed that tight junction transcripts were significantly increased by indole treatment in HCT116 cells; however, the effects were diminished by IDO1 overexpression. Using FMT experiments, we demonstrated that bacteria from Ido1-/- mice could directly attenuate the severity of DSS-induced colitis.<br><br>CONCLUSIONS: Our results provide evidence that a genetic defect in utilizing tryptophan affects intestinal microbiota profiles, altering microbial metabolites, and colitis development. This suggests that the host and intestinal microbiota communicate through shared nutrient metabolic networks.}, }
@article {pmid32053787, year = {2020}, author = {Carlson, PE}, title = {Regulatory Considerations for Fecal Microbiota Transplantation Products.}, journal = {Cell host &amp; microbe}, volume = {27}, number = {2}, pages = {173-175}, doi = {10.1016/j.chom.2020.01.018}, pmid = {32053787}, issn = {1934-6069}, abstract = {Fecal microbiota for transplantation (FMT) is being studied as a potential intervention for numerous conditions. The regulation of FMT by the FDA is discussed along with FMT donor screening and manufacturing considerations. The FDA is committed to ensuring that FMT products can be safely tested in clinical trials.}, }
@article {pmid32053786, year = {2020}, author = {Markey, KA and van den Brink, MRM and Peled, JU}, title = {Therapeutics Targeting the Gut Microbiome: Rigorous Pipelines for Drug Development.}, journal = {Cell host &amp; microbe}, volume = {27}, number = {2}, pages = {169-172}, doi = {10.1016/j.chom.2020.01.022}, pmid = {32053786}, issn = {1934-6069}, support = {R01 CA228358/CA/NCI NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; R01 HL147584/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; R01 HL125571/HL/NHLBI NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; K08 HL143189/HL/NHLBI NIH HHS/United States ; P01 AG052359/AG/NIA NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; }, mesh = {Drug Development ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; }, abstract = {Restoration of the gut microbiome is a promising preventive and therapeutic strategy in a number of clinical scenarios. We discuss here the scientific and clinical challenges of engineering and implementing these strategies.}, }
@article {pmid32047670, year = {2020}, author = {Meighani, A and Alimirah, M and Ramesh, M and Salgia, R}, title = {Fecal Microbiota Transplantation for Clostridioides Difficile Infection in Patients with Chronic Liver Disease.}, journal = {International journal of hepatology}, volume = {2020}, number = {}, pages = {1874570}, pmid = {32047670}, issn = {2090-3448}, abstract = {Background: Fecal microbiota transplantation (FMT) is a well-established therapeutic option for patients with antibiotic resistant Clostridioides difficile infection (CDI). However, the efficacy of FMT in patients with chronic liver disease remains elusive.<br><br>Aims: We studied the effect of FMT on chronic liver disease (CLD) patients with CDI at our tertiary medical center.<br><br>Methods: A cohort of all patients who received FMT from December 2012 to May 2014 for refractory or recurrent CDI was identified. Patients were monitored for a year after FMT. Descriptive analysis was conducted to compare the effect of FMT in patients with and without CLD.<br><br>Results: A total of 201 patients with CDI received FMT, 14 of which had a history of CLD. Nine of these patients exhibited cirrhosis of the liver with a mean Child-Turcotte-Pugh score of 8. CDI development in these patients was associated with recent exposure to antibiotics and was observed to be significantly different between both groups (17% of CLD patients vs. 58% in the general cohort, p = 0.01). Four patients with CLD received >1 FMT, of which 2 did not respond to treatment. There was no significant difference between patients with liver disease and the rest of the cohort with regard to FMT response (12/14 (87%) vs. 164/187 (88%), p = 0.01). Four patients with CLD received >1 FMT, of which 2 did not respond to treatment. There was no significant difference between patients with liver disease and the rest of the cohort with regard to FMT response (12/14 (87%) vs. 164/187 (88%).<br><br>Conclusion: FMT is a safe and effective therapy against CDI for patients with CLD and cirrhosis.}, }
@article {pmid32047611, year = {2020}, author = {Quigley, EMM and Gajula, P}, title = {Recent advances in modulating the microbiome.}, journal = {F1000Research}, volume = {9}, number = {}, pages = {}, pmid = {32047611}, issn = {2046-1402}, abstract = {We are in the midst of &quot;the microbiome revolution&quot;-not a day goes by without some new revelation on the potential role of the gut microbiome in some disease or disorder. From an ever-increasing recognition of the many roles of the gut microbiome in health and disease comes the expectation that its modulation could treat or prevent these very same diseases. A variety of interventions could, at least in theory, be employed to alter the composition or functional capacity of the microbiome, ranging from diet to fecal microbiota transplantation (FMT). For some, such as antibiotics, prebiotics, and probiotics, an extensive, albeit far from consistent, literature already exists; for others, such as other dietary supplements and FMT, high-quality clinical studies are still relatively few in number. Not surprisingly, researchers have turned to the microbiome itself as a source for new entities that could be used therapeutically to manipulate the microbiome; for example, some probiotic strains currently in use were sourced from the gastrointestinal tract of healthy humans. From all of the extant studies of interventions targeted at the gut microbiome, a number of important themes have emerged. First, with relatively few exceptions, we are still a long way from a precise definition of the role of the gut microbiome in many of the diseases where a disturbed microbiome has been described-association does not prove causation. Second, while animal models can provide fascinating insights into microbiota-host interactions, they rarely recapitulate the complete human phenotype. Third, studies of several interventions have been difficult to interpret because of variations in study population, test product, and outcome measures, not to mention limitations in study design. The goal of microbiome modulation is a laudable one, but we need to define our targets, refine our interventions, and agree on outcomes.}, }
@article {pmid32044171, year = {2020}, author = {Ding, X and Li, Q and Li, P and Chen, X and Xiang, L and Bi, L and Zhu, J and Huang, X and Cui, B and Zhang, F}, title = {Fecal microbiota transplantation: A promising treatment for radiation enteritis?.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.radonc.2020.01.011}, pmid = {32044171}, issn = {1879-0887}, abstract = {BACKGROUND: Increasing evidence has indicated that gut microbiota is closely associated with radiation-induced bowel injury. We aimed to evaluate the safety and efficacy of fecal microbiota transplantation (FMT) in patients with chronic radiation enteritis (CRE).<br><br>METHODS: A pilot study of FMT for CRE was performed. The primary outcomes were safety and response to FMT which was defined as a ≥1-grade reduction in Radiation Therapy Oncology Group (RTOG/EORTC) late toxicity grade from baseline, by 8 weeks post-FMT. The secondary outcomes included a decrease in the severity of four common symptoms (diarrhea, rectal hemorrhage, abdominal/rectal pain and fecal incontinence) in CRE and changes in Karnofsky Performance Status (KPS) score. Microbial analyses were performed by 16S rRNA sequencing.<br><br>RESULTS: Five female patients underwent FMT from January to November 2018 with a median age of 58 (range 45-81) years. The median baseline RTOG/EORTC grade was 2 (range 2-4). Three patients responded to FMT and experienced improvement in diarrhea, rectal hemorrhage, abdominal/rectal pain and fecal incontinence as well as a decrease in KPS score. No FMT-related death and infectious complications occurred. One mild FMT-related AE was observed during a follow-up ranged from 8 to 18 months. 16S rRNA sequencing indicated that FMT altered the composition of gut microbiota of patients.<br><br>CONCLUSION: The present case series first demonstrated that FMT might be safe and effective to improve intestinal symptoms and mucosal injury in patients with CRE for a period of time. Trial registration ID: NCT03516461.}, }
@article {pmid32043638, year = {2020}, author = {Han, J and Wang, X and Tang, S and Lu, C and Wan, H and Zhou, J and Li, Y and Ming, T and Wang, ZJ and Su, X}, title = {Protective effects of tuna meat oligopeptides (TMOP) supplementation on hyperuricemia and associated renal inflammation mediated by gut microbiota.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {}, number = {}, pages = {}, doi = {10.1096/fj.201902597RR}, pmid = {32043638}, issn = {1530-6860}, support = {LY19C010003//Natural Science Foundation of Zhejiang Province/ ; LY18C010001//Natural Science Foundation of Zhejiang Province/ ; 2018YFD0901102//National Key R&amp;D Program of China/ ; //Open Fund of State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products/ ; 2019C10064//Public Welfare Project of Ningbo city/ ; //Ningbo University/ ; }, abstract = {Recently, interest in using whole food-derived mixtures to alleviate chronic metabolic syndrome through potential synergistic interactions among different components is increasing. In this study, the effects and mechanisms of tuna meat oligopeptides (TMOP) on hyperuricemia and associated renal inflammation were investigated in mice. Dietary administration of TMOP alleviated hyperuricemia and renal inflammation phenotypes, reprogramed uric acid metabolism pathways, inhibited the activation of NLRP3 inflammasome and TLR4/MyD88/NF-κB signaling pathways, and suppressed the phosphorylation of p65-NF-κB. In addition, TMOP treatments repaired the intestinal epithelial barrier, reversed the gut microbiota dysbiosis and increased the production of short-chain fatty acids. Moreover, the antihyperuricemia effects of TMOP were transmissible by transplanting the fecal microbiota from TMOP-treated mice, indicating that the protective effects were at least partially mediated by the gut microbiota. Thus, for the first time, we clarify the potential effects of TMOP as a whole food derived ingredient on alleviating hyperuricemia and renal inflammation in mice, and additional efforts are needed to confirm the beneficial effects of TMOP on humans.}, }
@article {pmid32040664, year = {2020}, author = {Abu-Sbeih, H and Wang, Y}, title = {Gut Microbiome and Immune Checkpoint Inhibitor-Induced Enterocolitis.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {797-799}, pmid = {32040664}, issn = {1573-2568}, abstract = {The gut microbiome is increasingly being described as one of the underlying mechanisms for development of immune checkpoint inhibitor (ICI)-induced colitis. Similarities in gut microbiome profiles have been found among various diseases associated with intestinal inflammation, including inflammatory bowel disease. Certain bacterial species have been reported to be preventive for colitis, as well as beneficial for cancer outcome, in patients receiving ICI therapy. Alternatively, other bacterial classes have been shown to be associated with immunologic alterations causing intestinal inflammation with subsequent increase in the risk of ICI-related colitis. Gut microbiome manipulation by fecal transplantation has been proposed as one of the modalities to ameliorate inflammation in patients with ICI-related colitis refractory to immunosuppressive therapy. Additional investigations are needed to clarify the role of gut microbiome in the pathogenesis of ICI-related colitis.}, }
@article {pmid32040250, year = {2020}, author = {Guo, XY and Liu, XJ and Hao, JY}, title = {Gut Microbiota in Ulcerative Colitis: Insights on Pathogenesis and Treatment.}, journal = {Journal of digestive diseases}, volume = {}, number = {}, pages = {}, doi = {10.1111/1751-2980.12849}, pmid = {32040250}, issn = {1751-2980}, abstract = {Gut microbiota constitute the largest reservoir of the human microbiome, and is an abundant and stable ecosystem - based on its diversity, complexity, redundancy, and host interactions. This ecosystem is indispensable for human development and health. The integrity of the intestinal mucosal barrier depends on its interactions with gut microbiota. The commensal bacterial community is implicated in the pathogenesis of inflammatory bowel disease(IBD), including ulcerative colitis (UC). The dysbiosis of microbes is characterized by reduced biodiversity, abnormal composition, altered spatial distribution, as well as interactions among microbiota, between different strains of microbiota, and with the host. The defects in microecology, with the related metabolic pathways and molecular mechanisms, play a critical role in the innate immunity of the intestinal mucosa in UC. Fecal microbiota transplantation (FMT) has been used to treat many diseases related to gut microbiota, with the most promising outcome reported in antibiotic-associated diarrhea, followed by IBD. This review evaluated the results of various reports of FMT in UC. The efficacy of FMT remains highly controversial, and needs to be regularized by integrated management, standardization of procedures, and individualization of treatment.}, }
@article {pmid32039372, year = {2019}, author = {Schwenger, KJ and Clermont-Dejean, N and Allard, JP}, title = {The role of the gut microbiome in chronic liver disease: the clinical evidence revised.}, journal = {JHEP reports : innovation in hepatology}, volume = {1}, number = {3}, pages = {214-226}, pmid = {32039372}, issn = {2589-5559}, abstract = {Recent research has suggested a role for the intestinal microbiota in the pathogenesis and potential treatment of a wide range of liver diseases. The intestinal microbiota and bacterial products may contribute to the development of liver diseases through multiple mechanisms including increased intestinal permeability, chronic systemic inflammation, production of short-chain fatty acids and changes in metabolism. This suggests a potential role for pre-, pro- and synbiotic products in the prevention or treatment of some liver diseases. In addition, there is emerging evidence on the effects of faecal microbial transplant. Herein, we discuss the relationship between the intestinal microbiota and liver diseases, as well as reviewing intestinal microbiota-based treatment options that are currently being investigated.}, }
@article {pmid32036124, year = {2020}, author = {Wang, Y and Xu, L and Sun, X and Wan, X and Sun, G and Jiang, R and Li, W and Tian, Y and Liu, X and Kang, X}, title = {Characteristics of the fecal microbiota of high- and low-yield hens and effects of fecal microbiota transplantation on egg production performance.}, journal = {Research in veterinary science}, volume = {129}, number = {}, pages = {164-173}, doi = {10.1016/j.rvsc.2020.01.020}, pmid = {32036124}, issn = {1532-2661}, abstract = {The microbiota that resides in the digestive tract plays pivotal role in maintaining intestinal environmental stability by promoting nutrition digestion and intestinal mucosal immunity. However, whether the intestinal microbiota in laying hens affects egg laying- performance is not known. In this study, 16S rDNA gene sequencing and fecal microbiota transplantation were used to determine the structure of the intestinal microbiota and the effect of the intestinal microbiota on egg production. The results revealed that Firmicutes were dominant in both the H (high egg laying rates) and L (low egg laying rates) groups, while Bacteroides, Actinobacteria and Proteobacteria were significantly enriched in the L group compared to the H group. The laying rates were weakly affected in H hens transplanted with the fecal microbiota from L hens, except for temporary fluctuation, while the egg laying rates were significantly increased in L hens transplanted with the fecal microbiota from H hens. Therefore, we concluded that the population structure of the intestinal microbiota varied between the H and L groups, and the intestinal microbiota of high-yield laying hens had significant effects on low-yield laying hens performance.}, }
@article {pmid32024322, year = {2020}, author = {Park, S and Kang, Y and Koh, H and Kim, S}, title = {Increasing incidence of inflammatory bowel disease in children and adolescents: the significance of the environmental factors.}, journal = {Clinical and experimental pediatrics}, volume = {}, number = {}, pages = {}, doi = {10.3345/cep.2019.00500}, pmid = {32024322}, issn = {2713-4148}, abstract = {Inflammatory bowel disease is a chronic relapsing immune-mediated disease of the intestinal tract. Although its prevalence is investigated to be lower in Asia than in Western countries, the rapid increase in the incidence rate of inflammatory bowel disease has drawn attention to the etiology of inflammatory bowel disease, including genetic susceptibility and environmental factors. Specifically, recent studies concerning dietary treatments and intestinal microbiota suggest that these factors may interact with the immune system, and the imbalance of this relationship may lead to the immune dysregulation in inflammatory bowel disease. The changes in diet or alteration in the composition of intestinal microbiota may be associated with the increasing incidence of inflammatory bowel disease in Asia. Here, we aim to review the recent studies on the role of the diet and intestinal microbiota in inflammatory bowel disease pathogenesis and the results of the investigations performed to modulate these factors.}, }
@article {pmid32024079, year = {2020}, author = {Swarte, JC and Douwes, RM and Hu, S and Vich Vila, A and Eisenga, MF and van Londen, M and Gomes-Neto, AW and Weersma, RK and Harmsen, HJM and Bakker, SJL}, title = {Characteristics and Dysbiosis of the Gut Microbiome in Renal Transplant Recipients.}, journal = {Journal of clinical medicine}, volume = {9}, number = {2}, pages = {}, doi = {10.3390/jcm9020386}, pmid = {32024079}, issn = {2077-0383}, abstract = {Renal transplantation is life-changing in many aspects. This includes changes to the gut microbiome likely due to exposure to immunosuppressive drugs and antibiotics. As a consequence, renal transplant recipients (RTRs) might suffer from intestinal dysbiosis. We aimed to investigate the gut microbiome of RTRs and compare it with healthy controls and to identify determinants of the gut microbiome of RTRs. Therefore, RTRs and healthy controls participating in the TransplantLines Biobank and Cohort Study (NCT03272841) were included. We analyzed the gut microbiome using 16S rRNA sequencing and compared the composition of the gut microbiome of RTRs to healthy controls using multivariate association with linear models (MaAsLin). Fecal samples of 139 RTRs (50% male, mean age: 58.3 ± 12.8 years) and 105 healthy controls (57% male, mean age: 59.2 ± 10.6 years) were collected. Median time after transplantation of RTRs was 6.0 (1.5-12.5)years. The microbiome composition of RTRs was significantly different from that of healthy controls, and RTRs had a lower diversity of the gut microbiome (p < 0.01). Proton-pump inhibitors, mycophenolate mofetil, and estimated glomerular filtration rate (eGFR) are significant determinants of the gut microbiome of RTRs (p < 0.05). Use of mycophenolate mofetil correlated to a lower diversity (p < 0.01). Moreover, significant alterations were found in multiple bacterial taxa between RTRs and healthy controls. The gut microbiome of RTRs contained more Proteobacteria and less Actinobacteria, and there was a loss of butyrate-producing bacteria in the gut microbiome of RTRs. By comparing the gut microbiome of RTRs to healthy controls we have shown that RTRs suffer from dysbiosis, a disruption in the balance of the gut microbiome.}, }
@article {pmid32023967, year = {2020}, author = {Kachrimanidou, M and Tsintarakis, E}, title = {Insights into the Role of Human Gut Microbiota in Clostridioides difficile Infection.}, journal = {Microorganisms}, volume = {8}, number = {2}, pages = {}, doi = {10.3390/microorganisms8020200}, pmid = {32023967}, issn = {2076-2607}, abstract = {Clostridioides difficile infection (CDI) has emerged as a major health problem worldwide. A major risk factor for disease development is prior antibiotic use, which disrupts the normal gut microbiota by altering its composition and the gut's metabolic functions, leading to the loss of colonization resistance and subsequent CDI. Data from human studies have shown that the presence of C. difficile, either as a colonizer or as a pathogen, is associated with a decreased level of gut microbiota diversity. The investigation of the gut's microbial communities, in both healthy subjects and patients with CDI, elucidate the role of microbiota and improve the current biotherapeutics for patients with CDI. Fecal microbiota transplantation has a major role in managing CDI, aiming at re-establishing colonization resistance in the host gastrointestinal tract by replenishing the gut microbiota. New techniques, such as post-genomics, proteomics and metabolomics analyses, can possibly determine in the future the way in which C. difficile eradicates colonization resistance, paving the way for the development of new, more successful treatments and prevention. The aim of the present review is to present recent data concerning the human gut microbiota with a focus on its important role in health and disease.}, }
@article {pmid32020359, year = {2020}, author = {Lechner, S and Yee, M and Limketkai, BN and Pham, EA}, title = {Fecal Microbiota Transplantation for Chronic Liver Diseases: Current Understanding and Future Direction.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {897-905}, pmid = {32020359}, issn = {1573-2568}, abstract = {Chronic liver disease is a major cause of morbidity and mortality worldwide. Even though effective treatments are now available for most chronic viral hepatitis, treatment options for other causes of chronic liver disease remain inadequate. Recent research has revealed a previously unappreciated role that the human intestinal microbiome plays in mediating the development and progression of chronic liver diseases. The recent remarkable success of fecal microbiota transplantation (FMT) in treating Clostridioides difficile demonstrates that the intestinal microbiota can be manipulated to obtain favorable therapeutic benefits and that FMT may become an important component of a total therapeutic approach to effectively treat hepatic disorders.}, }
@article {pmid32019832, year = {2020}, author = {Ghimire, S and Roy, C and Wongkuna, S and Antony, L and Maji, A and Keena, MC and Foley, A and Scaria, J}, title = {Identification of Clostridioides difficile-Inhibiting Gut Commensals Using Culturomics, Phenotyping, and Combinatorial Community Assembly.}, journal = {mSystems}, volume = {5}, number = {1}, pages = {}, pmid = {32019832}, issn = {2379-5077}, abstract = {A major function of the gut microbiota is to provide colonization resistance, wherein pathogens are inhibited or suppressed below infectious levels. However, the fraction of gut microbiota required for colonization resistance remains unclear. We used culturomics to isolate a gut microbiota culture collection comprising 1,590 isolates belonging to 102 species. This culture collection represents 34.57% of the taxonomic diversity and 70% functional capacity, as estimated by metagenomic sequencing of the fecal samples used for culture. Using whole-genome sequencing, we characterized species representatives from this collection and predicted their phenotypic traits, further characterizing isolates by defining nutrient utilization profiles and short-chain fatty acid production. When screened with a coculture assay, 66 species in our culture collection inhibited Clostridioides difficile Several phenotypes, particularly, growth rate, production of SCFAs, and the utilization of mannitol, sorbitol, or succinate, correlated with C. difficile inhibition. We used a combinatorial community assembly approach to formulate defined bacterial mixes inhibitory to C. difficile We tested 256 combinations and found that both species composition and blend size were important in inhibition. Our results show that the interaction of bacteria with one another in a mix and with other members of gut commensals must be investigated to design defined bacterial mixes for inhibiting C. difficilein vivoIMPORTANCE Antibiotic treatment causes instability of gut microbiota and the loss of colonization resistance, thus allowing pathogens such as Clostridioides difficile to colonize and causing recurrent infection and mortality. Although fecal microbiome transplantation has been shown to be an effective treatment for C. difficile infection (CDI), a more desirable approach would be the use of a defined mix of inhibitory gut bacteria. The C. difficile-inhibiting species and bacterial combinations identified herein improve the understanding of the ecological interactions controlling colonization resistance against C. difficile and could aid in the design of defined bacteriotherapy as a nonantibiotic alternative against CDI.}, }
@article {pmid32017248, year = {2020}, author = {You, JHS and Jiang, X and Lee, WH and Chan, PKS and Ng, SC}, title = {Cost-effectiveness analysis of fecal microbiota transplantation for recurrent Clostridium difficile infection in patients with inflammatory bowel disease.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.15002}, pmid = {32017248}, issn = {1440-1746}, abstract = {BACKGROUND AND AIM: Inflammatory bowel disease (IBD) patients are at risk for recurrent Clostridium difficile infection (RCDI). We aimed to evaluate the potential health economic and clinical outcomes of four strategies for management of RCDI in IBD patients from the perspective of public health-care provider in Hong Kong.<br><br>METHODS: A decision-analytic model was designed to simulate outcomes of adult IBD patients with first RCDI treated with vancomycin, vancomycin plus bezlotoxumab, fidaxomicin and fecal microbiota transplantation (FMT). Model inputs were derived from literature and public data. Primary model outcomes were C. difficile infection (CDI)-related direct medical cost and quality-adjusted life-years (QALYs) loss. Base-case and sensitivity analysis were performed.<br><br>RESULTS: Comparing to vancomycin, fidaxomicin and vancomycin plus bezlotoxumab, FMT saved 0.00318, 0.00149 and 0.00306 QALYs and reduced cost by USD3180, USD3790 and USD5514, respectively, in base-case analysis. In probabilistic sensitivity analysis, FMT was cost-saving when comparing to vancomycin, fidaxomicin and vancomycin plus bezlotoxumab by USD3765 (95% confidence interval [CI] 3732-3798; P < 0.001), USD3854 (95%CI 3827-3883; P < 0.001) and USD6501 (95%CI 6465-6,536; P < 0.001), respectively. The QALYs saved by FMT (vs vancomycin) were 0.00386 QALYs (95%CI 0.00384-0.00388; P < 0.001), (vs fidaxomicin) 0.00179 QALYs (95%CI 0.00177-0.00180; P < 0.001) and (vs vancomycin plus bezlotoxumab) 0.00376 QALYs (95%CI 0.00374-0.00378; P < 0.001). FMT was found to save QALYs at lower cost in 99.3% (vs vancomycin), 99.7% (vs fidaxomicin) and 100.0% (vs vancomycin plus bezlotoxumab) of the 10 000 Monte Carlo simulations.<br><br>CONCLUSIONS: FMT for IBD patients with RCDI appeared to save both direct medical cost and QALYs when comparing to vancomycin (with or without bezlotoxumab) and fidaxomicin.}, }
@article {pmid32016290, year = {2020}, author = {Peng, Y and Thomas, AS and Wei, D and Tan, D and Wang, Y}, title = {An Aggressive Approach Toward a Case of Refractory Ulcerative Colitis With Uncertain Etiology in the Context of Chronic Myeloid Leukemia.}, journal = {Inflammatory bowel diseases}, volume = {26}, number = {4}, pages = {e26-e27}, doi = {10.1093/ibd/izaa016}, pmid = {32016290}, issn = {1536-4844}, }
@article {pmid32015948, year = {2020}, author = {Li, B and Yin, GF and Wang, YL and Tan, YM and Huang, CL and Fan, XM}, title = {Impact of fecal microbiota transplantation on TGF-β1/Smads/ERK signaling pathway of endotoxic acute lung injury in rats.}, journal = {3 Biotech}, volume = {10}, number = {2}, pages = {52}, pmid = {32015948}, issn = {2190-572X}, abstract = {Acute lung injury (ALI) is a common clinical disease with high morbidity in both humans and animals. Studies have shown that intestinal microbiota affect the pathology and immune function of respiratory diseases through the &quot;gut-lung axis&quot;. The authors investigated the therapeutic effect of fecal microbiota transplantation (FMT) in rats with ALI induced by lipopolysaccharide (LPS). Rats were treated with FMT, and then measured lung wet/dry ratio, PaO2 in artery, proinflammatory marker, and TGF-β1, Smad3, Smad7, and phosphorylated ERK (p-ERK) protein levels, as well as a histopathologic analysis and high-throughput sequencing of intestinal microbiota. FMT significantly reduced lung wet/dry ratio and TNF-α, IL-1β, and IL-6 levels, but increased the levels of PaO2 in artery. In addition, FMT significantly decreased the expression of TGF-β1, Smad3, and p-ERK, while increased the levels of Smad7. Lung histopathological analyses showed that FMT reduced the inflammatory cell infiltration and interstitial lung exudates. High-throughput sequencing of intestinal microbiota analyses showed that FMT reconstructed the structure of intestinal microbiota, and increased the gene abundance of the bacterial community. Therefore, FMT may act on the TGF-β1/Smads/ERK pathway by regulating intestinal microbiota, inhibiting immune inflammation, reducing the production of inflammatory markers in the body and release, and reducing alveolar epithelial damage and repair, thereby improving the endotoxic ALI in rats induced by LPS.}, }
@article {pmid32014035, year = {2020}, author = {Sokol, H and Landman, C and Seksik, P and Berard, L and Montil, M and Nion-Larmurier, I and Bourrier, A and Le Gall, G and Lalande, V and De Rougemont, A and Kirchgesner, J and Daguenel, A and Cachanado, M and Rousseau, A and Drouet, É and Rosenzwajg, M and Hagege, H and Dray, X and Klatzman, D and Marteau, P and ,  and Beaugerie, L and Simon, T}, title = {Fecal microbiota transplantation to maintain remission in Crohn's disease: a pilot randomized controlled study.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {12}, pmid = {32014035}, issn = {2049-2618}, support = {PHRCR-13-029//Ministère de l'Enseignement Supérieur, de la Recherche Scientifique et des Technologies de l'Information et de la Communication/ ; Fond Inkermann//Fondation de France/ ; CRC1-//Assistance Publique - Hôpitaux de Paris/ ; 2018//Association Francois Aupetit/ ; }, abstract = {BACKGROUND: The role of the gut microbiota in Crohn's disease (CD) is established and fecal microbiota transplantation (FMT) is an attractive therapeutic strategy. No randomized controlled clinical trial results are available. We performed a randomized, single-blind, sham-controlled pilot trial of FMT in adults with colonic or ileo-colonic CD.<br><br>METHOD: Patients enrolled while in flare received oral corticosteroid. Once in clinical remission, patients were randomized to receive either FMT or sham transplantation during a colonoscopy. Corticosteroids were tapered and a second colonoscopy was performed at week 6. The primary endpoint was the implantation of the donor microbiota at week 6 (Sorensen index > 0.6).<br><br>RESULTS: Eight patients received FMT and nine sham transplantation. None of the patients reached the primary endpoint. The steroid-free clinical remission rate at 10 and 24 weeks was 44.4% (4/9) and 33.3% (3/9) in the sham transplantation group and 87.5% (7/8) and 50.0% (4/8; one patient loss of follow-up while in remission at week 12 and considered in flare at week 24) in the FMT group. Crohn's Disease Endoscopic Index of Severity decreased 6 weeks after FMT (p = 0.03) but not after sham transplantation (p = 0.8). Conversely, the CRP level increased 6 weeks after sham transplantation (p = 0.008) but not after FMT (p = 0.5). Absence of donor microbiota engraftment was associated with flare. No safety signal was identified.<br><br>CONCLUSION: The primary endpoint was not reached for any patient. In this pilot study, higher colonization by donor microbiota was associated with maintenance of remission. These results must be confirmed in larger studies (NCT02097797). Video abstract.}, }
@article {pmid32011405, year = {2020}, author = {Perler, BK and Chen, B and Phelps, E and Allegretti, JR and Fischer, M and Ganapini, V and Krajiceck, E and Kumar, V and Marcus, J and Nativ, L and Kelly, CR}, title = {Long-Term Efficacy and Safety of Fecal Microbiota Transplantation for Treatment of Recurrent Clostridioides difficile Infection.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000001281}, pmid = {32011405}, issn = {1539-2031}, abstract = {GOALS: We investigated the long-term efficacy and safety of fecal microbiota transplant (FMT) for the treatment of recurrent Clostridioides difficile infection (rCDI).<br><br>BACKGROUND: FMT has emerged as a promising therapy for patients with rCDI unresponsive to standard medical therapy, though long-term efficacy and safety data are scarce.<br><br>MATERIALS AND METHODS: A multicenter retrospective study was performed on patients treated with FMT for rCDI with ≥6 months of clinical follow-up post-FMT. Patients were contacted to document sustained efficacy, potential adverse events, and antibiotic exposure. The electronic medical record was reviewed to confirm patient-reported outcomes and obtain additional data. The primary outcome was sustained cure, as defined by the absence of Clostridioides difficile infection (CDI) at any timepoint after FMT.<br><br>RESULTS: Of 528 patients treated, 207 were successfully contacted. The mean follow-up post-FMT was 34 (range: 6 to 84) months. One hundred fifty-seven patients (75.8%) reported sustained cure at the time of follow-up. One hundred patients (48%) reported the use of antibiotics for non-CDI indications post-FMT, of whom 11 (11%) had experienced CDI post-FMT. Fifty-two of the original 528 patients (9.8%) treated with FMT had died at the time of follow-up contact; none were felt attributable to the procedure. New medical conditions or diagnoses post-FMT were reported in 105 patients (50.5%). Fifteen reported improvement post-FMT in previously diagnosed medical conditions.<br><br>CONCLUSIONS: In this largest and longest study to date on efficacy and safety after FMT for treatment of rCDI, we found that the majority of patients experienced long-term cure. Although a number of new conditions developed post-FMT, there was no clustering of diseases associated with dysbiosis.}, }
@article {pmid32010641, year = {2019}, author = {Wang, H and Lu, Y and Yan, Y and Tian, S and Zheng, D and Leng, D and Wang, C and Jiao, J and Wang, Z and Bai, Y}, title = {Promising Treatment for Type 2 Diabetes: Fecal Microbiota Transplantation Reverses Insulin Resistance and Impaired Islets.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {455}, pmid = {32010641}, issn = {2235-2988}, abstract = {Type 2 diabetes is a common metabolic disorder related to insulin resistance, or deficiency of insulin secretion, caused by decreased insulin sensitivity and destruction of islet structure and function. As the second human genome, the microbiota has been observed to have a growing relationship with diabetes in recent years. Microbiota imbalance has been hypothesized to be involved in the regulation of energy metabolism and the inflammatory immune response in diabetes. The present study aimed to investigate whether fecal microbiota transplantation (FMT) could alleviate the symptoms associated with type 2 diabetes. To this end, a type 2 diabetes mouse model was first established through the consumption of a high-fat diet combined with streptozotocin (100 mg/kg), and FMT was used to rebuild the gut microbiota of diabetic mice. Fasting blood glucose, oral glucose tolerance tests, and HbA1c levels were monitored, while the hypoglycemic effects of FMT were also observed. Insulin levels were tested by ELISA and related indexes such as HOMA-IR, HOMA-IS, and HOMA-β were calculated. We found that insulin resistance and pancreatic islet β-cells were improved after FMT treatment. Meanwhile, the markers of inflammation in the pancreatic tissue were detected by ELISA and immunohistochemistry, which indicated that inflammatory response decreased following FMT treatment. Furthermore, flow cytometry and western blot results revealed that FMT inhibited the β-cell apoptosis. Here, the effect of FMT on hypoglycemia in type 2 diabetes was addressed by improving insulin resistance and repairing impaired islets, thereby providing a potential treatment strategy for type 2 diabetes.}, }
@article {pmid32010434, year = {2020}, author = {Zama, D and Bossù, G and Leardini, D and Muratore, E and Biagi, E and Prete, A and Pession, A and Masetti, R}, title = {Insights into the role of intestinal microbiota in hematopoietic stem-cell transplantation.}, journal = {Therapeutic advances in hematology}, volume = {11}, number = {}, pages = {2040620719896961}, pmid = {32010434}, issn = {2040-6207}, abstract = {The gut microbiota (GM) is able to modulate the human immune system. The development of novel investigation methods has provided better characterization of the GM, increasing our knowledge of the role of GM in the context of hematopoietic stem-cell transplantation (HSCT). In particular, the GM influences the development of the major complications seen after HSCT, having an impact on overall survival. In fact, this evidence highlights the possible therapeutic implications of modulation of the GM during HSCT. Insights into the complex mechanisms and functions of the GM are essential for the rational design of these therapeutics. To date, preemptive and curative approaches have been tested. The current state of understanding of the impact of the GM on HSCT, and therapies targeting the GM balance is reviewed herein.}, }
@article {pmid32009472, year = {2020}, author = {Zhou, HY and Guo, B and Lufumpa, E and Li, XM and Chen, LH and Meng, X and Li, BZ}, title = {Comparative of the Effectiveness and Safety of Biological Agents, Tofacitinib, and Fecal Microbiota Transplantation in Ulcerative Colitis: Systematic Review and Network Meta-Analysis.}, journal = {Immunological investigations}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/08820139.2020.1714650}, pmid = {32009472}, issn = {1532-4311}, abstract = {BACKGROUND: Biological agents are commonly used for the treatment of ulcerative colitis (UC). As new treatments, tofacitinib, and fecal microbiota transplantation (FMT) have demonstrated efficacy in treating UC. This network meta-analysis aims to determine the efficacy and safety of biological agents, tofacitinib, and FMT.<br><br>METHODS: A network meta-analysis was conducted by systematically searching the PubMed, Embase, and Cochrane Libraries. According to strict inclusion and exclusion criteria, we included randomized controlled trials (RCTs) of biological agents, tofacitinib, and FMT in UC. A random-effect model was chosen by the network meta-analysis and sensitivity analysis. Heterogeneity test and publication bias test were performed to determine the efficacy of treatments.<br><br>RESULTS: Data were extracted from 16 RCTs and we found that all treatments were more effective than the placebos. A total of 21 comparisons were made to determine efficiency. We found that infliximab, vedolizumab, and FMT performed better curative effect in terms of absolute effects and relative ranks. Furthermore, there was no statistical difference in the efficacy of biological agents, tofacitinib, and FMT. Moreover, no treatments were found to increase the occurrence of adverse events when compared with placebos, except infliximab. However, vedolizumab seemed to reduce the occurrence of adverse events compared with infliximab.<br><br>CONCLUSION: Of the biological agents, vedolizumab and infliximab were the most effective, suggesting that biological agents are still a better choice. Nevertheless, tofacitinib and FMT may be promising alternatives with high efficacies. However, more safety and maintenance studies need to be conducted in future for the acquisition of more accurate results.Abbreviations: FMT: Fecal microbiota transplantation; UC: Ulcerative colitis; RCTs: Randomized controlled trials; IBD: Inflammatory bowel disease; CD: Crohn's disease; IBS: Irritable bowel syndrome; CDI: Clostridium difficile infections; ITT: Intention-to-treat; RR: Relative risk; CI: Confidence interval; CrI: Credible intervals; IFX: Infliximab; ADA: Adalimumab; TFB: Tofacitinib; GLM: Golimumab; VDZ: Vedolizumab; PBO: Placebo; wk: week; F: Female; M: Male; AEs: Adverse events; SAEs: Serious adverse events; anti-TNF: Anti-tumor necrosis factors.}, }
@article {pmid32008133, year = {2020}, author = {DuPont, HL and Jiang, ZD and DuPont, AW and Utay, NS}, title = {Abnormal Intestinal Microbiome in Medical Disorders and Potential Reversibility by Fecal Microbiota Transplantation.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {741-756}, pmid = {32008133}, issn = {1573-2568}, abstract = {Reduction in diversity of the intestinal microbiome (dysbiosis) is being identified in many disease states, and studies are showing important biologic contributions of microbiome to health and disease. Fecal microbiota transplantation (FMT) is being evaluated as a way to reverse dysbiosis in diseases and disorders in an attempt to improve health. The published literature was reviewed to determine the value of FMT in the treatment of medical disorders for which clinical trials have recently been conducted. FMT is effective in treating recurrent C. difficile infection in one or two doses, with many healthy donors providing efficacious fecal-derived products. In inflammatory bowel disease (IBD), FMT may lead to remission in approximately one-third of moderate-to-severe illnesses with one study suggesting that more durable FMT responses may be seen when used once medical remissions have been achieved. Donor products differ in their efficacy in treatment of IBD. Combining donor products has been one way to increase the potential value of FMT in treating chronic disorders. FMT is being explored in a variety of clinical settings affecting different organ systems outside CDI, with positive preliminary signals, in treatment of functional constipation, immunotherapy-induced colitis, neurodegenerative disease, as well as prevention of cancer-related disorders like graft versus host disease and decolonization of patients with recurrent urinary tract infection due to antibiotic-resistant bacteria. Currently, intense research is underway to see how the microbiome products like FMT can be harnessed for health benefits.}, }
@article {pmid32006212, year = {2020}, author = {Oka, A and Sartor, RB}, title = {Microbial-Based and Microbial-Targeted Therapies for Inflammatory Bowel Diseases.}, journal = {Digestive diseases and sciences}, volume = {65}, number = {3}, pages = {757-788}, pmid = {32006212}, issn = {1573-2568}, abstract = {Inflammatory bowel diseases (IBD), including Crohn's disease, ulcerative colitis, and pouchitis, are chronic, relapsing intestinal inflammatory disorders mediated by dysregulated immune responses to resident microbiota. Current standard therapies that block immune activation with oral immunosuppressives or biologic agents are generally effective, but each therapy induces a sustained remission in only a minority of patients. Furthermore, these approaches can have severe adverse events. Recent compelling evidence of a role of unbalanced microbiota (dysbiosis) driving immune dysfunction and inflammation in IBD supports the therapeutic rationale for manipulating the dysbiotic microbiota. Traditional approaches using currently available antibiotics, probiotics, prebiotics, and synbiotics have not produced optimal results, but promising outcomes with fecal microbiota transplant provide a proof of principle for targeting the resident microbiota. Rationally designed oral biotherapeutic products (LBPs) composed of mixtures of protective commensal bacterial strains demonstrate impressive preclinical results. Resident microbial-based and microbial-targeted therapies are currently being studied with increasing intensity for IBD primary therapy with favorable early results. This review presents current evidence and therapeutic mechanisms of microbiota modulation, emphasizing clinical studies, and outlines prospects for future IBD treatment using new approaches, such as LBPs, bacteriophages, bacterial function-editing substrates, and engineered bacteria. We believe that the optimal clinical use of microbial manipulation may be as adjuvants to immunosuppressive for accelerated and improved induction of deep remission and as potential safer solo approaches to sustained remission using personalized regimens based on an individual patient's microbial profile.}, }
@article {pmid32003951, year = {2020}, author = {Mounsey, A and Lacy Smith, K and Reddy, VC and Nickolich, S}, title = {Clostridioides difficile Infection: Update on Management.}, journal = {American family physician}, volume = {101}, number = {3}, pages = {168-175}, pmid = {32003951}, issn = {1532-0650}, abstract = {Guidelines for the diagnosis and treatment of Clostridioides difficile infection have recently been updated. Risk factors include recent exposure to health care facilities or antibiotics, especially clindamycin. C. difficile infection is characterized by a wide range of symptoms, from mild or moderate diarrhea to severe disease with pseudomembranous colitis, colonic ileus, toxic megacolon, sepsis, or death. C. difficile infection should be considered in patients who are not taking laxatives and have three or more episodes of unexplained, unformed stools in 24 hours. Testing in these patients should start with enzyme immunoassays for glutamate dehydrogenase and toxins A and B or nucleic acid amplification testing. In children older than 12 months, testing is recommended only for those with prolonged diarrhea and risk factors. Treatment depends on whether the episode is an initial vs. recurrent infection and on the severity of the infection based on white blood cell count, serum creatinine level, and other clinical signs and symptoms. For an initial episode of nonsevere C. difficile infection, oral vancomycin or oral fidaxomicin is recommended. Metronidazole is no longer recommended as first-line therapy for adults. Fecal microbiota transplantation is a reasonable treatment option with high cure rates in patients who have had multiple recurrent episodes and have received appropriate antibiotic therapy for at least three of the episodes. Good antibiotic stewardship is a key strategy to decrease rates of C. difficile infection. In routine or endemic settings, hands should be cleaned with either soap and water or an alcohol-based product, but during outbreaks soap and water is superior. The Infectious Diseases Society of America does not recommend the use of probiotics for prevention of C. difficile infection.}, }
@article {pmid32001342, year = {2020}, author = {Ma, Y and Liu, S and Shu, H and Crawford, J and Xing, Y and Tao, F}, title = {Resveratrol alleviates temporomandibular joint inflammatory pain by recovering disturbed gut microbiota.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2020.01.016}, pmid = {32001342}, issn = {1090-2139}, abstract = {Patients with temporomandibular disorders (TMDs) often experience persistent facial pain. However, the treatment of TMD pain is still inadequate. In recent years, the disturbance of gut microbiota has been shown to play an important role in the pathogenesis of different neurological diseases including chronic pain. In the present study, we investigated the involvement of gut microbiota in the development of temporomandibular joint (TMJ) inflammation. Intra-temporomandibular joint injection of complete Freund's adjuvant (CFA) was employed to induce TMJ inflammation. Resveratrol (RSV), a natural bioactive compound with anti-inflammatory property, was used to treat the CFA-induced TMJ inflammation. We observed that CFA injection not only induces persistent joint pain, but also causes the reduction of short-chain fatty acids (SCFAs, including acetic acid, propionic acid and butyric acid) in the gut as well as decreases relevant gut bacteria Bacteroidetes and Lachnospiraceae. Interestingly, systemic administration of RSV (i.p.) dose-dependently inhibits CFA-induced TMJ inflammation, reverses CFA-caused reduction of SCFAs and these gut bacteria. Moreover, CFA injection causes blood-brain barrier (BBB) leakage, activates microglia and enhances tumor necrosis factor alpha (TNFα) release in the spinal trigeminal nucleus caudalis (Sp5C). The RSV treatment restores the BBB integrity, inhibits microglial activation and decreases the release of TNFα in the Sp5C. Furthermore, fecal microbiota transplantation with feces from RSV-treated mice significantly diminishes the CFA-induced TMJ inflammation. Taken together, our results suggest that gut microbiome perturbation is critical for the development of TMJ inflammation and that recovering gut microbiome to normal levels could be a new therapeutic approach for treating such pain.}, }
@article {pmid31993446, year = {2019}, author = {Pilla, R and Suchodolski, JS}, title = {The Role of the Canine Gut Microbiome and Metabolome in Health and Gastrointestinal Disease.}, journal = {Frontiers in veterinary science}, volume = {6}, number = {}, pages = {498}, pmid = {31993446}, issn = {2297-1769}, abstract = {The gut microbiome contributes to host metabolism, protects against pathogens, educates the immune system, and, through these basic functions, affects directly or indirectly most physiologic functions of its host. Molecular techniques have allowed us to expand our knowledge by unveiling a wide range of unculturable bacteria that were previously unknown. Most bacterial sequences identified in the canine gastrointestinal (GI) tract fall into five phyla: Firmicutes, Fusobacteria, Bacteroidetes, Proteobacteria, and Actinobacteria. While there are variations in the microbiome composition along the GI tract, most clinical studies concentrate on fecal microbiota. Age, diet, and many other environmental factors may play a significant role in the maintenance of a healthy microbiome, however, the alterations they cause pale in comparison with the alterations found in diseased animals. GI dysfunctions are the most obvious association with gut dysbiosis. In dogs, intestinal inflammation, whether chronic or acute, is associated with significant differences in the composition of the intestinal microbiota. Gut dysbiosis happens when such alterations result in functional changes in the microbial transcriptome, proteome, or metabolome. Commonly affected metabolites include short-chain fatty acids, and amino acids, including tryptophan and its catabolites. A recently developed PCR-based algorithm termed &quot;Dysbiosis Index&quot; is a tool that allows veterinarians to quantify gut dysbiosis and can be used to monitor disease progression and response to treatment. Alterations or imbalances in the microbiota affect immune function, and strategies to manipulate the gut microbiome may be useful for GI related diseases. Antibiotic usage induces a rapid and significant drop in taxonomic richness, diversity, and evenness. For that reason, a renewed interest has been put on probiotics, prebiotics, and fecal microbiota transplantation (FMT). Although probiotics are typically unable to colonize the gut, the metabolites they produce during their transit through the GI tract can ameliorate clinical signs and modify microbiome composition. Another interesting development is FMT, which may be a promising tool to aid recovery from dysbiosis, but further studies are needed to evaluate its potential and limitations.}, }
@article {pmid31993375, year = {2019}, author = {Albouery, M and Buteau, B and Grégoire, S and Cherbuy, C and Pais de Barros, JP and Martine, L and Chain, F and Cabaret, S and Berdeaux, O and Bron, AM and Acar, N and Langella, P and Bringer, MA}, title = {Age-Related Changes in the Gut Microbiota Modify Brain Lipid Composition.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {444}, pmid = {31993375}, issn = {2235-2988}, abstract = {Understanding the molecular mechanisms underlying the changes observed during aging is a prerequisite to design strategies to prevent age-related diseases. Aging is associated with metabolic changes, including alteration in the brain lipid metabolism. These alterations may contribute to the development of pathophysiological conditions. Modifications in the gut microbiota composition are also observed during aging. As communication axes exist between the gut microbiota and the brain and knowing that microbiota influences the host metabolism, we speculated on whether age-associated modifications in the gut microbiota could be involved in the lipid changes observed in aging brain. For that purpose, germ-free mice were colonized by the fecal microbiota of young or old donor mice. Lipid classes and fatty acid profiles were determined in the brain (cortex), plasma and liver by thin-layer chromatography on silica gel-coated quartz rods and gas chromatography. Gut colonization by microbiota of old mice resulted in a significant increase in total monounsaturated fatty acids (MUFA) and a significant decrease in the relative amounts of cholesterol and total polyunsaturated fatty acids (PUFA) in the cortex. Among the eight most represented fatty acids in the cortex, the relative abundances of five (C18:1n-9, C22:6n-3, C20:4n-6, C18:1n-7, and C20:1n-9) were significantly altered in mice inoculated with an aged microbiota. Liquid chromatography analyses revealed that the relative abundance of major species among phosphatidyl and plasmenylcholine (PC 16:0/18:1), phosphatidyl and plasmenylethanolamine (PE 18:0/22:6), lysophosphatidylethanolamine (LPE 22:6) and sphingomyelins (SM d18:1/18:0) were significantly altered in the cortex of mice colonized by the microbiota obtained from aged donors. Transplantation of microbiota from old mice also modified the lipid class and fatty acid content in the liver. Finally, we found that the expression of several genes involved in MUFA and PUFA synthesis (Scd1, Fads1, Fads2, Elovl2, and Elovl5) was dysregulated in mice inoculated with an aged microbiota. In conclusion, our data suggest that changes in gut microbiota that are associated with aging can impact brain and liver lipid metabolisms. Lipid changes induced by an aged microbiota recapitulate some features of aging, thus pointing out the potential role of microbiota alterations in the age-related degradation of the health status.}, }
@article {pmid31993353, year = {2019}, author = {Xi, D and Michail, S}, title = {Fecal microbiota transplantation in children does not significantly alter body mass index.}, journal = {Translational pediatrics}, volume = {8}, number = {5}, pages = {398-401}, pmid = {31993353}, issn = {2224-4344}, abstract = {Background: Fecal microbiota transplantation (FMT) is nowadays a promising therapy for Clostridium difficile infection (CDI) and a potential treatment for ulcerative colitis. However, it is still unclear whether the changes in intestinal microbiome will affect energy homeostasis or metabolism. This brings an intriguing question whether FMT from healthy donors affects recipient's body mass index (BMI).<br><br>Methods: In our randomized placebo-controlled study children patients with CDI or ulcerative colitis were randomly divided into control and FMT groups. The change of post-FMT BMI percentile at 1, 3, 6, 12 months was calculated. The age range of CDI cohort was 1 to 17 years, while the range was 8 to 21 years for ulcerative colitis cohort.<br><br>Results: We found that the BMI percentile was insignificantly changed by ‒0.7%, ‒1.8%, 1.3%, 4.6% in CDI, while by 3.6%, ‒3.3%, 3.7%, 7.1% in ulcerative colitis at 1, 3, 6, 12 months after FMT (&quot;‒&quot; means decrease).<br><br>Conclusions: We concluded that FMT from healthy donors does not significantly alter BMI in children with CDI and ulcerative colitis over 12 months.}, }
@article {pmid31992630, year = {2020}, author = {Oliphant, K and Cochrane, K and Schroeter, K and Daigneault, MC and Yen, S and Verdu, EF and Allen-Vercoe, E}, title = {Effects of Antibiotic Pretreatment of an Ulcerative Colitis-Derived Fecal Microbial Community on the Integration of Therapeutic Bacteria In Vitro.}, journal = {mSystems}, volume = {5}, number = {1}, pages = {}, pmid = {31992630}, issn = {2379-5077}, abstract = {Fecal microbiota transplantation (FMT) is a proposedly useful strategy for the treatment of gastrointestinal (GI) disorders through remediation of the patient gut microbiota. However, its therapeutic success has been variable, necessitating research to uncover mechanisms that improve patient response. Antibiotic pretreatment has been proposed as one method to enhance the success rate by increasing niche availability for introduced species. Several limitations hinder exploring this hypothesis in clinical studies, such as deleterious side effects and the development of antimicrobial resistance in patients. Thus, the purpose of this study was to evaluate the use of an in vitro, bioreactor-based, colonic ecosystem model as a form of preclinical testing by determining how pretreatment with the antibiotic rifaximin influenced engraftment of bacterial strains sourced from a healthy donor into an ulcerative colitis-derived defined microbial community. Distinct species integrated under the pretreated and untreated conditions, with the relative rifaximin resistance of the microbial strains being an important influencer. However, both conditions resulted in the integration of taxa from Clostridium clusters IV and XIVa, a concomitant reduction of Proteobacteria, and similar decreases in metabolites associated with poor health status. Our results agree with the findings of similar research in the clinic by others, which observed no difference in primary patient outcomes whether or not patients were given rifaximin prior to FMT. We therefore conclude that our model is useful for screening for antibiotics that could improve efficacy of FMT when used as a pretreatment.IMPORTANCE Patients with gastrointestinal disorders often exhibit derangements in their gut microbiota, which can exacerbate their symptoms. Replenishing these ecosystems with beneficial bacteria through fecal microbiota transplantation is thus a proposedly useful therapeutic; however, clinical success has varied, necessitating research into strategies to improve outcomes. Antibiotic pretreatment has been suggested as one such approach, but concerns over harmful side effects have hindered testing this hypothesis clinically. Here, we evaluate the use of bioreactors supporting defined microbial communities derived from human fecal samples as models of the colonic microbiota in determining the effectiveness of antibiotic pretreatment. We found that relative antimicrobial resistance was a key determinant of successful microbial engraftment with rifaximin (broad-spectrum antibiotic) pretreatment, despite careful timing of the application of the therapeutic agents, resulting in distinct species profiles from those of the control but with similar overall outcomes. Our model had results comparable to the clinical findings and thus can be used to screen for useful antibiotics.}, }
@article {pmid31991615, year = {2020}, author = {Feehan, A and Garcia-Diaz, J}, title = {Bacterial, Gut Microbiome-Modifying Therapies to Defend against Multidrug Resistant Organisms.}, journal = {Microorganisms}, volume = {8}, number = {2}, pages = {}, doi = {10.3390/microorganisms8020166}, pmid = {31991615}, issn = {2076-2607}, abstract = {Antibiotics have revolutionized human and animal healthcare, but their utility is reduced as bacteria evolve resistance mechanisms over time. Thankfully, there are novel antibiotics in the pipeline to overcome resistance, which are mentioned elsewhere in this special issue, but eventually bacteria are expected to evolve resistance to most new compounds as well. Multidrug resistant organisms (MDROs) that cause infections increase morbidity, mortality, and readmissions as compared with susceptible organisms. Consequently, many research and development pipelines are focused on non-antibiotic strategies, including fecal microbiota transplantation (FMT), probiotics and prebiotics, and a range of therapies in between. Studies reviewed here focus on efforts to directly treat or prevent MDRO infections or colonization. The studies were collected through clinicaltrials.gov, PubMed, and the International Conference on the Harmonisation Good Clinical Practice website (ichgcp.net). While the gold standard of clinical research is randomized controlled trials (RCTs), several pilot studies are included because the field is so young. Although a vast preclinical body of research has led to studies in humans, animal and in vitro studies are not within the scope of this review. This narrative review discusses microbiome-modifying therapies targeting MDROs in the gut and includes current results, ongoing clinical trials, companies with therapies in the pipeline specifically for MDROs, and commentary on clinical implementation and challenges.}, }
@article {pmid31991477, year = {2020}, author = {Fitzgibbon, G and Mills, KHG}, title = {The microbiota and immune-mediated diseases: Opportunities for therapeutic intervention.}, journal = {European journal of immunology}, volume = {50}, number = {3}, pages = {326-337}, doi = {10.1002/eji.201948322}, pmid = {31991477}, issn = {1521-4141}, support = {16/IA/4468/SFI_/Science Foundation Ireland/Ireland ; 12/RI/2340/SFI_/Science Foundation Ireland/Ireland ; }, abstract = {A multitude of diverse microorganisms, termed the microbiota, reside in the gut, respiratory tract, skin, and genital tract of humans and other animals. Recent advances in metagenomic sequencing and bioinformatics have enabled detailed characterization of these vital microbial communities. Studies in animal models have uncovered vital previously unrecognized roles for the microbiota in normal function of the immune responses, and when perturbed, in the pathogenesis of diseases of the gastrointestinal tract and lungs, but also at distant sites in the body including the brain. The composition of gut and respiratory microbiota can influence systemic inflammatory responses that mediate asthma, allergy, inflammatory bowel disease, obesity-related diseases, and neurodevelopmental or neurodegenerative conditions. Experiments in mouse models as well as emerging clinical studies have revealed that therapeutic manipulation of the microbiota, using fecal microbiota transplantation, probiotics, or engineered probiotics represent effective nontoxic approaches for the treatment or prevention of Clostridium difficile infection, allergy, and autoimmune diseases and may enhance the efficacy of certain cancer immunotherapeutics. This review discusses how commensal bacteria can influence immune responses that mediate a range of human diseases and how the microbiota are being targeted to treat these diseases, especially those resistant to pharmacological therapies.}, }
@article {pmid31986084, year = {2020}, author = {Schwabkey, ZI and Jenq, RR}, title = {Microbiome Anomalies in Allogeneic Hematopoietic Cell Transplantation.}, journal = {Annual review of medicine}, volume = {71}, number = {}, pages = {137-148}, doi = {10.1146/annurev-med-052918-122440}, pmid = {31986084}, issn = {1545-326X}, abstract = {The microbiome is an integrated part of the human body that can modulate a variety of disease processes and affect prognosis, treatment response, complications, and outcomes. The importance of allogeneic hematopoietic cell transplantation in cancer treatment has resulted in extensive investigations on the interaction between the microbiome and this treatment modality. These investigations are beginning to lead to clinical trials of microbiome-targeted interventions. Here we review some of these discoveries and describe strategies being investigated to manipulate the microbiome for favorable outcomes, such as the proper selection and timing of antibiotics, type of diet and route of administration, probiotics, prebiotics, and fecal microbiota transplantation.}, }
@article {pmid31982069, year = {2020}, author = {Allegretti, JR and Mullish, BH}, title = {Faecal microbiota transplantations and urinary tract infections - Authors' reply.}, journal = {Lancet (London, England)}, volume = {395}, number = {10220}, pages = {271}, doi = {10.1016/S0140-6736(19)32978-2}, pmid = {31982069}, issn = {1474-547X}, mesh = {*Clostridium Infections ; Fecal Microbiota Transplantation ; Humans ; *Urinary Tract Infections ; }, }
@article {pmid31982066, year = {2020}, author = {Lagier, JC and Raoult, D}, title = {Faecal microbiota transplantations and urinary tract infections.}, journal = {Lancet (London, England)}, volume = {395}, number = {10220}, pages = {270-271}, doi = {10.1016/S0140-6736(19)32992-7}, pmid = {31982066}, issn = {1474-547X}, mesh = {*Fecal Microbiota Transplantation ; Feces ; Humans ; *Urinary Tract Infections ; }, }
@article {pmid31976518, year = {2020}, author = {Stoma, I and Littmann, ER and Peled, JU and Giralt, S and van den Brink, MRM and Pamer, EG and Taur, Y}, title = {Compositional flux within the intestinal microbiota and risk for bloodstream infection with gram-negative bacteria.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaa068}, pmid = {31976518}, issn = {1537-6591}, abstract = {BACKGROUND: Gram-negative bloodstream infections represent a significant complication facing allogeneic hematopoietic cell transplant (allo-HCT) recipients, as a result of intestinal translocation during neutropenia. In this study we sought to better understand how the composition of the intestinal microbiota is connected to risk of gram-negative bloodstream infections, expanding on our prior work in these patients.<br><br>METHODS: Fecal specimens were collected from recipients of allo-HCT and analyzed using 16SrRNA gene sequencing. Samples and clinical data extending from the pre-transplant conditioning period through stem cell engraftment were used in the analysis. Intestinal domination (relative abundance ≥30%) by gram-negative bacteria was used as predictor of gram-negative bloodstream infection using Cox proportional hazards modelling. Further analysis of microbiota composition was performed at the genus level.<br><br>RESULTS: 708 allo-HCT subjects were studied (7.5% develop gram-negative infection), with 4,768 fecal samples for analysis. Gram-negative intestinal domination was associated with subsequent bloodstream infection, which was observed overall and individually at the genus level: Escherichia, Klebsiella, Enterobacter, Pseudomonas, and Stenotrophomonas. Fluoroquinolone prophylaxis was associated with decreased bloodstream infection and intestinal colonization by gram-negative microbes. In fluoroquinolone-prophylaxed patients, Escherichia coli was more frequently observed as breakthrough, both in terms of intestinal colonization and bloodstream infections, compared with non-prophylaxed patients. Initial colonization by members of Ruminococcaceae and Bacteroidetes were associated with protection against gram-negative bloodstream infection.<br><br>CONCLUSION: Gram-negative intestinal colonization is highly predictive of bloodstream infection, in the setting of allo-HCT. Fluoroquinolones appear to reduce these infections by influencing gut colonization.}, }
@article {pmid31976311, year = {2019}, author = {Garza-González, E and Mendoza-Olazarán, S and Morfin-Otero, R and Ramírez-Fontes, A and Rodríguez-Zulueta, P and Flores-Treviño, S and Bocanegra-Ibarias, P and Maldonado-Garza, H and Camacho-Ortiz, A}, title = {Intestinal Microbiome Changes in Fecal Microbiota Transplant (FMT) vs. FMT Enriched with Lactobacillus in the Treatment of Recurrent Clostridioides difficile Infection.}, journal = {Canadian journal of gastroenterology &amp; hepatology}, volume = {2019}, number = {}, pages = {4549298}, pmid = {31976311}, issn = {2291-2797}, abstract = {Aim: In this study, we conducted a comparative study to explore the differences in therapeutic efficacy and intestinal microbiome of fecal microbiota transplant (FMT) vs. FMT in addition with Lactobacillus (FMT-L) for treatment of recurrent Clostridioides difficile infection (R-CDI).<br><br>Methods: We designed a double-blinded randomized comparative two-arm pilot multicenter study to assess the efficacy and impact in the intestinal microbiome of standard capsules of FMT vs. FMT-L enriched with 3 species of Lactobacillus for patients with R-CDI. A 90-day follow-up of 21 patients was performed, starting at the beginning of the study. From the selected patients, fecal samples were obtained at days 0, 3, 7, and 28 after treatment. Fecal samples and FMT were analyzed by 16S rRNA sequencing.<br><br>Results: We included 21 patients (13 in the FMT group and 8 in the FMT-L group). Overall, both groups had a reduction in bowel movements per day, from 8.6 to 3.2 in the first 48 h (62.7% reduction, p=0.001). No severe adverse reactions or recurrences were recorded. Firmicutes were the most abundant phylum in donors. A low relative abundance of Proteobacteria was detected and mostly found in patients even at higher proportions than the donor. The donor's pool also had relatively few Bacteroidetes, and some patients showed a higher abundance of this phylum. Based on the ANOSIM R values, there is a significant difference between the microbial communities of basal samples and samples collected on day 7 (p=0.045) and at day 28 (0.041).<br><br>Conclusion: Fecal microbiota transplant by capsules was clinically and genomically similar between traditional FMT and enriched FMT with Lactobacillus spp. Restoration of bacterial diversity and resolution of dysbiosis at days 7 and 28 were observed. Patients with a first episode of recurrence treated with FMT had an excellent response without severe adverse events; FMT should be considered as an early treatment during R-CDI.}, }
@article {pmid31974041, year = {2020}, author = {Lou, JM and Ren, ZG and Li, A and Rao, BC and Yu, ZJ}, title = {Fecal microbiota transplantation has therapeutic effects on chronic hepatits B patients via altering composition of gut microbiota.}, journal = {Hepatobiliary &amp; pancreatic diseases international : HBPD INT}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.hbpd.2019.12.008}, pmid = {31974041}, issn = {1499-3872}, }
@article {pmid31973773, year = {2020}, author = {Stalder, T and Kapel, N and Diaz, S and Grenouillet, F and Koch, S and Limat, S and Daval, F and Vuitton, L and Nerich, V}, title = {A systematic review of economic evaluation in fecal microbiota transplantation.}, journal = {Infection control and hospital epidemiology}, volume = {}, number = {}, pages = {1-9}, doi = {10.1017/ice.2019.371}, pmid = {31973773}, issn = {1559-6834}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective therapy in recurrent Clostridium difficile infection (rCDI). It is only recommended for this indication by European and American guidelines. Other indications of FMT are being studied, such as inflammatory bowel disease (IBD), and they have shown promising results.<br><br>OBJECTIVES: To identify and review published FMT-related economic evaluations (EEs) to assess their quality and the economic impact of FMT in the treatment of these diseases.<br><br>DATA SOURCES: The systematic literature research was conducted in both PubMed and Cochrane to identify EEs published before July 1, 2019.<br><br>STUDY ELIGIBILITY CRITERIA: Articles were included if they concerned FMT (whatever the disease and its line of treatment), if they reported full or partial EEs, and if they were written in English. Articles were excluded if they did not concern FMT; if they did not report an EE; or if they were a systematic review, editorial, comment, letter to the editor, practice point, or poster.<br><br>METHODS: A measurement tool, AMSTAR, was used to optimize the quality of this systematic review. Based on the CHEERS checklist, data were identified and extracted from articles. The quality of each EE was assessed using the Drummond checklist.<br><br>RESULTS: Overall, 9 EEs were included: all EEs were full evaluations and 8 were cost-utility analyses (CUAs). All EEs had a Drummond score ≥ 7, which indicated high quality. All CUAs related to rCDI and IBD concluded that FMT was cost-effective compared with other reference treatments, at a threshold ≤$50,000/QALY. One EE about initial CDI showed that FMT was dominated by metronidazole.<br><br>CONCLUSIONS: Despite a limited number of EEs, FMT seems to be a promising and cost-effective treatment for rCDI. More EE studies on other diseases like IBD are necessary to address FMT efficiency for new indications. Therefore, our systematic review provides a framework for healthcare decision making.}, }
@article {pmid31973214, year = {2020}, author = {Safari, Z and Bruneau, A and Monnoye, M and Mariadassou, M and Philippe, C and Zatloukal, K and Gérard, P}, title = {Murine Genetic Background Overcomes Gut Microbiota Changes to Explain Metabolic Response to High-Fat Diet.}, journal = {Nutrients}, volume = {12}, number = {2}, pages = {}, doi = {10.3390/nu12020287}, pmid = {31973214}, issn = {2072-6643}, support = {W1226//FWF/ ; }, abstract = {Interactions of diet, gut microbiota, and host genetics play essential roles in the development of metabolic diseases. A/J and C57BL/6J (C57) are two mouse strains known to display different susceptibilities to metabolic disorders. In this context, we analyzed gut microbiota composition in A/J and C57 mice, and assessed its responses to high-fat diet (HFD) and antibiotic (AB) treatment. We also exchanged the gut microbiota between the two strains following AB treatment to evaluate its impact on the metabolism. We showed that A/J and C57 mice have different microbiome structure and composition at baseline. Moreover, A/J and C57 microbiomes responded differently to HFD and AB treatments. Exchange of the gut microbiota between the two strains was successful as recipients' microbiota resembled donor-strain microbiota. Seven weeks after inoculation, the differences between recipients persisted and were still closer from the donor-strain microbiota. Despite effective microbiota transplants, the response to HFD was not markedly modified in C57 and A/J mice. Particularly, body weight gain and glucose intolerance in response to HFD remained different in the two mouse strains whatever the changes in microbiome composition. This indicated that genetic background has a much stronger impact on metabolic responses to HFD than gut microbiome composition.}, }
@article {pmid31972620, year = {2020}, author = {Ekekezie, C and Perler, BK and Wexler, A and Duff, C and Lillis, CJ and Kelly, CR}, title = {Understanding the Scope of Do-It-Yourself Fecal Microbiota Transplant.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000000499}, pmid = {31972620}, issn = {1572-0241}, abstract = {OBJECTIVES: Fecal microbiota transplantation (FMT) has emerged as an effective treatment option for Clostridioides difficile infection (CDI) and is considered an investigational therapy for a number of other diseases. Social media has facilitated widespread exposure of the public to the gut microbiome and FMT, ultimately acting as a catalyst for the Do-It-Yourself (DIY)-FMT movement. The aims of this study were to identify factors that influenced willingness to pursue DIY-FMT including common indications, screening processes, sample preparation, and self-reported efficacy and safety outcomes.<br><br>METHODS: A twenty-five-point cross-sectional survey was posted online through the websites and social media pages of the Peggy Lillis Foundation, The Fecal Transplant Foundation, and The Power of Poop. Responses were cataloged through the Research Electronic Data Capture tool, and descriptive analyses were performed.<br><br>RESULTS: Eighty-four respondents completed the survey between January 2018 and February 2019. The majority were female (71%) and white (92%). Most (80%) reported performing FMT on themselves; 87% used Internet resources to assist in the process, and 92% knew their stool donor. Inflammatory bowel disease (35%) and irritable bowel syndrome (29%) were the 2 most common conditions that respondents attempted to treat. Only 12% reported adverse events, whereas 82% reported improvement in their condition.<br><br>DISCUSSION: DIY-FMT is being used for many indications, including those for which there is little evidence. There was a high self-reported success rate among respondents with few adverse events. There is a need for increased awareness around DIY-FMT and research around this phenomenon, which may impact public health.}, }
@article {pmid31968211, year = {2020}, author = {Antushevich, H}, title = {Fecal microbiota transplantation in disease therapy.}, journal = {Clinica chimica acta; international journal of clinical chemistry}, volume = {503}, number = {}, pages = {90-98}, doi = {10.1016/j.cca.2019.12.010}, pmid = {31968211}, issn = {1873-3492}, abstract = {Fecal microbiota transplantation (FMT) is the introduction (transplantation) of gut microbiota obtained from the faeces of a healthy donor into the patient's gastrointestinal tract. Most often, such therapy is used the treatment of gastrointestinal diseases caused by the activity of pathogenic or conditionally pathogenic microorganisms, however, recently an increasing number of studies have reported the use of fecal microbiota transplantation for the treatment of diseases such as metabolic syndrome, diabetes, cancer and Parkinson's disease. This review article presents the results of studies concerning the impact of FMT on weight gain, immunological response and the treatment of neurological and gastrointestinal diseases and cancer. The procedure of fecal microbiota transplantation and possible side effects that may appear in FMT recipients are also described.}, }
@article {pmid31964766, year = {2020}, author = {Bircher, L and Schwab, C and Geirnaert, A and Greppi, A and Lacroix, C}, title = {Planktonic and Sessile Artificial Colonic Microbiota Harbor Distinct Composition and Reestablish Differently upon Frozen and Freeze-Dried Long-Term Storage.}, journal = {mSystems}, volume = {5}, number = {1}, pages = {}, pmid = {31964766}, issn = {2379-5077}, abstract = {Biofilm-associated, sessile communities represent the major bacterial lifestyle, whereas planktonic cells mainly appear during initial colonization of new surfaces. Previous research, mainly performed with pathogens, demonstrated increased environmental stress tolerance of biofilm-growing compared to planktonic bacteria. The lifestyle-specific stress response of colonic microbiota, both natural and fermentation produced, has not been addressed before. Planktonic and sessile &quot;artificial&quot; colonic microbiota delivered by PolyFermS continuous fermentation models can provide a controllable and reproducible alternative to fecal transplantation in treating gastrointestinal disorders. We therefore characterized planktonic and sessile microbiota produced in two PolyFermS models inoculated with immobilized fecal microbiota and comparatively tested their levels of tolerance of frozen storage (-80°C) and freeze-dried storage (4°C) for 9 months to mimic preservation strategies for therapeutic applications. Sessile microbiota harbored next to shared taxa a unique community distinguishable from planktonic microbiota. Synergistetes and Proteobacteria were highly represented in sessile microbiota, while Firmicutes were more abundant in planktonic microbiota. The community structure and metabolic activity of both microbiota, monitored during standardized reactivation batch fermentations, were better preserved after frozen storage than dried storage, indicated by higher Bray-Curtis similarity and enhanced recovery of metabolite production. For both lifestyles, reestablishment of Bacteroidaceae was impaired after frozen and dried storage along with reduced propionate formation. In contrast, butyrate production was maintained after reactivation despite compositional rearrangements within the butyrate-producing community. Unexpectedly, the rate of recovery of metabolite production was lower after preservation of sessile than planktonic microbiota. We speculate that higher functional dependencies between microbes might have led to the lower stress tolerance of sessile than planktonic microbiota.IMPORTANCE Fecal microbiota transplantation has been successfully applied in the treatment of recurrent Clostridium difficile infection and has been suggested as an alternative therapy for other intestinal disorders such as inflammatory bowel disease or metabolic syndrome. &quot;Artificial&quot; colonic microbiota delivered by PolyFermS continuous fermentation models can provide a controllable and reproducible alternative to fecal transplantation, but effective preservation strategies must be developed. In this study, we systematically investigated the response of sessile and planktonic artificial colonic microbiota to cryopreservation and lyophilization. We suggest that functional redundancy is an important factor in providing functional stability with respect to exposure to stress during processing and storage. Functional redundancy in compositionally reduced microbial systems may be considered when designing microbial products for therapy.}, }
@article {pmid31963653, year = {2020}, author = {Xu, R and Wan, J and Lin, C and Su, Y}, title = {Effects of Early Intervention with Antibiotics and Maternal Fecal Microbiota on Transcriptomic Profiling Ileal Mucusa in Neonatal Pigs.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {9}, number = {1}, pages = {}, doi = {10.3390/antibiotics9010035}, pmid = {31963653}, issn = {2079-6382}, support = {31572414 and 31872362//National Natural Science Foundation of China/ ; }, abstract = {This study aimed to investigate the effects of early intervention with antibiotics and maternal fecal microbiota on ileal morphology and barrier function, and transcriptomic profiling in neonatal piglets. Piglets in the amoxicillin (AM), fecal microbiota transplantation (FMT), and control (CO) groups were orally administrated with amoxicillin solution (6.94 mg/mL), maternal fecal microbiota suspension [>109 colony forming unit (CFU)/mL], and physiological saline, respectively. Compared with the CO group, early intervention with AM or FMT significantly decreased ileal crypt depth on day 7 and altered gene expression profiles in ileum on days 7 and 21, and especially promoted the expression of chemokines (CCL5, CXCL9, and CXCL11) involved in the toll-like receptor signaling pathway on day 21. FMT changed major immune activities from B cell immunity on day 7 to T cell immunity on day 21 in the ileum. On the other hand, both AM and FMT predominantly downregulated the gene expression of toll-like receptor 4 (TLR4). In summary, both early interventions modulated intestinal barrier function and immune system in the ileum with a low impact on ileal morphology and development.}, }
@article {pmid31961792, year = {2020}, author = {Barcán, L and Ducatenzeiler, L and Bangher, MDC and Barcelona, L and Cornistein, W and Daciuk, L and De Paula, J and Desse, J and Dictar, M and Fernández-Canigia, L and Nacinovich, F and Scapellato, P and Martínez, JV and ,  and ,  and ,  and ,  and ,  and ,  and ,  and ,  and ,  and , }, title = {[Intersociety guidelines for diagnosis, treatment and prevention of Clostridioides difficile infections].}, journal = {Medicina}, volume = {80 Suppl 1}, number = {}, pages = {1-32}, pmid = {31961792}, issn = {1669-9106}, mesh = {Argentina ; Clinical Laboratory Techniques ; Clostridium Infections/*diagnosis/prevention &amp; control/*therapy ; Humans ; Risk Factors ; Societies, Medical ; }, abstract = {Clostridioides difficile infections (CDI) are among the leading causes of health care-associated infections. The epidemiology of CDI has undergone major changes in the last decade, showing an increase in incidence, severity, and rate of relapse. These guidelines were developed by specialists from four scientific societies: Sociedad Argentina de Infectología (SADI), Sociedad Argentina de Gastroenterología (SAGE), Sociedad Argentina de Bacteriología, Micología y Parasitología Clínicas (SADEBAC) and Asociación de Enfermeras en Control de Infecciones (ADECI). The objective of these intersociety guidelines is to provide national recommendations on CDI diagnosis, treatment and prevention. The methodology used involved the systematic review of the bibliography available up to December 2018, which was performed by six groups formed ad hoc: Epidemiology, Diagnosis, Treatment, Fecal Microbiota Transplantation, Special Populations, and Infection Control. The conclusions were presented and discussed in meetings held by each individual group and plenary meetings. In this document, updated diagnosis algorithms, therapeutic options (including fecal microbiota transplant) for immunocompetent and immunocompromised patients are presented, as well as strategies for the control of C. difficile infection.}, }
@article {pmid31958930, year = {2020}, author = {Chen, QY and Tian, HL and Yang, B and Lin, ZL and Zhao, D and Ma, CL and Chen, X and Jiang, J and Qin, HL and Li, N}, title = {[Diagnosis and treatment of superior mesenteric artery compression syndrome secondary to chronic constipation (Lee's triad syndrome)].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {1}, pages = {44-50}, doi = {10.3760/cma.j.issn.1671-0274.2020.01.008}, pmid = {31958930}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; }, mesh = {Chronic Disease ; Cohort Studies ; Constipation/*complications ; Enteral Nutrition ; Fecal Microbiota Transplantation ; Humans ; Knee-Chest Position ; Mesenteric Artery, Superior/diagnostic imaging ; Quality of Life ; Superior Mesenteric Artery Syndrome/*diagnosis/diagnostic imaging/etiology/*therapy ; Syndrome ; Treatment Outcome ; }, abstract = {Objective: To summarize the experience of diagnosis and treatment of superior mesenteric artery compression syndrome (SMACS) secondary to chronic constipation according to the concept of Lee's triad syndrome. Methods: The concept of Lee's triad syndrome: (1) clinical symptoms: triad of constipation, malnutrition, upper gastrointestinal obstruction (vomiting, difficulty in eating); (2) anatomical manifestations: with triple anatomy anomaly of transverse colon sagging, elevated spleen flexure, and mesentery arterial compression; (3) treatment: with triple treatment of enteral nutrition support, chest-knee posture and fecal microbiota transplantation. A descriptive cohort study was performed. According to Lee's triad syndrome criteria, clinical data of 78 patients with superior mesenteric artery compression syndrome secondary to chronic constipation in the Tenth People's Hospital of Tongji University and General Hospital of Eastern Theater Command from June 2004 to November 2018 were prospectively collected, including basic information, symptoms and signs, imaging findings, nutritional indicators, gastrointestinal quality of life index (GIQLI) and Wexner defecation score. The above parameters based on Lee's triad syndrome criteria were followed up and recorded at 1, 3, 6, 12 months after comprehensive treatment. Results: All the patients had Lee's triple symptoms of constipation, malnutrition, upper gastrointestinal obstruction (vomiting, eating difficulties), and triple anatomy anomaly of transverse colon sagging, elevated spleen curvature, and mesentery arterial compression before treatment. After triple treatment of enteral nutrition support, chest-knee posture, and fecal microbiota transplantation, 69 (88.5%) patients had a significant improvement of symptoms, and 9 patients had no significant improvement of symptoms and then eventually received surgery. The 69 cases without operation received follow-up for 12 months. All the patients eventually returned to normal eating, and upper gastrointestinal angiography and superior mesenteric artery imaging showed duodenal compression disappeared. After 1 month, the constipation-related indexes were improved. After 12 months, the number of autonomous defecation per week increased from 1.0±0.8 to 5.0±1.6 (P<0.001). The GIQLI score increased from 52.7±8.5 to 93.2±7.5 (P<0.001), and the Wexner score decreased from 19.1±2.5 to 6.2±2.1 (P<0.001). After 1 month, nutritional indexes were improved gradually. After 12 months, the BMI increased from (17.9±1.8) kg/m(2) to (21.0±1.3) kg/m(2), total protein increased from (65.2±5.7) g/L to (68.3±4.2) g/L, albumin increased from (32.1±5.1) g/L to (40.4±3.0) g/L, prealbumin increased from (163.2±53.7) mg/L to (259.1±45.6) mg/L, fibrinogen increased from (1.9±0.5) g/L to (2.4±0.5) g/L, whose differences were statistically significant (all P<0.001). Upper gastrointestinal angiography and superior mesenteric artery imaging showed duodenal compression were relieved. The angle between superior mesenteric artery and abdominal aorta increased from (17.4±3.8)° to (37.8±5.8)° (t=-22.26, P<0.001). Conclusion: When patients with SMACS secondary to chronic constipation have Lee's triple symptoms and triple anatomy anomaly, the triple combination treatment of enteral nutrition support, chest-knee posture and fecal microbiota transplantation should be applied.}, }
@article {pmid31958765, year = {2020}, author = {Chen, H and Zhang, F and Li, R and Liu, Y and Wang, X and Zhang, X and Xu, C and Li, Y and Guo, Y and Yao, Q}, title = {Berberine regulates fecal metabolites to ameliorate 5-fluorouracil induced intestinal mucositis through modulating gut microbiota.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {124}, number = {}, pages = {109829}, doi = {10.1016/j.biopha.2020.109829}, pmid = {31958765}, issn = {1950-6007}, abstract = {Berberine (BBR) is an isoquinoline alkaloid, which has been used in the treatment of intestinal mucositis. However, BBR on chemotherapy-induced mucositis in cancer patients remains largely unknown. Here, we investigated the effect of BBR on intestinal mucositis induced by 5-fluorouracil (5-Fu) using rat model. We detected the degree of intestinal mucosal damage and inflammatory response in 5-Fu treated rats with or without BBR administration, and investigated the changes of fecal metabolites and gut microbiota using 1H NMR spectroscopy and 16S rRNA. The mechanism was further explored by fecal microbiota transplantation (FMT). Results showed that BBR treated rats displayed less weight loss, lower diarrhea score and longer colon length in 5-Fu treated rats. Meanwhile, BBR treatment significantly increased the expression of Occludin in ileum and decreased the d-lactate content in serum. Moreover, the expression of IL-1β, IL-6 and TNF-α in ileum were suppressed by BBR treatment. The pattern of fecal metabolism changed obviously after treated with 5-Fu, which was reversed by BBR. Importantly, BBR significantly increased the levels of butyrate and glutamine in feces from 5-Fu treated rats. In terms of gut microbiota, BBR enriched the relative abundance of Firmicutes and decreased Proteobacteria at the phylum level. Meanwhile, BBR increased the propotion of unclassified_f_ Porphyromonadaceae, unclassified_f_ Lachnospiraceae, Lactobacillus, unclassified_o_ Clostridiales, Ruminococcus, Prevotella, Clostridium IV, and decreased Escherichia/Shigella at the genera level. Furthermore, principal component analysis (PCA) showed that fecal transplantation led to changes in fecal metabolites. Fecal transplantation from BBR treated rats had low diarrhea score, reduced inflammatory response in ileum, and relieved intestinal mucosal injury, which may be caused by the increased of butyrate level in fecal metabolites. In conclusion, our study provides evidence that BBR regulates fecal metabolites to ameliorate 5-Fu induced intestinal mucositis by modifying gut microbiota.}, }
@article {pmid31957587, year = {2019}, author = {Khoruts, A and Hoffmann, DE and Palumbo, FB}, title = {The Impact of Regulatory Policies on the Future of Fecal Microbiota Transplantation.}, journal = {The Journal of law, medicine &amp; ethics : a journal of the American Society of Law, Medicine &amp; Ethics}, volume = {47}, number = {4}, pages = {482-504}, doi = {10.1177/1073110519897726}, pmid = {31957587}, issn = {1748-720X}, abstract = {In this article, the authors explore the impact of a potential future regulatory decision by FDA whether or not to continue its enforcement discretion policy allowing physicians to perform, and stool banks to sell, stool product for fecal microbiota transplantation as a treatment for recurrent Clostridium Difficile infection without an Investigative New Drug (IND) application. The paper looks at the Agency's regulatory options in light of the current gut microbiota based products that are in the FDA pipeline for drug approval and the potential impact and repercussions of their approval on FDA action. In laying out FDA's options we consider the implications of market exclusivity and off-label use of newly approved drugs. Ultimately, we explore the potential impact of FDA's decision on patients, research, and innovation.}, }
@article {pmid31957577, year = {2019}, author = {DeLong, K and Zulfiqar, F and Hoffmann, DE and Tarzian, AJ and Ensign, LM}, title = {Vaginal Microbiota Transplantation: The Next Frontier.}, journal = {The Journal of law, medicine &amp; ethics : a journal of the American Society of Law, Medicine &amp; Ethics}, volume = {47}, number = {4}, pages = {555-567}, doi = {10.1177/1073110519897731}, pmid = {31957577}, issn = {1748-720X}, abstract = {The success of fecal microbiota transplantation (FMT) as a treatment for Clostrioides difficile infection (CDI) has stirred excitement about the potential for microbiota transplantation as a therapy for a wide range of diseases and conditions. In this article, we discuss vaginal microbiota transplantation (VMT) as &quot;the next frontier&quot; in microbiota transplantation and identify the medical, regulatory, and ethical challenges related to this nascent field. We further discuss what we anticipate will be the first context for testing VMT in clinical trials, prevention of the recurrence of a condition referred to as bacterial vaginosis (BV). We also compare clinical aspects of VMT with FMT and comment on how VMT may be similar to or different from FMT in ways that may affect research design and regulatory decisions.}, }
@article {pmid31957576, year = {2019}, author = {Murray, TS and Herbst, J}, title = {The Ethics of Fecal Microbiota Transplant as a Tool for Antimicrobial Stewardship Programs.}, journal = {The Journal of law, medicine &amp; ethics : a journal of the American Society of Law, Medicine &amp; Ethics}, volume = {47}, number = {4}, pages = {541-554}, doi = {10.1177/1073110519897730}, pmid = {31957576}, issn = {1748-720X}, abstract = {Multidrug resistant organisms (MDROs) are a public health threat that have reduced the effectiveness of many available antibiotics. Antimicrobial stewardship programs (ASPs) have been tasked with reducing antibiotic use and therefore the emergence of MDROs. While fecal microbiota transplant (FMT) has been proposed as therapy to reduce patient colonization of MDROs, this will require additional evidence to support an expansion of the current clinical indication for FMT. This article discusses the evidence and ethics of the expanded utilization of FMT by ASPs for reasons other than severe recurrent or refractory Clostridioides (formerly Clostridium) difficile infection.}, }
@article {pmid31957572, year = {2019}, author = {Scheeler, A}, title = {Where Stool is a Drug: International Approaches to Regulating the use of Fecal Microbiota for Transplantation.}, journal = {The Journal of law, medicine &amp; ethics : a journal of the American Society of Law, Medicine &amp; Ethics}, volume = {47}, number = {4}, pages = {524-540}, doi = {10.1177/1073110519897729}, pmid = {31957572}, issn = {1748-720X}, abstract = {Regulatory agencies vary widely in their classification of FMT, with significant impact on patient access. This article conducts a global survey of national regulations and collates existing FMT classification statuses, ultimately suggesting that the human cell and tissue product designation best fits FMT's characteristics and that definitional objectives to that classification may be overcome.}, }
@article {pmid31950808, year = {2019}, author = {Blanchaert, C and Strubbe, B and Peeters, H}, title = {Fecal microbiota transplantation in ulcerative colitis.}, journal = {Acta gastro-enterologica Belgica}, volume = {82}, number = {4}, pages = {519-528}, pmid = {31950808}, issn = {1784-3227}, mesh = {Clostridium Infections/microbiology/*therapy ; Clostridium difficile ; Colitis, Ulcerative/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; Intestines/microbiology ; *Microbiota ; Treatment Outcome ; }, abstract = {BACKGROUND/STUDY AIMS: Fecal microbiota transplantation (FMT), a treatment aiming to restore dysbiosis by transferring stool from a healthy donor into the patient, has cure rates up to 90% in the management of recurrent Clostridium difficile (C. difficile) diarrhea. This paper tries to determine whether FMT is safe and effective in the treatment of ulcerative colitis, and what the potential characteristics could be of a 'super donor'.<br><br>METHODS: The PubMed database was searched using the term fecal microbiota transplantation inflammatory bowel disease. Only articles discussing the use of FMT in the treatment of ulcerative colitis were withheld. Finally, 31 original studies (10 case reports, 17 open label trials, 4 randomized controlled trials (RCTs)) and 1 meta-analysis were included.<br><br>RESULTS: So far 4 RCTs have investigated the effectiveness of FMT in treating UC. Three RCTs reported a significant difference between FMT and a control group, achieving clinical remission in 24 to 44% of patients (vs. 5 to 20% of patients in control groups). The meta-analysis confirms that significantly more patients in the FMT-group achieve clinical remission in comparison to patients in the control group (p=0,01) : 42,1% vs. 22,6%. The composition of the gut microbiota plays an important role in the success of FMT-treatment.<br><br>CONCLUSION: FMT seems to be a promising and safe therapy in the management of UC. Further research, with larger cohorts, will be needed to confirm this and to determine the optimal FMT procedure.}, }
@article {pmid31950071, year = {2020}, author = {Oliva, A and Aversano, L and De Angelis, M and Mascellino, MT and Miele, MC and Morelli, S and Battaglia, R and Iera, J and Bruno, G and Corazziari, ES and Ciardi, MR and Venditti, M and Mastroianni, CM and Vullo, V}, title = {Persistent Systemic Microbial Translocation, Inflammation, and Intestinal Damage During Clostridioides difficile Infection.}, journal = {Open forum infectious diseases}, volume = {7}, number = {1}, pages = {ofz507}, pmid = {31950071}, issn = {2328-8957}, abstract = {Background: Clostridioides difficile infection (CDI) might be complicated by the development of nosocomial bloodstream infection (n-BSI). Based on the hypothesis that alteration of the normal gut integrity is present during CDI, we evaluated markers of microbial translocation, inflammation, and intestinal damage in patients with CDI.<br><br>Methods: Patients with documented CDI were enrolled in the study. For each subject, plasma samples were collected at T0 and T1 (before and after CDI therapy, respectively), and the following markers were evaluated: lipopolysaccharide-binding protein (LPB), EndoCab IgM, interleukin-6, intestinal fatty acid binding protein (I-FABP). Samples from nonhospitalized healthy controls were also included. The study population was divided into BSI+/BSI- and fecal microbiota transplantation (FMT) +/FMT- groups, according to the development of n-BSI and the receipt of FMT, respectively.<br><br>Results: Overall, 45 subjects were included; 8 (17.7%) developed primary n-BSI. Markers of microbial translocation and intestinal damage significantly decreased between T0 and T1, however, without reaching values similar to controls (P < .0001). Compared with BSI-, a persistent high level of microbial translocation in the BSI+ group was observed. In the FMT+ group, markers of microbial translocation and inflammation at T1 tended to reach control values.<br><br>Conclusions: CDI is associated with high levels of microbial translocation, inflammation, and intestinal damage, which are still present at clinical resolution of CDI. The role of residual mucosal perturbation and persistence of intestinal cell damage in the development of n-BSI following CDI, as well as the possible effect of FMT in the restoration of mucosal integrity, should be further investigated.}, }
@article {pmid31942825, year = {2020}, author = {Ho, J and Yeoh, YK and Barua, N and Chen, Z and Lui, G and Wong, SH and Yang, X and Chan, MC and Chan, PK and Hawkey, PM and Ip, M}, title = {Systematic review of human gut resistome studies revealed variable definitions and approaches.}, journal = {Gut microbes}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/19490976.2019.1700755}, pmid = {31942825}, issn = {1949-0984}, abstract = {In this review, we highlight the variations of gut resistome studies, which may preclude comparisons and translational interpretations. Of 22 included studies, a range of 12 to 2000 antibiotic resistance (AR) genes were profiled. Overall, studies defined a healthy gut resistome as subjects who had not taken antibiotics in the last three to 12 months prior to sampling. In studies with de novo assembly, AR genes were identified based on variable nucleotide or amino acid sequence similarities. Different marker genes were used for defining resistance to a given antibiotic class. Validation of phenotypic resistance in the laboratory is frequently lacking. Cryptic resistance, collateral sensitivity and the interaction with repressors or promotors were not investigated. International consensus is needed for selecting marker genes to define resistance to a given antibiotic class in addition to uniformity in phenotypic validation and bioinformatics pipelines.}, }
@article {pmid31941900, year = {2020}, author = {Siranosian, BA and Tamburini, FB and Sherlock, G and Bhatt, AS}, title = {Acquisition, transmission and strain diversity of human gut-colonizing crAss-like phages.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {280}, pmid = {31941900}, issn = {2041-1723}, support = {K08 CA184420/CA/NCI NIH HHS/United States ; P30 CA124435/CA/NCI NIH HHS/United States ; R01AI148623//U.S. Department of Health &amp; Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; Clinical Investigator Award//Damon Runyon Cancer Research Foundation (Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation)/ ; }, abstract = {CrAss-like phages are double-stranded DNA viruses that are prevalent in human gut microbiomes. Here, we analyze gut metagenomic data from mother-infant pairs and patients undergoing fecal microbiota transplantation to evaluate the patterns of acquisition, transmission and strain diversity of crAss-like phages. We find that crAss-like phages are rarely detected at birth but are increasingly prevalent in the infant microbiome after one month of life. We observe nearly identical genomes in 50% of cases where the same crAss-like clade is detected in both the mother and the infant, suggesting vertical transmission. In cases of putative transmission of prototypical crAssphage (p-crAssphage), we find that a subset of strains present in the mother are detected in the infant, and that strain diversity in infants increases with time. Putative tail fiber proteins are enriched for nonsynonymous strain variation compared to other genes, suggesting a potential evolutionary benefit to maintaining strain diversity in specific genes. Finally, we show that p-crAssphage can be acquired through fecal microbiota transplantation.}, }
@article {pmid31941102, year = {2020}, author = {Xiang, Q and Wu, X and Pan, Y and Wang, L and Cui, C and Guo, Y and Zhu, L and Peng, J and Wei, H}, title = {Early-Life Intervention Using Fecal Microbiota Combined with Probiotics Promotes Gut Microbiota Maturation, Regulates Immune System Development, and Alleviates Weaning Stress in Piglets.}, journal = {International journal of molecular sciences}, volume = {21}, number = {2}, pages = {}, doi = {10.3390/ijms21020503}, pmid = {31941102}, issn = {1422-0067}, support = {31772609//National Natural Science Foundation of China/ ; 2019-620-000-001-30//Hubei Agricultural Sciences and Technology Innovation Center/ ; CARS-36//China Agriculture Research System/ ; }, abstract = {Previous studies have suggested that immune system development and weaning stress are closely related to the maturation of gut microbiota. The early-life period is a &quot;window of opportunity&quot; for microbial colonization, which potentially has a critical impact on the development of the immune system. Fecal microbiota transplantation (FMT) and probiotics are often used to regulate gut microbial colonization. This study aims to test whether early intervention with FMT using fecal microbiota from gestation sows combined with Clostridium butyricum and Saccharomyces boulardii (FMT-CS) administration could promote the maturation of gut microbiota and development of immune system in piglets. Piglets were assigned to control (n = 84) and FMT-CS treatment (n = 106), which were treated with placebo and bacterial suspension during the first three days after birth, respectively. By 16S rRNA gene sequencing, we found that FMT-CS increased the α-diversity and reduced the unweighted UniFrac distances of the OTU community. Besides, FMT-CS increased the relative abundance of beneficial bacteria, while decreasing that of opportunistic pathogens. FMT-CS also enhanced the relative abundance of genes related to cofactors and vitamin, energy, and amino acid metabolisms during the early-life period. ELISA analysis revealed that FMT-CS gave rise to the plasma concentrations of IL-23, IL-17, and IL-22, as well as the plasma levels of anti-M.hyo and anti-PCV2 antibodies. Furthermore, the FMT-CS-treated piglets showed decreases in inflammation levels and oxidative stress injury, and improvement of intestinal barrier function after weaning as well. Taken together, our results suggest that early-life intervention with FMT-CS could promote the development of innate and adaptive immune system and vaccine efficacy, and subsequently alleviate weaning stress through promoting the maturation of gut microbiota in piglets.}, }
@article {pmid31938827, year = {2020}, author = {Antonelli, M and Martin-Loeches, I and Dimopoulos, G and Gasbarrini, A and Vallecoccia, MS}, title = {Clostridioides difficile (formerly Clostridium difficile) infection in the critically ill: an expert statement.}, journal = {Intensive care medicine}, volume = {46}, number = {2}, pages = {215-224}, pmid = {31938827}, issn = {1432-1238}, abstract = {Clostridioides difficile (formerly Clostridium difficile) infection (CDI) represents a worrisome condition, often underestimated, with severe clinical presentations, frequently requiring intensive care unit (ICU) admission. The aim of the present expert statement was to give an overview of the management of CDI in critically ill patients, for whom CDI represents a redoubtable problem, in large part related to the use and abuse of antibiotics. The available knowledge about pathophysiology, risk factors, diagnosis and treatment concerning critical care patients affected by CDI has been reviewed, even though most of the existing information come from studies performed outside the ICU and the evidence on several issues in this specific context is scarce. The adoption of potential preventive and therapeutic strategies aimed to stem the phenomenon were discussed, including the faecal microbiota transplantation. This possibility could represent a highly interesting option in critically ill patients, but current evidence is limited and future well designed studies are needed. A special insight on the specific challenges that the ICU physicians may face caring for the critically ill patients with CDI was also proposed.}, }
@article {pmid31937933, year = {2020}, author = {Zhang, PP and Li, LL and Han, X and Li, QW and Zhang, XH and Liu, JJ and Wang, Y}, title = {Fecal microbiota transplantation improves metabolism and gut microbiome composition in db/db mice.}, journal = {Acta pharmacologica Sinica}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41401-019-0330-9}, pmid = {31937933}, issn = {1745-7254}, abstract = {Fecal microbiota transplantation (FMT) has become an effective strategy to treat metabolic diseases, including type 2 diabetes mellitus (T2DM). We previously reported that the intestinal microbiome had significant difference between individuals with normal glucose tolerance and T2DM in Chinese Kazak ethnic group. In this study, we investigated the effects of transplanted fecal bacteria from Kazaks with normal glucose tolerance (KNGT) in db/db mice. The mice were treated with 0.2 mL of fecal bacteria solution from KNGT daily for 10 weeks. We showed that the fecal bacteria from KNGT successfully colonized in the intestinal tract of db/db mice detected on day 14. In the FMT-treated db/db mice, the levels of fasting blood glucose, postprandial glucose, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol were significantly downregulated, whereas high-density lipoprotein-cholesterol levels were upregulated. In the FMT-treated db/db mice, Desulfovibrio and Clostridium coccoides levels in gut were significantly decreased, but the fecal levels of Akkermansia muciniphila and colon histone deacetylase-3 (HDAC3) protein expression were increased. At 8 weeks, both intestinal target bacteria and HDAC3 were correlated with glycolipid levels; Akkermansia muciniphila level was positively correlated with HDAC3 protein expression (r = +0.620, P = 0.037). Our results suggest that fecal bacteria from KNGT could potentially be used to treat diabetic patients.}, }
@article {pmid31936237, year = {2020}, author = {Chang, CW and Lee, HC and Li, LH and Chiang Chiau, JS and Wang, TE and Chuang, WH and Chen, MJ and Wang, HY and Shih, SC and Liu, CY and Tsai, TH and Chen, YJ}, title = {Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer.}, journal = {International journal of molecular sciences}, volume = {21}, number = {2}, pages = {}, doi = {10.3390/ijms21020386}, pmid = {31936237}, issn = {1422-0067}, abstract = {FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), a 5-fluorouracil (5-FU)-based chemotherapy regimen, is one of most common therapeutic regimens for colorectal cancer. However, intestinal mucositis is a common adverse effect for which no effective preventive strategies exist. Moreover, the efficacy and the safety of fecal microbiota transplants (FMT) in cancer patients treated with anti-neoplastic agents are still scant. We investigated the effect of FMT on FOLFOX-induced mucosal injury. BALB/c mice implanted with syngeneic CT26 colorectal adenocarcinoma cells were orally administered FMT daily during and two days after five-day injection of FOLFOX regimen for seven days. Administration of FOLFOX significantly induced marked levels of diarrhea and intestinal injury. FMT reduced the severity of diarrhea and intestinal mucositis. Additionally, the number of goblet cells and zonula occludens-1 decreased, while apoptotic and NF-κB-positive cells increased following FOLFOX treatment. The expression of toll-like receptors (TLRs), MyD88, and serum IL-6 were upregulated following FOLFOX treatment. These responses were attenuated following FMT. The disrupted fecal gut microbiota composition was also restored by FMT after FOLFOX treatment. Importantly, FMT did not cause bacteremia and safely alleviated FOLFOX-induced intestinal mucositis in colorectal cancer-bearing mice. The putative mechanism may involve the gut microbiota TLR-MyD88-NF-κB signaling pathway in mice with implanted colorectal carcinoma cells.}, }
@article {pmid31934800, year = {2020}, author = {Harris, C and Kim, PT and Waterhouse, D and Feng, Z and Niergarth, J and Lee, CH}, title = {Precision medicine and gut dysbiosis.}, journal = {Healthcare management forum}, volume = {}, number = {}, pages = {840470419899426}, doi = {10.1177/0840470419899426}, pmid = {31934800}, issn = {0840-4704}, abstract = {Clostridioides difficile Infection (CDI) is a leading cause of healthcare-associated infections in Canada, affecting the gastrointestinal tract which can lead to fever, abdominal pain, and diarrhea. Effective treatment for patients with Recurrent CDI (rCDI) can be achieved by Fecal Microbiota Transplantation (FMT) by introducing the gut micro-organisms of a healthy person (donor) into the bowel of the affected individual. Research has shown that an increase in the specific bacterial phyla post-FMT may be partly responsible for this gut restoration and elimination of disease. Furthermore, in understanding the key bacteria associated with successful FMT, full treatment plans can be developed for the individual needs of the patient by matching an infected individual with a donor possessing ideal microbiota for the specific patient. This development of precision medicine and more systematic adoption of FMT can be the next step toward more rapid resolution of rCDI.}, }
@article {pmid31928124, year = {2020}, author = {Ye, Z and Wu, C and Zhang, N and Du, L and Cao, Q and Huang, X and Tang, J and Wang, Q and Li, F and Zhou, C and Xu, Q and Xiong, X and Kijlstra, A and Qin, N and Yang, P}, title = {Altered gut microbiome composition in patients with Vogt-Koyanagi-Harada disease.}, journal = {Gut microbes}, volume = {}, number = {}, pages = {1-17}, doi = {10.1080/19490976.2019.1700754}, pmid = {31928124}, issn = {1949-0984}, abstract = {Background: Vogt-Koyanagi-Harada (VKH) disease is a multisystemic autoimmune disorder characterized by granulomatous panuveitis. Gut microbiome has been considered to play a role in the pathogenesis of this disease but whether the alternation of gut microbiome was involved is unclear. This study was set up to identify abnormalities of gut microbiome composition in VKH disease.Results: Depleted butyrate-producing bacteria, lactate-producing bacteria and methanogens as well as enriched Gram-negative bacteria were identified in the active VKH patients, as well as in VKH patients of Mix enterotype and Bacteroides enterotype. Changes of gut microbiome in the VKH patients were partially restored after an immunosuppressive treatment. The disease susceptibility genotype HLA-DRA was associated with Bacteroides sp.2.1.33B, Paraprevotella clara, Alistipes finegoldii and Eubacterium eligens. A microbial marker profile including 40 disease-associated species was established to differentiate patients from controls. Another microbial marker profile including 37 species was found to be associated with the response to treatment. An animal experiment showed that transfer of gut microbiome from VKH patients could significantly exacerbate disease activity clinically and pathologically in the recipient mice.Conclusion: Our results revealed a distinct gut microbiome signature in VKH patients and showed an exacerbating effect of this gut microbiome on experimental autoimmune uveitis (EAU). We also developed two microbial marker profiles in differentiating VKH patients from healthy controls as well as predicting the effectiveness of treatment.}, }
@article {pmid31923639, year = {2020}, author = {Cheng, YW and Phelps, E and Nemes, S and Rogers, N and Sagi, S and Bohm, M and El-Halabi, M and Allegretti, JR and Kassam, Z and Xu, H and Fischer, M}, title = {Fecal Microbiota Transplant Decreases Mortality in Patients with Refractory Severe or Fulminant 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.2019.12.029}, pmid = {31923639}, issn = {1542-7714}, abstract = {BACKGROUND &amp; AIMS: Fecal microbiota transplantation (FMT) is recommended for recurrent Clostridioides difficile infection (CDI). FMT cures nearly 80% of patients with severe or fulminant CDI (SFCDI) when utilized in a sequential manner. We compared outcomes of hospitalized patients before and after implementation of an FMT program for SFCDI and investigated whether the changes could be directly attributed to the FMT program.<br><br>METHODS: We performed a retrospective analysis of characteristics and outcomes of patients hospitalized for SFCDI (430 hospitalizations) at a single center, from January 2009 through December 2016. We performed subgroup analyses of 199 patients with fulminant CDI and 110 patients with refractory SFCDI (no improvement after 5 or more days of maximal anti-CDI antibiotic therapy). We compared CDI-related mortality within 30 days of hospitalization, CDI-related colectomy, length of hospital stay, and readmission to the hospital within 30 days before (2009-2012) vs after (2013-2016) implementation of the inpatient FMT program.<br><br>RESULTS: CDI-related mortality and colectomy were lower after implementation of the FMT program. Overall, CDI-related mortality was 10.2% before the FMT program was implemented vs 4.4% after (P=.02). For patients with fulminant CDI, CDI-related mortality was 21.3% before the FMT program was implemented vs 9.1% after (P=.015). For patients with refractory SFCDI, CDI-related mortality was 43.2% before the FMT program vs 12.1% after (P < .001). The FMT program significantly reduced CDI-related colectomy in patients with SFCDI (6.8% before vs 2.7% after; P=.041), in patients with fulminant CDI (15.7% before vs 5.5% after; P=.017), and patients with refractory SFCDI (31.8% vs 7.6%; P = .001). The effect of FMT program implementation on CDI-related mortality remained significant for patients with refractory SFCDI after we accounted for the underlying secular trend (odds ratio, 0.09 for level change; P=.023).<br><br>CONCLUSIONS: An FMT program significantly decreased CDI-related mortality among patients hospitalized with refractory SFCDI.}, }
@article {pmid31922003, year = {2020}, author = {Zeng, SL and Li, SZ and Xiao, PT and Cai, YY and Chu, C and Chen, BZ and Li, P and Li, J and Liu, EH}, title = {Citrus polymethoxyflavones attenuate metabolic syndrome by regulating gut microbiome and amino acid metabolism.}, journal = {Science advances}, volume = {6}, number = {1}, pages = {eaax6208}, pmid = {31922003}, issn = {2375-2548}, abstract = {Metabolic syndrome (MetS) is intricately linked to dysregulation of gut microbiota and host metabolomes. Here, we first find that a purified citrus polymethoxyflavone-rich extract (PMFE) potently ameliorates high-fat diet (HFD)-induced MetS, alleviates gut dysbiosis, and regulates branched-chain amino acid (BCAA) metabolism using 16S rDNA amplicon sequencing and metabolomic profiling. The metabolic protective effects of PMFE are gut microbiota dependent, as demonstrated by antibiotic treatment and fecal microbiome transplantation (FMT). The modulation of gut microbiota altered BCAA levels in the host serum and feces, which were significantly associated with metabolic features and actively responsive to therapeutic interventions with PMFE. Notably, PMFE greatly enriched the commensal bacterium Bacteroides ovatus, and gavage with B. ovatus reduced BCAA concentrations and alleviated MetS in HFD mice. PMFE may be used as a prebiotic agent to attenuate MetS, and target-specific microbial species may have unique therapeutic promise for metabolic diseases.}, }
@article {pmid31921049, year = {2019}, author = {Li, X and Chu, Q and Huang, Y and Xiao, Y and Song, L and Zhu, S and Kang, Y and Lu, S and Xu, J and Ren, Z}, title = {Consortium of Probiotics Attenuates Colonization of Clostridioides difficile.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {2871}, pmid = {31921049}, issn = {1664-302X}, abstract = {Clostridioides difficile infection (CDI) is increasing morbidity and mortality rates globally. Fecal microbiota transplantation (FMT), an effective therapy for eliminating Clostridioides difficile (C. difficile), cannot be used extensive due to a range of challenges. Probiotics thus constitutes a promising alternative therapy. In our study, we evaluated the effect of consortium of probiotics including five Lactobacilli strains and two Bifidobacterium strains on the colonization of toxigenic BI/NAP1/027 C. difficile in a mouse model. The results of 16S rRNA sequencing and targeted metabolomics showed the consortium of probiotics effectively decreased the colonization of C. difficile, changed the α- and β-diversity of the gut microbiota, decreased the primary bile acids, and increased the secondary bile acids. Spearman's correlation showed that some of the OTUs such as Akkermansia, Bacteroides, Blautia et al. were positively correlated with C. difficile numbers and the primary bile acids, and negatively correlated with the secondary bile acids. However, some of the OTUs, such as Butyricicoccus, Ruminococcus, and Rikenellaceae, were negatively correlated with C. difficile copies and the primary bile acids, and positively correlated with the secondary bile acids. In summary, the consortium of probiotics effectively decreases the colonization of C. difficile, probably via alteration of gut microbiota and bile acids. Our probiotics mixture thus offers a promising FMT alternative.}, }
@article {pmid31919742, year = {2020}, author = {Zhang, T and Lu, G and Zhao, Z and Liu, Y and Shen, Q and Li, P and Chen, Y and Yin, H and Wang, H and Marcella, C and Cui, B and Cheng, L and Ji, G and Zhang, F}, title = {Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening.}, journal = {Protein &amp; cell}, volume = {}, number = {}, pages = {}, doi = {10.1007/s13238-019-00684-8}, pmid = {31919742}, issn = {1674-8018}, abstract = {Fecal microbiota transplantation (FMT) by manual preparation has been applied to treat diseases for thousands of years. However, this method still endures safety risks and challenges the psychological endurance and acceptance of doctors, patients and donors. Population evidence showed the washed microbiota preparation with microfiltration based on an automatic purification system followed by repeated centrifugation plus suspension for three times significantly reduced FMT-related adverse events. This washing preparation makes delivering a precise dose of the enriched microbiota feasible, instead of using the weight of stool. Intraperitoneal injection in mice with the fecal microbiota supernatant obtained after repeated centrifugation plus suspension for three times induced less toxic reaction than that by the first centrifugation following the microfiltration. The toxic reactions that include death, the change in the level of peripheral white blood cells, and the proliferation of germinal center in secondary lymphoid follicles in spleen were noted. The metagenomic next-generation sequencing (NGS) indicated the increasing types and amount of viruses could be washed out during the washing process. Metabolomics analysis indicated metabolites with pro-inflammatory effects in the fecal microbiota supernatant such as leukotriene B4, corticosterone, and prostaglandin G2 could be removed by repeated washing. Near-infrared absorption spectroscopy could be served as a rapid detection method to control the quality of the washing-process. In conclusion, this study for the first time provides evidence linking clinical findings and animal experiments to support that washed microbiota transplantation (WMT) is safer, more precise and more quality-controllable than the crude FMT by manual.}, }
@article {pmid31917160, year = {2020}, author = {Zhou, A and Tang, L and Zeng, S and Lei, Y and Yang, S and Tang, B}, title = {Gut microbiota: A new piece in understanding hepatocarcinogenesis.}, journal = {Cancer letters}, volume = {474}, number = {}, pages = {15-22}, doi = {10.1016/j.canlet.2020.01.002}, pmid = {31917160}, issn = {1872-7980}, abstract = {The gut microbiota forms a symbiotic relationship with the host and benefits the body in many critical aspects of life. However, immune system defects, alterations in the gut microbiota and environmental changes can destroy this symbiotic relationship and may lead to diseases, including cancer. Due to the anatomic and functional connection of the gut and liver, increasing studies show the important role of the gut microbiota in the carcinogenesis of hepatocellular carcinoma (HCC). In this manuscript, we review the available evidence and analyze some potential mechanisms of the gut microbiota, including bacterial dysbiosis, lipopolysaccharide (LPS), and genotoxins, in the progression and promotion of HCC. Furthermore, we discuss the possible therapeutic applications of probiotics, chemotherapy modulation, immunotherapy, targeted drugs and fecal microbiota transplantation (FMT) in targeting the gut microbiota.}, }
@article {pmid31910984, year = {2020}, author = {Glassner, KL and Abraham, BP and Quigley, EMM}, title = {The microbiome and inflammatory bowel disease.}, journal = {The Journal of allergy and clinical immunology}, volume = {145}, number = {1}, pages = {16-27}, doi = {10.1016/j.jaci.2019.11.003}, pmid = {31910984}, issn = {1097-6825}, abstract = {Inflammatory bowel disease (IBD) is a chronic immune-mediated disease affecting the gastrointestinal tract. IBD consists of 2 subtypes: ulcerative colitis and Crohn disease. IBD is thought to develop as a result of interactions between environmental, microbial, and immune-mediated factors in a genetically susceptible host. Of late, the potential role of the microbiome in the development, progression, and treatment of IBD has been a subject of considerable interest and enquiry. Indeed, studies in human subjects have shown that the gut microbiome is different in patients with IBD compared with that in healthy control subjects. Other evidence in support of a fundamental role for the microbiome in patients with IBD includes identification of mutations in genes involved in microbiome-immune interactions among patients with IBD and epidemiologic observations implicating such microbiota-modulating risk factors as antibiotic use, cigarette smoking, levels of sanitation, and diet in the pathogenesis of IBD. Consequently, there has been much interest in the possible benefits of microbiome-modulating interventions, such as probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and gene manipulation in the treatment of IBD. In this review we will discuss the role of the gut microbiome in patients with IBD; our focus will be on human studies.}, }
@article {pmid31910227, year = {2020}, author = {Lecronier, M and Tashk, P and Tamzali, Y and Tenaillon, O and Denamur, E and Barrou, B and Aron-Wisnewsky, J and Tourret, J}, title = {Gut microbiota composition alterations are associated with the onset of diabetes in kidney transplant recipients.}, journal = {PloS one}, volume = {15}, number = {1}, pages = {e0227373}, pmid = {31910227}, issn = {1932-6203}, abstract = {METHODS: Patients transplanted at our institution provided fecal samples before, and 3-9 months after KT. Fecal bacterial DNA was extracted and 9 bacteria or bacterial groups were quantified by qPCR.<br><br>RESULTS: 50 patients (19 controls without diabetes, 15 who developed New Onset Diabetes After Transplantation, NODAT, and 16 with type 2 diabetes before KT) were included. Before KT, Lactobacillus sp. tended to be less frequently detected in controls than in those who would become diabetic following KT (NODAT) and in initially diabetic patients (60%, 87.5%, and 100%, respectively, p = 0.08). The relative abundance of Faecalibacterium prausnitzii was 30 times lower in initially diabetic patients than in controls (p = 0.002). The relative abundance of F. prausnitzii of NODAT patients was statistically indistinguishable from controls and from diabetic patients. The relative abundance of Lactobacillus sp. increased following KT in NODAT and in initially diabetic patients (20-fold, p = 0.06, and 25-fold, p = 0.02, respectively). In contrast, the proportion of Akkermansia muciniphila decreased following KT in NODAT and in initially diabetic patients (2,500-fold, p = 0.04, and 50,000-fold, p<0.0001, respectively). The proportion of Lactobacillus and A. muciniphila did not change in controls between before and after the transplantation. Consequently, after KT the relative abundance of Lactobacillus sp. was 25 times higher (p = 0.07) and the relative abundance of A. muciniphila was 2,000 times lower (p = 0.002) in diabetics than in controls.<br><br>CONCLUSION: An alteration of the gut microbiota composition involving Lactobacillus sp., A. muciniphila and F. prausnitzii is associated with the glycemic status in KT recipients, raising the question of their role in the genesis of NODAT.}, }
@article {pmid31905350, year = {2020}, author = {Settanni, CR and Ianiro, G and Franceschi, F and Gasbarrini, G and Gasbarrini, A}, title = {From Regular Catharsis with Castor Oil to Recognizing the Importance of the Intestinal Microbiota.}, journal = {Digestive diseases (Basel, Switzerland)}, volume = {}, number = {}, pages = {1-9}, doi = {10.1159/000505395}, pmid = {31905350}, issn = {1421-9875}, abstract = {The need to shed light on the unknown aspects of pathophysiology of common disorders, such as gastrointestinal ones, has led researchers through last decades to study and define the role of microorganisms within the human intestine and their interactions with the host. The progress of technology has permitted the overcoming of culture-based methods to study microbes and paved the way to molecular techniques, which allow the analysis of microbial genome, microbial functions, and metabolism. These progresses opened a window on the world of microbiology and permitted to deepen into the key role played by gut microbiota and dysbiosis in health status and diseases, both gastrointestinal and extraintestinal. So, scientists focused their attention in developing new strategies to restore eubiosis and to manipulate gut microbes by modifying dietary habits, administrating antibiotics, probiotics, and prebiotics and using fecal microbiota transplantation as treatment of gastrointestinal, infectious, cardiovascular, metabolic, immune-mediated, neuro-psychiatric, and oncological disorders. The next challenges will be to elaborate standard protocols with definite outcomes predictors in disease-specific settings.}, }
@article {pmid31897587, year = {2020}, author = {Wang, Y and Zhang, C and Lai, J and Zhao, Y and Lu, D and Bao, R and Feng, X and Zhang, T and Liu, Z}, title = {Noninvasive PET tracking of post-transplant gut microbiota in living mice.}, journal = {European journal of nuclear medicine and molecular imaging}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00259-019-04639-3}, pmid = {31897587}, issn = {1619-7089}, abstract = {PURPOSE: The role that gut microbiota plays in determining the efficacy of the anti-tumor effect of immune checkpoint inhibitors is gaining increasing attention, and fecal bacterial transplantation has been recognized as a promising strategy for improving or rescuing the effect of immune checkpoint inhibition. However, techniques for the precise monitoring of in vivo bacterial behaviors after transplantation are limited. In this study, we aimed to use metabolic labeling and subsequent positron emission tomography (PET) imaging to track the in vivo behaviors of gut bacteria that are responsible for the efficacy of anti-PD-1 therapy in living mice.<br><br>METHODS: The antitumor effect of anti-PD-1 blockade was tested in a low-response 4T1 syngeneic mouse model with or without fecal transplantation and with or without broad-spectrum antibiotic imipenem treatment. High-throughput sequencing analyses of 16S rRNA gene amplicons in feces of 4T1 tumor-bearing mice pre- and post-anti-PD-1 treatment were performed. The identified bacteria, Bacteroides fragilis (B. fragilis), were labeled with 64Cu and fluorescence dye by the metabolic labeling of N3 followed by click chemistry. In vivo PET and optical imaging of B. fragilis were performed in mice after oral gavage.<br><br>RESULTS: The disturbance of gut microbiota reduced the efficacy of anti-PD-1 treatment, and the combination of B. fragilis gavage and PD-1 blockade was beneficial in rescuing the antitumor effect of anti-PD-1 therapy. Metabolic oligosaccharide engineering and biorthogonal click chemistry resulted in successful B. fragilis labeling with 64Cu and fluorescence dye with high in vitro and in vivo stability and no effect on viability. PET imaging successfully detected the in vivo behaviors of B. fragilis after transplantation.<br><br>CONCLUSION: PET tracking by metabolic labeling is a powerful, noninvasive tool for the real-time tracking and quantitative imaging of gut microbiota. This strategy is clinically translatable and may also be extended to the PET tracking of other functional cells to guide cell-based adoptive therapies.}, }
@article {pmid31896938, year = {2019}, author = {Pierrard, J and Seront, E}, title = {Impact of the gut microbiome on immune checkpoint inhibitor efficacy-a systematic review.}, journal = {Current oncology (Toronto, Ont.)}, volume = {26}, number = {6}, pages = {395-403}, pmid = {31896938}, issn = {1718-7729}, abstract = {Background: Immune checkpoint inhibitors (icis) are increasingly being used in clinical practice, improving outcomes for cancer patients. Preclinical models showed significant interaction between the gut microbiome (gm) and response to icis. However, that interaction remains unclear in clinical practice.<br><br>Methods: We performed a systematic review in medline to determine■ whether antibiotics affect ici efficacy,■ whether baseline gm composition and ici efficacy show any correlations,■ whether baseline gm composition and emergence of immune-related adverse events (iraes) show any correlations, and■ whether gm manipulation can alleviate the iraes.Included publications had to be written in English or French and had to describe a quantifiable link between gm composition or its modification and the response to icis or the occurrence of iraes, or both.<br><br>Results: Of 1451 articles published before December 2018, 13 publications met the inclusion criteria. Five full-text articles and two abstracts highlighted a negative effect of antibiotics on ici efficacy. The composition of the gm was associated with ici efficacy in five full-text articles and one abstract, and with iraes in two full-text articles. In 2 cases, fecal microbiota transplantation was reported to reduce immune colitis.<br><br>Conclusions: If possible, antibiotics should be avoided before ici treatment because of their negative effect on ici anticancer efficacy. No specific commensal bacterium was associated with ici efficacy, but an intact gm with high bacterial diversity and a good ratio of &quot;responder-associated&quot; bacteria to &quot;non-responder-associated&quot; bacteria seem to be correlated with better patient outcomes. Fecal microbiota transplantation is a promising technique for reducing ici-associated colitis.}, }
@article {pmid31888470, year = {2019}, author = {Goloshchapov, OV and Olekhnovich, EI and Sidorenko, SV and Moiseev, IS and Kucher, MA and Fedorov, DE and Pavlenko, AV and Manolov, AI and Gostev, VV and Veselovsky, VA and Klimina, KM and Kostryukova, ES and Bakin, EA and Shvetcov, AN and Gumbatova, ED and Klementeva, RV and Shcherbakov, AA and Gorchakova, MV and Egozcue, JJ and Pawlowsky-Glahn, V and Suvorova, MA and Chukhlovin, AB and Govorun, VM and Ilina, EN and Afanasyev, BV}, title = {Long-term impact of fecal transplantation in healthy volunteers.}, journal = {BMC microbiology}, volume = {19}, number = {1}, pages = {312}, pmid = {31888470}, issn = {1471-2180}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been recently approved by FDA for the treatment of refractory recurrent clostridial colitis (rCDI). Success of FTM in treatment of rCDI led to a number of studies investigating the effectiveness of its application in the other gastrointestinal diseases. However, in the majority of studies the effects of FMT were evaluated on the patients with initially altered microbiota. The aim of our study was to estimate effects of FMT on the gut microbiota composition in healthy volunteers and to monitor its long-term outcomes.<br><br>RESULTS: We have performed a combined analysis of three healthy volunteers before and after capsule FMT by evaluating their general condition, adverse clinical effects, changes of basic laboratory parameters, and several immune markers. Intestinal microbiota samples were evaluated by 16S rRNA gene and shotgun sequencing. The data analysis demonstrated profound shift towards the donor microbiota taxonomic composition in all volunteers. Following FMT, all the volunteers exhibited gut colonization with donor gut bacteria and persistence of this effect for almost ∼1 year of observation. Transient changes of immune parameters were consistent with suppression of T-cell cytotoxicity. FMT was well tolerated with mild gastrointestinal adverse events, however, one volunteer developed a systemic inflammatory response syndrome.<br><br>CONCLUSIONS: The FMT leads to significant long-term changes of the gut microbiota in healthy volunteers with the shift towards donor microbiota composition and represents a relatively safe procedure to the recipients without long-term adverse events.}, }
@article {pmid31887116, year = {2019}, author = {Hantschel, J and Weis, S and Schäfer, KH and Menger, MD and Kohl, M and Egert, M and Laschke, MW}, title = {Effect of endometriosis on the fecal bacteriota composition of mice during the acute phase of lesion formation.}, journal = {PloS one}, volume = {14}, number = {12}, pages = {e0226835}, pmid = {31887116}, issn = {1932-6203}, abstract = {Accumulating evidence indicates that there is an interaction between the gut microbiota and endometriotic lesions. The new formation of these lesions is associated with stem cell recruitment, angiogenesis and inflammation, which may affect the composition of the gut microbiota. To test this hypothesis, we herein induced endometriotic lesions by transplantation of uterine tissue fragments from green fluorescent protein (GFP)+ donor mice into the peritoneal cavity of GFP- C57BL/6 wild-type mice. Sham-transplanted animals served as controls. Fecal pellets of the animals were collected 3 days before as well as 7 and 21 days after the induction of endometriosis to analyze the composition of the gut microbiota by means of 16S ribosomal RNA gene sequencing. The transplantation of uterine tissue fragments resulted in the establishment of endometriotic lesions in all analyzed mice. These lesions exhibited a typical histomorphology with endometrial glands surrounded by a vascularized stroma. Due to their bright GFP signal, they could be easily differentiated from the surrounding GFP- host tissue. Bacterial 16S rRNA genes were successfully PCR-amplified from the DNA extracts of all obtained mice fecal samples. However, no significant effect of endometriosis induction on the composition of the bacterial microbiota was detected with our experimental setup. Our findings allow careful speculation that endometriosis in mice does not induce pronounced dysbiosis during the acute phase of lesion formation.}, }
@article {pmid31886921, year = {2019}, author = {Schepper, JD and Collins, F and Rios-Arce, ND and Kang, HJ and Schaefer, L and Gardinier, JD and Raghuvanshi, R and Quinn, RA and Britton, R and Parameswaran, N and McCabe, LR}, title = {Involvement of the Gut Microbiota and Barrier Function in Glucocorticoid-Induced Osteoporosis.}, journal = {Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research}, volume = {}, number = {}, pages = {}, doi = {10.1002/jbmr.3947}, pmid = {31886921}, issn = {1523-4681}, support = {R01 AT007695/AT/NCCIH NIH HHS/United States ; R01 DK101050/DK/NIDDK NIH HHS/United States ; RO1 AT007695/AT/NCCIH NIH HHS/United States ; }, abstract = {Glucocorticoids (GCs) are potent immune-modulating drugs with significant side effects, including glucocorticoid-induced osteoporosis (GIO). GCs directly induce osteoblast and osteocyte apoptosis but also alter intestinal microbiota composition. Although the gut microbiota is known to contribute to the regulation of bone density, its role in GIO has never been examined. To test this, male C57/Bl6J mice were treated for 8 weeks with GC (prednisolone, GC-Tx) in the presence or absence of broad-spectrum antibiotic treatment (ABX) to deplete the microbiota. Long-term ABX prevented GC-Tx-induced trabecular bone loss, showing the requirement of gut microbiota for GIO. Treatment of GC-Tx mice with a probiotic (Lactobacillus reuteri [LR]) prevented trabecular bone loss. Microbiota analyses indicated that GC-Tx changed the abundance of Verrucomicobiales and Bacteriodales phyla and random forest analyses indicated significant differences in abundance of Porphyromonadaceae and Clostridiales operational taxonomic units (OTUs) between groups. Furthermore, transplantation of GC-Tx mouse fecal material into recipient naïve, untreated WT mice caused bone loss, supporting a functional role for microbiota in GIO. We also report that GC caused intestinal barrier breaks, as evidenced by increased serum endotoxin level (2.4-fold), that were prevented by LR and ABX treatments. Enhancement of barrier function with a mucus supplement prevented both GC-Tx-induced barrier leakage and trabecular GIO. In bone, treatment with ABX, LR or a mucus supplement reduced GC-Tx-induced osteoblast and osteocyte apoptosis. GC-Tx suppression of Wnt10b in bone was restored by the LR and high-molecular-weight polymer (MDY) treatments as well as microbiota depletion. Finally, we identified that bone-specific Wnt10b overexpression prevented GIO. Taken together, our data highlight the previously unappreciated involvement of the gut microbiota and intestinal barrier function in trabecular GIO pathogenesis (including Wnt10b suppression and osteoblast and osteocyte apoptosis) and identify the gut as a novel therapeutic target for preventing GIO. © 2019 American Society for Bone and Mineral Research.}, }
@article {pmid31885549, year = {2019}, author = {Wang, Y and Zheng, F and Liu, S and Luo, H}, title = {Research Progress in Fecal Microbiota Transplantation as Treatment for Irritable Bowel Syndrome.}, journal = {Gastroenterology research and practice}, volume = {2019}, number = {}, pages = {9759138}, pmid = {31885549}, issn = {1687-6121}, abstract = {Irritable bowel syndrome is a functional disorder characterized by abdominal pain or discomfort associated with altered bowel habits. Due to the uncertainty of the pathogenesis of IBS and the diversity of its clinical manifestations, IBS cannot be completely cured. Increasing evidence suggests the key role of altered intestinal microbiota in the pathogenesis of IBS. Therefore, attention is being shifted to adjusting the changes in intestinal microbiota to control IBS symptoms. Fecal microbiota transplantation (FMT), antibiotics, probiotics, and synbiotics are currently often employed as treatment for IBS. And FMT is the most significant therapeutic efficacy with the least number of side effects. FMT provides a creative way to restore the abnormal gut microbiome in patients with IBS. But although current clinical studies confirm the effectiveness of FMT in the treatment of IBS, they are short-term studies of small samples, and there is still a lack of large-scale long-term studies. In this paper, we review the intestinal microbiota changes of IBS, the common methods of treating IBS with intestinal microbes, and the research status of FMT for the treatment of IBS. Finally, we put forward some opinions on the future research direction of FMT treatment of IBS.}, }
@article {pmid31880660, year = {2020}, author = {}, title = {Addendum for: 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 = {70}, number = {3}, pages = {404}, doi = {10.1097/MPG.0000000000002601}, pmid = {31880660}, issn = {1536-4801}, }
@article {pmid31879393, year = {2019}, author = {Ichikawa, M and Sujino, T and Kanai, T}, title = {[The Relationship between Gut Microbiome, Immune System, and Cancer].}, journal = {Gan to kagaku ryoho. Cancer &amp; chemotherapy}, volume = {46}, number = {12}, pages = {1807-1813}, pmid = {31879393}, issn = {0385-0684}, mesh = {Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immune System ; }, abstract = {Various microbes having been living in our intestine and forming the gut microbiome. When dysbiosis which is typically characterized by reduced microbial diversity occurs, many types of diseases are triggered in our bodies. Recently, relationship between gut microbiome and our immune function are discovered gradually. From this view point, the gut microbiome may have an influence on cancer medicine such as development, therapy(immune checkpoint blockade or chemotherapy), and therapeutic toxicity. In real clinical practice, this influence is reported in some cases such as colorectal cancer and other malignancies. In the near future, the approach from gut microbiome may be a clue to improve the existent cancer diagnosis and therapy. In addition, the modulation of gut microbiome in itself, for example fecal microbiota transplant(FMT), probiotics, and limited usage of antibiotics, is expected to be hints for cancer medicine, though this is not yet established and further studies are needed.}, }
@article {pmid31877418, year = {2020}, author = {Johnsen, PH and Hilpüsch, F and Valle, PC and Goll, R}, title = {The effect of fecal microbiota transplantation on IBS related quality of life and fatigue in moderate to severe non-constipated irritable bowel: Secondary endpoints of a double blind, randomized, placebo-controlled trial.}, journal = {EBioMedicine}, volume = {51}, number = {}, pages = {102562}, pmid = {31877418}, issn = {2352-3964}, abstract = {BACKGROUND: Severity in irritable bowel syndrome (IBS) is associated to impaired quality of life and fatigue. Fecal microbiota transplantation (FMT) induces significant relief in gastro-intestinal related complaints. The objective was to evaluate the effect of FMT on the secondary endpoints: IBS-related quality of life and fatigue in patients with non-constipated IBS.<br><br>METHOD: In this double-blind randomized placebo-controlled, parallel-group, single-center study, we enrolled patients with non-constipated IBS, defined by the ROME 3 criteria. We randomly assigned participants (2:1) in blocks of six to active or placebo FMT. Responder in fatigue and quality of life were defined as a decrease of 20 points in total Fatigue Impact Scale score, and improvement of 14 points in the IBS-quality of life questionnaire, respectively. In a modified-intention-to-treat population, we excluded participants who did not undergo treatment or who were diagnosed with any other disease by pinch biopsies during the treatment procedure.<br><br>FINDINGS: Between Jan1, and Oct 30, 2015, we recruited 90 participants and randomly assigned them to active treatment (n = 60) or placebo (n = 30). Three participants did not undergo FMT and four were excluded after diagnosis of microscopic colitis, leaving 83 for final modified intention-to-treat analysis (55 in the active treatment group and 28 in the placebo group). Significant improvement in QoL (Odds ratio (OR) 3,801; confidence interval (CI) = 1,309-11,042 p = 0.011) and fatigue (OR = 4,398; CI = 1,175-16,468 and p = 0,020) was found at six months. Absence of other self reported functional disorders and presence of depression at baseline is suggested to predict a lasting effect of FMT in QoL and fatigue, respectively.<br><br>INTERPRETATION: FMT induced significant relief in quality of life and fatigue. Results suggest a lasting effect of FMT in subgroups that should be further investigated in future studies. Funding Helse Nord, Norway and the Norwegian Centre of Rural Medicine, University of Tromsø, Norway.}, }
@article {pmid31876732, year = {2019}, author = {Wei, Y and Li, N and Xing, H and Guo, T and Gong, H and Chen, D}, title = {Effectiveness of fecal microbiota transplantation for severe diarrhea after drug-induced hypersensitivity syndrome.}, journal = {Medicine}, volume = {98}, number = {52}, pages = {e18476}, pmid = {31876732}, issn = {1536-5964}, mesh = {Acute Disease ; Adult ; Diarrhea/etiology/*therapy ; Drug Hypersensitivity Syndrome/*complications ; *Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Microbiome/genetics ; Humans ; Intestine, Small/diagnostic imaging ; Multiple Organ Failure/diagnostic imaging/etiology/therapy ; RNA, Ribosomal, 16S/genetics ; Tomography, X-Ray Computed ; Treatment Outcome ; }, abstract = {The aim of this study was to assess effectiveness of fecal microbiota transplantation (FMT) in treating intestinal failure associated with drug-induced hypersensitivity syndrome (DIHS).A 32-year-old Chinese woman, who developed DIHS-associated multiple organ dysfunction syndrome (MODS) manifesting as combined dysfunction of the intestine, liver, and kidney, was treated with 4 times of FMT at a frequency of once every 6 days. The structure and composition of the patient's fecal microbiota were analyzed by 16S rRNA-based molecular techniques. The clinical outcomes after FMT treatment were assessed by abdominal contrast-enhanced computed tomography (CT), characterization of fecal microbiota, measurement of serum inflammatory markers, and other clinical examinations.After 4 rounds of FMT were administered, the patient showed dramatic improvement in MODS and severe diarrhea with these clinical conditions under control. We consistently observed significant alteration in her gut microbiota, mainly involving considerable enrichment in Firmicutes members and depletion of Proteobacteria opportunistic organisms. Moreover, this reconstituted bacterial community composition correlated with fecal output, T helper cells, and inflammatory markers. Abdominal contrast-enhanced CT scans before and after FMT indicated significant improvement in inflammation and edema within the small intestine and colon of the patient. Notably, after completion of the fourth FMT, the level of inflammation in the intestine and colon had returned to normal. Over 6 months of follow-up, the intestinal mucous remained normal.Our results represent a breakthrough in the clinical management of MODS and suggest new therapeutic avenues to pursue for microbiota-related indications.}, }
@article {pmid31875037, year = {2019}, author = {Heimesaat, MM and Mrazek, K and Bereswill, S}, title = {Murine fecal microbiota transplantation lowers gastrointestinal pathogen loads and dampens pro-inflammatory immune responses in Campylobacter jejuni infected secondary abiotic mice.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {19797}, pmid = {31875037}, issn = {2045-2322}, support = {ZIM, ZF4117908 AJ8//Bundesministerium für Wirtschaft und Energie (Federal Ministry for Economic Affairs and Energy)/ ; ZIM, ZF4117908 AJ8//Bundesministerium für Wirtschaft und Energie (Federal Ministry for Economic Affairs and Energy)/ ; PAC-Campylobacter, IP7/ 01KI1725D//Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (Federal Ministry for Education, Science, Research and Technology)/ ; PAC-Campylobacter, IP7/ 01KI1725D//Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (Federal Ministry for Education, Science, Research and Technology)/ ; }, abstract = {Conventional mice are protected from Campylobacter jejuni infection by the murine host-specific gut microbiota composition. We here addressed whether peroral fecal microbiota transplantation (FMT) might be an antibiotics-independent option to lower even high gastrointestinal C. jejuni loads in the infected vertebrate host. To address this, secondary abiotic mice were generated by broad-spectrum antibiotic treatment and perorally infected with C. jejuni by gavage. One week later, mice were stably colonized with more than 109 C. jejuni and subjected to peroral FMT from murine donors on three consecutive days. Two weeks post-intervention, gastrointestinal C. jejuni loads were up to 7.5 orders of magnitude lower following murine FMT versus mock challenge. Remarkably, FMT reversed C. jejuni induced colonic epithelial apoptosis, but enhanced proliferative and regenerative responses in the colon thereby counteracting pathogenic cell damage. Furthermore, FMT dampened both, innate and adaptive immune cell responses in the large intestines upon C. jejuni infection that were accompanied by less C. jejuni-induced colonic nitric oxide secretion. Our study provides strong evidence that novel probiotic formulations developed as alternative option to FMT in severe intestinal inflammatory morbidities including Clostridoides difficile infection might be effective to treat campylobacteriosis and lower pathogen loads in colonized vertebrates including farm animals.}, }
@article {pmid31872304, year = {2019}, author = {Ocansey, DKW and Wang, L and Wang, J and Yan, Y and Qian, H and Zhang, X and Xu, W and Mao, F}, title = {Mesenchymal stem cell-gut microbiota interaction in the repair of inflammatory bowel disease: an enhanced therapeutic effect.}, journal = {Clinical and translational medicine}, volume = {8}, number = {1}, pages = {31}, pmid = {31872304}, issn = {2001-1326}, support = {81670502//the National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Several investigations affirm that, patients with inflammatory bowel disease (IBD) exhibit dysbiosis characterized by restricted biodiversity and imbalanced bacterial composition intertwined with immune dysregulation. The interaction between stem cells and gut microbiota is a novel and highly promising field that could add up to a better understanding of the gut physiology, as well as therapeutic improvement towards diseases like IBD. Through direct contact or release of products and/or metabolites, gut bacteria regulate gut homeostasis, damage repair, regeneration and differentiation of stem cells. In the same way, mesenchymal stem cells (MSCs) produce similar effects including restoration of gut-microbiome composition. BODY: We reviewed the anti-inflammatory, antimicrobial, pathogenic bacterial clearance, proliferation and tissue remodeling effects of mesenchymal stem cells (MSCs) and fecal microbiota transplantation (FMT) as separate transplants in IBD, and the outcome of the interaction between MSCs and gut microbiota.<br><br>CONCLUSION: The two therapies share several points of connection in therapeutics with enhanced functionalities in their interaction with each other. Focused investigations of MSC-gut bacteria interactions could lead to a novel discovery in therapeutics. We also anticipate an improved clinical remission rate in a combined FMT-MSC transplantation approach in IBD than the current single FMT or MSC approach.}, }
@article {pmid31870137, year = {2019}, author = {Woldeamlak, B and Yirdaw, K and Biadgo, B}, title = {Role of Gut Microbiota in Type 2 Diabetes Mellitus and Its Complications: Novel Insights and Potential Intervention Strategies.}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {74}, number = {6}, pages = {314-320}, doi = {10.4166/kjg.2019.74.6.314}, pmid = {31870137}, issn = {2233-6869}, abstract = {Type 2 diabetes mellitus has become one of the fastest growing public health problems worldwide. The disease is believed to involve a complex process involving genetic susceptibility and environmental factors. The human intestine harbors hundreds of trillions of bacteria, as well as bacteriophage particles, viruses, fungi, and archaea, which constitute a complex and dynamic ecosystem referred to as the gut microbiota. Increasing evidence has indicated changes in the gut microbiota composition or function in type 2 diabetic patients. An analysis of 'dysbiosis' enables the detection of alterations in the specific bacteria, clusters of bacteria, or bacterial functions associated with the occurrence of type 2 diabetes. These bacteria are involved predominantly in the control of inflammation and energy homeostasis. This review attempts to show that the gut microbiota are important factors for the occurrence of type 2 diabetes and are important for the treatment of gut microbiota dysbiosis through bariatric surgery, fecal microbiota transplantation, prebiotics, and probiotics.}, }
@article {pmid31862370, year = {2020}, author = {Yan, T and Nian, T and Liao, Z and Xiao, F and Wu, B and Bi, K and He, B and Jia, Y}, title = {Antidepressant effects of a polysaccharide from okra (Abelmoschus esculentus (L) Moench) by anti-inflammation and rebalancing the gut microbiota.}, journal = {International journal of biological macromolecules}, volume = {144}, number = {}, pages = {427-440}, doi = {10.1016/j.ijbiomac.2019.12.138}, pmid = {31862370}, issn = {1879-0003}, abstract = {The present study aimed to evaluate the antidepressant-like effect of a polysaccharide (OP), which is isolated from okra (Abelmoschus esculentus (L) Moench), in CUMS-induced mice and its possible mechanisms. OPT, FST and TST were employed to examine the anxiety and depressive behavior in CUMS-induced mice and fecal microbiota transplantation (FMT) CUMS-induced mice, while proinflammatory cytokines, TLR4/NF-κB pathway and MAPKs signaling were detected in both CUMS-induced mice and LPS-induced BV2 cells. The results showed that anxiety- and depressive-like behaviors, gut microbiota dysbiosis and changes of SCFAs, and activation of inflammatory reactions in the colon, serum, and hippocampus of CUMS-induced mice, as well as activation of inflammatory reactions in BV2 cells, could be alleviated by the treatment of OP. The mice that were colonized by OP microbiota showed improved anxiety and depressive behaviors and lower inflammatory response. Furthermore, OP inhibited the expression of TLR4, the nuclear translocation of NF-κB and high levels of proinflammatory cytokines, and enhanced the MAPKs signaling, these effects of OP also observed in LPS-induced BV2 cells. Above all, suggested that the potential mechanism of the antidepressant-like effects of OP was closely correlated with the bidirectional communication of microbiota-gut-brain axis via regulation of inflammation response.}, }
@article {pmid31859812, year = {2019}, author = {Lara, A and Espadín, C}, title = {[Considerations should be taken into account to avoid complexities in the transplantation of fecal microbiota.].}, journal = {Revista chilena de infectologia : organo oficial de la Sociedad Chilena de Infectologia}, volume = {36}, number = {5}, pages = {674}, doi = {10.4067/S0716-10182019000500674}, pmid = {31859812}, issn = {0717-6341}, mesh = {*Clostridium Infections ; Colonoscopy ; Fecal Microbiota Transplantation ; Feces ; Humans ; *Microbiota ; Universities ; }, }
@article {pmid31859781, year = {2019}, author = {Quera, R and Sedano, R and Espinoza, R and Rivera, D}, title = {[Transplantation of fecal matter in octogenarian patients with recurrent Clostridioides difficile infection].}, journal = {Revista chilena de infectologia : organo oficial de la Sociedad Chilena de Infectologia}, volume = {36}, number = {4}, pages = {536-540}, doi = {10.4067/S0716-10182019000400536}, pmid = {31859781}, issn = {0717-6341}, mesh = {Aged, 80 and over ; Clostridium Infections/*therapy ; Diarrhea/*microbiology ; *Fecal Microbiota Transplantation ; Female ; Humans ; Recurrence ; }, abstract = {Clostridioides (formerly Clostridium) difficile infection has become a major health problem due to the increase in its incidence, severity, and recurrence. In this last scenario, age over 65 has been associated with a more unfavorable evolution. Risk factors such as the presence of altered immunity, comorbidities, malnutrition, polypharmacy, and changes in the intestinal microbiota would explain this higher risk in this group of patients. On the other hand, fecal microbiota transplantation (FMT) is an effective strategy in the treatment of recurrent Clostridioides difficile infection when standard therapy fails. Recently published guidelines suggest that this strategy can be used from the second recurrence. However, few studies have evaluated the results of the FMT in patients over 65 years old, and for our knowledge, there is limited national experience in this group of patients. We present two cases of TMF in octogenarian patients with a recurrent infection due to Clostridioides difficile, with satisfactory recovery at the long term.}, }
@article {pmid31858856, year = {2020}, author = {Hoffmann-Vold, AM and Fretheim, H and Didriksen, H and Molberg, Ø}, title = {The potential of fecal microbiota transplantation in systemic sclerosis.}, journal = {Expert review of clinical immunology}, volume = {16}, number = {2}, pages = {117-118}, doi = {10.1080/1744666X.2019.1707665}, pmid = {31858856}, issn = {1744-8409}, }
@article {pmid31858698, year = {2019}, author = {Liwinski, T and Elinav, E}, title = {Harnessing the microbiota for therapeutic purposes.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {}, number = {}, pages = {}, doi = {10.1111/ajt.15753}, pmid = {31858698}, issn = {1600-6143}, support = {420943353//Deutsche Forschungsgemeinschaft/ ; }, abstract = {The myriads of microorganisms colonizing the human host (microbiome) affect virtually every aspect of its physiology in health and disease. The past decade witnessed unprecedented advances in microbiome research. The field rapidly transitioned from descriptive studies to deep mechanistic insights into host-microbiome interactions. This offers the opportunity for microbiome-targeted therapeutic manipulation. Currently, several strategies of microbiome-targeted interventions are intensively explored. Best evidence from human randomized clinical trials is available for fecal microbiota transplantation (FMT). However, patient eligibility as well as long-term efficacy and safety are not sufficiently defined. Therefore, there is currently no officially approved indication for FMT. Probiotics (live microorganisms) have long been discussed as a means to aid human health but have yielded varying results. Emerging techniques utilizing microbiota-targeted diets, small microbial molecules, recombinant bacteriophages, and precise control of strain abundance recently yielded promising results but require further investigation. The rapid technological progress of &quot;omics&quot; tools spurs advances in personalized medicine. Understanding and integration of interindividual microbiome variability holds potential to promote personalized preventive and therapeutic approaches. Emerging evidence points towards the microbiome as an important player having an impact on transplantation outcomes. Microbiome-targeted interventions have potential to aid against the many challenges faced by transplant recipients.}, }
@article {pmid31850117, year = {2019}, author = {Vojvodic, A and Peric-Hajzler, Z and Matovic, D and Vojvodic, P and Vlaskovic-Jovicevic, T and Sijan, G and Dimitrijevic, S and Stepic, N and Wollina, U and Badr, BAE and Badawi, A and Goldust, M and Tirant, M and Nguyen, VT and Fioranelli, M and Lotti, T}, title = {Gut Microbiota and the Alteration of Immune Balance in Skin Diseases: From Nutraceuticals to Fecal Transplantation.}, journal = {Open access Macedonian journal of medical sciences}, volume = {7}, number = {18}, pages = {3034-3038}, pmid = {31850117}, issn = {1857-9655}, abstract = {The P.N.E.I. (Psycho-Neuro-Endocrine-Immunology) approach is represented by the interdisciplinary concept of bidirectional cross-talk between the psycho-neuro-endocrine and immune systems, which can influence the immune response. The well-known Gut-Brain Axis and the Gut-Skin Axis can be merged in a bigger network- the Gut-Brain-Skin Axis, with complex regulation by cytokines, neuro-peptides, neuro-hormones and another messenger (signalling) molecules and maybe the most important modulator of the Gut-Brain-Skin Axis/ the gut microbiota. The role of gut bacterial homeostasis is very important, and the homeostatic imbalance of the immune response may be a relevant etiologic/pathophysiologic factor for extra-intestinal and intestinal inflammatory, allergic and autoimmune diseases. The Low Dose Cytokines Medicine (LDM) is an innovative therapeutic approach. It is based on the most advanced knowledge in molecular biology and low dose pharmacology with the primary outcome. The SKA (Sequential Kinetic Activation) technology, codified and standardised by GUNA S.p.a. -Italy- makes the low doses of signalling molecules able to be active even below the minimum dose classically considered as effective and the significative efficacy of orally administered low-dose signalling molecules is the most representative aspect of LDM. The Physiologic Nutraceuticals and the Low Dose Medicine are two of the most promising approaches for the treatment of skin diseases based on the rebalance of the immune response and the recovery of gut dysbiosis.}, }
@article {pmid31846840, year = {2020}, author = {Xu, J and Song, J and Zhang, Y and Wang, Y and Yang, L and Sha, Y and Sun, B and You, N and Tian, X and Lin, R and Wu, Y}, title = {Jinzhi protects lipopolysaccharide-treated mice against mortality by repairing intestinal mucosal barrier damage and intestinal microecology.}, journal = {Biomedicine &amp; pharmacotherapy = Biomedecine &amp; pharmacotherapie}, volume = {123}, number = {}, pages = {109749}, doi = {10.1016/j.biopha.2019.109749}, pmid = {31846840}, issn = {1950-6007}, abstract = {OBJECTIVE: Intestinal mucosal barrier damage is an important mechanism for the development of sepsis and multiple organ dysfunction syndrome. At present, there are no satisfactory and effective methods for the protection of the intestinal mucosal barrier. Jinzhi, the first fecal microbiota transplantation worldwide, is often used to treat critically ill patients; however, the specific mechanism involved in this process remains unclear. The aim of this study was to investigate the therapeutic effect and mechanism of Jinzhi intervention on mice with sepsis induced through treatment with lipopolysaccharide (LPS).<br><br>METHODS: Mice were intraperitoneally injected with LPS to simulate intestinal mucosal barrier function damage in sepsis; intervention was performed through the oral administration of Jinzhi. The effect of Jinzhi on LPS-induced sepsis was analyzed by comparing the vital signs and survival rate of mice under different treatments. Pathological staining and enzyme-linked immunosorbent assay were used to identify the effects of LPS or treatment with Jinzhi on the intestinal mucosal barrier in mice. The effect of LPS or treatment with Jinzhi on the intestinal flora was analyzed via 16S rRNA gene sequencing of ileal contents.<br><br>RESULTS: Immunohistochemistry and enzyme-linked immunosorbent assay showed that treatment with LPS increased levels of inflammatory factors (interleukin-1α, interleukin-6, tumor necrosis factor-α), caspase-3, and caspase-8 in the serum and ileum, and destroyed the tight junction between epithelial cells. Intervention with Jinzhi reduced levels of serum LPS and tumor necrosis factor-α, and repaired the tight junction between epithelial cells. Furthermore, 16S rRNA gene sequencing analysis showed that treatment with Jinzhi improved the diversity and physiological function of the intestinal flora.<br><br>CONCLUSIONS: These results suggest that Jinzhi may be a promising option for the treatment of sepsis caused by LPS, and emphasize that Jinzhi exerts a recovery effect on the imbalance of intestinal flora.}, }
@article {pmid31845054, year = {2020}, author = {Hu, H and Lin, A and Kong, M and Yao, X and Yin, M and Xia, H and Ma, J and Liu, H}, title = {Intestinal microbiome and NAFLD: molecular insights and therapeutic perspectives.}, journal = {Journal of gastroenterology}, volume = {55}, number = {2}, pages = {142-158}, pmid = {31845054}, issn = {1435-5922}, support = {81873098//National Natural Science Foundation of China/ ; 31300716//National Natural Science Foundation of China/ ; 2018ZYYD017//Science and Technology Commission of Hubei Province of China/ ; ZY2019Q003//Health Commission of Hubei Province of China/ ; 2017060201010221//Wuhan Science and Technology Bureau of Hubei Province of China/ ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of dysregulated lipid and glucose metabolism, which is often associated with obesity, dyslipidemia and insulin resistance. In view of the high morbidity and health risks of NAFLD, the lack of effective cure has drawn great attention. In recent years, a line of evidence has suggested a close linkage between the intestine and liver diseases such as NAFLD. We summarized the composition and characteristics of intestinal microbes and reviewed molecular insights into the intestinal microbiome in development and progression of NAFLD. Intestinal microbes mainly include bacteria, archaea, viruses and fungi, and the crosstalk between non-bacterial intestinal microbes and human liver diseases should be paid more attention. Intestinal microbiota imbalance may not only increase the intestinal permeability to gut microbes but also lead to liver exposure to harmful substances that promote hepatic lipogenesis and fibrosis. Furthermore, we focused on reviewing the latest &quot;gut-liver axis&quot;-targeting treatment, including the application of antibiotics, probiotics, prebiotics, synbiotics, farnesoid X receptor agonists, bile acid sequestrants, gut-derived hormones, adsorbents and fecal microbiota transplantation for NAFLD. In this review, we also discussed the potential mechanisms of &quot;gut-liver axis&quot; manipulation and efficacy of these therapeutic strategies for NAFLD treatment.}, }
@article {pmid31842339, year = {2019}, author = {Herremans, KM and Riner, AN and Cameron, ME and Trevino, JG}, title = {The Microbiota and Cancer Cachexia.}, journal = {International journal of molecular sciences}, volume = {20}, number = {24}, pages = {}, pmid = {31842339}, issn = {1422-0067}, abstract = {Cancer cachexia is a multifactorial syndrome defined by weight loss, muscle wasting, and systemic inflammation. It affects the majority of patients with advanced cancer and is associated with poor treatment response, early mortality and decreased quality of life. The microbiota has been implicated in cancer cachexia through pathways of systemic inflammation, gut barrier dysfunction and muscle wasting. The imbalance of the microbiota, known as dysbiosis, has been shown to influence cancer cachexia. Bacteria that play beneficial and detrimental roles in the disease pathogenesis have been identified. The phenotype of cancer cachexia is associated with decreased levels of Lactobacillales and increased levels of Enterobacteriaceae and Parabacteroides. Currently, there are no treatment options that demonstrate increased survival or the quality of life in patients suffering from cancer cachexia. Through the manipulation of beneficial bacteria in the gut microbiota, different treatment options have been explored. Prebiotics and probiotics have been shown to improve outcomes in animal models of cachexia. Expounding on this mechanism, fecal microbiota transplant (FMT) holds promise for a future treatment of cancer cachexia. Further research is necessary to address this detrimental disease process and improve the lives of patients suffering from cancer cachexia.}, }
@article {pmid31839966, year = {2019}, author = {Keller, JJ and Vehreschild, MJ and Hvas, CL and Jørgensen, SM and Kupciskas, J and Link, A and Mulder, CJ and Goldenberg, SD and Arasaradnam, R and Sokol, H and Gasbarrini, A and Hoegenauer, C and Terveer, EM and Kuijper, EJ and Arkkila, P and , }, title = {Stool for fecal microbiota transplantation should be classified as a transplant product and not as a drug.}, journal = {United European gastroenterology journal}, volume = {7}, number = {10}, pages = {1408-1410}, pmid = {31839966}, issn = {2050-6414}, }
@article {pmid31830335, year = {2019}, author = {Hong, AS and Yu, WY and Hong, JM and Cross, CL and Azab, M and Ohning, G and Jayaraj, M}, title = {Proton pump inhibitor in upper gastrointestinal fecal microbiota transplant: A systematic review and analysis.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.14958}, pmid = {31830335}, issn = {1440-1746}, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) is used in recurrent Clostridioides difficile infections. However, protocols are facility dependent, and one variable is whether pre-procedural proton pump inhibitors (PPIs) are given. In theory, PPIs reduce acidity and protect the transplanted microbiome for the most potent dose. We conducted a systematic review to study the effect of PPIs on FMT delivered by upper gastrointestinal (GI) routes.<br><br>METHODS: We searched Pubmed/Medline, Cochrane Library, Embase, Scopus, and Web of Science through December 16, 2018 using variations of keywords &quot;fecal microbiota transplant&quot; and &quot;Clostridium difficile infection.&quot; Two authors independently reviewed 4210 results and found 11 qualifying studies with data on upper GI FMT, use of PPIs, and the rate of treatment failure at follow-up.<br><br>RESULTS: Of 233 included patients, treatment failure occurred in 20.6% of those with use of PPIs versus 22.6% in the group without (relative risk 0.91; confidence interval 0.56-1.50). Limitations include the lack of studies directly comparing outcomes based on use of PPIs and inability to control for possible confounders such as chronic PPI use, amount of stool transplanted, and pre-FMT antibiotics.<br><br>CONCLUSIONS: We did not find evidence supporting a clinically significant benefit from routine use of PPIs in FMT protocol. It is possible that the theoretical benefit from improved survival of transplanted microbiota is offset by negative effects on the microbiome. We suggest that routine use of PPIs in upper GI FMT be reconsidered. Further investigation is needed to optimize protocols for safety and efficacy.}, }
@article {pmid31828683, year = {2019}, author = {Ebrahimzadeh Leylabadlo, H and Ghotaslou, R and Samadi Kafil, H and Feizabadi, MM and Moaddab, SY and Farajnia, S and Sheykhsaran, E and Sanaie, S and Shanehbandi, D and Bannazadeh Baghi, H}, title = {Non-alcoholic fatty liver diseases: from role of gut microbiota to microbial-based therapies.}, journal = {European journal of clinical microbiology &amp; infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10096-019-03746-1}, pmid = {31828683}, issn = {1435-4373}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is the well-known disease of the liver in adults and children throughout the world. The main manifestations related to NAFLD are an unusual storage of lipid in hepatocytes (hepatic steatosis) and progression of inflammation for non-alcoholic steatohepatitis (NASH). NAFLD is described as a multifactorial complication due to the genetic predisposition, metabolic functions, inflammatory, gut microbiota (GM), and environmental factors. The GM dysregulation among these factors is correlated to NAFLD development. In recent decades, advanced microbial profiling methods are continuing to shed light on the nature of the changes in the GM caused by NASH and NAFLD. In the current review, we aim to perform a literature review in different library databases and electronic searches (Science Direct, PubMed, and Google Scholar) which were randomly obtained. This will be done in order to provide an overview of the relation between GM and NAFLD, and the role of prebiotics, probiotics, and fecal microbiota transplantation (FMT), as potential therapeutic challenges for NAFLD.}, }
@article {pmid31827467, year = {2019}, author = {Quaranta, G and Sanguinetti, M and Masucci, L}, title = {Fecal Microbiota Transplantation: A Potential Tool for Treatment of Human Female Reproductive Tract Diseases.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {2653}, pmid = {31827467}, issn = {1664-3224}, abstract = {The gastro-intestinal tract is an extensive organ involved in several activities, with a crucial role in immunity. Billions of commensal and transient microorganisms, known as the gut microbiota, and potential pathogens, which are constantly stimulating intestinal immunity, colonize the intestinal epithelial surface. The gut microbiota may be regarded as analogous to a solid organ with multiple different functions. In the last decade, many studies have demonstrated that intestinal bacteria can be a decisive factor in the health-disease balance of the intestine, and they can also be responsible for illnesses in other locations. For this reason, fecal microbiota transplantation (FMT) represents an important therapeutic option for Clostridium difficile infections and hold promise for different clinical conditions, such as multiple sclerosis, autism, obesity, and other systemic diseases. FMT consists of the infusion of a fecal suspension from a healthy donor to a recipient in order to restore gut flora alterations. Similar to the gut, the female reproductive tract is an example of a very complex biological ecosystem. Recent studies indicate a possible relationship between the gut and female tract microbiota, associating specific intestinal bacteria patterns with genital female diseases, such as polycystic ovary syndrome (PCOS), endometriosis and bacterial vaginosis (BV). FMT could represent a potential innovative treatment option in this field.}, }
@article {pmid31824463, year = {2019}, author = {Freitag, TL and Hartikainen, A and Jouhten, H and Sahl, C and Meri, S and Anttila, VJ and Mattila, E and Arkkila, P and Jalanka, J and Satokari, R}, title = {Minor Effect of Antibiotic Pre-treatment on the Engraftment of Donor Microbiota in Fecal Transplantation in Mice.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {2685}, pmid = {31824463}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI) and is also considered a potential treatment for a wide range of intestinal and systemic diseases. FMT corrects the microbial dysbiosis associated with rCDI, and the engraftment of donor microbiota is likely to play a key role in treatment efficacy. For disease indications other than rCDI, FMT treatment efficacy has been moderate. This may be partly due to stronger resilience of resident host microbiota in patients who do not suffer from rCDI. In rCDI, patients typically have undergone several antibiotic treatments prior to FMT, depleting the microbiota. In this study, we addressed the effect of broad-spectrum antibiotics (Ab) as a pre-treatment to FMT on the engraftment of donor microbiota in recipients. We conducted a pre-clinical study of FMT between two healthy mouse strains, Balb/c as donors and C57BL/6 as recipients, to perform FMT within the same species and to mimic interindividual FMT between human donors and patients. Microbiota composition was assessed with high-throughput 16S rDNA amplicon sequencing. The microbiota of Balb/c and C57BL/6 mice differed significantly, which allowed for the assessment of microbiota transplantation from the donor strain to the recipient. Our results showed that Ab-treatment depleted microbiota in C57BL/6 recipient mice prior to FMT. The diversity of microbiota did not recover spontaneously to baseline levels during 8 weeks after Ab-treatment, but was restored already at 2 weeks in mice receiving FMT. Interestingly, pre-treatment with antibiotics prior to FMT did not increase the overall similarity of the recipient's microbiota to that of the donor's, as compared with mice receiving FMT without Ab-treatment. Pre-treatment with Ab improved the establishment of only a few donor-derived taxa, such as Bifidobacterium, in the recipients, thus having a minor effect on the engraftment of donor microbiota in FMT. In conclusion, pre-treatment with broad-spectrum antibiotics did not improve the overall engraftment of donor microbiota, but did improve the engraftment of specific taxa. These results may inform future therapeutic studies of FMT.}, }
@article {pmid31821444, year = {2019}, author = {Tariq, R and Disbrow, MB and Dibaise, JK and Orenstein, R and Saha, S and Solanky, D and Loftus, EV and Pardi, DS and Khanna, S}, title = {Efficacy of Fecal Microbiota Transplantation for Recurrent C. Difficile Infection in Inflammatory Bowel Disease.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izz299}, pmid = {31821444}, issn = {1536-4844}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is associated with poor outcomes in inflammatory bowel disease (IBD) patients. Data are scarce on efficacy of fecal microbiota transplant (FMT) for recurrent CDI in IBD patients.<br><br>METHODS: We reviewed health records of IBD patients (18 years of age or older) with recurrent CDI who underwent FMT. Outcomes of FMT for CDI were assessed on the basis of symptoms and stool test results.<br><br>RESULTS: We included 145 patients (75 women [51.7%]; median age, 46 years). Median IBD duration was 8 (range, 0-47) years, 36.6% had Crohn disease, 61.4% had ulcerative colitis, and 2.1% had indeterminate colitis. Median number of prior CDI episodes was 3 (range, 3-20), and 61.4% had received vancomycin taper. Diarrhea resolved after FMT in 48 patients (33.1%) without further testing. Ninety-five patients (65.5%) underwent CDI testing owing to post-FMT recurrent diarrhea; 29 (20.0%) had positive results. After FMT, 2 patients received empiric treatment of recurrent CDI without symptom resolution, suggesting IBD was the cause of symptoms. The overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1-51) months. Forty-three patients (29.7%) had planned IBD therapy escalation after CDI resolution; none de-escalated or discontinued IBD therapy. Overall, 7.6% had worsening IBD symptoms after FMT that were treated as new IBD flares. No clinical predictors of FMT failure were identified.<br><br>CONCLUSIONS: Few patients had new IBD flare after FMT. Fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.}, }
@article {pmid31820171, year = {2019}, author = {Chavira, A and Belda-Ferre, P and Kosciolek, T and Ali, F and Dorrestein, PC and Knight, R}, title = {The Microbiome and Its Potential for Pharmacology.}, journal = {Handbook of experimental pharmacology}, volume = {260}, number = {}, pages = {301-326}, doi = {10.1007/164_2019_317}, pmid = {31820171}, issn = {0171-2004}, mesh = {Humans ; *Microbiota ; Neoplasms ; Nervous System Diseases ; Obesity ; Pharmaceutical Preparations/metabolism ; *Precision Medicine ; }, abstract = {The human microbiota (the microscopic organisms that inhabit us) and microbiome (their genes) hold considerable potential for improving pharmacological practice. Recent advances in multi-&quot;omics&quot; techniques have dramatically improved our understanding of the constituents of the microbiome and their functions. The implications of this research for human health, including microbiome links to obesity, drug metabolism, neurological diseases, cancer, and many other health conditions, have sparked considerable interest in exploiting the microbiome for targeted therapeutics. Links between microbial pathways and disease states further highlight a rich potential for companion diagnostics and precision medicine approaches. For example, the success of fecal microbiota transplantation to treat Clostridium difficile infection has already started to redefine standard of care with a microbiome-directed therapy. In this review we briefly discuss the nature of human microbial ecosystems and with pathologies and biological processes linked to the microbiome. We then review emerging computational metagenomic, metabolomic, and wet lab techniques researchers are using today to learn about the roles host-microbial interactions have with respect to pharmacological purposes and vice versa. Finally, we describe how drugs affect the microbiome, how the microbiome can impact drug response in different people, and the potential of the microbiome itself as a source of new therapeutics.}, }
@article {pmid31819862, year = {2019}, author = {Niina, A and Kibe, R and Suzuki, R and Yuchi, Y and Teshima, T and Matsumoto, H and Kataoka, Y and Koyama, H}, title = {Improvement in Clinical Symptoms and Fecal Microbiome After Fecal Microbiota Transplantation in a Dog with Inflammatory Bowel Disease.}, journal = {Veterinary medicine (Auckland, N.Z.)}, volume = {10}, number = {}, pages = {197-201}, pmid = {31819862}, issn = {2230-2034}, abstract = {Purpose: Recently, fecal microbiota transplantation (FMT) has been tested in veterinary medicine as a treatment option for multiple gastrointestinal (GI) diseases, such as inflammatory bowel disease (IBD). However, there are no reports of changes in the microbial diversity of fecal microbiome after treatment with FMT in canine IBD cases. Moreover, little is known about the long-term efficacy and safety of FMT treatment for dogs. Herein, we present a case of canine intractable IBD treated with repeated, long-term FMT.<br><br>Patients and methods: The patient was a 10-year-old, neutered, male, 4-kg Toy Poodle with a prolonged history of vomiting and diarrhea. Fecal examination for pathogens was negative. Despite treatment with multiple antibacterial and antidiarrheal agents, the patient showed no improvement. Endoscopic mucus sampling diagnosed a case of lymphocytic-plasmacytic duodenitis, ie, idiopathic IBD. Eventually, we performed periodic, long-term fecal microbiota transplantation of fresh donor feces collected from a 4-year-old, 32.8-kg, neutered male Golden Retriever by rectal enema. Additionally, we performed 16S rRNA sequence analysis, before and after FMT, to evaluate the microbiome diversity.<br><br>Results: Fecal microbiome diversity after FMT resembled that of the healthy donor dog's fecal microbiome, before FMT, which led us to conclude that the fecal microbiome in our patient normalized with FMT. Moreover, the clinical symptoms improved remarkably with regard to the changes in the fecal microbiome. Additionally, we noted no observable side effects during FMT treatment.<br><br>Conclusion: This report indicates the efficacy and safety of long-term, periodic FMT for a case of canine IBD based on attenuation of clinical symptoms and changes in fecal microbiome diversity. Therefore, FMT could be chosen as a treatment option for IBD in canines in the future.}, }
@article {pmid31819762, year = {2019}, author = {Jia, Q and Li, H and Zhou, H and Zhang, X and Zhang, A and Xie, Y and Li, Y and Lv, S and Zhang, J}, title = {Role and Effective Therapeutic Target of Gut Microbiota in Heart Failure.}, journal = {Cardiovascular therapeutics}, volume = {2019}, number = {}, pages = {5164298}, pmid = {31819762}, issn = {1755-5922}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Bacteria/drug effects/metabolism/*pathogenicity ; Bacterial Translocation ; Diet, Healthy ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Heart Failure/metabolism/microbiology/physiopathology/*therapy ; Host-Pathogen Interactions ; Humans ; Intestines/drug effects/*microbiology ; Probiotics/therapeutic use ; Treatment Outcome ; }, abstract = {Although the mechanism of the occurrence and development of heart failure has been continuously explored in the past ten years, the mortality and readmission rate of heart failure is still very high. Modern studies have shown that gut microbiota is associated with a variety of cardiovascular diseases, among which the study of gut microbiota and heart failure attracts particular attention. Therefore, understanding the role of gut microbiota in the occurrence and development of heart failure will help us further understand the pathogenesis of heart failure and provide new ideas for its treatment. This paper introduced intestinal flora and its metabolites, summarized the changes of intestinal flora in patients with heart failure, clarified that intestinal barrier damage and bacterial translocation induced inflammation and immune response aggravated heart failure, and altered intestinal microflora affected various metabolic pathways including trimethylamine/TMAO, SCFA, and Bile acid pathway leads to heart failure. At the same time, regulating intestinal microflora through diet, probiotics, antibiotics, fecal transplantation and microbial enzyme inhibitors has grown up to be a potential treatment for many metabolic disorders.}, }
@article {pmid31819450, year = {2019}, author = {Liang, W and Huang, Y and Tan, X and Wu, J and Duan, J and Zhang, H and Yin, B and Li, Y and Zheng, P and Wei, H and Xie, P}, title = {Alterations Of Glycerophospholipid And Fatty Acyl Metabolism In Multiple Brain Regions Of Schizophrenia Microbiota Recipient Mice.}, journal = {Neuropsychiatric disease and treatment}, volume = {15}, number = {}, pages = {3219-3229}, pmid = {31819450}, issn = {1176-6328}, abstract = {Background: Schizophrenia is a debilitating psychiatric disorder characterized by molecular and anatomical abnormalities of multiple brain regions. Our recent study showed that dysbiosis of the gut microbiota contributes to the onset of schizophrenia-relevant behaviors, but the underlying mechanisms remain largely unknown.<br><br>Purpose: This study aimed to investigate how gut microbiota shapes metabolic signatures in multiple brain regions of schizophrenia microbiota recipient mice.<br><br>Methods: Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) were used to compare the metabolic signatures in the cortex, cerebellum and striatum of schizophrenia microbiota and healthy microbiota recipient mice. Enrichment analysis was further conducted to uncover the crucial metabolic pathways related to schizophrenia-relevant behaviors.<br><br>Results: We found that the metabolic phenotypes of these three regions were substantially different in schizophrenia microbiota recipient mice from those in healthy microbiota recipient mice. In total, we identified 499 differential metabolites that could discriminate the two groups in the three brain regions. These differential metabolites were mainly involved in glycerophospholipid and fatty acyl metabolism. Moreover, we found four of fatty acyl metabolites that were consistently altered in the three brain regions.<br><br>Conclusion: Taken together, our study suggests that alterations of glycerophospholipid and fatty acyl metabolism are implicated in the onset of schizophrenia-relevant behaviors, which may provide a new understanding of the etiology of schizophrenia.}, }
@article {pmid31817895, year = {2019}, author = {Moron, R and Galvez, J and Colmenero, M and Anderson, P and Cabeza, J and Rodriguez-Cabezas, ME}, title = {The Importance of the Microbiome in Critically Ill Patients: Role of Nutrition.}, journal = {Nutrients}, volume = {11}, number = {12}, pages = {}, pmid = {31817895}, issn = {2072-6643}, support = {PI-0206-2016//Junta de Andalucia/ ; }, abstract = {Critically ill patients have an alteration in the microbiome in which it becomes a disease-promoting pathobiome. It is characterized by lower bacterial diversity, loss of commensal phyla, like Firmicutes and Bacteroidetes, and a domination of pathogens belonging to the Proteobacteria phylum. Although these alterations are multicausal, many of the treatments administered to these patients, like antibiotics, play a significant role. Critically ill patients also have a hyperpermeable gut barrier and dysregulation of the inflammatory response that favor the development of the pathobiome, translocation of pathogens, and facilitate the emergence of sepsis. In order to restore the homeostasis of the microbiome, several nutritional strategies have been evaluated with the aim to improve the management of critically ill patients. Importantly, enteral nutrition has proven to be more efficient in promoting the homeostasis of the gut microbiome compared to parenteral nutrition. Several nutritional therapies, including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation, are currently being used, showing variable results, possibly due to the unevenness of clinical trial conditions and the fact that the beneficial effects of probiotics are specific to particular species or even strains. Thus, it is of great importance to better understand the mechanisms by which nutrition and supplement therapies can heal the microbiome in critically ill patients in order to finally implement them in clinical practice with optimal safety and efficacy.}, }
@article {pmid31813093, year = {2019}, author = {Zhang, X and Tian, H and Chen, Q and Qin, H and Li, N}, title = {Fecal microbiota transplantation: standardization or diversification?.}, journal = {Science China. Life sciences}, volume = {62}, number = {12}, pages = {1714-1716}, doi = {10.1007/s11427-019-1592-8}, pmid = {31813093}, issn = {1869-1889}, }
@article {pmid31811801, year = {2020}, author = {Janket, SJ and Ackerson, LK and Diamandis, EP}, title = {Potential risks in fecal microbiota transplantation.}, journal = {Clinical chemistry and laboratory medicine}, volume = {58}, number = {4}, pages = {e95}, doi = {10.1515/cclm-2019-1076}, pmid = {31811801}, issn = {1437-4331}, }
@article {pmid31811292, year = {2019}, author = {Sun, Y and Baptista, LC and Roberts, LM and Jumbo-Lucioni, P and McMahon, LL and Buford, TW and Carter, CS}, title = {The Gut Microbiome as a Therapeutic Target for Cognitive Impairment.}, journal = {The journals of gerontology. Series A, Biological sciences and medical sciences}, volume = {}, number = {}, pages = {}, doi = {10.1093/gerona/glz281}, pmid = {31811292}, issn = {1758-535X}, abstract = {Declining cognitive functions in older individuals have enormous emotional, clinical and public health consequences. Thus therapeutics for preserving function and keeping older adults living independently are imperative. Aging is associated dysbiosis, defined as a loss of number and diversity in gut microbiota, which has been linked with various aspects of cognitive functions. Therefore, the gut microbiome has the potential to be an important therapeutic target for symptoms of cognitive impairment. In this review, we summarize the current literature regarding the potential for gut-targeted therapeutic strategies for prevention/treatment of the symptoms of cognitive impairment. Specifically, we discuss four primary therapeutic strategies: wild-type and genetically modified probiotics, fecal microbiota transplantation, physical exercise, and high-fiber diets and specifically link these therapies to reducing inflammation. These strategies may hold promise as treatment paradigms symptoms related to cognitive impairment.}, }
@article {pmid31808861, year = {2019}, author = {Severyn, CJ and Brewster, R and Andermann, TM}, title = {Microbiota modification in hematology: still at the bench or ready for the bedside?.}, journal = {Hematology. American Society of Hematology. Education Program}, volume = {2019}, number = {1}, pages = {303-314}, pmid = {31808861}, issn = {1520-4383}, abstract = {Growing evidence suggests that human microbiota likely influence diverse processes including hematopoiesis, chemotherapy metabolism, and efficacy, as well as overall survival in patients with hematologic malignancies and other cancers. Both host genetic susceptibility and host-microbiota interactions may impact cancer risk and response to treatment; however, microbiota have the potential to be uniquely modifiable and accessible targets for treatment. Here, we focus on strategies to modify microbiota composition and function in patients with cancer. First, we evaluate the use of fecal microbiota transplant to restore microbial equilibrium following perturbation by antibiotics and chemotherapy, and as a treatment of complications of hematopoietic stem cell transplantation (HSCT), such as graft-versus-host disease and colonization with multidrug-resistant organisms. We then address the potential use of both probiotics and dietary prebiotic compounds in targeted modulation of the microbiota intended to improve outcomes in hematologic diseases. With each type of therapy, we highlight the role that abnormal, or dysbiotic, microbiota play in disease, treatment efficacy, and toxicity and evaluate their potential promise as emerging strategies for microbiota manipulation in patients with hematologic malignancies and in those undergoing HSCT.}, }
@article {pmid31808596, year = {2020}, author = {Mohammed, Y and Kootte, RS and Kopatz, WF and Borchers, CH and Büller, HR and Versteeg, HH and Nieuwdorp, M and van Mens, TE}, title = {The intestinal microbiome potentially affects thrombin generation in human subjects.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {18}, number = {3}, pages = {642-650}, doi = {10.1111/jth.14699}, pmid = {31808596}, issn = {1538-7836}, support = {016.146.327//ZONMW-VIDI grant/ ; //Amsterdam Cardiovascular Sciences MD/PhD grant/ ; //Dutch Heart Foundation CVON IN CONTROL Young Talent Grant 2013/ ; 204PRO//Genome Canada and Genome British Columbia/ ; 214PRO//Genome Canada and Genome British Columbia/ ; //Novo Nordisk Foundation GUT-MMM grant 2016/ ; //Le Ducq consortium grant 17CVD01/ ; }, abstract = {BACKGROUND: The intestinal microbiome plays a versatile role in the etiology of arterial thrombosis. In venous thrombosis, driven chiefly by plasma coagulation, no such role has yet been established. We hypothesized that the intestinal microbiome composition affects coagulation in humans.<br><br>METHODS: We used healthy donor fecal microbiota transplant (FMT) to experimentally change the microbiome composition in metabolic syndrome patients. Thirty-five subjects were randomized in a blinded fashion to healthy donor FMT or autologous FMT as a control in a 2:1 ratio. We measured thrombin generation at baseline and after 6 weeks using automated calibrated thrombinography, and we determined plasma abundance of 32 coagulation related proteins using a targeted mass spectrometry-based quantitative proteomics assay with heavy labeled internal standards.<br><br>RESULTS: Healthy donor FMT prolonged the thrombinography lag time (median delta 0.0 versus 0.25 minutes, P = .039). The other thrombinography parameters showed no significant difference. Unsupervised cluster analysis suggested overall downregulation of coagulation related plasma proteins in subject clusters containing predominantly subjects that had a metabolic response to healthy donor FMT. FMT treatment status itself showed no clear clustering pattern with up- or downregulation, however, and proteins did not cluster according to an apparent biological grouping.<br><br>DISCUSSION: A single healthy donor FMT tends to modestly suppress the onset thrombin generation in metabolic syndrome patients, representing initial proof-of-principle that the intestinal microbiota composition might affect the coagulation system in humans. The findings merit external validation as a role for intestinal microbiota in coagulation can have clinically important implications.}, }
@article {pmid31806059, year = {2020}, author = {Vaughn, VM and Greene, MT and Ratz, D and Fowler, KE and Krein, SL and Flanders, SA and Dubberke, ER and Saint, S and Patel, PK}, title = {Antibiotic stewardship teams and Clostridioides difficile practices in United States hospitals: A national survey in The Joint Commission antibiotic stewardship standard era.}, journal = {Infection control and hospital epidemiology}, volume = {41}, number = {2}, pages = {143-148}, doi = {10.1017/ice.2019.313}, pmid = {31806059}, issn = {1559-6834}, abstract = {OBJECTIVE: Clostridioides difficile infection (CDI) can be prevented through infection prevention practices and antibiotic stewardship. Diagnostic stewardship (ie, strategies to improve use of microbiological testing) can also improve antibiotic use. However, little is known about the use of such practices in US hospitals, especially after multidisciplinary stewardship programs became a requirement for US hospital accreditation in 2017. Thus, we surveyed US hospitals to assess antibiotic stewardship program composition, practices related to CDI, and diagnostic stewardship.<br><br>METHODS: Surveys were mailed to infection preventionists at 900 randomly sampled US hospitals between May and October 2017. Hospitals were surveyed on antibiotic stewardship programs; CDI prevention, treatment, and testing practices; and diagnostic stewardship strategies. Responses were compared by hospital bed size using weighted logistic regression.<br><br>RESULTS: Overall, 528 surveys were completed (59% response rate). Almost all (95%) responding hospitals had an antibiotic stewardship program. Smaller hospitals were less likely to have stewardship team members with infectious diseases (ID) training, and only 41% of hospitals met The Joint Commission accreditation standards for multidisciplinary teams. Guideline-recommended CDI prevention practices were common. Smaller hospitals were less likely to use high-tech disinfection devices, fecal microbiota transplantation, or diagnostic stewardship strategies.<br><br>CONCLUSIONS: Following changes in accreditation standards, nearly all US hospitals now have an antibiotic stewardship program. However, many hospitals, especially smaller hospitals, appear to struggle with access to ID expertise and with deploying diagnostic stewardship strategies. CDI prevention could be enhanced through diagnostic stewardship and by emphasizing the role of non-ID-trained pharmacists and clinicians in antibiotic stewardship.}, }
@article {pmid31803633, year = {2019}, author = {He, Y and Li, X and Yu, H and Ge, Y and Liu, Y and Qin, X and Jiang, M and Wang, X}, title = {The Functional Role of Fecal Microbiota Transplantation on Dextran Sulfate Sodium-Induced Colitis in Mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {393}, pmid = {31803633}, issn = {2235-2988}, abstract = {Increasingly studies revealed that dysbiosis of gut microbiota plays a pivotal role in the pathogenesis of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) has drawn more and more attention and become an important therapeutic approach. This study aims to examine the facts about the effective components and look into potential mechanisms of FMT. Colitis was induced by 3% (w/v) dextran sulfate sodium (DSS) in drinking water for 7 days. Colitis mice were administered by oral gavage with fecal suspension, fecal supernatant, fecal bacteria, or boiling-killed fecal bacteria from healthy controls and the disease activity index was monitored daily. On the seventh day, mice were euthanized. The length, histological score, parameters related to inflammation, gut barrier functions of the colon, activities of digestive protease and β-glucuronidase in feces were measured. All of the four fecal components showed certain degree of efficacy in DSS-induced colitis, while transplantation of fecal suspension showed the most potent effect as demonstrated by less body weight loss, lower disease activity scores, more expression of tight junction proteins and TRAF6 and IκBα, less expression of TNF-α, IL-1β, IL-10, TLR-4, and MyD88 in gut tissue, as well as restoration of fecal β-glucuronidase and decreases in fecal digestive proteases. These results provide a novel insight into the possible mechanism of FMT and may help to improve and optimize clinical use of FMT.}, }
@article {pmid31803631, year = {2019}, author = {Yin, A and Luo, Y and Chen, W and He, M and Deng, JH and Zhao, N and Cao, L and Wang, L}, title = {FAM96A Protects Mice From Dextran Sulfate Sodium (DSS)-Induced Colitis by Preventing Microbial Dysbiosis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {381}, pmid = {31803631}, issn = {2235-2988}, abstract = {Family with sequence similarity 96 member A (FAM96A) is an evolutionarily conserved intracellular protein that is involved in the maturation of the Fe/S protein, iron regulatory protein 1 (IRP1), and the mitochondria-related apoptosis of gastrointestinal stromal tumor cells. In this study, we used a mouse model of chemically induced colitis to investigate the physiological role of FAM96A in intestinal homeostasis and inflammation. At baseline, colons from Fam96a-/- mice exhibited microbial dysbiosis, dysregulated epithelial cell turnover, an increased number of goblet cells, and disordered tight junctions with functional deficits affecting intestinal permeability. After cohousing, the differences between wild-type and Fam96a-/- colons were abrogated, suggesting that FAM96A affects colonic epithelial cells in a microbiota-dependent manner. Fam96a deficiency in mice resulted in increased susceptibility to dextran sulfate sodium (DSS)-induced colitis. Importantly, the colitogenic activity of Fam96a-/- intestinal microbiota was transferable to wild-type littermate mice via fecal microbial transplantation (FMT), leading to exacerbation of DSS-induced colitis. Taken together, our data indicate that FAM96A helps to maintain colonic homeostasis and protect against DSS-induced colitis by preventing gut microbial dysbiosis. This study used gene knockout animals to help to understand the in vivo effects of the Fam96a gene for the first time and provides new evidence regarding host-microbiota interactions.}, }
@article {pmid31798539, year = {2019}, author = {Wang, Z and Hua, W and Li, C and Chang, H and Liu, R and Ni, Y and Sun, H and Li, Y and Wang, X and Hou, M and Liu, Y and Xu, Z and Ji, M}, title = {Protective Role of Fecal Microbiota Transplantation on Colitis and Colitis-Associated Colon Cancer in Mice Is Associated With Treg Cells.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {2498}, pmid = {31798539}, issn = {1664-302X}, abstract = {Colitis-associated cancer (CAC) is the most serious outcome of inflammatory bowel disease, which has an alteration of commensal intestinal microbiota. However, the role of intestinal microbiota on CAC progression is not well-understood. Fecal microbiota transplantation (FMT) was used for treating murine azoxymethane-dextran sodium sulfate (AOM-DSS) model of CAC. Composition of gut microbiota during FMT treatment was analyzed. RT-PCR and ELISA were used to detect the inflammatory factors, and immunofluorescence was applied to examine the phospho-nuclear factor (NF)-κB p65/p100 and Ki67-positive cells in the colons. In addition, flow cytometry was performed to analyze the immune cell after FMT treatment. Rehabilitation of the intestinal microbiota by FMT restored both the ratio and diversity of microbiota during CAC progression. Remarkably, a favorable morphometric outcome characterized by decreased tumor load and size was observed in CAC mice with FMT treatment. In addition, an anti-inflammatory function of FMT was demonstrated by decreasing pro-inflammatory factors but increasing anti-inflammatory factors through inhibiting canonical NF-κB activity and cellular proliferation in colons of CAC mice. The expression of CD4+CD25+Foxp3+ regulatory T cells (Tregs) was significantly increased after FMT treatment in CAC mice, but not T helper (Th)1/2/17 cells. Our study aids in the understanding of CAC pathogenesis and reveals a previously unrecognized role for FMT in the treatment of CAC through restoring the intestinal microbiota and inducing regulatory T cells.}, }
@article {pmid31797927, year = {2019}, author = {Magruder, M and Sholi, AN and Gong, C and Zhang, L and Edusei, E and Huang, J and Albakry, S and Satlin, MJ and Westblade, LF and Crawford, C and Dadhania, DM and Lubetzky, M and Taur, Y and Littman, E and Ling, L and Burnham, P and De Vlaminck, I and Pamer, E and Suthanthiran, M and Lee, JR}, title = {Gut uropathogen abundance is a risk factor for development of bacteriuria and urinary tract infection.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {5521}, pmid = {31797927}, issn = {2041-1723}, support = {K23 AI124464/AI/NIAID NIH HHS/United States ; R21 AI133331/AI/NIAID NIH HHS/United States ; R37 AI051652/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/classification/*genetics ; Bacterial Infections/*microbiology ; Bacteriuria/etiology/microbiology/urine ; DNA, Bacterial/analysis/*genetics ; Escherichia coli Infections/etiology/microbiology ; Feces/microbiology ; Gastrointestinal Microbiome/genetics ; Humans ; Kidney Transplantation/adverse effects/methods ; RNA, Ribosomal, 16S/*genetics ; Risk Factors ; Urinary Tract Infections/etiology/*microbiology/urine ; }, abstract = {The origin of most bacterial infections in the urinary tract is often presumed to be the gut. Herein, we investigate the relationship between the gut microbiota and future development of bacteriuria and urinary tract infection (UTI). We perform gut microbial profiling using 16S rRNA gene deep sequencing on 510 fecal specimens from 168 kidney transplant recipients and metagenomic sequencing on a subset of fecal specimens and urine supernatant specimens. We report that a 1% relative gut abundance of Escherichia is an independent risk factor for Escherichia bacteriuria and UTI and a 1% relative gut abundance of Enterococcus is an independent risk factor for Enterococcus bacteriuria. Strain analysis establishes a close strain level alignment between species found in the gut and in the urine in the same subjects. Our results support a gut microbiota-UTI axis, suggesting that modulating the gut microbiota may be a potential novel strategy to prevent UTIs.}, }
@article {pmid31789724, year = {2020}, author = {Canakis, A and Haroon, M and Weber, HC}, title = {Irritable bowel syndrome and gut microbiota.}, journal = {Current opinion in endocrinology, diabetes, and obesity}, volume = {27}, number = {1}, pages = {28-35}, doi = {10.1097/MED.0000000000000523}, pmid = {31789724}, issn = {1752-2978}, abstract = {PURPOSE OF REVIEW: To provide an overview of recent studies exploring the gut microbiota in pathogenesis and treatment of irritable bowel syndrome (IBS).<br><br>RECENT FINDINGS: Primary bacterial gut disturbances have been linked to the development and severity of IBS. Dysbiosis, or alteration in the normal intestinal flora, modulates intestinal permeability, inflammation, gut motility and likely quality of life. These biomechanical changes are associated with enteric and central nervous system processing as well. When compared to healthy controls, IBS patients display poor quality of life measures and are at increased risk of depression and anxiety. The severity of psychological and gastrointestinal symptoms in IBS has been linked with a distinct intestinal microbiota signature. Efforts to modulate intestinal dysbiosis in IBS have shown little improvement in large systematic reviews. The low FODMAP diet reduces bacteria, such as Bifidobacterum and Actinobacteria. Although rifaximin improves symptoms, it may only stimulate a transient effect on the gut microbiota. Fecal microbiota transplant does not provide prolonged symptom relief in IBS.<br><br>SUMMARY: This review elucidates recent advances in IBS and the gut microbiota. Microbiota changes are one underlying factor in perpetuating global IBS symptoms. The opportunity to exploit this disturbance through treatment modalities requires further investigation.}, }
@article {pmid31787855, year = {2019}, author = {Grinspan, A}, title = {Fecal Microbiota Transplantation in Inflammatory Bowel Disease Patients With Clostridium difficile Infection.}, journal = {Gastroenterology &amp; hepatology}, volume = {15}, number = {9}, pages = {481-483}, pmid = {31787855}, issn = {1554-7914}, }
@article {pmid31786155, year = {2020}, author = {Liu, Y and Wang, Y and Ni, Y and Cheung, CKY and Lam, KSL and Wang, Y and Xia, Z and Ye, D and Guo, J and Tse, MA and Panagiotou, G and Xu, A}, title = {Gut Microbiome Fermentation Determines the Efficacy of Exercise for Diabetes Prevention.}, journal = {Cell metabolism}, volume = {31}, number = {1}, pages = {77-91.e5}, doi = {10.1016/j.cmet.2019.11.001}, pmid = {31786155}, issn = {1932-7420}, abstract = {Exercise is an effective strategy for diabetes management but is limited by the phenomenon of exercise resistance (i.e., the lack of or the adverse response to exercise on metabolic health). Here, in 39 medication-naive men with prediabetes, we found that exercise-induced alterations in the gut microbiota correlated closely with improvements in glucose homeostasis and insulin sensitivity (clinicaltrials.gov entry NCT03240978). The microbiome of responders exhibited an enhanced capacity for biosynthesis of short-chain fatty acids and catabolism of branched-chain amino acids, whereas those of non-responders were characterized by increased production of metabolically detrimental compounds. Fecal microbial transplantation from responders, but not non-responders, mimicked the effects of exercise on alleviation of insulin resistance in obese mice. Furthermore, a machine-learning algorithm integrating baseline microbial signatures accurately predicted personalized glycemic response to exercise in an additional 30 subjects. These findings raise the possibility of maximizing the benefits of exercise by targeting the gut microbiota.}, }
@article {pmid31782606, year = {2020}, author = {Herndon, CC and Wang, YP and Lu, CL}, title = {Targeting the gut microbiota for the treatment of irritable bowel syndrome.}, journal = {The Kaohsiung journal of medical sciences}, volume = {36}, number = {3}, pages = {160-170}, doi = {10.1002/kjm2.12154}, pmid = {31782606}, issn = {2410-8650}, abstract = {Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder that affects an estimated 11% of people across the world. IBS patients are one of the largest subgroups seen in gastroenterology clinics, exhibit a lesser quality of life, and take greater use of the healthcare system. The exact etiology of IBS remains uncertain. Alterations in the gut microbiome may characterize apotential mechanism in the pathogenesis of IBS. This hypothesis is paralleled by rodent models in which manipulation of the gut microbiota leads to disturbed physiological functions along the brain-gut axis. Recent research in IBS treatments has redirected its focus towards gu microbiome based therapeutics. In this review, we discuss potential roles of enteric bacteria in the pathogenesis of IBS and its comorbidities. We then explore the manipulation of the enteric microbiota by prebiotics, probiotics, antibiotics, dietary changes, and fecal microbiota transfer. We also discuss the positive and negative effects of these therapeutics on IBS symptoms.}, }
@article {pmid31779704, year = {2019}, author = {Wang, W and Zhai, S and Xia, Y and Wang, H and Ruan, D and Zhou, T and Zhu, Y and Zhang, H and Zhang, M and Ye, H and Ren, W and Yang, L}, title = {Ochratoxin A induces liver inflammation: involvement of intestinal microbiota.}, journal = {Microbiome}, volume = {7}, number = {1}, pages = {151}, pmid = {31779704}, issn = {2049-2618}, abstract = {BACKGROUND: Ochratoxin A (OTA) is a widespread mycotoxin and induces liver inflammation to human and various species of animals. The intestinal microbiota has critical importance in liver inflammation; however, it remains to know whether intestinal microbiota mediates the liver inflammation induced by OTA. Here, we treated ducklings with oral gavage of OTA (235 μg/kg body weight) for 2 weeks. Then, the microbiota in the cecum and liver were analyzed with 16S rRNA sequencing, and the inflammation in the liver was analyzed. To explore the role of intestinal microbiota in OTA-induced liver inflammation, intestinal microbiota was cleared with antibiotics and fecal microbiota transplantation was conducted.<br><br>RESULTS: Here, we find that OTA treatment in ducks altered the intestinal microbiota composition and structure [e.g., increasing the relative abundance of lipopolysaccharides (LPS)-producing Bacteroides], and induced the accumulation of LPS and inflammation in the liver. Intriguingly, in antibiotic-treated ducks, OTA failed to induce these alterations in the liver. Notably, with the fecal microbiota transplantation (FMT) program, in which ducks were colonized with intestinal microbiota from control or OTA-treated ducks, we elucidated the involvement of intestinal microbiota, especially Bacteroides, in liver inflammation induced by OTA.<br><br>CONCLUSIONS: These results highlight the role of gut microbiota in OTA-induced liver inflammation and open a new window for novel preventative or therapeutic intervention for mycotoxicosis.}, }
@article {pmid31775486, year = {2019}, author = {Wang, Q and Fu, YW and Wang, YQ and Ai, H and Yuan, FF and Wei, XD and Song, YP}, title = {[Fecal microbiota transplantation for patients with refractory diarrhea after allogeneic hematopoietic stem cell transplantation].}, journal = {Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi}, volume = {40}, number = {10}, pages = {853-855}, doi = {10.3760/cma.j.issn.0253-2727.2019.10.011}, pmid = {31775486}, issn = {0253-2727}, mesh = {Diarrhea/etiology/*therapy ; *Fecal Microbiota Transplantation ; *Graft vs Host Disease ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; *Leukemia, Myeloid, Acute ; }, abstract = {Objective: To explore the availability and safety of fecal microbiota transplantation for patients with refractory diarrhea after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Four acute leukemia patients suffered from refractory diarrhea after allo-HSCT. One of them was refractory intestinal infection, the others were intestinal graft versus host disease. One or two doses of fecal microbiota, 3.4-6.0 U for one dose, were infused via nasal-jejunal tube. The curative effect and side effects were reviewed. Results: Three cases achieved complete remission while 1 was stable disease. The side effects included fever, abdominal pain and diarrhea, which all were Ⅰ grade. Conclusion: Fecal microbiota transplantation was effective and safe for refractory diarrhea after allo-HSCT.}, }
@article {pmid31772709, year = {2019}, author = {Lv, WJ and Wu, XL and Chen, WQ and Li, YF and Zhang, GF and Chao, LM and Zhou, JH and Guo, A and Liu, C and Guo, SN}, title = {The Gut Microbiome Modulates the Changes in Liver Metabolism and in Inflammatory Processes in the Brain of Chronic Unpredictable Mild Stress Rats.}, journal = {Oxidative medicine and cellular longevity}, volume = {2019}, number = {}, pages = {7902874}, pmid = {31772709}, issn = {1942-0994}, abstract = {Generally, depression is the result of complex gene-environment interactions. Recent studies have showed that the gut microbiota can affect brain function through the microbiota-gut-brain axis. However, the underlying mechanism of the microbiota and potential influence of depression remain elusive. We aimed to determine how gut microbiome contributes to the process of depression and further influences the host. Chronic unpredictable mild stress (CUMS) is used to establish a depression model. Fecal microbiota transplant (FMT) is applied to illustrate that depression can be transmitted via microbiota, and metabolism of liver analysis is applied to demonstrate further influence to the liver. We also analyzed the astrocyte activation in the brain by immunofluorescence (IF). Here, we show that the structure of the gut microbiome changes markedly after rats undergo CUMS. Notably, we found that the ratio of Lactobacillus to Clostridium can be a vital index for the development of depression. Depression-like behavior can be duplicated through FMT. Moreover, increased zonulin and fatty acid binding protein-2 indicates that gut barrier integrity is broken after FMT. Subsequently, metabolomics shows that liver metabolic disorder occurs and leads to liver coagulative necrosis. In addition, increased inflammatory cytokine expression and higher astrocyte activation indicate an inflammatory process in the brain. These findings suggest that dysbiosis gut microbiome contributes to development of depression and further causes liver metabolic disorders in a way that may be relevant to the Lactobacillus to Clostridium ratio.}, }
@article {pmid31769569, year = {2020}, author = {Lee, MSL and Ramakrishna, B and Moss, AC and Gold, HS and Branch-Elliman, W}, title = {Successful treatment of fulminant Clostridioides difficile infection with emergent fecal microbiota transplantation in a patient with acute myeloid leukemia and prolonged, severe neutropenia.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {22}, number = {1}, pages = {e13216}, doi = {10.1111/tid.13216}, pmid = {31769569}, issn = {1399-3062}, abstract = {We present a patient with acute myeloid leukemia and prolonged, severe neutropenia who developed fulminant Clostridioides difficile infection refractory to medical therapy and was high-risk for surgical intervention. He was treated with fecal microbiota transplantation (FMT) for life-saving cure. The patient had subsequent clinical improvement, however, developed multidrug-resistant Pseudomonas aeruginosa bacteremia 2 days post-procedure. We describe subsequent investigation of this event that found this bacteremia was not related to the donor stool administered during FMT. This case adds to the literature that FMT could be considered in heavily immunocompromised patients with fulminant Clostridioides difficile infection where maximal medical therapy has been ineffective and surgery may carry an excessively high mortality risk.}, }
@article {pmid31768834, year = {2020}, author = {Bowman, JA and Utter, GH}, title = {Evolving Strategies to Manage Clostridium difficile Colitis.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {24}, number = {2}, pages = {484-491}, pmid = {31768834}, issn = {1873-4626}, support = {T32 HS022236/HS/AHRQ HHS/United States ; UL1 TR001860/TR/NCATS NIH HHS/United States ; T32HS022236//Agency for Healthcare Research and Quality (US)/ ; }, abstract = {Clostridium difficile infection remains a common nosocomial illness with a significant impact on health care delivery. As molecular phenotyping of this organism has changed our understanding of its transmission and virulence, so too have diagnostic methods and treatment strategies evolved in recent years. The burden of this infection falls predominantly on elderly patients with comorbidities who have recently received antibiotics. Oral or enteral vancomycin is now preferred for first-line antimicrobial treatment across the disease spectrum, including mild-moderate initial cases. Fidaxomicin (a novel macrolide antibiotic), bezlotoxumab (a monoclonal antibody against toxin TcdB), and fecal microbiota transplantation expand the therapeutic armamentarium, particularly for recurrent infection. Operative treatment should be reserved for patients with fulminant infection, and early identification of patients who would benefit from an operation remains a challenge. Less invasive surgical options-such as laparoscopic diverting ileostomy with colonic irrigation-may improve survival and other outcomes relative to total abdominal colectomy and represent an attractive alternative particularly for frail patients.}, }
@article {pmid31767028, year = {2019}, author = {Seishima, J and Iida, N and Kitamura, K and Yutani, M and Wang, Z and Seki, A and Yamashita, T and Sakai, Y and Honda, M and Yamashita, T and Kagaya, T and Shirota, Y and Fujinaga, Y and Mizukoshi, E and Kaneko, S}, title = {Gut-derived Enterococcus faecium from ulcerative colitis patients promotes colitis in a genetically susceptible mouse host.}, journal = {Genome biology}, volume = {20}, number = {1}, pages = {252}, pmid = {31767028}, issn = {1474-760X}, abstract = {BACKGROUND: Recent metagenomic analyses have revealed dysbiosis of the gut microbiota of ulcerative colitis (UC) patients. However, the impacts of this dysbiosis are not fully understood, particularly at the strain level.<br><br>RESULTS: We perform whole-genome shotgun sequencing of fecal DNA extracts from 13 healthy donors and 16 UC and 8 Crohn's disease (CD) patients. The microbiota of UC and CD patients is taxonomically and functionally divergent from that of healthy donors, with E. faecium being the most differentially abundant species between the two microbial communities. Transplantation of feces from UC or CD patients into Il10-/- mice promotes pathological inflammation and cytokine expression in the mouse colon, although distinct cytokine expression profiles are observed between UC and CD. Unlike isolates derived from healthy donors, E. faecium isolates from the feces of UC patients, along with E. faecium strain ATCC 19434, promotes colitis and colonic cytokine expression. Inflammatory E. faecium strains, including ATCC 19434 and a UC-derived strain, cluster separately from commercially available probiotic strains based on whole-genome shotgun sequencing analysis. The presence of E. faecium in fecal samples is associated with large disease extent and the need for multiple medications in UC patients.<br><br>CONCLUSIONS: E. faecium strains derived from UC patients display an inflammatory genotype that causes colitis.}, }
@article {pmid31761117, year = {2020}, author = {Albuhairi, S and Rachid, R}, title = {Novel Therapies for Treatment of Food Allergy.}, journal = {Immunology and allergy clinics of North America}, volume = {40}, number = {1}, pages = {175-186}, doi = {10.1016/j.iac.2019.09.007}, pmid = {31761117}, issn = {1557-8607}, abstract = {Food allergy prevalence has increased over the past 2 decades and is estimated to affect 8% of children and 4% to 10% of adults. There is an unmet need to evaluate new therapeutic modalities that may decrease the risk of food-induced anaphylaxis and improve patients' quality of life. Oral, epicutaneous, and sublingual food immunotherapies have different safety and efficacy profiles, and their long-term outcome and applicability are unclear. Food allergy trials are currently evaluating different biologics (given as monotherapy or adjunct to immunotherapy), modified food proteins, DNA vaccines, and fecal microbiota transplantation.}, }
@article {pmid31759038, year = {2020}, author = {Chen, Y and Zhang, L and Hong, G and Huang, C and Qian, W and Bai, T and Song, J and Song, Y and Hou, X}, title = {Probiotic mixtures with aerobic constituent promoted the recovery of multi-barriers in DSS-induced chronic colitis.}, journal = {Life sciences}, volume = {240}, number = {}, pages = {117089}, doi = {10.1016/j.lfs.2019.117089}, pmid = {31759038}, issn = {1879-0631}, mesh = {Animals ; *Bacteria, Aerobic ; Cell Membrane Permeability ; Chronic Disease ; Colitis/*chemically induced/*drug therapy/pathology ; Dextran Sulfate ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Intestinal Mucosa/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Probiotics/administration &amp; dosage/*therapeutic use ; Tight Junctions ; }, abstract = {AIMS: Gut microbiota has been closely linked to the mucosal immune and been regarded as a reliable target for intestinal inflammation. This study aimed to explore the therapeutic roles of probiotic mixtures of Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis with (quadruple probiotics, P-qua) or without (triple probiotics, P-tri) aerobic Bacillus cereus in colitis, focusing on the multiple barrier functions.<br><br>MATERIALS AND METHODS: Chronic colitis was induced by dextran sulfate sodium (DSS) in C57BL/6 mice. The probiotic mixtures P-qua or P-tri was gavage administrated respectively, while fecal microbiota transplantation (FMT) as a positive control. The intestinal inflammation and functions of multiple barriers were assessed, including the mucus barrier, epithelial barrier and endothelial barrier known as gut-vascular barrier (GVB). Altered composition and diversity in gut microbiota were observed via sequencing analysis.<br><br>KEY FINDINGS: Both P-qua and P-tri relieved the intestinal inflammation and improved the functions of multiple barriers with increased integrity of mucous layer, enhanced transepithelial electrical resistance, declined epithelial and endothelial permeability to macromolecules in DSS-colitis. Aerobe-contained P-qua revealed a more active role in barrier recovering relative to P-tri, while FMT as a positive control seemed to get better results than pure probiotics. Indeed, P-qua was effective in rebuilding the structure and diversity of gut flora in DSS-colitis, especially increased abundance of Bifidobacterium, Akkermansia, Lactobacillus and Bacteroides.<br><br>SIGNIFICANCE: Aerobe-contained P-qua was a powerful adjuvant therapy for chronic colitis, via restoring the intestinal microflora and recovering the multi-barriers in the inflamed gut.}, }
@article {pmid31756956, year = {2019}, author = {Cheng, H and Guan, X and Chen, D and Ma, W}, title = {The Th17/Treg Cell Balance: A Gut Microbiota-Modulated Story.}, journal = {Microorganisms}, volume = {7}, number = {12}, pages = {}, pmid = {31756956}, issn = {2076-2607}, support = {31902282//National Natural Science Foundation of China/ ; 2018-NK-125//Qinghai province Major R&amp;D and Transformation Project/ ; }, abstract = {The intestinal tract of vertebrates is normally colonized with a remarkable number of commensal microorganisms that are collectively referred to as gut microbiota. Gut microbiota has been demonstrated to interact with immune cells and to modulate specific signaling pathways involving both innate and adaptive immune processes. Accumulated evidence suggests that the imbalance of Th17 and Treg cells is associated with the development of many diseases. Herein, we emphatically present recent findings to show how specific gut microbiota organisms and metabolites shape the balance of Th17 and Treg cells. We also discuss the therapeutic potential of fecal microbiota transplantation (FMT) in diseases caused by the imbalance of Th17 and Treg cells.}, }
@article {pmid31750921, year = {2020}, author = {Basson, AR and Gomez-Nguyen, A and Menghini, P and Buttó, LF and Di Martino, L and Aladyshkina, N and Osme, A and LaSalla, A and Fischer, D and Ezeji, JC and Erkkila, HL and Brennan, CJ and Lam, M and Rodriguez-Palacios, A and Cominelli, F}, title = {Human Gut Microbiome Transplantation in Ileitis Prone Mice: A Tool for the Functional Characterization of the Microbiota in Inflammatory Bowel Disease Patients.}, journal = {Inflammatory bowel diseases}, volume = {26}, number = {3}, pages = {347-359}, pmid = {31750921}, issn = {1536-4844}, support = {T32 DK083251/DK/NIDDK NIH HHS/United States ; P01 DK091222/DK/NIDDK NIH HHS/United States ; F32 DK117585/DK/NIDDK NIH HHS/United States ; P30 DK097948/DK/NIDDK NIH HHS/United States ; R01 DK042191/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a lifelong digestive disease characterized by periods of severe inflammation and remission. To our knowledge, this is the first study showing a variable effect on ileitis severity from human gut microbiota isolated from IBD donors in remission and that of healthy controls in a mouse model of IBD.<br><br>METHODS: We conducted a series of single-donor intensive and nonintensive fecal microbiota transplantation (FMT) experiments using feces from IBD patients in remission and healthy non-IBD controls (N = 9 donors) in a mouse model of Crohn's disease (CD)-like ileitis that develops ileitis in germ-free (GF) conditions (SAMP1/YitFC; N = 96 mice).<br><br>RESULTS: Engraftment studies demonstrated that the microbiome of IBD in remission could have variable effects on the ileum of CD-prone mice (pro-inflammatory, nonmodulatory, or anti-inflammatory), depending on the human donor. Fecal microbiota transplantation achieved a 95% ± 0.03 genus-level engraftment of human gut taxa in mice, as confirmed at the operational taxonomic unit level. In most donors, microbiome colonization abundance patterns remained consistent over 60 days. Microbiome-based metabolic predictions of GF mice with Crohn's or ileitic-mouse donor microbiota indicate that chronic amino/fatty acid (valine, leucine, isoleucine, histidine; linoleic; P < 1e-15) alterations (and not bacterial virulence markers; P > 0.37) precede severe ileitis in mice, supporting their potential use as predictors/biomarkers in human CD.<br><br>CONCLUSION: The gut microbiome of IBD remission patients is not necessarily innocuous. Characterizing the inflammatory potential of each microbiota in IBD patients using mice may help identify the patients' best anti-inflammatory fecal sample for future use as an anti-inflammatory microbial autograft during disease flare-ups.}, }
@article {pmid31750259, year = {2019}, author = {Lin, DM and Koskella, B and Ritz, NL and Lin, D and Carroll-Portillo, A and Lin, HC}, title = {Transplanting Fecal Virus-Like Particles Reduces High-Fat Diet-Induced Small Intestinal Bacterial Overgrowth in Mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {348}, pmid = {31750259}, issn = {2235-2988}, abstract = {Fecal microbiota transplantation (FMT) is an effective tool for treating Clostridium difficile infection in the setting of dysbiosis of the intestinal microbiome. FMT for other forms of human disorders linked to dysbiosis have been less effective. The fecal microbiota contains a high density of virus-like particles (VLP), up to 90% of which are bacteriophages, thought to have a role in regulating gut bacterial populations. We hypothesized that transplantation of the phage-containing fecal VLP fraction may reduce bacterial density in the dysbiotic setting of small intestinal bacterial overgrowth (SIBO). In an experiment using fecal transplantation, we compared the effect of the fecal VLP fraction (bacteria removed) against &quot;Whole&quot; FMT (bacteria intact) on the ileal microbiome. Recipients were either treated with a 30-day high-fat diet (HFD) as a model of dysbiosis to induce SIBO or were on a standard diet (SD). We observed that transplantation of fecal VLPs from donors on a HFD was sufficient to alter the ileal microbiota, but the effect was dependent on diet of the recipient. In recipients on a HFD, ileal bacterial density was reduced. In recipients on a SD, the ileal microbiome transitioned toward the composition associated with a HFD. In both recipient groups, transplantation of fecal VLP fraction alone produced the same outcome as whole FMT. Neither treatment altered expression of antimicrobial peptides. These findings demonstrated a potential role of VLPs, likely phages, for modifying the gut microbiome during dysbiosis.}, }
@article {pmid31745820, year = {2019}, author = {Cheng, YW and Fischer, M}, title = {Treatment of Severe and Fulminnant Clostridioides difficile Infection.}, journal = {Current treatment options in gastroenterology}, volume = {17}, number = {4}, pages = {524-533}, pmid = {31745820}, issn = {1092-8472}, abstract = {PURPOSE OF REVIEW: This article will review current management strategies for severe and fulminant Clostridioides difficile infection (CDI).<br><br>RECENT FINDINGS: Clostridioides difficile is the most common nosocomial cause of infectious diarrhea. With the rise of hypervirulent strains of CDI, almost 8% of patients hospitalized with CDI are afflicted with severe CDI (SCDI) or fulminant CDI (FCDI). A significant proportion of these patients do not respond to recommended anti-CDI antibiotic therapy such as oral vancomycin and fidaxomicin. Current recommendations suggest that patients with refractory CDI should proceed to colectomy or diverting loop ileostomy with colonic lavage. However, both of these surgical interventions result in high rates of post-surgical mortality approaching 30%. Fecal microbiota transplantation (FMT) is a promising therapy that is recommended in recurrent CDI. Recent studies have found that FMT can safely produce cure rates between 70 and 90% in patients with SCDI and FCDI, while significantly decreasing rates of CDI-related mortality and colectomy. A patient population likely to benefit the most from FMT is elderly patients due to their increased risk for CDI, treatment failure, and high comorbidity burden that may preclude surgical intervention. FMT should be considered in patients with SCDI or FCDI particularly when traditional anti-CDI antibiotics are ineffective.}, }
@article {pmid31742290, year = {2019}, author = {Fu, A and Mo, Q and Wu, Y and Wang, B and Liu, R and Tang, L and Zeng, Z and Zhang, X and Li, W}, title = {Protective effect of Bacillus amyloliquefaciens against Salmonella via polarizing macrophages to M1 phenotype directly and to M2 depended on microbiota.}, journal = {Food &amp; function}, volume = {10}, number = {12}, pages = {7653-7666}, doi = {10.1039/c9fo01651a}, pmid = {31742290}, issn = {2042-650X}, abstract = {Bacillus amyloliquefaciens SC06 (BaSC06), a potential probiotic, plays a positive role in animal growth performance and immune function. The aim of the present study was to investigate the protective effect of BaSC06 against Salmonella infection and its association with macrophage polarization. C57BL/6 mice were fed with or without a BaSC06-containing diet before Salmonella enterica Typhimurium (ST) challenge. Results showed that BaSC06 had a protective effect against ST inoculation and induced both M1 and M2 macrophage polarization in the cecum. An in vitro co-culture model demonstrated that BaSC06 promoted M1 polarization directly, and thus increased the phagocytosis and bactericidal activity against ST. In addition, adoptive transfer of bone marrow-derived macrophages (BMDMs) stimulated by BaSC06 significantly decreased the counts of ST in the spleen. Furthermore, 16S rRNA-based analysis of cecal content showed that BaSC06 significantly increased the proportion of Verrucomicrobia and decreased Bacterodetes. Transplantation of the fecal microbiota from BaSC06-treated animals promoted M2 macrophage polarization in the cecum and significantly relieved inflammation caused by ST. In conclusion, BaSC06 polarized macrophages to the M1 type directly resulting in excellent bactericidal activity. Meanwhile, the microbiota modified by BaSC06 can induce M2 polarization which ameliorates the inflammation caused by ST.}, }
@article {pmid31739374, year = {2019}, author = {Schulte, LA and Schäfer, A and Steding, K and Rauschek, L and Klaus, J}, title = {[Acceptance of fecal microbiota transfer among patients with chronic inflammatory bowel diseases in a highly specialized outpatient department: a questionnaire-based survey].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {57}, number = {11}, pages = {1291-1297}, doi = {10.1055/a-1010-6920}, pmid = {31739374}, issn = {1439-7803}, mesh = {Fecal Microbiota Transplantation/adverse effects/*methods ; Feces ; Humans ; Inflammatory Bowel Diseases/*therapy ; Microbiota ; *Patient Acceptance of Health Care ; Perception ; Surveys and Questionnaires ; }, abstract = {Recently, research in the treatment of inflammatory bowel diseases has become increasingly focused on fecal microbiota transfer (FMT) due to increasing evidence of its possible benefits. Still, there are doubts about this method, because there is contradicting evidence regarding its effectiveness and the possible side effects are not well known. Furthermore, the majority of patients are not open to this procedure. We performed a questionnaire-based survey amongst 302 patients with an inflammatory bowel disease that received treatment in our specialized outpatient clinic to determine the factors relevant for acceptance or rejection of fecal microbiota transfer as a possible treatment for Crohn's disease or ulcerative colitis. Our data supports the hypothesis that a lack of information about FMT is a key factor for hypothetical acceptance of this method (68 % of pre-informed participants vs. 30 % of not pre-informed participants would accept FMT as treatment, p < 0.001), and, therefore, it highlights patient education as a possible intervention to improve acceptance. The main concern regarding FMT was possible transmission of infections (ranked first by 98 participants). The most accepted method to perform FMT was application via oral capsule (44 % of participants).}, }
@article {pmid31737727, year = {2019}, author = {Krajicek, E and Bohm, M and Sagi, S and Fischer, M}, title = {Fulminant Clostridium difficile Infection Cured by Fecal Microbiota Transplantation in a Bone Marrow Transplant Recipient With Critical Neutropenia.}, journal = {ACG case reports journal}, volume = {6}, number = {8}, pages = {e00198}, pmid = {31737727}, issn = {2326-3253}, abstract = {Clostridium difficile infection is the most prevalent health care-associated infection. Treatment relies on antimicrobial therapy with mounting evidence supporting fecal microbiota transplant (FMT) in refractory cases. Cohort studies have documented the safety of FMT in immunocompromised patients. However, the safety of FMT in patients with critically low (<500/μL) absolute neutrophil count is unknown. Currently, in severely immunocompromised bone marrow or solid organ transplant recipients, FMT is delayed until normalization of absolute neutrophil count. We present a patient with absolute neutropenia in whom sequential FMTs were safely and successfully administered, resulting in cure of fulminant C. difficile infection.}, }
@article {pmid31728525, year = {2019}, author = {Terveer, EM and van Gool, T and Ooijevaar, RE and Sanders, IMJG and Boeije-Koppenol, E and Keller, JJ and Bart, A and Kuijper, EJ and Terveer, EM and Vendrik, K and Ooijevaar, R and van Lingen, E and Boeije-Koppenol, E and van Beurden, Y and Bauer, MP and van Nood, E and Goorhuis, A and Seegers, JFML and Dijkgraaf, MGW and Mulder, CJJ and Vandenbroucke-Grauls, CMJE and Verspaget, HW and Kuijper, EJ and Keller, JJ}, title = {Human transmission of Blastocystis by Fecal Microbiota Transplantation without development of gastrointestinal symptoms in recipients.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciz1122}, pmid = {31728525}, issn = {1537-6591}, abstract = {BACKGROUND: Patients with multiple recurrent Clostridioides difficile infections (rCDI) are treated with fecal microbiota transplantation (FMT) provided by healthy donors. Blastocystis colonization of donors is considered an exclusion criterion, whereas its pathogenicity is still under debate.<br><br>METHODS: The introduction of molecular screening for Blastocystis sp. at our stool bank identified two donors with prior negative microscopy but positive PCR. Potential transmission of Blastocystis sp. to patients was assessed on 16 fecal patient samples, pre- and post-FMT, by PCR and subtype (ST) analysis. In addition, clinical outcome for treatment of rCDI (n=31), as well as development of gastrointestinal symptoms was assessed.<br><br>RESULTS: One donor carried Blastocystis ST1, the other contained ST3. All patients tested Blastocystis negative prior to FMT. With a median of 20.5 days after FMT, 8 of 16 (50%) patients developed intestinal colonization with Blastocystis, with identical ST-sequences as their respective donors. Blastocystis containing fecal suspensions were used to treat 31 rCDI patients, with a FMT success rate of 84%. This success rate was not statistically different from patients transferred with Blastocystis sp. negative donor feces (93%, 76/82). Patients transferred with Blastocystis sp. positive donor feces did not report any significant difference in bowel complaints in the first week, after 3 weeks and the months following FMT.<br><br>CONCLUSIONS: We demonstrated the first transmission of Blastocystis ST1 and ST3 from donor to patients by FMT. This did not result in gastrointestinal symptomatology or have any significant effect on rCDI treatment outcome.}, }
@article {pmid31726747, year = {2019}, author = {Fukui, H}, title = {Role of Gut Dysbiosis in Liver Diseases: What Have We Learned So Far?.}, journal = {Diseases (Basel, Switzerland)}, volume = {7}, number = {4}, pages = {}, pmid = {31726747}, issn = {2079-9721}, abstract = {Accumulating evidence supports that gut dysbiosis may relate to various liver diseases. Alcoholics with high intestinal permeability had a decrease in the abundance of Ruminnococcus. Intestinal dysmotility, increased gastric pH, and altered immune responses in addition to environmental and genetic factors are likely to cause alcohol-associated gut microbial changes. Alcohol-induced dysbiosis may be associated with gut barrier dysfunction, as microbiota and their products modulate barrier function by affecting epithelial pro-inflammatory responses and mucosal repair functions. High levels of plasma endotoxin are detected in alcoholics, in moderate fatty liver to advanced cirrhosis. Decreased abundance of Faecalibacterium prausnitzii, an anti-inflammatory commensal, stimulating IL-10 secretion and inhibiting IL-12 and interferon-γ expression. Proteobacteria, Enterobacteriaceae, and Escherichia were reported to be increased in NAFLD (nonalcoholic fatty liver disease) patients. Increased abundance of fecal Escherichia to elevated blood alcohol levels in these patients and gut microbiota enriched in alcohol-producing bacteria produce more alcohol (alcohol hypothesis). Some undetermined pathological sequences related to gut dysbiosis may facilitate energy-producing and proinflammatory conditions for the progression of NAFLD. A shortage of autochthonous non-pathogenic bacteria and an overgrowth of potentially pathogenic bacteria are common findings in cirrhotic patients. The ratio of the amounts of beneficial autochthonous taxa (Lachnospiraceae + Ruminococaceae + Veillonellaceae + Clostridiales Incertae Sedis XIV) to those of potentially pathogenic taxa (Enterobacteriaceae + Bacteroidaceae) was low in those with early death and organ failure. Cirrhotic patients with decreased microbial diversity before liver transplantation were more likely to develop post-transplant infections and cognitive impairment related to residual dysbiosis. Patients with PSC had marked reduction of bacterial diversity. Enterococcus and Lactobacillus were increased in PSC patients (without liver cirrhosis.) Treatment-naive PBC patients were associated with altered composition and function of gut microbiota, as well as a lower level of diversity. As serum anti-gp210 antibody has been considered as an index of disease progression, relatively lower species richness and lower abundance of Faecalibacterium spp. in gp210-positive patients are interesting. The dysbiosis-induced altered bacterial metabolites such as a hepatocarcinogenesis promotor DCA, together with a leaky gut and bacterial translocation. Gut protective Akkermansia and butyrate-producing genera were decreased, while genera producing-lipopolysaccharide were increased in early hepatocellular carcinoma (HCC) patients.}, }
@article {pmid31714965, year = {2019}, author = {Severyn, CJ and Brewster, R and Andermann, TM}, title = {Microbiota modification in hematology: still at the bench or ready for the bedside?.}, journal = {Blood advances}, volume = {3}, number = {21}, pages = {3461-3472}, pmid = {31714965}, issn = {2473-9537}, support = {T32 DK098132/DK/NIDDK NIH HHS/United States ; }, abstract = {Growing evidence suggests that human microbiota likely influence diverse processes including hematopoiesis, chemotherapy metabolism, and efficacy, as well as overall survival in patients with hematologic malignancies and other cancers. Both host genetic susceptibility and host-microbiota interactions may impact cancer risk and response to treatment; however, microbiota have the potential to be uniquely modifiable and accessible targets for treatment. Here, we focus on strategies to modify microbiota composition and function in patients with cancer. First, we evaluate the use of fecal microbiota transplant to restore microbial equilibrium following perturbation by antibiotics and chemotherapy, and as a treatment of complications of hematopoietic stem cell transplantation (HSCT), such as graft-versus-host disease and colonization with multidrug-resistant organisms. We then address the potential use of both probiotics and dietary prebiotic compounds in targeted modulation of the microbiota intended to improve outcomes in hematologic diseases. With each type of therapy, we highlight the role that abnormal, or dysbiotic, microbiota play in disease, treatment efficacy, and toxicity and evaluate their potential promise as emerging strategies for microbiota manipulation in patients with hematologic malignancies and in those undergoing HSCT.}, }
@article {pmid31700231, year = {2019}, author = {Hadjivasilis, A and Tsioutis, C and Michalinos, A and Ntourakis, D and Christodoulou, DK and Agouridis, AP}, title = {New insights into irritable bowel syndrome: from pathophysiology to treatment.}, journal = {Annals of gastroenterology}, volume = {32}, number = {6}, pages = {554-564}, pmid = {31700231}, issn = {1108-7471}, abstract = {Irritable bowel syndrome (IBS) is the most common reason to visit a gastroenterologist. IBS was believed to be a functional disease, but many possible pathophysiologic mechanisms can now explain the symptoms. IBS patients are classified into subtypes according to their predominant bowel habit, based on the Rome IV criteria. These include diarrhea-predominant and constipation-predominant IBS, as well as the mixed type, a combination of the two. Usually, IBS treatment is based on the predominant symptoms, with many options for each subtype. A new promising treatment option, fecal microbiota transplantation, seems to have beneficial effects on IBS. However, treating the pathophysiological causative agent responsible for the symptoms is an emerging approach. Therefore, before the appropriate therapeutic option is chosen for treating IBS, a clinical evaluation of its pathophysiology should be performed.}, }
@article {pmid31699731, year = {2019}, author = {Alhifany, AA and Almutairi, AR and Almangour, TA and Shahbar, AN and Abraham, I and Alessa, M and Alnezary, FS and Cheema, E}, title = {Comparing the efficacy and safety of faecal microbiota transplantation with bezlotoxumab in reducing the risk of recurrent Clostridium difficile infections: a systematic review and Bayesian network meta-analysis of randomised controlled trials.}, journal = {BMJ open}, volume = {9}, number = {11}, pages = {e031145}, pmid = {31699731}, issn = {2044-6055}, abstract = {OBJECTIVES: The risk of recurrent Clostridium difficile infections (RCDIs) is high when treated with standard antibiotics therapy (SAT) alone. It is suggested that the addition of faecal microbiota transplantation (FMT) or bezlotoxumab after SAT reduces the risk of RCDI. In the absence of head-to-head randomised controlled trials (RCTs), this review attempts to compare the efficacy and safety of bezlotoxumab with FMT in reducing the risk of RCDI in hospitalised patients.<br><br>DESIGN: A systematic review and Bayesian network meta-analysis.<br><br>DATA SOURCE: A comprehensive search from inception to 30 February 2019 was conducted in four databases (Medline/PubMed, Embase, Scopus, ClinicalTrials.gov).<br><br>ELIGIBILITY CRITERIA: RCTs reporting the resolution of diarrhoea associated with RCDI without relapse for at least 60 days after the end of treatments as the primary outcome.<br><br>DATA EXTRACTION AND SYNTHESIS: We extracted author, year of publication, study design and binomial data that represented the resolution of diarrhoea or adverse events of monoclonal antibodies and FMT infusion. Random-effects models were used for resolution rate of RCDI and adverse events. The Cochrane Risk of Bias tool was used to assess the quality of included RCTs.<br><br>RESULTS: Out of 1003 articles identified, seven RCTs involving 3043 patients contributed to the review. No difference was reported between single or multiple infusions of FMT and bezlotoxumab in resolving RCDI, (OR 1.53, 95% credible interval (CrI) 0.39 to 5.16) and (OR 2.86, 95% CrI 1.29 to 6.57), respectively. Patients treated with SAT alone or bezlotoxumab with SAT showed significantly lower rates of diarrhoea than FMT (OR 0, 95% CrI 0 to 0.09) and (OR 0, 95% CrI 0 to 0.19), respectively. There was no difference in terms of other adverse events.<br><br>CONCLUSIONS: This is the first network meta-analysis that has compared the recently Food and Drug Administration-approved monoclonal antibody bezlotoxumab with FMT for resolving RCDI. The quality of the included RCTs was variable. The findings of this study suggested no difference between single or multiple infusions of FMT and bezlotoxumab. However, FMT was associated with a higher rate of non-serious diarrhoea as opposed to SAT used alone or in combination with bezlotoxumab.}, }
@article {pmid31698603, year = {2019}, author = {Kang, XX and Yan, J and Huang, F and Yang, L}, title = {On the mechanism of antibiotic resistance and fecal microbiota transplantation.}, journal = {Mathematical biosciences and engineering : MBE}, volume = {16}, number = {6}, pages = {7057-7084}, doi = {10.3934/mbe.2019354}, pmid = {31698603}, issn = {1551-0018}, abstract = {Antibiotic resistance is a growing threat to human health and is caused by mainly the overuse of antibiotics in clinical medicine. Clinically, drug resistance emerges after a series of antibiotic treatments, implying that each treatment changes the intestinal flora composition and the accumulations of these changes induce the resistance. But mathematically, this cumulative effect cannot be achieved by a general population model, because the system will return to its pre-treatment state (an isolated steady state) after each cure. Based on the fact that sensitive bacteria and resistant bacteria are similar in most respects except their reactions to antibiotics, we developed a mathematical model with a specific phase-space structure: instead of isolated points, the steady states of this system compose one-dimensional manifolds (line segments). This structure explains the fundamental mechanism of antibiotic resistance: after antibiotic treatment, the system cannot return to the pretreatment healthy steady state but rather slightly moves along the manifold to a different steady state. Each use of antibiotics can change the ratio of resistant to susceptible pathogens in the host. The change the ratio can persist and accumulate, and finally promotes the emergence of antimicrobial resistance. We also assessed key factors (such as pathogen composition, the amount and composition of beneficial bacteria, medication duration and bactericidal rates of drugs) influencing the development of drug resistance. In addition, we clarified how fecal microbiota transplantation affects the treatment of antibiotic-resistant infections. The effect is essentially a transfer towards the healthy state in the phase space. Finally, based on the mechanisms revealed by the mathematical models, we suggested some strategies to delay or prevent the emergence of drug resistance. These findings not only provide a solid theoretical basis for the treatment of antimicrobial resistance, but also inspire clues to the phenomenon of drug resistance.}, }
@article {pmid31690638, year = {2020}, author = {Manca, C and Boubertakh, B and Leblanc, N and Deschênes, T and Lacroix, S and Martin, C and Houde, A and Veilleux, A and Flamand, N and Muccioli, GG and Raymond, F and Cani, PD and Di Marzo, V and Silvestri, C}, title = {Germ-free mice exhibit profound gut microbiota-dependent alterations of intestinal endocannabinoidome signaling.}, journal = {Journal of lipid research}, volume = {61}, number = {1}, pages = {70-85}, pmid = {31690638}, issn = {1539-7262}, abstract = {The gut microbiota is a unique ecosystem of microorganisms interacting with the host through several biochemical mechanisms. The endocannabinoidome (eCBome), a complex signaling system including the endocannabinoid system, approximately 50 receptors and metabolic enzymes, and more than 20 lipid mediators with important physiopathologic functions, modulates gastrointestinal tract function and may mediate host cell-microbe communications there. Germ-free (GF) mice, which lack an intestinal microbiome and so differ drastically from conventionally raised (CR) mice, offer a unique opportunity to explore the eCBome in a microbe-free model and in the presence of a reintroduced functional gut microbiome through fecal microbiota transplant (FMT). We aimed to gain direct evidence for a link between the microbiome and eCBome systems by investigating eCBome alterations in the gut in GF mice before and after FMT. Basal eCBome gene expression and lipid profiles were measured in various segments of the intestine of GF and CR mice at juvenile and adult ages using targeted quantitative PCR transcriptomics and LC-MS/MS lipidomics. GF mice exhibited age-dependent modifications in intestinal eCBome gene expression and lipid mediator levels. FMT from CR donor mice to age-matched GF male mice reversed several of these alterations, particularly in the ileum and jejunum, after only 1 week, demonstrating that the gut microbiome directly impacts the host eCBome and providing a cause-effect relationship between the presence or absence of intestinal microbes and eCBome signaling. These results open the way to new studies investigating the mechanisms through which intestinal microorganisms exploit eCBome signaling to exert some of their physiopathologic functions.}, }
@article {pmid31690143, year = {2020}, author = {Kumar, V and Fischer, M}, title = {Expert opinion on fecal microbiota transplantation for the treatment of Clostridioides difficile infection and beyond.}, journal = {Expert opinion on biological therapy}, volume = {20}, number = {1}, pages = {73-81}, doi = {10.1080/14712598.2020.1689952}, pmid = {31690143}, issn = {1744-7682}, abstract = {Introduction: Fecal microbiota transplantation (FMT) is a procedure involving transfer of stool from a healthy donor into the intestinal tract of a diseased recipient to restore intestinal microbial composition and functionality. FMT's tremendous success in recurrent and refractory Clostridioides difficile infection (CDI) catalyzed gut microbiota research and opened the door to microbiome-based therapy for various gastrointestinal and other disorders.Areas covered: We used PubMed search engine to identify significant publications in the field of CDI and FMT. Here we present an overview of the current literature on FMT's use for recurrent, non-severe, severe, and fulminant CDI and on promising future application.Expert opinion: FMT as the best tool for treatment of antibiotic-refractory CDI has gained immense popularity over the last decade. The future of gut microbiota-based therapy should include oral formulations that contain well-described ingredients in effective doses, clear mechanism of action, and excellent safety profile.}, }
@article {pmid31689519, year = {2019}, author = {Wu, M and Li, P and An, Y and Ren, J and Yan, D and Cui, J and Li, D and Li, M and Wang, M and Zhong, G}, title = {Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota.}, journal = {Pharmacological research}, volume = {150}, number = {}, pages = {104489}, doi = {10.1016/j.phrs.2019.104489}, pmid = {31689519}, issn = {1096-1186}, abstract = {Phloretin, extracted from the pericarp and velamen of apples or pears, is a dihydrochalcone flavonoid with anti-bacterial and anti-inflammatory activities. It has been reported that phloretin has anti-inflammatory effects in ulcerative colitis (UC) mice. However, the role of the gut microbiota in the phloretin anti-UC process remains unclear. In this study, we observed that the anti-UC effect of phloretin was affected by co-housing, probably because of the transmissible nature of the gut micobiota. Through fecal micobiota transplantation (FMT), the effects of the gut microbiota on the anti-UC of phloretin were further confirmed. UC was induced in mice by administrating 3% dextran sulfate sodium (DSS) in drinking water for 7 days. Phloretin (60 mg/kg) was administered by gavage every day during the experiment. Fecal microbes (109 CFU/mL) from phloretin-treated UC mice were administered by gavage to non-phloretin-treated UC mice for 7 days. The results showed that FMT, like phloretin, ameliorated UC by improving disease symptoms and colon inflammation, balancing inflammatory cytokines, maintaining intestinal barrier integrity, restoring systemic immune function, inhibiting NF-κB and NLRP3 inflammasome activation and ameliorating the oxidant stress. Both FMT and phloretin treatment increased the levels of Bacteroidetes, Alistipes and Lactobacillus and decreased those of Firmicutes, Oscillibacter and Ruminiclostridium_6. Correlation analysis between gut microbes and micro-environmental factors revealed that Alistipes abundance was negatively correlated with DAI, pathological score, and TNF-α, IL-6 and IL-1β levels, and Alistipes was more abundant in phloretin or FMT treated UC mice. Oscillibacter abundance was significantly positively correlated with IL-6 and IL-1β levels and pathological score, and Oscillibacter was increased in UC mice. Furthermore, network analysis of the dominant genera revealed that Alistipes abundance was negatively related to Oscillibacter abundance. In conclusion, this study suggests that the anti-UC effects of phloretin are achieved through regulation of the gut microbiota and phloretin has the potential to be developed as a promising agent for the treatment of UC.}, }
@article {pmid31688252, year = {2019}, author = {Singh, H and Ross, L and Smith, H and Borody, TJ and Lemberg, DA}, title = {Oral fecal microbiota transplant for recurrent Clostridium difficile in pediatric autoimmune enteropathy.}, journal = {European journal of gastroenterology &amp; hepatology}, volume = {31}, number = {12}, pages = {1602-1603}, doi = {10.1097/MEG.0000000000001548}, pmid = {31688252}, issn = {1473-5687}, }
@article {pmid31683278, year = {2019}, author = {Ianiro, G and Murri, R and Sciumè, GD and Impagnatiello, M and Masucci, L and Ford, AC and Law, GR and Tilg, H and Sanguinetti, M and Cauda, R and Gasbarrini, A and Fantoni, M and Cammarota, G}, title = {Incidence of Bloodstream Infections, Length of Hospital Stay, and Survival in Patients With Recurrent Clostridioides difficile Infection Treated With Fecal Microbiota Transplantation or Antibiotics: A Prospective Cohort Study.}, journal = {Annals of internal medicine}, volume = {}, number = {}, pages = {}, doi = {10.7326/M18-3635}, pmid = {31683278}, issn = {1539-3704}, abstract = {Background: Clostridioides difficile infection (CDI) is a risk factor for bloodstream infection (BSI). Fecal microbiota transplantation (FMT) is more effective than antibiotics in treating recurrent CDI, but its efficacy in preventing CDI-related BSI is uncertain.<br><br>Objective: To assess incidence of primary BSI in patients with recurrent CDI treated with FMT versus antibiotics.<br><br>Design: Prospective cohort study. Patients treated with FMT and those treated with antibiotics were matched on propensity score.<br><br>Setting: Single academic medical center.<br><br>Patients: 290 inpatients with recurrent CDI (57 patients per treatment in matched cohort).<br><br>Intervention: FMT or antibiotics.<br><br>Measurements: The primary outcome was primary BSI within 90 days. Secondary outcomes were length of hospitalization and overall survival (OS) at 90 days.<br><br>Results: Of the 290 patients, 109 were treated with FMT and 181 received antibiotics. Five patients in the FMT group and 40 in the antibiotic group developed BSI. Because of differences in the patients treated with FMT versus antibiotics in many baseline characteristics, including number of recurrences and CDI severity, comparative analyses were limited to the matched cohort. Risk for BSI was 23 percentage points (95% CI, 10 to 35 percentage points) lower in the FMT group; the FMT group also had 14 fewer days of hospitalization (CI, 9 to 20 fewer days) and a 32-percentage point increase in OS (CI, 16 to 47 percentage points) compared with the antibiotic group.<br><br>Limitation: Nonrandomized study with potential for unmeasured or residual confounding; limited generalizability of the propensity score-matched cohort.<br><br>Conclusion: In a propensity score-matched cohort, patients with recurrent CDI treated with FMT were less likely to develop primary BSI.<br><br>Primary Funding Source: None.}, }
@article {pmid31682032, year = {2020}, author = {Rosa, CP and Pereira, JA and Cristina de Melo Santos, N and Brancaglion, GA and Silva, EN and Tagliati, CA and Novaes, RD and Corsetti, PP and de Almeida, LA}, title = {Vancomycin-induced gut dysbiosis during Pseudomonas aeruginosa pulmonary infection in a mice model.}, journal = {Journal of leukocyte biology}, volume = {107}, number = {1}, pages = {95-104}, doi = {10.1002/JLB.4AB0919-432R}, pmid = {31682032}, issn = {1938-3673}, abstract = {Pseudomonas aeruginosa is one of the most common opportunistic pathogens causing respiratory infections in hospitals. Vancomycin, the antimicrobial agent usually used to treat bacterial nosocomial infections, is associated with gut dysbiosis. As a lung-gut immunologic axis has been described, this study aimed to evaluate both the immunologic and histopathologic effects on the lungs and the large intestine resulting from vancomycin-induced gut dysbiosis in the P. aeruginosa pneumonia murine model. Metagenomic analysis demonstrated that vancomycin-induced gut dysbiosis resulted in higher Proteobacteria and lower Bacteroidetes populations in feces. Given that gut dysbiosis could augment the proinflammatory status of the intestines leading to a variety of acute inflammatory diseases, bone marrow-derived macrophages were stimulated with cecal content from dysbiotic mice showing a higher expression of proinflammatory cytokines and lower expression of IL-10. Dysbiotic mice showed higher levels of viable bacteria in the lungs and spleen when acutely infected with P. aeruginosa, with more lung and cecal damage and increased IL-10 expression in bronchoalveolar lavage. The susceptible and tissue damage phenotype was reversed when dysbiotic mice received fecal microbiota transplantation. In spite of higher recruitment of CD11b+ cells in the lungs, there was no higher CD80+ expression, DC+ cell amounts or proinflammatory cytokine expression. Taken together, our results indicate that the bacterial community found in vancomycin-induced dysbiosis dysregulates the gut inflammatory status, influencing the lung-gut immunologic axis to favor increased opportunistic infections, for example, by P. aeruginosa.}, }
@article {pmid31676058, year = {2019}, author = {Kuhnen, A}, title = {Genetic and Environmental Considerations for Inflammatory Bowel Disease.}, journal = {The Surgical clinics of North America}, volume = {99}, number = {6}, pages = {1197-1207}, doi = {10.1016/j.suc.2019.08.014}, pmid = {31676058}, issn = {1558-3171}, mesh = {Environment ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Inflammatory Bowel Diseases/diagnosis/*genetics/*surgery ; Male ; Postoperative Complications/physiopathology/therapy ; Pouchitis/microbiology/*therapy ; Proctocolectomy, Restorative/adverse effects/*methods ; Prognosis ; Risk Assessment ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract driven by an exaggerated immune response to luminal microbiota in susceptible individuals. It presents with a heterogenous pattern of clinical disease severity, location, and behavior. Understanding the interaction between the host genome, gut microbiome, and further environmental exposures in the development of IBD is in the early stages, and factors that trigger onset of disease in susceptible individuals remain unknown. This article addresses the genetic, microbial, and environmental influences on development of inflammatory bowel disease and the ability to manipulate these factors through surgery and medical therapy.}, }
@article {pmid31672964, year = {2019}, author = {Huang, F and Zheng, X and Ma, X and Jiang, R and Zhou, W and Zhou, S and Zhang, Y and Lei, S and Wang, S and Kuang, J and Han, X and Wei, M and You, Y and Li, M and Li, Y and Liang, D and Liu, J and Chen, T and Yan, C and Wei, R and Rajani, C and Shen, C and Xie, G and Bian, Z and Li, H and Zhao, A and Jia, W}, title = {Theabrownin from Pu-erh tea attenuates hypercholesterolemia via modulation of gut microbiota and bile acid metabolism.}, journal = {Nature communications}, volume = {10}, number = {1}, pages = {4971}, pmid = {31672964}, issn = {2041-1723}, mesh = {Adult ; Amidohydrolases/metabolism ; Animals ; Bile Acids and Salts/*metabolism ; Catechin/*analogs &amp; derivatives/pharmacology ; Chenodeoxycholic Acid/metabolism ; Cholesterol/metabolism ; Diet, High-Fat ; Fecal Microbiota Transplantation ; *Fermented Foods and Beverages ; Fibroblast Growth Factors/drug effects/metabolism ; Gastrointestinal Microbiome/*drug effects/genetics/physiology ; Humans ; Hypercholesterolemia/*metabolism ; Ileum/drug effects/metabolism ; Lipogenesis/drug effects ; Liver/drug effects/metabolism ; Male ; Metabolomics ; Mice ; Plant Extracts/pharmacology ; RNA, Ribosomal, 16S ; Receptors, Cytoplasmic and Nuclear/drug effects/metabolism ; Signal Transduction ; *Tea ; Young Adult ; }, abstract = {Pu-erh tea displays cholesterol-lowering properties, but the underlying mechanism has not been elucidated. Theabrownin is one of the most active and abundant pigments in Pu-erh tea. Here, we show that theabrownin alters the gut microbiota in mice and humans, predominantly suppressing microbes associated with bile-salt hydrolase (BSH) activity. Theabrownin increases the levels of ileal conjugated bile acids (BAs) which, in turn, inhibit the intestinal FXR-FGF15 signaling pathway, resulting in increased hepatic production and fecal excretion of BAs, reduced hepatic cholesterol, and decreased lipogenesis. The inhibition of intestinal FXR-FGF15 signaling is accompanied by increased gene expression of enzymes in the alternative BA synthetic pathway, production of hepatic chenodeoxycholic acid, activation of hepatic FXR, and hepatic lipolysis. Our results shed light into the mechanisms behind the cholesterol- and lipid-lowering effects of Pu-erh tea, and suggest that decreased intestinal BSH microbes and/or decreased FXR-FGF15 signaling may be potential anti-hypercholesterolemia and anti-hyperlipidemia therapies.}, }
@article {pmid31665947, year = {2019}, author = {Adams, JB and Borody, TJ and Kang, DW and Khoruts, A and Krajmalnik-Brown, R and Sadowsky, MJ}, title = {Microbiota transplant therapy and autism: lessons for the clinic.}, journal = {Expert review of gastroenterology &amp; hepatology}, volume = {13}, number = {11}, pages = {1033-1037}, doi = {10.1080/17474124.2019.1687293}, pmid = {31665947}, issn = {1747-4132}, abstract = {Introduction: The purpose of this review is to discuss Microbiota Transplant Therapy (MTT), a type of intensive intestinal microbiota transplantation (IMT), for people with autism spectrum disorders (ASD) and chronic gastrointestinal disorders (constipation and/or diarrhea).Areas covered: This paper briefly reviews IMT, gastrointestinal symptoms and gastrointestinal bacteria in children with ASD, and results and lessons learned from intensive MTT for autism.Expert opinion: An open-label study and a two-year follow-up suggest that MTT is relatively safe and effective in significantly reducing gastrointestinal disorders and autism symptoms, changing the gut microbiome structure, and increasing gut microbial diversity. Further research with larger, randomized, double-blind, placebo-controlled studies is warranted.}, }
@article {pmid31665575, year = {2019}, author = {DeFilipp, Z and Bloom, PP and Torres Soto, M and Mansour, MK and Sater, MRA and Huntley, MH and Turbett, S and Chung, RT and Chen, YB and Hohmann, EL}, title = {Drug-Resistant E. coli Bacteremia Transmitted by Fecal Microbiota Transplant.}, journal = {The New England journal of medicine}, volume = {381}, number = {21}, pages = {2043-2050}, doi = {10.1056/NEJMoa1910437}, pmid = {31665575}, issn = {1533-4406}, mesh = {Aged ; Bacteremia/*etiology/microbiology ; Drug Resistance, Bacterial ; Dysbiosis/etiology/*therapy ; Escherichia coli/drug effects/*isolation &amp; purification/metabolism ; Fatal Outcome ; Fecal Microbiota Transplantation/*adverse effects ; Feces/*microbiology ; Hepatic Encephalopathy/complications/therapy ; Humans ; Male ; Myelodysplastic Syndromes/complications/therapy ; beta-Lactamases/metabolism ; }, abstract = {Fecal microbiota transplantation (FMT) is an emerging therapy for recurrent or refractory Clostridioides difficile infection and is being actively investigated for other conditions. We describe two patients in whom extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli bacteremia occurred after they had undergone FMT in two independent clinical trials; both cases were linked to the same stool donor by means of genomic sequencing. One of the patients died. Enhanced donor screening to limit the transmission of microorganisms that could lead to adverse infectious events and continued vigilance to define the benefits and risks of FMT across different patient populations are warranted.}, }
@article {pmid31665573, year = {2019}, author = {Blaser, MJ}, title = {Fecal Microbiota Transplantation for Dysbiosis - Predictable Risks.}, journal = {The New England journal of medicine}, volume = {381}, number = {21}, pages = {2064-2066}, doi = {10.1056/NEJMe1913807}, pmid = {31665573}, issn = {1533-4406}, mesh = {*Bacteremia ; Dysbiosis ; Escherichia coli ; Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, }
@article {pmid31665572, year = {2019}, author = {Kassam, Z and Dubois, N and Ramakrishna, B and Ling, K and Qazi, T and Smith, M and Kelly, CR and Fischer, M and Allegretti, JR and Budree, S and Panchal, P and Kelly, CP and Osman, M}, title = {Donor Screening for Fecal Microbiota Transplantation.}, journal = {The New England journal of medicine}, volume = {381}, number = {21}, pages = {2070-2072}, doi = {10.1056/NEJMc1913670}, pmid = {31665572}, issn = {1533-4406}, mesh = {*Donor Selection/methods/statistics &amp; numerical data ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Nose/microbiology ; Prospective Studies ; }, }
@article {pmid31662862, year = {2019}, author = {Rokkas, T and Gisbert, JP and Gasbarrini, A and Hold, GL and Tilg, H and Malfertheiner, P and Megraud, F and O'Morain, C}, title = {A network meta-analysis of randomized controlled trials exploring the role of fecal microbiota transplantation in recurrent Clostridium difficile infection.}, journal = {United European gastroenterology journal}, volume = {7}, number = {8}, pages = {1051-1063}, pmid = {31662862}, issn = {2050-6406}, abstract = {Background: Recurrence remains a challenge in Clostridium difficile infection (CDI), and in this field fecal microbiota transplantation (FMT) has attracted significant interest. Network meta-analysis (NWM) has been established as an evidence-synthesis tool that incorporates direct and indirect evidence in a collection of randomized controlled trials. So far no NWM exists concerning therapeutic interventions for recurrent CDI (rCDI).<br><br>Objective: In this NWM we assessed the comparative effectiveness of various therapies for rCDI to examine the efficacy rank order and determine the optimum therapeutic approach.<br><br>Methods: A Bayesian network meta-analysis was performed to investigate the efficacy rank order of rCDI interventions.<br><br>Results: Six eligible RCTs were entered into an NWM. They included 348 rCDI patients, in whom seven therapeutic interventions were used, i.e. donor fecal microbiota transplantation (DFMT), vancomycin, fidaxomicin, vancomycin + DFMT, vancomycin + bowel lavage, autologous FMT and placebo. DFMT showed the highest efficacy in comparison with vancomycin [odds ratio (95% credible interval), 20.02 (7.05-70.03)] and fidaxomicin (22.01 (4.38-109.63)).<br><br>Conclusion: This NWM showed that DFMT is the optimum therapeutic approach for rCDI, as it was the most efficacious among various therapeutic interventions, particularly in comparison with commonly used antibiotics such as vancomycin or fidaxomicin.}, }
@article {pmid31662860, year = {2019}, author = {Myneedu, K and Deoker, A and Schmulson, MJ and Bashashati, M}, title = {Fecal microbiota transplantation in irritable bowel syndrome: A systematic review and meta-analysis.}, journal = {United European gastroenterology journal}, volume = {7}, number = {8}, pages = {1033-1041}, pmid = {31662860}, issn = {2050-6406}, abstract = {Background: Modulating gut microbiota is a potential treatment for irritable bowel syndrome (IBS). This meta-analysis explored whether fecal microbiota transplantation (FMT) is successful in treating IBS.<br><br>Methods: A systematic review was performed to find trials on FMT in IBS. Ratios and relative ratios (RR) of improvement for single-arm trials (SATs) and randomized controlled trials (RCTs) were calculated, respectively. Changes in IBS Severity Scoring System (IBS-SSS) and IBS Quality of Life (IBS-QOL) instrument compared to baseline in FMT versus placebo groups were pooled.<br><br>Results: In SATs, 59.5% (95% confidence interval (CI) 49.1-69.3) of IBS patients showed significant improvement. In RCTs, there were no differences between FMT and control in improvement (RR=0.93 (95% CI 0.50-1.75)) or changes in the IBS-SSS and IBS-QOL.<br><br>Conclusions: FMT was not effective in IBS. Variations in FMT methods and patient factors may contribute to the heterogeneous results of the trials.}, }
@article {pmid31660360, year = {2019}, author = {Hocquart, M and Pham, T and Kuete, E and Tomei, E and Lagier, JC and Raoult, D}, title = {Successful Fecal Microbiota Transplantation in a Patient Suffering From Irritable Bowel Syndrome and Recurrent Urinary Tract Infections.}, journal = {Open forum infectious diseases}, volume = {6}, number = {10}, pages = {ofz398}, pmid = {31660360}, issn = {2328-8957}, abstract = {Background: Irritable bowel syndrome (IBS) is a chronic and debilitating functional gastrointestinal disorder affecting 9%-23% of the population across the world. The relative efficacy of fecal microbiota transplantation (FMT) on IBS symptoms was demonstrated in a double-blind, randomized study.<br><br>Methods: We describe the case of a 73-year-old woman suffering from IBS (abdominal pain, bloating, and abundant and disabling diarrhea, with 10-15 stools a day) and repetitive urinary tract infection (UTI; 5 episodes in 6 months, including 3 the last 2 months) for several years, generating an impaired quality of life. She received an FMT with 400 mL of fecal infusion from a healthy donor via a nasogastric tube after bowel lavage. Her digestive microbiota was analyzed using culturomic and metagenomic targeting 16S rRNA sequencing methods.<br><br>Results: Eight months after transplantation, we observed a significant reduction in frequency and improvement in stool consistency (3-4 molded stools a day against 10-15 before the transplant) and no recurrence of urinary infection (as previously reported). Using culturomics, we found 12 bacteria present in the fecal infusion and post-transplant stool; these were absent pretransplant. Three of them (Intestinimonas massiliensis, Oscillibacter massiliensis, and Provencibacter massiliensis) were previously discovered and cultivated in our laboratory using culturomics. Using metagenomics, we also observed 12 bacteria, different from those observed during culture, that could have been transferred to the patient by FMT.<br><br>Conclusions: In this case report, IBS symptoms and UTI frequency decreased after FMT UTI. Further studies involving more patients would be relevant to confirm this work and develop bacteriotherapy.}, }
@article {pmid31660354, year = {2019}, author = {Woodworth, MH and Hayden, MK and Young, VB and Kwon, JH}, title = {Corrigendum: 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 = {10}, pages = {ofz391}, doi = {10.1093/ofid/ofz391}, pmid = {31660354}, issn = {2328-8957}, abstract = {[This corrects the article DOI: 10.1093/ofid/ofz288.][This corrects the article DOI: 10.1093/ofid/ofz288.].}, }
@article {pmid31660343, year = {2019}, author = {Hourigan, SK and Ahn, M and Gibson, KM and Pérez-Losada, M and Felix, G and Weidner, M and Leibowitz, I and Niederhuber, JE and Sears, CL and Crandall, KA and Oliva-Hemker, M}, title = {Fecal Transplant in Children With Clostridioides difficile Gives Sustained Reduction in Antimicrobial Resistance and Potential Pathogen Burden.}, journal = {Open forum infectious diseases}, volume = {6}, number = {10}, pages = {ofz379}, pmid = {31660343}, issn = {2328-8957}, support = {KL2 TR001877/TR/NCATS NIH HHS/United States ; UL1 TR001876/TR/NCATS NIH HHS/United States ; }, abstract = {Background: Fecal microbiota transplantation (FMT) treats Clostridioides difficile infection (CDI). Little is known regarding the changes in antimicrobial resistance (AMR) genes and potential pathogen burden that occur in pediatric recipients of FMT. The aim of this study was to investigate changes in AMR genes, potential pathogens, species, and functional pathways with FMT in children.<br><br>Methods: Nine children with recurrent CDI underwent FMT. Stool was collected from donor and recipient pre-FMT and longitudinally post-FMT for up to 24 weeks. Shotgun metagenomic sequencing was performed. Reads were analyzed using PathoScope 2.0.<br><br>Results: All children had resolution of CDI. AMR genes decreased post-FMT (P < .001), with a sustained decrease in multidrug resistance genes (P < .001). Tetracycline resistance genes increased post-FMT (P < .001). Very low levels of potential pathogens were identified in donors and recipients, with an overall decrease post-FMT (P < .001). Prevotella sp. 109 expanded in all recipients post-FMT, and no recipients had any clinical infection. Alpha diversity was lower in recipients vs donors pre-FMT (P < .001), with an increase post-FMT (P ≤ .002) that was sustained. Beta diversity differed significantly in pre- vs post-FMT recipient samples (P < .001). Bacterial species Faecalibacterium prausnitzii and Bacteroides ovatus showed higher abundance in donors than recipients (P = .008 and P = .040, respectively), with expansion post-FMT. Biosynthetic pathways predominated in the donor and increased in the recipient post-FMT.<br><br>Conclusions: FMT for CDI in children decreases AMR genes and potential pathogens and changes microbiota composition and function. However, acquisition of certain AMR genes post-FMT combined with low levels of potential pathogens found in donors suggests that further study is warranted regarding screening donors using metagenomics sequencing before FMT.}, }
@article {pmid31657333, year = {2019}, author = {Li, S and Xu, N and Hua, R and Niu, X and Lyu, C and Li, M and Li, J}, title = {[Fecal microbiota transplantation regulates the cholinergic anti-inflammatory pathway in cerebral cortex of septic rats through intestinal microbiota].}, journal = {Zhonghua wei zhong bing ji jiu yi xue}, volume = {31}, number = {9}, pages = {1102-1107}, doi = {10.3760/cma.j.issn.2095-4352.2019.09.009}, pmid = {31657333}, issn = {2095-4352}, mesh = {Animals ; Anti-Inflammatory Agents ; Cerebral Cortex ; Cholinergic Agents ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Male ; Rats ; Rats, Sprague-Dawley ; *Sepsis ; Tumor Necrosis Factor-alpha ; }, abstract = {OBJECTIVE: To investigate the effects of fecal microbiota transplantation on septic gut flora and the cortex cholinergic anti-inflammatory pathway in rats.<br><br>METHODS: Sixty clean grade male Sprague-Dawley (SD) rats were divided into normal saline (NS) control group, sepsis model group and fecal microbiota transplantation group by random number table, with 20 rats in each group. The rat model of sepsis was reproduced by injection of 10 mg/kg lipopolysaccharide (LPS) via tail vein, the rats in the NS control group was given the same amount of NS. The rats in the fecal microbiota transplantation group received nasogastric infusion of feces from healthy donor on the 1st day, 2 mL each time, for 3 times a day, the other two groups were given equal dose of NS by gavage. Fecal samples were collected on the 7th day after modeling, the levels of intestinal microbiota composition was determined using the 16SrDNA gene sequencing technology. The brain function was evaluated by electroencephalogram (EEG), and the proportion of each waveform in EEG was calculated. After sacrifice of rats, the brain tissues were harvested, the levels of protein expression of α7 nicotinic acetylcholine receptor (α7nAChR) were determined by Western Blot, and positive cells of Iba-1 in brain tissue were detected by immunohistochemistry method. The levels of interleukins (IL-6 and IL-1β) and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay (ELISA).<br><br>RESULTS: Seven days after the reproduction of the model, all rats in the NS control group survived, while 10 rats and 8 rats died in the sepsis model group and fecal microbiota transplantation group, respectively, with mortality rates of 50% and 40% respectively. Finally, there were 20 rats in the NS control group, 10 in the sepsis model group and 12 in the fecal microbiota transplantation group. Compared with the NS control group, the diversity and composition of intestinal flora were changed, the incidence of abnormal EEG increased significantly, the expression of α7nAchR in the cortex decreased significantly, and the levels of Iba-1, TNF-α, IL-6 and IL-1β were significantly increased in the model group, suggested that the intestinal flora was dysbiosis, and severe inflammatory reaction occurred in the cerebral cortex, and brain function was impaired. Compared with the model group, the diversity of intestinal flora in the fecal microbiota transplantation group was significantly increased (species index: 510.24±58.76 vs. 282.50±47.42, Chao1 index: 852.75±25.24 vs. 705.50±46.50, both P < 0.05), the dysbiosis of intestinal flora at phylum, family, genus level induced by LPS were also significantly reversed, and with the improvement of intestinal flora, the incidence of abnormal EEG waveforms was lower in the fecal microbiota transplantation group compared with that in the model group [25.0% (3/12) vs. 80.0% (8/10), P < 0.05], and the expression of α7nAChR protein in the cerebral cortex was significantly increased (α7nAChR/β-actin: 1.56±0.05 vs. 0.82±0.07, P < 0.05), immunohistochemistry analysis showed that Iba-1 positive expression of microglia decreased significantly, and cerebral cortex TNF-α, IL-6, IL-1β levels were significantly decreased [TNF-α (ng/L): 6.28±0.61 vs. 12.02±0.54, IL-6 (ng/L): 28.26±3.15 vs. 60.58±4.62, IL-1β (ng/L): 33.63±3.48 vs. 72.56±2.25, all P < 0.05].<br><br>CONCLUSIONS: The results reveal that fecal microbiota transplantation has remarkably modulated the dysbiosis of intestinal microbiota and activated cholinergic anti-inflammatory pathway, and ameliorate the brain dysfunction in septic rats.}, }
@article {pmid31654298, year = {2019}, author = {Aira, A and Fehér, C and Rubio, E and Soriano, A}, title = {The Intestinal Microbiota as a Reservoir and a Therapeutic Target to Fight Multi-Drug-Resistant Bacteria: A Narrative Review of the Literature.}, journal = {Infectious diseases and therapy}, volume = {8}, number = {4}, pages = {469-482}, pmid = {31654298}, issn = {2193-8229}, abstract = {The appearance and dissemination of antibiotic-resistant bacteria, particularly in specific closed environments such as intensive care units of acute care hospitals, have become a major health concern. The intestinal microbiota has various functions including host protection from overgrowth or colonization by unwanted bacteria. The exposure to antibiotics significantly reduces the bacterial density of intestinal microbiota leaving an ecologic void that can be occupied by potentially pathogenic and/or resistant bacteria frequently present in hospital settings. Consequently, the intestinal microbiota of inpatients acts as a major reservoir and plays a critical role in perpetuating the spread of resistant bacteria. There are novel innovative methods to protect the host microbiota during antibiotic treatment, but they do not offer a solution for already established colonization by resistant microorganisms. Fecal microbiota transfer (FMT) is a promising intervention to achieve this goal; however, controlled trials report lower success rates than initial retrospective studies, especially in case of gram negatives. The aim of the present article is to highlight the importance of the intestinal microbiota in the global spread of multi-drug-resistant (MDR) microorganisms and to review the recent advances to protect the human microbiota from the action of antibiotics as well as a critical discussion about the evidence of decolonization of MDR microorganisms by FMT.}, }
@article {pmid31644957, year = {2019}, author = {Cammarota, G and Gallo, A and Bibbò, S}, title = {Fecal microbiota transplant for C. difficile infection: Just say yes.}, journal = {Anaerobe}, volume = {60}, number = {}, pages = {102109}, doi = {10.1016/j.anaerobe.2019.102109}, pmid = {31644957}, issn = {1095-8274}, abstract = {The burden of Clostridium difficile associated diarrhea is a worrying clinical issue worldwide, mainly as regarding the high incidence of recurrences after standard antibiotic therapy and the risk for more severe clinical manifestations. For this reason, new and more effective therapies are needed for the treatment of recurrent episodes. Fecal microbiota transplantation seems to be a valid tool considering the mechanism of action and the growing number of studies that demonstrate its clinical efficacy.}, }
@article {pmid31639033, year = {2019}, author = {Dai, M and Liu, Y and Chen, W and Buch, H and Shan, Y and Chang, L and Bai, Y and Shen, C and Zhang, X and Huo, Y and Huang, D and Yang, Z and Hu, Z and He, X and Pan, J and Hu, L and Pan, X and Wu, X and Deng, B and Li, Z and Cui, B and Zhang, F}, title = {Rescue fecal microbiota transplantation for antibiotic-associated diarrhea in critically ill patients.}, journal = {Critical care (London, England)}, volume = {23}, number = {1}, pages = {324}, pmid = {31639033}, issn = {1466-609X}, support = {-//Intestine Initiative Foundation/International ; BE2018751//Primary Research &amp; Development Plan of Jiangsu Province/International ; -//Jiangsu Provincial Medical Innovation Team/International ; 81600417//National Natural Science Foundation of China/International ; 2015BAI13B07//China Clinical Research Center for Digestive Diseases/International ; }, abstract = {BACKGROUND: Antibiotic-associated diarrhea (AAD) is a risk factor for exacerbating the outcome of critically ill patients. Dysbiosis induced by the exposure to antibiotics reveals the potential therapeutic role of fecal microbiota transplantation (FMT) in these patients. Herein, we aimed to evaluate the safety and potential benefit of rescue FMT for AAD in critically ill patients.<br><br>METHODS: A series of critically ill patients with AAD received rescue FMT from Chinese fmtBank, from September 2015 to February 2019. Adverse events (AEs) and rescue FMT success which focused on the improvement of abdominal symptoms and post-ICU survival rate during a minimum of 12 weeks follow-up were assessed.<br><br>RESULTS: Twenty critically ill patients with AAD underwent rescue FMT, and 18 of them were included for analysis. The mean of Acute Physiology and Chronic Health Evaluation (APACHE) II scores at intensive care unit (ICU) admission was 21.7 ± 8.3 (range 11-37). Thirteen patients received FMT through nasojejunal tube, four through gastroscopy, and one through enema. Patients were treated with four (4.2 ± 2.1, range 2-9) types of antibiotics before and during the onset of AAD. 38.9% (7/18) of patients had FMT-related AEs during follow-up, including increased diarrhea frequency, abdominal pain, increased serum amylase, and fever. Eight deaths unrelated to FMT occurred during follow-up. One hundred percent (2/2) of abdominal pain, 86.7% (13/15) of diarrhea, 69.2% (9/13) of abdominal distention, and 50% (1/2) of hematochezia were improved after FMT. 44.4% (8/18) of patients recovered from abdominal symptoms without recurrence and survived for a minimum of 12 weeks after being discharged from ICU.<br><br>CONCLUSION: In this case series studying the use of FMT in critically ill patients with AAD, good clinical outcomes without infectious complications were observed. These findings could potentially encourage researchers to set up new clinical trials that will provide more insight into the potential benefit and safety of the procedure in the ICU.<br><br>TRIAL REGISTRATION: ClinicalTrials.gov, Number NCT03895593 . Registered 29 March 2019 (retrospectively registered).}, }
@article {pmid31634731, year = {2019}, author = {Gori, S and Inno, A and Belluomini, L and Bocus, P and Bisoffi, Z and Russo, A and Arcaro, G}, title = {Gut microbiota and cancer: How gut microbiota modulates activity, efficacy and toxicity of antitumoral therapy.}, journal = {Critical reviews in oncology/hematology}, volume = {143}, number = {}, pages = {139-147}, doi = {10.1016/j.critrevonc.2019.09.003}, pmid = {31634731}, issn = {1879-0461}, mesh = {Animals ; Antineoplastic Agents/adverse effects/pharmacology/*therapeutic use ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immunotherapy/methods ; Neoplasms/*drug therapy/*microbiology ; }, abstract = {Gut microbiota is involved in gastrointestinal carcinogenesis. Also, it modulates the activity, efficacy and toxicity of several chemotherapy agents, such as gemcitabine, cyclophosphamide, irinotecan, cisplatin and 5-Fluorouracil, and target therapy, such as tyrosine kinase inhibitors. More recently, accumulating data suggest that the composition of gut microbiota may also affect efficacy and toxicity of cancer immunotherapy. Therefore, the manipulation of gut microbiota through antibiotics, probiotics, prebiotics or fecal transplantation has been investigating with the aim to improve efficacy and mitigate toxicity of anticancer drugs.}, }
@article {pmid31628414, year = {2019}, author = {Houben, T and Penders, J and Oligschlaeger, Y and Dos Reis, IAM and Bonder, MJ and Koonen, DP and Fu, J and Hofker, MH and Shiri-Sverdlov, R}, title = {Hematopoietic Npc1 mutation shifts gut microbiota composition in Ldlr-/- mice on a high-fat, high-cholesterol diet.}, journal = {Scientific reports}, volume = {9}, number = {1}, pages = {14956}, pmid = {31628414}, issn = {2045-2322}, support = {VIDI 864.13.013//ZonMw (Netherlands Organisation for Health Research and Development)/ ; VIDI 016.126.327//ZonMw (Netherlands Organisation for Health Research and Development)/ ; ASPASIA 015.008.043//ZonMw (Netherlands Organisation for Health Research and Development)/ ; }, abstract = {While the link between diet-induced changes in gut microbiota and lipid metabolism in metabolic syndrome (MetS) has been established, the contribution of host genetics is rather unexplored. As several findings suggested a role for the lysosomal lipid transporter Niemann-Pick type C1 (NPC1) in macrophages during MetS, we here explored whether a hematopoietic Npc1 mutation, induced via bone marrow transplantation, influences gut microbiota composition in low-density lipoprotein receptor knockout (Ldlr-/-) mice fed a high-fat, high-cholesterol (HFC) diet for 12 weeks. Ldlr-/- mice fed a HFC diet mimic a human plasma lipoprotein profile and show features of MetS, providing a model to explore the role of host genetics on gut microbiota under MetS conditions. Fecal samples were used to profile the microbial composition by 16 s ribosomal RNA gene sequencing. The hematopoietic Npc1 mutation shifted the gut microbiota composition and increased microbial richness and diversity. Variations in plasma lipid levels correlated with microbial diversity and richness as well as with several bacterial genera. This study suggests that host genetic influences on lipid metabolism affect the gut microbiome under MetS conditions. Future research investigating the role of host genetics on gut microbiota might therefore lead to identification of diagnostic and therapeutic targets for MetS.}, }
@article {pmid31627163, year = {2019}, author = {Lützhøft, DO and Sánchez-Alcoholado, L and Tougaard, P and Junker Mentzel, CM and Kot, W and Nielsen, DS and Hansen, AK}, title = {Short communication: Gut microbial colonization of the mouse colon using faecal transfer was equally effective when comparing rectal inoculation and oral inoculation based on 16S rRNA sequencing.}, journal = {Research in veterinary science}, volume = {126}, number = {}, pages = {227-232}, doi = {10.1016/j.rvsc.2019.09.009}, pmid = {31627163}, issn = {1532-2661}, mesh = {*Administration, Oral ; Animals ; Anti-Bacterial Agents/administration &amp; dosage ; Colon/microbiology ; Fecal Microbiota Transplantation/methods/*veterinary ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Male ; Mice/microbiology/*surgery ; Mice, Inbred C57BL ; RNA, Bacterial/analysis ; RNA, Ribosomal, 16S/analysis ; Random Allocation ; Specific Pathogen-Free Organisms/drug effects ; }, abstract = {In the present study we hypothesized that a higher degree of gut microbiota (GM) transfer and colonization could be reached by rectal inoculation compared to oral inoculation, which is commonly used in mouse studies for GM transfer. We treated C57BL/6NTac Specific Pathogen Free (SPF) mice with antibiotics and subsequently we inoculated these with GM from donor mice of the same strain by either the oral or the rectal inoculation method. 16S rRNA gene sequencing of the colon microbiota showed no difference in microbial community on account of inoculation method as determined by unweighted UniFrac distance metrics in C57BL/6NTac SPF mice. In addition, qPCR analysis on colon tissue revealed no difference in mRNA expression between the inoculation methods. Next, the SPF mice were compared to germ-free (GF)-mice to identify differences in inoculation efficacy. Whether the mice were antibiotic treated SPF or GF clearly influenced GM determined by 16S rRNA gene sequencing where the SPF mice experienced up-regulation of S24-7 (p = .0001) and a decrease in Rikenellaceae (p = .016) compared to GF mice. qPCR analysis on colon tissue revealed up-regulation in mRNA gene expression of Il6, Il10, Reg3g and transcription factor RORγt (Rorc) in GF mice compared to SPF mice on a significant level (p < .05). This gene expression profile is consistent with post colonization development of the intestinal barrier in GF mice.}, }
@article {pmid31624757, year = {2019}, author = {Xie, WR and Yang, XY and Xia, HH and Wu, LH and He, XX}, title = {Hair regrowth following fecal microbiota transplantation in an elderly patient with alopecia areata: A case report and review of the literature.}, journal = {World journal of clinical cases}, volume = {7}, number = {19}, pages = {3074-3081}, pmid = {31624757}, issn = {2307-8960}, abstract = {BACKGROUND: Alopecia areata is a hair loss disease associated with genetics, autoimmunity, and other factors. There is an intriguing link between alopecia areata and gut dysbiosis. Fecal microbiota transplantation (FMT) has been recommended to treat Clostridium difficile (previously known as Clostridioides difficile) infection, and has also shown potentials in the treatment of inflammatory bowel disease, irritable bowel syndrome, and non-alcohol fatty liver disease.<br><br>CASE SUMMARY: An 86-year-old man, with a history of sigmoid colon carcinoma, suffered from recurrent abdominal pain and distension, and diarrhea for six months, with inappetence. At admission, he was also diagnosed with depression. Upon physical examination, the patient presented with a 1.5 cm × 2.0 cm alopecia areata on his right occiput. Due to the negative results of laboratory testing, capsule endoscopy, and colonoscopy, the patient was diagnosed with noninfectious diarrhea, depressive disorder, and patchy alopecia areata. Considering that noninfectious diarrhea in the elderly patient was mainly caused by gut dysbiosis, he was given six rounds of FMT. His diarrhea improved remarkably one month after FMT, with improved appetite and disappearance of abdominal pain, distension, and depressive symptoms. Surprisingly, he reported new hair growth on the affected region of his scalp, with some of his white hair gradually turning to black, without taking any other therapies for alopecia areata before and after FMT.<br><br>CONCLUSION: FMT might act as a potential therapy for patients who suffer from alopecia areata. Large and well-designed studies are required to confirm the role of FMT in alopecia areata.}, }
@article {pmid31623075, year = {2019}, author = {Barathikannan, K and Chelliah, R and Rubab, M and Daliri, EB and Elahi, F and Kim, DH and Agastian, P and Oh, SY and Oh, DH}, title = {Gut Microbiome Modulation Based on Probiotic Application for Anti-Obesity: A Review on Efficacy and Validation.}, journal = {Microorganisms}, volume = {7}, number = {10}, pages = {}, pmid = {31623075}, issn = {2076-2607}, support = {2018-2019//Kangwon National University/ ; P00004989//Korean Ministry of SMEs and start-ups (MSS), under the supervision of the Korea Institute for Advancement of Technology (KIAT), &quot;Regional specialized industrial development program/ ; 2018007551//National Research Foundation of Korea (NRF)/ ; }, abstract = {The growing prevalence of obesity has become an important problem worldwide as obesity has several health risks. Notably, factors such as excessive food consumption, a sedentary way of life, high sugar consumption, a fat-rich diet, and a certain genetic profile may lead to obesity. The present review brings together recent advances regarding the significance of interventions involving intestinal gut bacteria and host metabolic phenotypes. We assess important biological molecular mechanisms underlying the impact of gut microbiota on hosts including bile salt metabolism, short-chain fatty acids, and metabolic endotoxemia. Some previous studies have shown a link between microbiota and obesity, and associated disease reports have been documented. Thus, this review focuses on obesity and gut microbiota interactions and further develops the mechanism of the gut microbiome approach related to human obesity. Specifically, we highlight several alternative diet treatments including dietary changes and supplementation with probiotics. The future direction or comparative significance of fecal transplantation, synbiotics, and metabolomics as an approach to the modulation of intestinal microbes is also discussed.}, }
@article {pmid31622538, year = {2020}, author = {Zou, M and Jie, Z and Cui, B and Wang, H and Feng, Q and Zou, Y and Zhang, X and Yang, H and Wang, J and Zhang, F and Jia, H}, title = {Fecal microbiota transplantation results in bacterial strain displacement in patients with inflammatory bowel diseases.}, journal = {FEBS open bio}, volume = {10}, number = {1}, pages = {41-55}, pmid = {31622538}, issn = {2211-5463}, support = {102/2016/A3//Macau Technology Development Fund/ ; JSGG20160229172752028//Shenzhen Municipal Government of China/ ; JCYJ20160229172757249//Shenzhen Municipal Government of China/ ; 81670606//National Natural Science Foundation of China/ ; 81670495//National Natural Science Foundation of China/ ; }, abstract = {Fecal microbiota transplantation (FMT), which is thought to have the potential to correct dysbiosis of gut microbiota, has been used to treat inflammatory bowel disease (IBD) for almost a decade. Here, we report an interventional prospective cohort study performed to elucidate the extent of and processes underlying microbiota engraftment in IBD patients after FMT treatment. The cohort included two categories of patients: (a) patients with moderate to severe Crohn's disease (CD) (Harvey-Bradshaw Index ≥ 7, n = 11) and (b) patients with ulcerative colitis (UC) (Montreal classification S2 and S3, n = 4). All patients were treated with a single FMT (via mid-gut, from healthy donors), and follow-up visits were performed at baseline, 3 days, 1 week, and 1 month after FMT (missing time points included). At each follow-up time point, fecal samples and clinical metadata were collected. For comparative analysis, 10 fecal samples from 10 healthy donors were included to represent the diversity level of normal gut microbiota. Additionally, the metagenomic data of 25 fecal samples from five individuals with metabolic syndrome who underwent autologous FMT treatment were downloaded from a previous published paper to represent fluctuations in microbiota induced during FMT. All fecal samples underwent shotgun metagenomic sequencing. We found that 3 days after FMT, 11 out of 15 recipients were in remission (three out of four UC recipients; 8 out of 11 CD recipients). Generally, bacterial colonization was observed to be lower in CD recipients than in UC recipients at both species and strain levels. Furthermore, across species, different strains displayed disease-specific displacement advantages under two-disease status. Finally, most post-FMT species (> 80%) could be properly predicted (area under the curve > 85%) using a random forest classification model, with the gut microbiota composition and clinical parameters of pre-FMT recipients acting as factors that contribute to prediction accuracy.}, }
@article {pmid31620079, year = {2019}, author = {Mandrioli, J and Amedei, A and Cammarota, G and Niccolai, E and Zucchi, E and D'Amico, R and Ricci, F and Quaranta, G and Spanu, T and Masucci, L}, title = {FETR-ALS Study Protocol: A Randomized Clinical Trial of Fecal Microbiota Transplantation in Amyotrophic Lateral Sclerosis.}, journal = {Frontiers in neurology}, volume = {10}, number = {}, pages = {1021}, pmid = {31620079}, issn = {1664-2295}, abstract = {Background and Rationale: Among the key players in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), microglia and T regulatory lymphocytes (Treg) are candidate cells for modifying the course of the disease. The gut microbiota (GM) acts by shaping immune tolerance and regulating the Treg number and suppressive function, besides circulating neuropeptides, and other immune cells that play in concert through the gut-brain axis. Previous mouse models have shown an altered enteric flora in early stage ALS, pointing to a possible GM role in ALS pathogenesis. Fecal Microbial Transplantation (FMT) is a well-known therapeutic intervention used to re-establish the proper microenvironment and to modulate enteric and systemic immunity. Methods: We are going to perform a multicenter randomized double-blind clinical trial employing FMT as a therapeutic intervention for ALS patients (NCT0376632). Forty-two ALS patients, at an early stage, will be enrolled with a 2:1 allocation ratio (28 FMT-treated patients vs. 14 controls). Study duration will be 12 months per patient. Three endoscopic procedures for intestinal biopsies in FMT and control groups are predicted at baseline, month 6 and month 12; at baseline and at month 6 fresh feces from healthy donors will be infused at patients in the intervention arm. The primary outcome is a significant change in Treg number between FMT-treated patients and control arm from baseline to month 6. Secondary outcomes include specific biological aims, involving in-depth analysis of immune cells and inflammatory status changes, central and peripheral biomarkers of ALS, besides comprehensive analysis of the gut, saliva and fecal microbiota. Other secondary aims include validated clinical outcomes of ALS (survival, forced vital capacity, and modifications in ALSFRS-R), besides safety and quality of life. Expected Results: We await FMT to increase Treg number and suppressive functionality, switching the immune system surrounding motorneurons to an anti-inflammatory, neuroprotective status. Extensive analysis on immune cell populations, cytokines levels, and microbiota (gut, fecal and saliva) will shed light on early processes possibly leading the degenerative ALS course. Conclusions: This is the first trial with FMT as a potential intervention to modify immunological response to ALS and disease progression at an early stage.}, }
@article {pmid31617299, year = {2020}, author = {Spinner, JA and Bocchini, CE and Luna, RA and Thapa, S and Balderas, MA and Denfield, SW and Dreyer, WJ and Nagy-Szakal, D and Ihekweazu, FD and Versalovic, J and Savidge, T and Kellermayer, R}, title = {Fecal microbiota transplantation in a toddler after heart transplant was a safe and effective treatment for recurrent Clostridiodes difficile infection: A case report.}, journal = {Pediatric transplantation}, volume = {24}, number = {1}, pages = {e13598}, pmid = {31617299}, issn = {1399-3046}, support = {U01 AI124290/AI/NIAID NIH HHS/United States ; U01-AI24290/NH/NIH HHS/United States ; }, abstract = {Pediatric recipients of SOT have a significantly increased risk of Clostridiodes (formerly Clostridium) difficile infection (CDI), which is associated with adverse outcomes after SOT. Alterations to the intestinal microbiota community structure increase the risk of CDI. FMT is a safe and effective treatment for recurrent CDI in immunocompetent children and adults. While there are increasing data that FMT in immunosuppressed patients is safe and effective without increased risk of infection, data regarding safety and efficacy of FMT in children after SOT are limited. To our knowledge, we report the youngest immunocompromised patient to undergo FMT and the third overall case of FMT in a child after HTx. Our patient presented with five episodes of rCDI in 6 months, and 16S rRNA genetic analysis revealed significant loss of overall microbiota community structure and diversity prior to FMT compared with a donor and a healthy, age-matched control. After FMT, marked and prolonged (at least 16 months) shifts in the recipient microbiota community structure and diversity were evident, approaching that of donor and healthy, age-matched control. FMT was well tolerated, restored microbial diversity without any graft or transplant complications, and prevented further rCDI episodes after more than 4 years of follow-up.}, }
@article {pmid31617205, year = {2020}, author = {Sharma, A and Das, P and Buschmann, M and Gilbert, JA}, title = {The Future of Microbiome-Based Therapeutics in Clinical Applications.}, journal = {Clinical pharmacology and therapeutics}, volume = {107}, number = {1}, pages = {123-128}, doi = {10.1002/cpt.1677}, pmid = {31617205}, issn = {1532-6535}, abstract = {The microbiome, a collection of microorganisms, their genomes, and the surrounding environmental conditions, is akin to a human organ, and knowledge is emerging on its role in human health and diseases. The influence of the microbiome in drug response has only been investigated in detail for the last 10 years. The human microbiome is a complex and highly dynamic system, which varies dramatically between individuals, yet there exists a common core microbiome that is heritable and can be transmitted to progeny. Here, we review the role of the human microbiome, which is now widely accepted as a major factor that drives the interpersonal variation in therapeutic response. We describe examples in which the microbiome modifies drug action. Despite its complexity, the microbiome can be readily altered, with the potential to increase the benefits and reduce the toxicity and side effects associated with pharmaceutical drugs. The potential of new microbiome-based strategies, such as fecal microbiota transplant, probiotics, and phage therapy, as promising medical therapeutics are outlined. We also suggest a combination reductionist and system-level approaches that could be applied to further investigate the role of microbiota in drug metabolism modulation of drug response. Finally, we emphasize the importance of combining microbiome and pharmacology studies as a novel means to treat disease and reduce side effects.}, }
@article {pmid31616437, year = {2019}, author = {Heimesaat, MM and Mrazek, K and Bereswill, S}, title = {Murine Fecal Microbiota Transplantation Alleviates Intestinal and Systemic Immune Responses in Campylobacter jejuni Infected Mice Harboring a Human Gut Microbiota.}, journal = {Frontiers in immunology}, volume = {10}, number = {}, pages = {2272}, pmid = {31616437}, issn = {1664-3224}, abstract = {Human campylobacteriosis constitutes a zoonotic food-borne disease and a progressively rising health burden of significant socioeconomic impact. We have recently shown that conventional mice are protected from Campylobacter jejuni infection, which was not the case for human microbiota associated (hma) mice indicating that the host-specific gut microbiota composition primarily determines susceptibility to or resistance against C. jejuni infection. In our present preclinical intervention study we addressed whether gut microbiota changes in stably C. jejuni infected hma mice following murine fecal microbiota transplantation (mFMT) could alleviate pathogen-induced immune responses. To accomplish this, secondary abiotic C57BL/6 mice were generated by broad-spectrum antibiotic treatment, perorally reassociated with a complex human gut microbiota and challenged with C. jejuni by gavage. Seven days later C. jejuni infected hma mice were subjected to peroral mFMT on 3 consecutive days. Within a week post-mFMT fecal pathogenic burdens had decreased by two orders of magnitude, whereas distinct changes in the gut microbiota composition with elevated numbers of lactobacilli and bifidobacteria could be assessed. In addition, mFMT resulted in less C. jejuni induced apoptotic responses in colonic epithelia, reduced numbers of macrophages and monocytes as well as of T lymphocytes in the large intestinal mucosa and lamina propria and in less distinct intestinal pro-inflammatory cytokine secretion as compared to mock challenge. Strikingly, inflammation dampening effects of mFMT were not restricted to the intestinal tract, but could also be observed systemically as indicated by elevated serum concentrations of pro-inflammatory cytokines such as TNF-α, IL-12p70, and IL-6 in C. jejuni infected hma mice of the mock, but not the mFMT cohort. In conclusion, our preclinical mFMT intervention study provides evidence that changes in the gut microbiota composition which might be achieved by pre- or probiotic formulations may effectively lower intestinal C. jejuni loads, dampen both, pathogen-induced intestinal and systemic inflammatory sequelae and may represent a useful tool to treat continuous shedding of C. jejuni by asymptomatic carriers which is critical in the context of food production, hospitalization and immunosuppression.}, }
@article {pmid31613980, year = {2019}, author = {Ersöz Alan, B and Gülerman, F}, title = {[The Role of Gut Microbiota in Autism Spectrum Disorder].}, journal = {Turk psikiyatri dergisi = Turkish journal of psychiatry}, volume = {30}, number = {3}, pages = {210-219}, pmid = {31613980}, issn = {1300-2163}, abstract = {Human microbiota are colonies of microorganisms located in different parts of the human body with diverse functions. Healthy gut microbiota comprises differing ratios of microoganisms wholly contributing to metabolic and other molecular reactions in a healthy, functioning body. After the demonstration of the bidirectional interaction between the central nervous system and gut microbiota through neuroendocrine, neuroimmune, and autonomic nervous mechanisms, investigations have been started on the microbiota-gut-brain axis in psychiatric disorders. Autism spectrum disorder (ASD), which is a neurodevelopmental disorder of early childhood, is one of these disorders. Most of such studies were cross-sectional and mainly investigated the bacterial species. Changes in gut microbiota composition and the leaky gut syndrome are some of the hypotheses proposed to explain the core symptoms and gastrointestinal (GI) symptoms of ASD. Probiotics, prebiotics, fecal microbiota transplantation, diet have been proposed as treatment options. However, the role of microbiota in diagnosis, followup, and treatment is not yet clear. The bidirectional interaction between central nervous system and intestinal microbiota makes it difficult to establish the cause-effect relationship. The current data on microbiota may be useful to plan patient-specific treatment in autistic children with GI symptoms. This article aims to review the results of the studies on microbiota in animal models and children and discuss the emerging clinical relationship of ASD and gut microbiota.}, }
@article {pmid31611298, year = {2020}, author = {Ng, SC and Kamm, MA and Yeoh, YK and Chan, PKS and Zuo, T and Tang, W and Sood, A and Andoh, A and Ohmiya, N and Zhou, Y and Ooi, CJ and Mahachai, V and Wu, CY and Zhang, F and Sugano, K and Chan, FKL}, title = {Scientific frontiers in faecal microbiota transplantation: joint document of Asia-Pacific Association of Gastroenterology (APAGE) and Asia-Pacific Society for Digestive Endoscopy (APSDE).}, journal = {Gut}, volume = {69}, number = {1}, pages = {83-91}, pmid = {31611298}, issn = {1468-3288}, mesh = {Anti-Bacterial Agents/pharmacology ; Clostridium difficile ; Endoscopy, Gastrointestinal ; Enterocolitis, Pseudomembranous/therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome/drug effects/physiology ; Humans ; Inflammatory Bowel Diseases/therapy ; Prognosis ; Recurrence ; Tissue Donors ; Treatment Outcome ; }, abstract = {OBJECTIVE: The underlying microbial basis, predictors of therapeutic outcome and active constituent(s) of faecal microbiota transplantation (FMT) mediating benefit remain unknown. An international panel of experts presented key elements that will shape forthcoming FMT research and practice.<br><br>DESIGN: Systematic search was performed, FMT literature was critically appraised and a 1-day round-table discussion was conducted to derive expert consensus on key issues in FMT research.<br><br>RESULTS: 16 experts convened and discussed five questions regarding (1) the role of donor and recipient microbial (bacteria, viruses, fungi) parameters in FMT; (2) methods to assess microbiota alterations; (3) concept of keystone species and microbial predictors of FMT, (4) influence of recipient profile and antibiotics pretreatment on FMT engraftment and maintenance and (5) new developments in FMT formulations and delivery. The panel considered that variable outcomes of FMT relate to compositional and functional differences in recipient's microbiota, and likely donor-associated and recipient-associated physiological and genetic factors. Taxonomic composition of donor intestinal microbiota may influence the efficacy of FMT in recurrent Clostridioides difficile infections and UC. FMT not only alters bacteria composition but also establishes trans-kingdom equilibrium between gut fungi, viruses and bacteria to promote the recovery of microbial homeostasis. FMT is not a one size fits all and studies are required to identify microbial components that have specific effects in patients with different diseases.<br><br>CONCLUSION: FMT requires optimisation before their therapeutic promise can be evaluated for different diseases. This summary will guide future directions and priorities in advancement of the science and practice of FMT.}, }
@article {pmid31609734, year = {2020}, author = {Abu-Sbeih, H and Ali, FS and Wang, Y}, title = {Immune-checkpoint inhibitors induced diarrhea and colitis: a review of incidence, pathogenesis and management.}, journal = {Current opinion in gastroenterology}, volume = {36}, number = {1}, pages = {25-32}, doi = {10.1097/MOG.0000000000000593}, pmid = {31609734}, issn = {1531-7056}, abstract = {PURPOSE OF REVIEW: Diarrhea and colitis are among the most commonly encountered immune-mediated adverse events among patients receiving antiprogrammed cell death protein/ligand-1 (PD-1/L1) as well as anticytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies. With growing indications and widespread use of immune checkpoint inhibitors, it is imperative to summarize the current body of evidence concerning the incidence, pathogenesis, risk factors, diagnostic challenges, and treatment options currently available for the management of immune-mediated diarrhea and colitis. Additionally, with emerging evidence analyzing the resumption of immune checkpoint inhibitors, it is pivotal to summarize our current understanding and future challenges.<br><br>RECENT FINDINGS: Immune-mediated diarrhea and colitis can potentially be a viable surrogate marker for improved survival as it is validated further in large-scale studies. Early endoscopic evaluation can aid in the identification of patients at risk of developing steroid refractory immune-mediated colitis, and hence can be chosen to receive early add-on therapy with infliximab, vedolizumab or fecal microbiota transplantation, an emerging treatment option for immune-mediated diarrhea and colitis. Resuming immune checkpoint inhibitors carries a manageable risk of recurrent diarrhea and colitis, with most cases being mild and effectively managed with immunosuppressive therapy.<br><br>SUMMARY: As our understanding of immune-mediated diarrhea and colitis grows, it is likely that this clinicopathologic entity will represent more than just an adverse event. With a growing number of treatment options, the management algorithms for immune-mediated diarrhea/colitis are likely to evolve in the future.}, }
@article {pmid31609455, year = {2019}, author = {Bruno, G and Gagliardi, A and Oliva, A and Trancassini, M and Macone, A and Cicerone, C and D'Abramo, A and Iebba, V and Auria, S and Bonfiglio, G and Zingaropoli, MA and D'Ettorre, G and Badiali, D and Vullo, V and Corazziari, ES and Schippa, S}, title = {Fecal Microbial Transplantation impact on gut microbiota composition and metabolome, microbial translocation and T-lymphocyte immune activation in recurrent Clostridium difficile infection patients.}, journal = {The new microbiologica}, volume = {42}, number = {4}, pages = {221-224}, pmid = {31609455}, issn = {1121-7138}, mesh = {Aged ; Aged, 80 and over ; *Clostridium Infections/immunology/microbiology/therapy ; *Clostridium difficile ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; *Metabolome ; Middle Aged ; Recurrence ; *T-Lymphocytes/immunology ; Treatment Outcome ; }, abstract = {This short communication reports the preliminary results of Fecal Microbial Transplantation (FMT) impact on microbiota, microbial translocation (MT), and immune activation in four recurrent Clostridium difficile infection (R-CDI) patients. After FMT a restore of gut microbiota composition with a significant increase of fecal acetyl-putrescine and spermidine and fecal acetate and butyrate, a decrease of immune activation of T cells CD4+ and CD8+levels, and of LPS binding protein (LBP) level, were observed. Preliminary results indicate that FMT seems to be helpful not only as a CDI radical cure, with an impact on fecal microbiota and metabolome profiles, but also on MT and immune activation.}, }
@article {pmid31607571, year = {2019}, author = {Lin, TC and Hung, YP and Ko, WC and Ruan, JW}, title = {Fecal microbiota transplantation for Clostridium difficile infection in Taiwan: Establishment and implementation.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {52}, number = {6}, pages = {841-850}, doi = {10.1016/j.jmii.2019.08.009}, pmid = {31607571}, issn = {1995-9133}, abstract = {Clostridium difficile infection (CDI) remains a major public health issue, and fecal microbiota transplantation (FMT) has become one of the standard therapies for recurrent or refractory CDI. When compared to medical therapies, such as metronidazole or vancomycin, FMT has a high rate of treatment response with acceptable safety and efficiency. Following promulgation of the amendments in September 2018 in Taiwan, FMT has been indicated for recurrent or refractory CDI. The Taiwan Microbiota Consortium contributed to the Taiwan FMT Expert Consensus, which established basic norms and stipulated essential principles, including the indications for transplantation, eligible locations and personnel, donor screening policies, fecal sample handling, and post-FMT follow-up. However, establishing an eligible FMT team in a qualified hospital remains a clinical challenge, and the requirement for facilities and well-screened donors impedes the implementation of FMT. In this review, we aim to provide domestic FMT teams with explicit instructions to facilitate realization and increase the practice of FMT. Based on the Taiwan FMT Expert Consensus and current regulations, we performed a literature review and integrated the experiences of Taiwanese multidisciplinary experts into this article. The content intends to offer clinicians up-to-date evidence and highlight the essential points of FMT.}, }
@article {pmid31606552, year = {2020}, author = {Chu, H and Duan, Y and Lang, S and Jiang, L and Wang, Y and Llorente, C and Liu, J and Mogavero, S and Bosques-Padilla, F and Abraldes, JG and Vargas, V and Tu, XM and Yang, L and Hou, X and Hube, B and Stärkel, P and Schnabl, B}, title = {The Candida albicans exotoxin candidalysin promotes alcohol-associated liver disease.}, journal = {Journal of hepatology}, volume = {72}, number = {3}, pages = {391-400}, pmid = {31606552}, issn = {1600-0641}, support = {R01 AA020703/AA/NIAAA NIH HHS/United States ; I01 BX004594/BX/BLRD VA/United States ; P30 DK120515/DK/NIDDK NIH HHS/United States ; R01 AA024726/AA/NIAAA NIH HHS/United States ; P50 AA011999/AA/NIAAA NIH HHS/United States ; U01 AA026939/AA/NIAAA NIH HHS/United States ; }, abstract = {BACKGROUND &amp; AIMS: Alcohol-associated liver disease is a leading indication for liver transplantation and a leading cause of mortality. Alterations to the gut microbiota contribute to the pathogenesis of alcohol-associated liver disease. Patients with alcohol-associated liver disease have increased proportions of Candida spp. in the fecal mycobiome, yet little is known about the effect of intestinal Candida on the disease. Herein, we evaluated the contributions of Candida albicans and its exotoxin candidalysin in alcohol-associated liver disease.<br><br>METHODS: C. albicans and the extent of cell elongation 1 (ECE1) were analyzed in fecal samples from controls, patients with alcohol use disorder and those with alcoholic hepatitis. Mice colonized with different and genetically manipulated C. albicans strains were subjected to the chronic-plus-binge ethanol diet model. Primary hepatocytes were isolated and incubated with candidalysin.<br><br>RESULTS: The percentages of individuals carrying ECE1 were 0%, 4.76% and 30.77% in non-alcoholic controls, patients with alcohol use disorder and patients with alcoholic hepatitis, respectively. Candidalysin exacerbates ethanol-induced liver disease and is associated with increased mortality in mice. Candidalysin enhances ethanol-induced liver disease independently of the β-glucan receptor C-type lectin domain family 7 member A (CLEC7A) on bone marrow-derived cells, and candidalysin does not alter gut barrier function. Candidalysin can damage primary hepatocytes in a dose-dependent manner in vitro and is associated with liver disease severity and mortality in patients with alcoholic hepatitis.<br><br>CONCLUSIONS: Candidalysin is associated with the progression of ethanol-induced liver disease in preclinical models and worse clinical outcomes in patients with alcoholic hepatitis.<br><br>LAY SUMMARY: Candidalysin is a peptide toxin secreted by the commensal gut fungus Candida albicans. Candidalysin enhances alcohol-associated liver disease independently of the β-glucan receptor CLEC7A on bone marrow-derived cells in mice without affecting intestinal permeability. Candidalysin is cytotoxic to primary hepatocytes, indicating a direct role of candidalysin on ethanol-induced liver disease. Candidalysin might be an effective target for therapy in patients with alcohol-associated liver disease.}, }
@article {pmid31601212, year = {2019}, author = {Madar, PC and Petre, O and Baban, A and Dumitrascu, DL}, title = {Medical students' perception on fecal microbiota transplantation.}, journal = {BMC medical education}, volume = {19}, number = {1}, pages = {368}, pmid = {31601212}, issn = {1472-6920}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has become an emergent method in the therapy of several intestinal diseases, mainly in Clostridium difficile recurrence. The training of FMT in medical schools is at its beginning and in countries where FMT is only occasionally carried out, it is important to know the perception of medical students on FMT.<br><br>METHODS: We undertook a survey of 3rd year medical students not exposed to official academic information on FMT in order to find out their knowledge, beliefs and attitude toward FMT. A number of 80 students were asked to fill a dedicated online questionnaire.<br><br>RESULTS: 52 out of 80 third year medical students anonymously filled the questionnaire (65% response rate). 34% of respondents reported to have at least a medium level of knowledge regarding FMT. The top indication for FMT identified by 76.9% was C. difficile infection; however, 60% believed FMT to be a promising therapy for a high number of conditions and while almost all respondents (98.1%) would recommend it, 88.4% would explore other options first. Colonoscopy was considered the optimal method of delivery by 42.3%. Only 39% of participants believed that patients would accept FMT, however 71% considered that a more socially acceptable name for the procedure and anonymous donors would increase acceptance rate. The risk of transmitting a disease undetected by donor stool screening procedures to the recipient was the most worrying side effect considered by 75% of respondents. 54% believed that more research is required for FMT to enter clinical practice and 55.7% of respondents would enroll patients in controlled clinical trials.<br><br>CONCLUSIONS: Medical students not exposed to educational information on FMT seem to be somewhat well informed about this method and would recommend it to their patients. Students, however, need to know more on the indications of FMT.}, }
@article {pmid31600222, year = {2019}, author = {Duvallet, C and Zellmer, C and Panchal, P and Budree, S and Osman, M and Alm, EJ}, title = {Framework for rational donor selection in fecal microbiota transplant clinical trials.}, journal = {PloS one}, volume = {14}, number = {10}, pages = {e0222881}, pmid = {31600222}, issn = {1932-6203}, abstract = {Early clinical successes are driving enthusiasm for fecal microbiota transplantation (FMT), the transfer of healthy gut bacteria through whole stool, as emerging research is linking the microbiome to many different diseases. However, preliminary trials have yielded mixed results and suggest that heterogeneity in donor stool may play a role in patient response. Thus, clinical trials may fail because an ineffective donor was chosen rather than because FMT is not appropriate for the indication. Here, we describe a conceptual framework to guide rational donor selection to increase the likelihood that FMT clinical trials will succeed. We argue that the mechanism by which the microbiome is hypothesized to be associated with a given indication should inform how healthy donors are selected for FMT trials, categorizing these mechanisms into four disease models and presenting associated donor selection strategies. We next walk through examples based on previously published FMT trials and ongoing investigations to illustrate how donor selection might occur in practice. Finally, we show that typical FMT trials are not powered to discover individual taxa mediating patient responses, suggesting that clinicians should develop targeted hypotheses for retrospective analyses and design their clinical trials accordingly. Moving forward, developing and applying novel clinical trial design methodologies like rational donor selection will be necessary to ensure that FMT successfully translates into clinical impact.}, }
@article {pmid31599752, year = {2020}, author = {Shah, H and Zezos, P}, title = {Pouchitis: diagnosis and management.}, journal = {Current opinion in gastroenterology}, volume = {36}, number = {1}, pages = {41-47}, doi = {10.1097/MOG.0000000000000594}, pmid = {31599752}, issn = {1531-7056}, abstract = {PURPOSE OF REVIEW: Pouchitis is the most common complication in patients who undergo ileal pouch-anal anastomosis (IPAA), occurring more frequently in patients with ulcerative colitis. Pouchitis - the inflammation of the pouch - can be due to idiopathic or secondary causes. Chronic antibiotic-dependent pouchitis (CADP) and chronic antibiotic-resistant pouchitis (CARP) are the most difficult forms of chronic idiopathic pouchitis to treat. Crohn's disease of the pouch may develop de novo in ulcerative colitis patients following colectomy with IPAA. It carries a high risk for pouch failure, and its diagnosis and management are challenging. The purpose of this review is to illustrate the present trends in the diagnosis and treatment of idiopathic pouchitis and Crohn's disease of the pouch.<br><br>RECENT FINDINGS: The use of the newer biologic agents, vedolizumab and ustekinumab, has shown promising results in patients with CADP, CARP, and Crohn's disease of the pouch. Fecal microbiota transplantation has also been reported to have encouraging preliminary results in small studies and case series for the treatment of chronic pouchitis.<br><br>SUMMARY: Promising new treatments are emerging for difficult-to-treat forms of pouchitis. Larger prospective and head-to-head comparative studies among the various treatments are needed to evaluate the efficacy and safety of these agents across the pouchitis subgroups, and to identify predictors of response.}, }
@article {pmid31596218, year = {2019}, author = {Mashaqi, S and Gozal, D}, title = {Obstructive Sleep Apnea and Systemic Hypertension: Gut Dysbiosis as the Mediator?.}, journal = {Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine}, volume = {15}, number = {10}, pages = {1517-1527}, pmid = {31596218}, issn = {1550-9397}, abstract = {INTRODUCTION: Obstructive sleep apnea (OSA) and systemic hypertension (SH) are common and interrelated diseases. It is estimated that approximately 75% of treatment-resistant hypertension cases have an underlying OSA. Exploration of the gut microbiome is a new advance in medicine that has been linked to many comorbid illnesses, including SH and OSA. Here, we will review the literature in SH and gut dysbiosis, OSA and gut dysbiosis, and whether gut dysbiosis is common in both conditions.<br><br>METHODS: We reviewed the National Center for Biotechnology Information database, including PubMed and PubMed Central. We identified a total of 230 articles. The literature search was conducted using the phrase &quot;obstructive sleep apnea and gut dysbiosis.&quot; Only original research articles were included. This yielded a total of 12 articles.<br><br>RESULTS: Most of the research conducted in this field was on animal models, and almost all trials confirmed that intermittent hypoxia models resulted in gut dysbiosis. Gut dysbiosis, however, can cause a state of low-grade inflammation through damage to the gut wall barrier resulting in &quot;leaky gut.&quot; Neuroinflammation is a hallmark of the pathophysiology of OSA-induced SH.<br><br>CONCLUSIONS: Gut dysbiosis seems to be an important factor in the pathophysiology of OSA-induced hypertension. Reversing gut dysbiosis at an early stage through prebiotics and probiotics and fecal microbiota transplantation combined with positive airway pressure therapy may open new horizons of treatment to prevent SH. More studies are needed in humans to elicit the effect of positive airway pressure therapy on gut dysbiosis.}, }
@article {pmid31594750, year = {2019}, author = {Li, L and Li, X and Zhong, W and Yang, M and Xu, M and Sun, Y and Ma, J and Liu, T and Song, X and Dong, W and Liu, X and Chen, Y and Liu, Y and Abla, Z and Liu, W and Wang, B and Jiang, K and Cao, H}, title = {Gut microbiota from colorectal cancer patients enhances the progression of intestinal adenoma in Apcmin/+ mice.}, journal = {EBioMedicine}, volume = {48}, number = {}, pages = {301-315}, pmid = {31594750}, issn = {2352-3964}, abstract = {BACKGROUND: Accumulating evidence points to a close relationship between gut dysbiosis and colorectal cancer (CRC). As >90% of CRC develop from adenoma, we aimed to investigate the crucial role of imbalanced gut microbiota on the progression of intestinal adenoma.<br><br>METHODS: The Apcmin/+ mice gavage with phosphate-buffered saline (PBS), feces from healthy controls or CRC patients after antibiotic cocktails. The intestinal tissues were isolated for histopathology, western blotting, and RNA-seq. The microbiota of feces and short-chain fatty acids (SCFAs) were analysed by 16S rDNA Amplicon Sequencing and gas chromatography.<br><br>FINDINGS: The Apcmin/+mice gavaged by feces from CRC patients had more intestinal tumours compared with those fed with feces from healthy controls or PBS. Administration of feces from CRC patients increased tumour proliferation and decreased apoptosis in tumour cells, accompanied by impairment of gut barrier function and up-regulation the pro-inflammatory cytokines profile. The up-regulated the expression of β-catenin and cyclinD1 further indicating the activation of Wnt signalling pathway. The abundance of pathogenic bacteria was increased after FMT, while producing SCFAs bacteria and SCFAs production were decreased.<br><br>INTERPRETATION: Gut microbiota of CRC patients disrupted intestinal barrier, induced low-grade inflammation and dysbiosis. The altered gut microbiota enhanced the progression of intestinal adenomas in Apcmin/+mice, suggesting that a new strategy to target gut microbiota against CRC could be noted. FUND: The study was supported by the National Natural Science Foundation of China, Tianjin Research Programme of Application Foundation and Advanced Technology of China, and China Postdoctoral Science Foundation.}, }
@article {pmid31594647, year = {2019}, author = {Benno, P and Norin, E and Midtvedt, T and Hellström, PM}, title = {Therapeutic potential of an anaerobic cultured human intestinal microbiota, ACHIM, for treatment of IBS.}, journal = {Best practice &amp; research. Clinical gastroenterology}, volume = {40-41}, number = {}, pages = {101607}, doi = {10.1016/j.bpg.2019.03.003}, pmid = {31594647}, issn = {1532-1916}, mesh = {Adult ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Irritable Bowel Syndrome/pathology/*therapy ; Male ; Middle Aged ; }, abstract = {By administering an anaerobic cultivated human intestinal microbiota (ACHIM) via upper gastrointestinal route using endoscopy we aimed to rectify intestinal dysbiosis and simultaneously achieve a treatment response in IBS patients. The study population fulfilled the Rome III IBS criteria and comprised 50 patients. During 10 days, patients recorded the irritable bowel syndrome symptom severity scale (IBS-SSS) along with the Bristol stool scale and number of stools/day. The enrolled patients were categorized as follows: 37 with diarrhea, 5 with constipation and 8 with mixed symptoms. The treatment response showed reduction in a majority of patients, 32 of which with 50-point reduction of IBS-SSS and 21 with a 100-point IBS-SSS reduction. The percentage improvement was 36 (23-49) and 28 (18-38) for women and men respectively. Short-chain fatty acids were not changed. We consider fecal microbiota transplantation in the form of ACHIM as an option for the future therapeutic armamentarium in IBS. REGISTERED TRIAL: www.clinicaltrials.gov NCT02857257.}, }
@article {pmid31594178, year = {2019}, author = {Yin, G and Li, JF and Sun, YF and Ding, X and Zeng, JQ and Zhang, T and Peng, LH and Yang, YS and Zhao, H}, title = {[Fecal microbiota transplantation as a novel therapy for severe psoriasis].}, journal = {Zhonghua nei ke za zhi}, volume = {58}, number = {10}, pages = {782-785}, doi = {10.3760/cma.j.issn.0578-1426.2019.10.011}, pmid = {31594178}, issn = {0578-1426}, mesh = {Adult ; Endoscopy ; *Fecal Microbiota Transplantation/trends ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Intestines ; Irritable Bowel Syndrome/complications/microbiology/psychology/*therapy ; Male ; Psoriasis/psychology/*therapy ; Quality of Life ; Treatment Outcome ; Tumor Necrosis Factor-alpha/*blood ; }, abstract = {To explore the therapeutic effect of fecal microbiota transplantation (FMT) for severe psoriasis. A patient, male, 36 years old, diagnosed as severe plaque psoriasis for 10 years and irritable bowel syndrome (IBS) for 15 years, was administrated twice FMT via both upper endoscopy and colonoscopy with a 5-week interval. The following items were used to evaluate responses: body surface area (BSA), psoriasis area and severity index (PASI), dermatology life quality index (DLQI), histological examination, intestinal symptoms, adverse reactions and serum level of tumor necrosis factor (TNF)-α. After second FMT treatment for 5 weeks, aforementioned items were improved greatly compared with those before treatment. Moreover, IBS was completely relieved and no adverse reactions were observed during the treatment and follow-up. In conclusion, FMT could be a novel therapy for psoriasis. Further clinical trials are needed to provide solid evidences.}, }
@article {pmid31586663, year = {2019}, author = {Aggeletopoulou, I and Konstantakis, C and Assimakopoulos, SF and Triantos, C}, title = {The role of the gut microbiota in the treatment of inflammatory bowel diseases.}, journal = {Microbial pathogenesis}, volume = {137}, number = {}, pages = {103774}, doi = {10.1016/j.micpath.2019.103774}, pmid = {31586663}, issn = {1096-1208}, abstract = {The human intestinal microbiota coevolves with its host through a symbiotic relationship and exerts great influence on substantial functions including aspects of physiology, metabolism, nutrition and regulation of immune responses leading to physiological homeostasis. Over the last years, several studies have been conducted toward the assessment of the host-gut microbiota interaction, aiming to elucidate the mechanisms underlying the pathogenesis of several diseases. A defect on the microbiota-host crosstalk and the concomitant dysregulation of immune responses combined with genetic and environmental factors have been implicated in the pathogenesis of inflammatory bowel diseases (IBD). To this end, novel therapeutic options based on the gut microbiota modulation have been an area of extensive research interest. In this review we present the recent findings on the association of dysbiosis with IBD pathogenesis, we focus on the role of gut microbiota on the treatment of IBD and discuss the novel and currently available therapeutic strategies in manipulating the composition and function of gut microbiota in IBD patients. Applicable and emerging microbiota treatment modalities, such as the use of antibiotics, prebiotics, probiotics, postbiotics, synbiotics and fecal microbiota transplantation (FMT) constitute promising therapeutic options. However, the therapeutic potential of the aforementioned approaches is a topic of investigation and further studies are needed to elucidate their position in the present treatment algorithms of IBD.}, }
@article {pmid31586566, year = {2020}, author = {Song, M and Chan, AT and Sun, J}, title = {Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer.}, journal = {Gastroenterology}, volume = {158}, number = {2}, pages = {322-340}, pmid = {31586566}, issn = {1528-0012}, support = {K01 DK075386/DK/NIDDK NIH HHS/United States ; R01 DK105118/DK/NIDDK NIH HHS/United States ; R01 DK114126/DK/NIDDK NIH HHS/United States ; R03 DK089010/DK/NIDDK NIH HHS/United States ; K99 CA215314/CA/NCI NIH HHS/United States ; R00 CA215314/CA/NCI NIH HHS/United States ; K24 DK098311/DK/NIDDK NIH HHS/United States ; R01 CA137178/CA/NCI NIH HHS/United States ; R01 CA202704/CA/NCI NIH HHS/United States ; }, mesh = {Bacteria/isolation &amp; purification ; Colon/microbiology/pathology ; Colorectal Neoplasms/diagnosis/*epidemiology/etiology/prevention &amp; control ; Early Detection of Cancer/methods ; Exercise/*physiology ; Feeding Behavior/*physiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Incidence ; Intestinal Mucosa/microbiology/pathology ; Mass Screening/methods ; Risk Factors ; }, abstract = {Researchers have discovered associations between elements of the intestinal microbiome (including specific microbes, signaling pathways, and microbiota-related metabolites) and risk of colorectal cancer (CRC). However, it is unclear whether changes in the intestinal microbiome contribute to the development of sporadic CRC or result from it. Changes in the intestinal microbiome can mediate or modify the effects of environmental factors on risk of CRC. Factors that affect risk of CRC also affect the intestinal microbiome, including overweight and obesity; physical activity; and dietary intake of fiber, whole grains, and red and processed meat. These factors alter microbiome structure and function, along with the metabolic and immune pathways that mediate CRC development. We review epidemiologic and laboratory evidence for the influence of the microbiome, diet, and environmental factors on CRC incidence and outcomes. Based on these data, features of the intestinal microbiome might be used for CRC screening and modified for chemoprevention and treatment. Integrated prospective studies are urgently needed to investigate these strategies.}, }
@article {pmid31582175, year = {2020}, author = {Dougé, A and Bay, JO and Ravinet, A and Scanzi, J}, title = {[Intestinal microbiota and allogeneic stem cell transplantation].}, journal = {Bulletin du cancer}, volume = {107}, number = {1}, pages = {72-83}, doi = {10.1016/j.bulcan.2019.08.014}, pmid = {31582175}, issn = {1769-6917}, mesh = {Allografts ; Clostridium Infections/etiology/prevention &amp; control ; Clostridium difficile ; Disease Susceptibility ; Dysbiosis/etiology/microbiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects/physiology/radiation effects ; Graft vs Host Disease/etiology/microbiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Infections/etiology ; Neoplasms/microbiology/therapy ; Recurrence ; Transplantation Conditioning/adverse effects ; }, abstract = {Allogeneic hematopoïetic stem cell transplantation is one of the most efficient curative treatment for acute leukemia. But it is also a heavy process with an important risk of complications, particularly infection and graft versus host disease. Increasing data in literature show that an alteration of the intestinal microbiota of allogeneic stem cell recipients is associated with these complications. Indeed, treatments used during conditioning regimen lead to an impaired microbiota, which cannot fulfill its protective functions anymore. To limit this microbiota impairment, we could restore a healthy microbiota by a fecal microbiota transplantation, which has already shown its efficiency in the treatment of Clostridium difficile infection. The aim of this review is to describe the intestinal microbiota, the link between microbiota and complications of allogeneic stem cells transplantation, and the recent published data on fecal microbiota transplantation in this field.}, }
@article {pmid31578306, year = {2019}, author = {Drewes, JL and Corona, A and Sanchez, U and Fan, Y and Hourigan, SK and Weidner, M and Sidhu, SD and Simner, PJ and Wang, H and Timp, W and Oliva-Hemker, M and Sears, CL}, title = {Transmission and clearance of potential procarcinogenic bacteria during fecal microbiota transplantation for recurrent Clostridioides difficile.}, journal = {JCI insight}, volume = {4}, number = {19}, pages = {}, pmid = {31578306}, issn = {2379-3708}, support = {K99 CA230192/CA/NCI NIH HHS/United States ; T32 HD044355/HD/NICHD NIH HHS/United States ; }, abstract = {BACKGROUNDFecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI) in adults and children, but donor stool samples are currently screened for only a limited number of potential pathogens. We sought to determine whether putative procarcinogenic bacteria (enterotoxigenic Bacteroides fragilis, Fusobacterium nucleatum, and Escherichia coli harboring the colibactin toxin) could be durably transmitted from donors to patients during FMT.METHODSStool samples were collected from 11 pediatric rCDI patients and their respective FMT donors prior to FMT as well as from the patients at 2-10 weeks, 10-20 weeks, and 6 months after FMT. Bacterial virulence factors in stool DNA extracts and stool cultures were measured by quantitative PCR: Bacteroides fragilis toxin (bft), Fusobacterium adhesin A (fadA), and Escherichia coli colibactin (clbB).RESULTSFour of 11 patients demonstrated sustained acquisition of a procarcinogenic bacteria. Whole genome sequencing was performed on colony isolates from one of these donor/recipient pairs and demonstrated that clbB+ E. coli strains present in the recipient after FMT were identical to a strain present in the donor, confirming strain transmission. Conversely, 2 patients exhibited clearance of procarcinogenic bacteria following FMT from a negative donor.CONCLUSIONBoth durable transmission and clearance of procarcinogenic bacteria occurred following FMT, suggesting that additional studies on appropriate screening measures for FMT donors and the long-term consequences and/or benefits of FMT are warranted.FUNDINGCrohn's &amp; Colitis Foundation, the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University School of Medicine, the National Cancer Institute, and the Canadian Institutes of Health Research.}, }
@article {pmid31572686, year = {2019}, author = {Genton, L and Mareschal, J and Charretier, Y and Lazarevic, V and Bindels, LB and Schrenzel, J}, title = {Targeting the Gut Microbiota to Treat Cachexia.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {305}, pmid = {31572686}, issn = {2235-2988}, abstract = {Cachexia occurs in many chronic diseases and is associated with increased morbidity and mortality. It is treated by nutritional support but often with limited effectiveness, leading to the search of other therapeutic strategies. The modulation of gut microbiota, whether through pro-, pre-, syn- or antibiotics or fecal transplantation, is attracting ever-growing interest in the field of obesity, but could also be an interesting and innovative alternative for treating cachexia. This article reviews the evidence linking the features of malnutrition, as defined by the Global Leadership Initiative on Malnutrition [low body mass index (BMI), unintentional body weight loss, low muscle mass, low appetite, and systemic inflammation] and the gut microbiota in human adults with cachexia-associated diseases, and shows the limitations of the present research in that field with suggestions for future directions.}, }
@article {pmid31572201, year = {2019}, author = {Zhou, H and Tai, J and Xu, H and Lu, X and Meng, D}, title = {Xanthoceraside Could Ameliorate Alzheimer's Disease Symptoms of Rats by Affecting the Gut Microbiota Composition and Modulating the Endogenous Metabolite Levels.}, journal = {Frontiers in pharmacology}, volume = {10}, number = {}, pages = {1035}, pmid = {31572201}, issn = {1663-9812}, abstract = {Xanthoceraside (XAN) is a natural-derived compound with anti-Alzheimer activity from the husks of Xanthoceras sorbifolia. Although its therapeutic effect had been confirmed in previous studies, the mechanism was still unclear due to its poor solubility and low permeability. In this study, the pharmacological effect of XAN on Alzheimer's disease (AD) was confirmed by behavior experiments and H&amp;E staining observation. Fecal microbiota transplantation (FMT) experiment also replicated the therapeutic effects, which indicates the potential targets of XAN on gut microbiota. The sequencing of 16S rRNA genes in fecal samples demonstrated that XAN reversed gut microbiota dysbiosis in AD animals. XAN could change the relative abundances of several phyla and genus of bacterial, particularly the ratio of Firmicutes/Bacteroidetes. Among them, Clostridium IV, Desulfovibrio, Corynebacterium, and Enterorhabdus had been reported to be involved in the pathologic developments of AD and other central nervous system disease. In metabolomics study, a series of host endogenous metabolites were detected, including amino acids, lysophosphatidylcholine, dihydrosphingosine, phytosphingosine, inosine, and hypoxanthine, which were all closely associated with the development of AD. Combined with the Spearman's correlation analysis, it was confirmed that the increases of five bacterial strains and decreases of six bacterial strains were closely correlated with the increases of nine host metabolites and the decreases of another five host metabolites. Therefore, XAN can modulate the structure of gut microbiota in AD rats; the changes of gut microbiota were significantly correlated with endogenous metabolites, and symptom of AD was ultimately alleviated. Our findings suggest that XAN may be a potential therapeutic drug for AD, and the gut microbiota may be potential targeting territory of XAN via microbiome-gut-brain pathway.}, }
@article {pmid31571251, year = {2019}, author = {Liu, Y and Chen, K and Li, F and Gu, Z and Liu, Q and He, L and Shao, T and Song, Q and Zhu, F and Zhang, L and Jiang, M and Zhou, Y and Barve, S and Zhang, X and McClain, CJ and Feng, W}, title = {Probiotic LGG prevents liver fibrosis through inhibiting hepatic bile acid synthesis and enhancing bile acid excretion in mice.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/hep.30975}, pmid = {31571251}, issn = {1527-3350}, support = {R21 AA022416/AA/NIAAA NIH HHS/United States ; U01 AA021893/AA/NIAAA NIH HHS/United States ; U01 AA022489/AA/NIAAA NIH HHS/United States ; }, abstract = {Cholestatic liver disease is characterized by gut dysbiosis and excessive toxic hepatic bile acids (BAs). Modification of gut microbiota and repression of BA synthesis are potential strategies for the treatment of cholestatic liver disease. The purpose of this study was to examine the effects and to understand the mechanisms of the probiotic, Lactobacillus rhamnosus GG (LGG), on hepatic bile acid synthesis, liver injury and fibrosis in bile-duct ligation (BDL) and Mdr2-/- mice. Global and intestinal specific FXR inhibitors were used to dissect the role of FXR. LGG treatment significantly attenuated liver inflammation, injury and fibrosis with a significant reduction of hepatic BAs in BDL mice. Hepatic concentration of T-βMCA, an FXR antagonist, was markedly increased in BDL mice and reduced in LGG-treated mice, while chenodeoxycholic acid (CDCA), an FXR agonist, was decreased in BDL mice and normalized in LGG-treated mice. LGG treatment significantly increased the expression of serum and ileum FGF15 and subsequently reduced hepatic CYP7A1 and BA synthesis in BDL and Mdr2-/- mice. At the molecular level, these changes were reversed by global and intestinal specific FXR inhibitors in BDL mice. In addition, LGG treatment altered gut microbiota, which was associated with increased BA de-conjugation and increased fecal and urine BA excretion both in BDL and Mdr2-/- mice. In vitro studies showed that LGG suppressed the inhibitory effect of T-βMCA on FXR and FGF19 expression in Caco-2 cells. Conclusion: LGG supplementation decreases hepatic BA by increasing intestinal FXR/FGF15 signaling pathway-mediated suppression of BA de novo synthesis and enhances BA excretion, which prevents excessive BA-induced liver injury and fibrosis in mice.}, }
@article {pmid31570017, year = {2019}, author = {Elangovan, A and Allegretti, JR and Fischer, M}, title = {Microbiota modulation-based therapy for luminal GI disorders: current applications of probiotics and fecal microbiota transplantation.}, journal = {Expert opinion on biological therapy}, volume = {19}, number = {12}, pages = {1343-1355}, doi = {10.1080/14712598.2019.1673725}, pmid = {31570017}, issn = {1744-7682}, abstract = {Introduction: Alteration in the intestinal microbiota also termed as intestinal dysbiosis has been demonstrated in numerous gastrointestinal disorders linked to aberrant immune processes, acquisition of pathogenic organisms and often administration of antibiotics. Restoration of microbiota through probiotics and fecal microbiota transplantation (FMT) has gained tremendous popularity among researchers in the prevention and treatment of gastrointestinal diseases.Areas covered: In this review, studies testing the safety and efficacy of probiotics and FMT for the treatment of various infectious and inflammatory luminal gastrointestinal diseases are reviewed. Randomized control studies are given priority while important uncontrolled studies are also highlighted.Expert opinion: Probiotics have demonstrated efficacy in the prevention of antibiotic-associated diarrhea and in the eradication of Helicobacter pylori infection. Their utility in the primary and secondary prevention of Clostridioides difficile infection is debatable. The future of medicine should bring forth a personalized approach to probiotic use. FMT has revolutionized the treatment of recurrent CDI as well as severe and fulminant CDI. At the same time, it has galvanized gut microbiota research in the last decade. While FMT in ulcerative colitis appears promising, further studies on the durability and long-term safety are needed before it can be recommended in clinical practice.}, }
@article {pmid31570003, year = {2019}, author = {Ma, J and Li, J and Qian, M and He, N and Cao, Y and Liu, Y and Wu, K and He, S}, title = {The comprehensive pathophysiological changes in a novel rat model of postinflammatory visceral hypersensitivity.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {33}, number = {12}, pages = {13560-13571}, doi = {10.1096/fj.201901489R}, pmid = {31570003}, issn = {1530-6860}, abstract = {So far, a comprehensive animal model that can mimic both the central and peripheral pathophysiological changes of irritable bowel syndrome (IBS) is lacking. Here, we developed a novel IBS rat model combining trinitro-benzene-sulfonic acid (TNBS) and chronic unpredictable mild stress (CUMS) (designated as TC-IBS) and compared it with the TNBS-induced and CUMS-induced models. TC-IBS showed a pronounced depression phenotype with increased corticotropin-releasing hormone receptor (CRHR)1 and CRHR2 expression at the frontal cortex and increased serum ACTH concentration. Visceral hypersensitivity (VH), as evidenced by colorectal distention (CRD) test, was highest in TC-IBS, accompanied by increased serum 5-hydroxytryptamine (5-HT) level and colonic 5-HT receptor 3A (5-HT3AR)/5-HT receptor 2B expression, impaired tight junction protein expression including occludin, zonula occludens-1, and phosphorylated myosin light chain. Palonosetron, a second generation of 5-HT3AR antagonist, alleviated VH significantly in TC-IBS. 16S rRNA sequencing showed that TNBS plus CUMS induced a significant disturbance of the gut microbiota. Cytokine profile analysis of TC-IBS model indicated an innate immune activation both in serum and colonic mucosa. Further, fecal microbiota transplantation improved VH and some pathophysiological changes in TC-IBS. In summary, we established a postinflammatory IBS model covering multifactorial pathophysiological changes, which may help to develop therapies that target specific IBS subtype.-Ma, J., Li, J., Qian, M., He, N., Cao, Y., Liu, Y., Wu, K., He, S. The comprehensive pathophysiological changes in a novel rat model of postinflammatory visceral hypersensitivity.}, }
@article {pmid31563878, year = {2019}, author = {Cammarota, G and Ianiro, G and Kelly, CR and Mullish, BH and Allegretti, JR and Kassam, Z and Putignani, L and Fischer, M and Keller, JJ and Costello, SP and Sokol, H and Kump, P and Satokari, R and Kahn, SA and Kao, D and Arkkila, P and Kuijper, EJ and Vehreschild, MJG and Pintus, C and Lopetuso, L and Masucci, L and Scaldaferri, F and Terveer, EM and Nieuwdorp, M and López-Sanromán, A and Kupcinskas, J and Hart, A and Tilg, H and Gasbarrini, A}, title = {International consensus conference on stool banking for faecal microbiota transplantation in clinical practice.}, journal = {Gut}, volume = {68}, number = {12}, pages = {2111-2121}, pmid = {31563878}, issn = {1468-3288}, mesh = {Clostridium Infections/microbiology/*therapy ; Clostridium difficile/*isolation &amp; purification ; *Consensus ; Donor Selection ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome ; Humans ; Specimen Handling/methods ; }, abstract = {Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres.Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice,Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.}, }
@article {pmid31560944, year = {2019}, author = {Gong, Y and Dong, R and Gao, X and Li, J and Jiang, L and Zheng, J and Cui, S and Ying, M and Yang, B and Cao, J and He, Q}, title = {Neohesperidin prevents colorectal tumorigenesis by altering the gut microbiota.}, journal = {Pharmacological research}, volume = {148}, number = {}, pages = {104460}, doi = {10.1016/j.phrs.2019.104460}, pmid = {31560944}, issn = {1096-1186}, abstract = {Neohesperidin (NHP), derived from citrus fruits, has attracted considerable interest due to its preventative and therapeutic effects on numerous diseases. However, little progress has been made in determining the exact function of NHP on tumorigenesis. In the current study, we found that NHP inhibited colorectal tumorigenesis in the APC min/+ transgenic mouse model, as well as induced apoptosis and blocked angiogenesis in vivo. Our in-cell study suggested that this tumorigenic preventative effect of NHP is not due to the direct impact on tumor cells. Intriguingly, by utilizing 16 s rRNA gene-based microbiota sequencing, the relative abundance of Bacteroidetes was decreased, while Firmicutes and Proteobacteria were increased in the presence of NHP. Additionally, the fecal microbiota transplantation experiment further revealed that feeding with fecal of NHP-treated mice induced considerable inhibition of tumorigenesis, which indicates that the alteration of gut microbiota is responsible for NHP-mediated prevention of colorectal tumorigenesis. Thus, our study not only suggests the efficacy of NHP as a potent natural product for preventing colorectal cancer but also proposes a compelling model to connect the gut microbiota to the preventative effect of NHP on tumorigenesis.}, }
@article {pmid31560732, year = {2019}, author = {Smith, AD and Foss, ED and Zhang, I and Hastie, JL and Giordano, NP and Gasparyan, L and VinhNguyen, LP and Schubert, AM and Prasad, D and McMichael, HL and Sun, J and Beger, RD and Simonyan, V and Cowley, SC and Carlson, PE}, title = {Microbiota of MR1 deficient mice confer resistance against Clostridium difficile infection.}, journal = {PloS one}, volume = {14}, number = {9}, pages = {e0223025}, pmid = {31560732}, issn = {1932-6203}, abstract = {Clostridium difficile (Cd) infection (CDI) typically occurs after antibiotic usage perturbs the gut microbiota. Mucosa-associated invariant T cells (MAIT) are found in the gut and their development is dependent on Major histocompatibility complex-related protein 1 (MR1) and the host microbiome. Here we were interested in determining whether the absence of MR1 impacts resistance to CDI. To this end, wild-type (WT) and MR1-/- mice were treated with antibiotics and then infected with Cd spores. Surprisingly, MR1-/- mice exhibited resistance to Cd colonization. 16S rRNA gene sequencing of feces revealed inherent differences in microbial composition. This colonization resistance was transferred from MR1-/- to WT mice via fecal microbiota transplantation, suggesting that MR1-dependent factors influence the microbiota, leading to CDI susceptibility.}, }
@article {pmid31560045, year = {2019}, author = {Abu-Sbeih, H and Wang, Y}, title = {Management Considerations for Immune Checkpoint Inhibitor-Induced Enterocolitis Based on Management of Inflammatory Bowel Disease.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izz212}, pmid = {31560045}, issn = {1536-4844}, abstract = {BACKGROUND: Immune checkpoint inhibitor therapy has significantly improved the outcomes of various advanced malignancies that were deemed unruly prior to its invention. Immune-mediated diarrhea and enterocolitis are among the most frequently encountered adverse events of immune checkpoint inhibitor therapy. Given the increasing use of these therapies in the treatment of an ever-growing number of malignancies, providing appropriate treatment for such adverse effects has become crucial.<br><br>METHODS: In this review, we summarize the current body of evidence concerning the management of immune-mediated diarrhea and enterocolitis. Additionally, management of immune-mediated diarrhea and enterocolitis is likened to that of inflammatory bowel disease, given the resemblance between both entities in pathogenesis and clinical features. Reviewing the literature raised several points regarding this devastating toxicity that still need further investigation by future efforts.<br><br>RESULTS: Endoscopic and histologic evaluation is pivotal in the assessment of immune-mediated diarrhea and enterocolitis and provides vital information regarding the severity of the disease to guide treatment. Corticosteroids are the main therapy for immune-mediated diarrhea and enterocolitis, with infliximab and vedolizumab as second-line agents. Recently, fecal microbiota transplantation has emerged as a treatment option for immune-mediated diarrhea and enterocolitis that is refractory to corticosteroids. Restarting immune checkpoint inhibitor therapy after resolution of immune-mediated diarrhea and enterocolitis carries a risk of recurrence that is mostly controllable with current immune-suppressive treatment.<br><br>CONCLUSIONS: Lastly, we propose a management algorithm for immune-mediated diarrhea and enterocolitis. Prospective research, preferably as collaborative efforts from oncology and gastroenterology specialists, is needed to refine the management of immune-mediated diarrhea and enterocolitis.}, }
@article {pmid31559298, year = {2019}, author = {Hu, Y and Xiao, HY and He, C and Lv, NH and Zhu, L}, title = {Fecal microbiota transplantation as an effective initial therapy for pancreatitis complicated with severe Clostridium difficile infection: A case report.}, journal = {World journal of clinical cases}, volume = {7}, number = {17}, pages = {2597-2604}, pmid = {31559298}, issn = {2307-8960}, abstract = {BACKGROUND: Moderately severe acute pancreatitis (MSAP) is a critical form of acute pancreatitis that is related with high morbidity and mortality. Severe Clostridium difficile infection (sCDI) is a serious and rare nosocomial diarrheal complication, especially in MSAP patients. Fecal microbiota transplantation (FMT) is a highly effective treatment for refractory and recurrent CDI (rCDI). However, knowledge regarding the initial use of FMT in patients suffering from sCDI is limited.<br><br>CASE SUMMARY: Here, we report an MSAP patient complicated with sCDI who was treated by FMT as a first-line therapy. The patient was a 51-year-old man who suffered from diarrhea in his course of acute pancreatitis. An enzyme immunoassay was performed to detect toxins, and the result was positive for toxin-producing C. difficile and toxin B and negative for C. difficile ribotype 027. The colonoscopy revealed pseudomembranous colitis. Due to these findings, sCDI was our primary consideration. Because the patient provided informed consent for FMT treatment, we initially treated the patient by FMT rather than metronidazole. Diarrhea resolved within 5 d after FMT. The patient remained asymptomatic, and the follow-up colonoscopy performed 40 d after discharge showed a complete recovery. Our case is the first reported in China.<br><br>CONCLUSION: This case explores the possibilities of initially using FMT to treat severe CDI. Moreover, FMT may become a critical component of the treatment for severe CDI in MSAP patients.}, }
@article {pmid31559142, year = {2019}, author = {Zheng, P and Li, Y and Wu, J and Zhang, H and Huang, Y and Tan, X and Pan, J and Duan, J and Liang, W and Yin, B and Deng, F and Perry, SW and Wong, ML and Licinio, J and Wei, H and Yu, G and Xie, P}, title = {Perturbed Microbial Ecology in Myasthenia Gravis: Evidence from the Gut Microbiome and Fecal Metabolome.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {6}, number = {18}, pages = {1901441}, pmid = {31559142}, issn = {2198-3844}, abstract = {Myasthenia gravis (MG) is a devastating acquired autoimmune disease. Emerging evidence indicates that the gut microbiome plays a key role in maintaining immune system homeostasis. This work reports that MG is characterized by decreased α-phylogenetic diversity, and significantly disturbed gut microbiome and fecal metabolome. The altered gut microbial composition is associated with fecal metabolome changes, with 38.75% of altered bacterial operational taxonomic units showing significant correlations with a range of metabolite biomarkers. Some microbes are particularly linked with MG severity. Moreover, a combination of microbial makers and their correlated metabolites enable discriminating MG from healthy controls (HCs) with 100% accuracy. To investigate whether disturbed gut mcirobiome might contribute to the onset of MG, germ-free (GF) mice are initially colonized with MG microbiota (MMb) or healthy microbiota (HMb), and then immunized in a classic mouse model of MG. The MMb mice demonstrate substantially impaired locomotion ability compared with the HMb mice. This effect could be reversed by cocolonizing GF mice with both MMb and HMb. The MMb mice also exhibit similar disturbances of fecal metabolic pathways as found in MG. Together these data demonstrate disturbances in microbiome composition and activity that are likely to be relevant to the pathogenesis of MG.}, }
@article {pmid31558007, year = {2019}, author = {Son, DH and Park, WJ and Lee, YJ}, title = {Recent Advances in Anti-Aging Medicine.}, journal = {Korean journal of family medicine}, volume = {40}, number = {5}, pages = {289-296}, pmid = {31558007}, issn = {2005-6443}, abstract = {A rapidly aging population in Korea has led to increased attention in the field of anti-aging medicine. The purpose of anti-aging medicine is to slow, stop, or reverse the aging process and its associated effects, such as disability and frailty. Anti-aging medicine is emerging as a growing industry, but many supplements or protocols are available that do not have scientific evidence to support their claims. In this review, the mechanisms of action and the clinical implications of anti-aging interventions were examined and explained. Calorie restriction mimetics define compounds that imitate the outcome of calorie restriction, including an activator of AMP protein kinase (metformin), inhibitor of growth hormone/insulin-like growth factor-1 axis (pegvisomant), inhibitor of mammalian target of rapamycin (rapamycin), and activator of the sirtuin pathway (resveratrol). Hormonal replacement has also been widely used in the elderly population to improve their quality of life. Manipulating healthy gut microbiota through prebiotic/probiotics or fecal microbiota transplantation has significant potential in anti-aging medicine. Vitamin D is expected to be a primary anti-aging medicine in the near future due to its numerous positive effects in the elderly population.}, }
@article {pmid31557953, year = {2019}, author = {Zhang, Z and Mocanu, V and Cai, C and Dang, J and Slater, L and Deehan, EC and Walter, J and Madsen, KL}, title = {Impact of Fecal Microbiota Transplantation on Obesity and Metabolic Syndrome-A Systematic Review.}, journal = {Nutrients}, volume = {11}, number = {10}, pages = {}, pmid = {31557953}, issn = {2072-6643}, support = {./CAPMC/CIHR/Canada ; }, mesh = {*Fecal Microbiota Transplantation ; Humans ; Metabolic Syndrome/*therapy ; Obesity/*therapy ; }, abstract = {Fecal microbiota transplantation (FMT) is a gut microbial-modulation strategy that has been investigated for the treatment of a variety of human diseases, including obesity-associated metabolic disorders. This study appraises current literature and provides an overview of the effectiveness and limitations of FMT as a potential therapeutic strategy for obesity and metabolic syndrome (MS). Five electronic databases and two gray literature sources were searched up to 10 December 2018. All interventional and observational studies that contained information on the relevant population (adult patients with obesity and MS), intervention (receiving allogeneic FMT) and outcomes (metabolic parameters) were eligible. From 1096 unique citations, three randomized placebo-controlled studies (76 patients with obesity and MS, body mass index = 34.8 ± 4.1 kg/m2, fasting plasma glucose = 5.8 ± 0.7 mmol/L) were included for review. Studies reported mixed results with regards to improvement in metabolic parameters. Two studies reported improved peripheral insulin sensitivity (rate of glucose disappearance, RD) at 6 weeks in patients receiving donor FMT versus patients receiving the placebo control. In addition, one study observed lower HbA1c levels in FMT patients at 6 weeks. No differences in fasting plasma glucose, hepatic insulin sensitivity, body mass index (BMI), or cholesterol markers were observed between two groups across all included studies. While promising, the influence of FMT on long-term clinical endpoints needs to be further explored. Future studies are also required to better understand the mechanisms through which changes in gut microbial ecology and engraftment of microbiota affect metabolic outcomes for patients with obesity and MS. In addition, further research is needed to better define the optimal fecal microbial preparation, dosing, and method of delivery.}, }
@article {pmid31555606, year = {2019}, author = {DeLong, K and Bensouda, S and Zulfiqar, F and Zierden, HC and Hoang, TM and Abraham, AG and Coleman, JS and Cone, RA and Gravitt, PE and Hendrix, CW and Fuchs, EJ and Gaydos, CA and Weld, ED and Ensign, LM}, title = {Conceptual Design of a Universal Donor Screening Approach for Vaginal Microbiota Transplant.}, journal = {Frontiers in cellular and infection microbiology}, volume = {9}, number = {}, pages = {306}, pmid = {31555606}, issn = {2235-2988}, support = {R01 HD092013/HD/NICHD NIH HHS/United States ; }, abstract = {The success of fecal microbiota transplant (FMT) in treating recurrent Clostridioides difficile infection has led to growing excitement about the potential of using transplanted human material as a therapy for a wide range of diseases and conditions related to microbial dysbiosis. We anticipate that the next frontier of microbiota transplantation will be vaginal microbiota transplant (VMT). The composition of the vaginal microbiota has broad impact on sexual and reproductive health. The vaginal microbiota in the &quot;optimal&quot; state are one of the simplest communities, dominated by one of only a few species of Lactobacillus. Diversity in the microbiota and the concomitant depletion of lactobacilli, a condition referred to as bacterial vaginosis (BV), is associated with a wide range of deleterious effects, including increased risk of acquiring sexually transmitted infections and increased likelihood of having a preterm birth. However, we have very few treatment options available, and none of them curative or restorative, for &quot;resetting&quot; the vaginal microbiota to a more protective state. In order to test the hypothesis that VMT may be a more effective treatment option, we must first determine how to screen donors to find those with minimal risk of pathogen transmission and &quot;optimal&quot; vaginal microbiota for transplant. Here, we describe a universal donor screening approach that was implemented in a small pilot study of 20 women. We further characterized key physicochemical properties of donor cervicovaginal secretions (CVS) and the corresponding composition of the vaginal microbiota to delineate criteria for inclusion/exclusion. We anticipate that the framework described here will help accelerate clinical studies of VMT.}, }
@article {pmid31551944, year = {2019}, author = {Kim, J and Lee, H and An, J and Song, Y and Lee, CK and Kim, K and Kong, H}, title = {Alterations in Gut Microbiota by Statin Therapy and Possible Intermediate Effects on Hyperglycemia and Hyperlipidemia.}, journal = {Frontiers in microbiology}, volume = {10}, number = {}, pages = {1947}, pmid = {31551944}, issn = {1664-302X}, abstract = {Dysbiosis of the gut microbiota is a contributing factor for obesity-related metabolic diseases such as hyperglycemia and hyperlipidemia. Pharmacotherapy for metabolic diseases involves the modulation of gut microbiota, which is suggested to be a potential therapeutic target. In this study, the modulation of gut microbiota by statins (cholesterol-lowering drugs: atorvastatin and rosuvastatin) was investigated in an aged mouse model of high-fat diet-induced obesity, and the association between gut microbiota and immune responses was described. Atorvastatin and rosuvastatin significantly increased the abundance of the genera Bacteroides, Butyricimonas, and Mucispirillum. Moreover, the abundance of these genera was correlated with the inflammatory response, including levels of IL-1β and TGFβ1 in the ileum. In addition, oral fecal microbiota transplantation with fecal material collected from rosuvastatin-treated mouse groups improved hyperglycemia. From these results, the effect of statins on metabolic improvements could be explained by altered gut microbiota. Our findings suggest that the modulation of gut microbiota by statins has an important role in the therapeutic actions of these drugs.}, }
@article {pmid31550826, year = {2019}, author = {Li, N and Tian, HL and Chen, QY and Yang, B and Ma, CL and Lin, ZL and Zhang, XY and Zhao, D and Huang, ZX and Jiang, J and Qin, HL}, title = {[Efficacy analysis of fecal microbiota transplantation in the treatment of 2010 patients with intestinal disorders].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {22}, number = {9}, pages = {861-868}, doi = {10.3760/cma.j.issn.1671-0274.2019.09.011}, pmid = {31550826}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; 04.99.18001//Special Fund for the Construction of the Clinical Center of Tenth People's Hospital of Tongji University/ ; }, mesh = {Adolescent ; Adult ; Aged ; Bacteria/genetics ; China ; Cohort Studies ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; *Intestinal Diseases/therapy ; Male ; Middle Aged ; RNA, Ribosomal, 16S ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {Objective: To evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for intestinal disorders. Methods: A retrospectively descriptive cohort study was carried out. Clinical data of 2010 patients who underwent FMT and received follow-up for more than 3 months from May 2014 to November 2018 were collected, including 1,206 cases from Tongji University Shanghai Tenth People's Hospital and 804 cases from Nanjing Eastern Military General Hospital. Of the 2,010 patients, 797 were male and 1,213 were female, with a mean age of (49.4±16.5) years old. Inclusion criteria were those with indications for FMT and voluntary treatment of FMT. Pregnant or lactating women, patients with end-stage disease, cases who were participating or participated in other clinical trials within 3 months, and patients with previous bowel history of pathogen infection, oral antibiotics or proton pump inhibitors (PPI) for the recent2 weeks, and those at immunosuppressive state were excluded. Informed consent was obtained from the enrolled patients and their families. There were 1,356 cases of constipation, 175 cases of inflammatory bowel disease, 148 cases of chronic diarrhea, 127 cases of radiation enteritis, 119 cases of irritable bowel syndrome, and 85 cases of autism (complicating with intestinal disorders). FMT donor requirements: (1) 18 to 30 years old non-relatives, non-pregnant healthy adults with healthy lifestyle and good eating habits as volunteers to participate in fecal donation; (2) no administration of antibiotics within 3 months; (3) no chronic diseases such as constipation, irritable bowel syndrome, inflammatory bowel disease, etc., no autoimmune disease, not in immunosuppressive state, no history of malignant disease; (4) negative pathogen examination of infectious diseases (hepatitis B virus, hepatitis C virus, syphilis, HIV, etc.); (5) negative fecal examination (C.difficile, dysentery bacillus, Shigella, Campylobacter, parasites, etc.). The donor requirements after enrollment: (1) physical examination was reviewed once every two months, and the result still met the above requirements; (2) 16S rRNA sequencing was performed for every fecal donation in order to ensure that the composition and diversity of the fecal flora was stable and reliable. The preparation of the stool suspension referred to the Amsterdam criteria and the preparation process was less than 1 hour. The preparation of the FMT capsule was processed by pre-freezing the stool suspension after the preparation of the above suspension, and the frozen sample was transferred into a freeze dryer for freezing. The dried and lyophilized powder was encapsulated in capsules, and the capsule shell was made of acid-resistant hypromellose capsule (No.0) and pediatric-specific capsule (No.3), sealed and packaged in a-20℃ refrigerator. Three ways of accepting FMT treatment pathways included 6-day transplantation after the placement of the nasointestinal tube, 6-day oral FMT capsule transplantation and one-time transplantation through colonoscopy. Intestinal preparation (nasointestinal tube feeding of polyethylene glycol until watery stool) was carried out before transplantation. Other treatments were stopped during treatment and follow-up, and any medication was not recommended when necessary. Results: Of the 2010 patients, 1,497 cases received nasointestinal tube transplantation (nasointestinal tube group), 452 cases oral capsule transplantation (oral capsule group) and 61 cases colonoscopy (colonoscopy group). At 3 time points of 3, 12, and 36 months after FMT, the clinical cure rates and the clinical improvement rates were 41.3% (560/1 356), 35.2% (320/909), 31.4% (69/220), and 29.0% (393/1 356), 27.8% (253/909), 29.1% (64/220), respectively in constipation patients; 33.1% (58/175), 29.9% (35/117), 24.5% (12/49), and 31.4% (55/175), 27.4% (32/117), 57.1% (28/49), respectively in inflammatory bowel disease patients; 87.8% (130/148), 81.8% (81/99), 78.3% (36/46), and 8.1% (12/148), 7.1% (7/99), 4.3% (2/46), respectively in chronic diarrhea patients; 61.4% (78/127), 56.5% (48/85), 47.6% (20/42), and 21.2% (27/127), 15.3% (13/85), 14.3% (6/42), respectively in radiation enteritis patients; 53.8% (64/119), 45.0% (36/80), 6/15, and 21.0% (25/119), 26.2% (21/80), 4/15, respectively in irritable bowel syndrome patients; 23.5% (20/85), 22.8% (13/57), 20.0%(5/25), and 55.3% (47/85), 49.1% (28/57), 40.0% (10/25), respectively in autism patients. Meanwhile the clinical cure rates and the clinical improvement rates at 3, 12, and 36 months were 47.7% (714/1 497), 42.8% (425/994), 39.1% (128/327), and 29.1% (436/1 497), 27.0% (268/994), 28.1% (92/327), respectively in the nasointestinal tube group; 38.7% (175/452), 30.2% (91/301), 33.3% (16/48), and 24.3% (110/452), 26.2% (79/301), 25.0% (12/48), respectively in the oral capsule group; 34.4% (21/61), 32.7% (17/52), 18.2% (4/22), and 21.3% (13/61), 13.5% (7/52), 45.5% (10/22), respectively in colonoscopy group. No serious adverse events occurred during treatment and follow-up period. The adverse event of nasointestinal tube group presented higher ratio of discomfort in respiratorytract accounting for 13.1% (196/1497); the oral capsule group had a higher proportion of nausea and vomiting when swallowing capsules accounting for 7.1% (32/452); the colonoscopy group was mainly diarrhea, accounting for 37.7% (23/61). The above symptoms disappeared after the nasointestinal tube was removed, or after treatment ended, or within 1 to 3 days after hospitalization. Conclusion: FMT is a safe and effective method for the treatment of intestinal dysfunction.}, }
@article {pmid31550348, year = {2019}, author = {Cotter, JM and Nicholson, MR and Kociolek, LK}, title = {An Infectious Diseases Perspective on Fecal Microbiota Transplantation for Clostridioides difficile Infection in Children.}, journal = {Journal of the Pediatric Infectious Diseases Society}, volume = {8}, number = {6}, pages = {580-584}, doi = {10.1093/jpids/piz062}, pmid = {31550348}, issn = {2048-7207}, support = {K23 AI123525/AI/NIAID NIH HHS/United States ; KL2 TR002245/TR/NCATS NIH HHS/United States ; }, abstract = {Fecal microbiota transplantation (FMT) is efficacious for treatment of recurrent Clostridioides difficile infections (rCDIs). Pediatric experience with FMT for rCDIs is increasing, particularly at large centers. While retrospective studies suggest that FMT is generally safe in the short term, particularly in immunocompetent patients and with rigorous donor screening, additional large prospective studies are needed. This particularly includes those at high risk for infectious complications, such as immunocompromised hosts. Further, long-term implications of altering the intestinal microbiome with FMT are not well understood. The role of FMT in children, particularly in high-risk patients, will require continual reexamination with future availability of pediatric safety and efficacy data. This review summarizes key points for infectious diseases physicians to consider when evaluating a child for FMT.}, }
@article {pmid31545802, year = {2019}, author = {Guirro, M and Costa, A and Gual-Grau, A and Herrero, P and Torrell, H and Canela, N and Arola, L}, title = {Effects from diet-induced gut microbiota dysbiosis and obesity can be ameliorated by fecal microbiota transplantation: A multiomics approach.}, journal = {PloS one}, volume = {14}, number = {9}, pages = {e0218143}, pmid = {31545802}, issn = {1932-6203}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Biodiversity ; Body Weight ; *Diet ; Disease Models, Animal ; *Dysbiosis ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Male ; Metagenome ; Metagenomics ; Obesity/*physiopathology/therapy ; Rats ; }, abstract = {Obesity and its comorbidities are currently considered an epidemic, and the involved pathophysiology is well studied. Hypercaloric diets are tightly related to the obesity etiology and also cause alterations in gut microbiota functionality. Diet and antibiotics are known to play crucial roles in changes in the microbiota ecosystem and the disruption of its balance; therefore, the manipulation of gut microbiota may represent an accurate strategy to understand its relationship with obesity caused by diet. Fecal microbiota transplantation, during which fecal microbiota from a healthy donor is transplanted to an obese subject, has aroused interest as an effective approach for the treatment of obesity. To determine its success, a multiomics approach was used that combined metagenomics and metaproteomics to study microbiota composition and function. To do this, a study was performed in rats that evaluated the effect of a hypercaloric diet on the gut microbiota, and this was combined with antibiotic treatment to deplete the microbiota before fecal microbiota transplantation to verify its effects on gut microbiota-host homeostasis. Our results showed that a high-fat diet induces changes in microbiota biodiversity and alters its function in the host. Moreover, we found that antibiotics depleted the microbiota enough to reduce its bacterial content. Finally, we assessed the use of fecal microbiota transplantation as a complementary obesity therapy, and we found that it reversed the effects of antibiotics and reestablished the microbiota balance, which restored normal functioning and alleviated microbiota disruption. This new approach could be implemented to support the dietary and healthy habits recommended as a first option to maintain the homeostasis of the microbiota.}, }
@article {pmid31544324, year = {2019}, author = {Lee, JR and Huang, J and Magruder, M and Zhang, LT and Gong, C and Sholi, AN and Albakry, S and Edusei, E and Muthukumar, T and Lubetzky, M and Dadhania, DM and Taur, Y and Pamer, EG and Suthanthiran, M}, title = {Butyrate-producing gut bacteria and viral infections in kidney transplant recipients: A pilot study.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {21}, number = {6}, pages = {e13180}, pmid = {31544324}, issn = {1399-3062}, support = {K23 AI124464/AI/NIAID NIH HHS/United States ; R37 AI051652/AI/NIAID NIH HHS/United States ; R37 AI 051652//National Institute of Allergy and Infectious Diseases/ ; K23 AI 124464//National Institute of Allergy and Infectious Diseases/ ; }, abstract = {BACKGROUND: The gut microbiome is being associated increasingly with development of infections besides Clostridium difficile infection. A recent study found an association between butyrate-producing gut (BPG) bacteria and less frequent development of lower respiratory viral infections in allogeneic hematopoietic stem cell transplant recipients (Haak et al, Blood 131(26): 2978, 2018). In this investigation, we examine the relationship between the abundance of BPG bacteria and the development of viral infections in a cohort of kidney transplant recipients.<br><br>METHODS: We recruited 168 kidney transplant recipients who provided 510 fecal specimens in the first 3 months after transplantation and profiled the gut microbiota using 16S rRNA gene sequencing of the V4-V5 hypervariable region. We classified the kidney transplant recipients into higher BPG Bacteria Group and lower BPG Bacteria Group using the same criteria of 1% relative gut abundance of BPG bacteria as the Haak et al study.<br><br>RESULTS: Administration of antibiotics against anaerobes was associated with a significant decrease in the relative gut abundance of BPG bacteria. The higher BPG Bacteria Group was associated with less development of respiratory viral infections (Hazard Ratio [HR]: 0.28, P = .01) but not with less development of CMV viremia (HR: 0.38, P = .13) or BK viremia (HR: 1.02, P = .98) at 2 years post transplantation.<br><br>CONCLUSION: Our pilot investigation supports future validation of the relationship between high relative gut abundance of BPG bacteria and decreased risk for development of respiratory viral infections.}, }
@article {pmid31543403, year = {2019}, author = {Yuan, J and Chen, C and Cui, J and Lu, J and Yan, C and Wei, X and Zhao, X and Li, N and Li, S and Xue, G and Cheng, W and Li, B and Li, H and Lin, W and Tian, C and Zhao, J and Han, J and An, D and Zhang, Q and Wei, H and Zheng, M and Ma, X and Li, W and Chen, X and Zhang, Z and Zeng, H and Ying, S and Wu, J and Yang, R and Liu, D}, title = {Fatty Liver Disease Caused by High-Alcohol-Producing Klebsiella pneumoniae.}, journal = {Cell metabolism}, volume = {30}, number = {4}, pages = {675-688.e7}, doi = {10.1016/j.cmet.2019.08.018}, pmid = {31543403}, issn = {1932-7420}, abstract = {The underlying etiology of nonalcoholic fatty liver disease (NAFLD) is believed to be quite varied. Changes in the gut microbiota have been investigated and are believed to contribute to at least some cases of the disease, though a causal relationship remains unclear. Here, we show that high-alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) is associated with up to 60% of individuals with NAFLD in a Chinese cohort. Transfer of clinical isolates of HiAlc Kpn by oral gavage into mice induced NAFLD. Likewise, fecal microbiota transplant (FMT) into mice using a HiAlc-Kpn-strain-containing microbiota isolated from an individual with NASH induced NAFLD. However, selective elimination of the HiAlc Kpn strain before FMT prevented NAFLD in the recipient mice. These results suggest that at least in some cases of NAFLD an alteration in the gut microbiome drives the condition due to excess endogenous alcohol production.}, }
@article {pmid31540133, year = {2019}, author = {Meroni, M and Longo, M and Dongiovanni, P}, title = {Alcohol or Gut Microbiota: Who Is the Guilty?.}, journal = {International journal of molecular sciences}, volume = {20}, number = {18}, pages = {}, pmid = {31540133}, issn = {1422-0067}, mesh = {Alcoholism/genetics/immunology/*microbiology/physiopathology ; Animals ; Anti-Bacterial Agents/adverse effects ; Bile Acids and Salts/metabolism ; Diet ; Dietary Supplements/microbiology ; Dysbiosis/immunology/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Hepatocytes/metabolism ; Humans ; Intestines/microbiology ; Liver/metabolism/physiopathology ; Liver Diseases, Alcoholic/immunology/metabolism/*microbiology/physiopathology ; }, abstract = {Alcoholic liver disease (ALD), a disorder caused by excessive alcohol intake represents a global health care burden. ALD encompasses a broad spectrum of hepatic injuries including asymptomatic steatosis, alcoholic steatohepatitis (ASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The susceptibility of alcoholic patients to develop ALD is highly variable and its progression to more advanced stages is strongly influenced by several hits (i.e., amount and duration of alcohol abuse). Among them, the intestinal microbiota and its metabolites have been recently identified as paramount in ALD pathophysiology. Ethanol abuse triggers qualitative and quantitative modifications in intestinal flora taxonomic composition, mucosal inflammation, and intestinal barrier derangement. Intestinal hypermeability results in the translocation of viable pathogenic bacteria, Gram-negative microbial products, and pro-inflammatory luminal metabolites into the bloodstream, further corroborating the alcohol-induced liver damage. Thus, the premise of this review is to discuss the beneficial effect of gut microbiota modulation as a novel therapeutic approach in ALD management.}, }
@article {pmid31534208, year = {2019}, author = {Giles, EM and D'Adamo, GL and Forster, SC}, title = {The future of faecal transplants.}, journal = {Nature reviews. Microbiology}, volume = {17}, number = {12}, pages = {719}, doi = {10.1038/s41579-019-0271-9}, pmid = {31534208}, issn = {1740-1534}, mesh = {Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/methods/*standards/*trends ; Humans ; Patient Safety/*standards ; }, }
@article {pmid31533218, year = {2019}, author = {Villéger, R and Lopès, A and Carrier, G and Veziant, J and Billard, E and Barnich, N and Gagnière, J and Vazeille, E and Bonnet, M}, title = {Intestinal Microbiota: A Novel Target to Improve Anti-Tumor Treatment?.}, journal = {International journal of molecular sciences}, volume = {20}, number = {18}, pages = {}, pmid = {31533218}, issn = {1422-0067}, support = {1071//the Ministère de la Recherche et de la Technologie, Inserm and Université Clermont-Auvergne/ ; USC2018//INRA/ ; 63//la ligue contre le cancer/ ; 16-IDEX-0001-CAP 20-25//French government IDEX-ISITE initiative/ ; 2015/622//CIFRE grant/ ; 2016//CPER EPICURE/ ; }, mesh = {Animals ; Combined Modality Therapy ; *Gastrointestinal Microbiome/drug effects/radiation effects ; Humans ; Neoplasms/diagnosis/*therapy ; Prognosis ; Treatment Outcome ; }, abstract = {Recently, preclinical and clinical studies targeting several types of cancer strongly supported the key role of the gut microbiota in the modulation of host response to anti-tumoral therapies such as chemotherapy, immunotherapy, radiotherapy and even surgery. Intestinal microbiome has been shown to participate in the resistance to a wide range of anticancer treatments by direct interaction with the treatment or by indirectly stimulating host response through immunomodulation. Interestingly, these effects were described on colorectal cancer but also in other types of malignancies. In addition to their role in therapy efficacy, gut microbiota could also impact side effects induced by anticancer treatments. In the first part of this review, we summarized the role of the gut microbiome on the efficacy and side effects of various anticancer treatments and underlying mechanisms. In the second part, we described the new microbiota-targeting strategies, such as probiotics and prebiotics, antibiotics, fecal microbiota transplantation and physical activity, which could be effective adjuvant therapies developed in order to improve anticancer therapeutic efficiency.}, }
@article {pmid31529413, year = {2019}, author = {Castaño-Rodríguez, N and Paramsothy, S and Kaakoush, NO}, title = {Promise of Fecal Microbiota Transplantation Therapy in Pouchitis.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-019-05831-z}, pmid = {31529413}, issn = {1573-2568}, }
@article {pmid31528199, year = {2019}, author = {Du, H and Kuang, TT and Qiu, S and Xu, T and Gang Huan, CL and Fan, G and Zhang, Y}, title = {Fecal medicines used in traditional medical system of China: a systematic review of their names, original species, traditional uses, and modern investigations.}, journal = {Chinese medicine}, volume = {14}, number = {}, pages = {31}, pmid = {31528199}, issn = {1749-8546}, abstract = {In China, the medical use of fecal matter (fresh fecal suspension or dry feces) can be dated back to the fourth century, approximately 1700 years ago. In long-term clinical practice, Chinese doctors have accumulated unique and invaluable medical experience in the use of fecal materials. In view of their good curative effect and medicinal potential, fecal medicines should be paid much attention. This study aimed to provide the first comprehensive data compilation of fecal medicines used in various Chinese traditional medical systems by bibliographic investigation of 31 medicine monographs and standards. A total of 54 fecal medicines were found to be used in 14 traditional Chinese medical systems. Their names, original species, medicinal forms, and traditional uses were described in detail. These fecal medicines were commonly used to treat gastrointestinal, nervous system, skin, and gynecological diseases. Commonly used fecal medicines include Wu-Ling-Zhi, Jiu-Fen and Hei-Bing-Pian. The information summarized in this study can provide a good reference for the development and utilization of fecal medicines. Further studies are necessary to prove their medicinal value, identify their active ingredients, and elucidate their mechanisms of action so that more people can accept these special medicines.}, }
@article {pmid31526871, year = {2019}, author = {Wu, R and Mei, X and Ye, Y and Xue, T and Wang, J and Sun, W and Lin, C and Xue, R and Zhang, J and Xu, D}, title = {Zn(II)-curcumin solid dispersion impairs hepatocellular carcinoma growth and enhances chemotherapy by modulating gut microbiota-mediated zinc homeostasis.}, journal = {Pharmacological research}, volume = {150}, number = {}, pages = {104454}, doi = {10.1016/j.phrs.2019.104454}, pmid = {31526871}, issn = {1096-1186}, abstract = {Zinc(II) complexes of curcumin display moderate cytotoxicity towards cancer cells at low micromolar concentrations. However, the clinical use of zinc(II) complexes is hampered by hydrolytic insolubility and poor bioavailability and their anticancer mechanisms remain unclear. Here, we investigated the efficacy and mechanism of action of a polyvinylpyrrolidone (PVP-k30)-based solid dispersion of Zn(II)-curcumin (ZnCM-SD) against hepatocellular carcinoma (HCC) in vitro and in vivo. In vitro assays revealed ZnCM-SD not only reduced the viability of HepG2 cells and SK-HEP1 cells in a dose-dependent manner, but also potently and synergistically enhanced cell growth inhibition and cell death in response to doxorubicin by regulating cellular zinc homeostasis. ZnCM-SD was internalized into the cells via non-specific endocytosis and degraded to release curcumin and Zn2+ ions within cells. The anticancer effects also occur in vivo in animals following the oral administration of ZnCM-SD, without significantly affecting the weight of the animals. Interestingly, ZnCM-SD did not reduce tumor growth or affect zinc homeostasis in HepG2-bearing mice after gut microbiome depletion. Moreover, administration of ZnCM-SD alone or in combination with doxorubicin significantly attenuated gut dysbiosis and zinc dyshomeostasis in a rat HCC model. Notably, fecal microbiota transplantation revealed the ability of ZnCM-SD to regulate zinc homeostasis and act as a chemosensitizer for doxorubicin were dependent on the gut microbiota. The crucial role of the gut microbiota in the chemosensitizing ability of ZnCM-SD was confirmed by broad-spectrum antibiotic treatment. Collectively, ZnCM-SD could represent a simple, well-tolerated, safe, effective therapy and function as a novel chemosensitizing agent for cancer.}, }
@article {pmid31526431, year = {2019}, author = {Lavazza, A and Sironi, VA}, title = {Are we Ready for a &quot;Microbiome-Guided Behaviour&quot; Approach?.}, journal = {Cambridge quarterly of healthcare ethics : CQ : the international journal of healthcare ethics committees}, volume = {28}, number = {4}, pages = {708-724}, doi = {10.1017/S0963180119000653}, pmid = {31526431}, issn = {1469-2147}, abstract = {The microbiome is proving to be increasingly important for human brain functioning. A series of recent studies have shown that the microbiome influences the central nervous system in various ways, and consequently acts on the psychological well-being of the individual by mediating, among others, the reactions of stress and anxiety. From a specifically neuroethical point of view, according to some scholars, the particular composition of the microbiome-qua microbial community-can have consequences on the traditional idea of human individuality. Another neuroethical aspect concerns the reception of this new knowledge in relation to clinical applications. In fact, attention to the balance of the microbiome-which includes eating behavior, the use of psychobiotics and, in the treatment of certain diseases, the use of fecal microbiota transplantation-may be limited or even prevented by a biased negative attitude. This attitude derives from a prejudice related to everything that has to do with the organic processing of food and, in general, with the human stomach and intestine: the latter have traditionally been regarded as low, dirty, contaminated and opposed to what belongs to the mind and the brain. This biased attitude can lead one to fail to adequately consider the new anthropological conceptions related to the microbiome, resulting in a state of health, both physical and psychological, inferior to what one might have by paying the right attention to the knowledge available today. Shifting from the ubiquitous high-low metaphor (which is synonymous with superior-inferior) to an inside-outside metaphor can thus be a neuroethical strategy to achieve a new and unbiased reception of the discoveries related to the microbiome.}, }
@article {pmid31526274, year = {2019}, author = {Schwartz, DJ and Rebeck, ON and Dantas, G}, title = {Complex interactions between the microbiome and cancer immune therapy.}, journal = {Critical reviews in clinical laboratory sciences}, volume = {56}, number = {8}, pages = {567-585}, pmid = {31526274}, issn = {1549-781X}, support = {R01 AI123394/AI/NIAID NIH HHS/United States ; R01 AT009741/AT/NCCIH NIH HHS/United States ; R01 HD092414/HD/NICHD NIH HHS/United States ; R25 GM103757/GM/NIGMS NIH HHS/United States ; }, abstract = {Immuno-oncology has rapidly grown in the last thirty years, and immunotherapeutic agents are now approved to treat many disparate cancers. Immune checkpoint inhibitors (ICIs) are employed to augment cytotoxic anti-cancer activity by inhibiting negative regulatory elements of the immune system. Modulating the immune system to target neoplasms has improved survivability of numerous cancers in many individuals, but forecasting outcomes post therapy is difficult due to insufficient predictive biomarkers. Recently, the tumor and gastrointestinal microbiome and immune milieu have been investigated as predictors and influencers of cancer immune therapy. In this review, we discuss: (1) ways to measure the microbiome including relevant bioinformatic analyses, (2) recent developments in animal studies and human clinical trials utilizing gut microbial composition and function as biomarkers of cancer immune therapy response and toxicity, and (3) using prebiotics, probiotics, postbiotics, antibiotics, and fecal microbiota transplant (FMT) to modulate immune therapy. We discuss the respective benefits of 16S ribosomal RNA (rRNA) gene and shotgun metagenomic sequencing including important considerations in obtaining samples and in designing and interpreting human and animal microbiome studies. We then focus on studies discussing the differences in response to ICIs in relation to the microbiome and inflammatory mediators. ICIs cause colitis in up to 25% of individuals, and colitis is often refractory to common immunosuppressive medications. Researchers have measured microbiota composition prior to ICI therapy and correlated baseline microbiota composition with efficacy and colitis. Certain bacterial taxa that appear to enhance therapeutic benefit are also implicated in increased susceptibility to colitis, alluding to a delicate balance between pro-inflammatory tumor killing and anti-inflammatory protection from colitis. Pre-clinical and clinical models have trialed probiotic administration, e.g. Bifidobacterium spp. or FMT, to treat colitis when immune suppressive agents fail. We are excited about the future of modulating the microbiome to predict and influence cancer outcomes. Furthermore, novel therapies employed for other illnesses including bacteriophage and genetically-engineered microbes can be adapted in the future to promote increased advancements in cancer treatment and side effect management.}, }
@article {pmid31525370, year = {2019}, author = {Faivre, B and Bellenger, J and Rieu, A and Guivier, E and Galan, M and Ollivier, A and Poloni, L and Sorci, G}, title = {Disentangling the effect of host genetics and gut microbiota on resistance to an intestinal parasite.}, journal = {International journal for parasitology}, volume = {49}, number = {11}, pages = {873-883}, doi = {10.1016/j.ijpara.2019.06.001}, pmid = {31525370}, issn = {1879-0135}, abstract = {Resistance to infection is a multifactorial trait, and recent work has suggested that the gut microbiota can also contribute to resistance. Here, we performed a fecal microbiota transplant to disentangle the contribution of the gut microbiota and host genetics as drivers of resistance to the intestinal nematode Heligmosomoides polygyrus. We transplanted the microbiota of a strain of mice (SJL), resistant to H. polygyrus, into a susceptible strain (CBA) and vice-versa. We predicted that if the microbiota shapes resistance to H. polygyrus, the FMT should reverse the pattern of resistance between the two host strains. The two host strains had different microbiota diversities and compositions before the start of the experiment, and the FMT altered the microbiota of recipient mice. One mouse strain (SJL) was more resistant to colonization by the heterologous microbiota, and it maintained its resistance profile to H. polygyrus (lower parasite burden) independently of the FMT. On the contrary, CBA mice harbored parasites with lower fecundity during the early stage of the infection, and had an up-regulated expression of the cytokine IL-4 (a marker of H. polygyrus resistance) after receiving the heterologous microbiota. Therefore, while host genetics remains the main factor shaping the pattern of resistance to H. polygyrus, the composition of the gut microbiota also seems to play a strain-specific role.}, }
@article {pmid31519656, year = {2019}, author = {McCormack, UM and Curião, T and Metzler-Zebeli, BU and Wilkinson, T and Reyer, H and Crispie, F and Cotter, PD and Creevey, CJ and Gardiner, GE and Lawlor, PG}, title = {Improvement of Feed Efficiency in Pigs through Microbial Modulation via Fecal Microbiota Transplantation in Sows and Dietary Supplementation of Inulin in Offspring.}, journal = {Applied and environmental microbiology}, volume = {85}, number = {22}, pages = {}, pmid = {31519656}, issn = {1098-5336}, abstract = {As previous studies have demonstrated a link between the porcine intestinal microbiome and feed efficiency (FE), microbiota manipulation may offer a means of improving FE in pigs. A fecal microbiota transplantation procedure (FMTp), using fecal extracts from highly feed-efficient pigs, was performed in pregnant sows (n = 11), with a control group (n = 11) receiving no FMTp. At weaning, offspring were allocated, within sow treatment, to (i) control (n = 67; no dietary supplement) or (ii) inulin (n = 65; 6-week dietary inulin supplementation) treatments. The sow FMTp, alone or in combination with inulin supplementation in offspring, reduced offspring body weight by 8.1 to 10.6 kg at ∼140 days of age, but there was no effect on feed intake. It resulted in better FE, greater bacterial diversity, and higher relative abundances of potentially beneficial bacterial taxa (Fibrobacter and Prevotella) in offspring. Due to the FMTp and/or inulin supplementation, relative abundances of potential pathogens (Chlamydia and Treponema) in the ileum and cecal concentrations of butyric acid were significantly lower. The maternal FMTp led to a greater number of jejunal goblet cells in offspring. Inulin supplementation alone did not affect growth or FE but upregulated duodenal genes linked to glucose and volatile fatty acid homeostasis and increased the mean platelet volume but reduced ileal propionic acid concentrations, granulocyte counts, and serum urea concentrations. Overall, the FMTp in pregnant sows, with or without dietary inulin supplementation in offspring, beneficially modulated offspring intestinal microbiota (albeit mostly low-relative-abundance taxa) and associated physiological parameters. Although FE was improved, the detrimental effect on growth limits the application of this FMTp-inulin strategy in commercial pig production.IMPORTANCE As previous research suggests a link between microbiota and FE, modulation of the intestinal microbiome may be effective in improving FE in pigs. The FMTp in gestating sows, alone or in combination with postweaning dietary inulin supplementation in offspring, achieved improvements in FE and resulted in a higher relative abundance of intestinal bacteria associated with fiber degradation and a lower relative abundance of potential pathogens. However, there was a detrimental effect on growth, although this may not be wholly attributable to microbiota transplantation, as antibiotic and other interventions were also part of the FMT regimen. Therefore, further work with additional control groups is needed to disentangle the effects of each component of the FMTp in order to develop a regimen with practical applications in pig production. Additional research based on findings from this study may also identify specific dietary supplements for the promotion/maintenance of the microbiota transferred via the maternal FMTp, thereby optimizing pig growth and FE.}, }
@article {pmid31518024, year = {2020}, author = {Zhao, W and Hu, Y and Li, C and Li, N and Zhu, S and Tan, X and Li, M and Zhang, Y and Xu, Z and Ding, Z and Hu, L and Liu, Z and Sun, J}, title = {Transplantation of fecal microbiota from patients with alcoholism induces anxiety/depression behaviors and decreases brain mGluR1/PKC ε levels in mouse.}, journal = {BioFactors (Oxford, England)}, volume = {46}, number = {1}, pages = {38-54}, doi = {10.1002/biof.1567}, pmid = {31518024}, issn = {1872-8081}, support = {2016GSF201054//Key Research Plan of Shandong Province/ ; 81671320//National Natural Science Foundation of China/ ; 81871044//National Natural Science Foundation of China/ ; }, abstract = {Recent studies have revealed that the gut microbiota participates in the psychiatric behavior changes in disorders associated with alcohol. But it still remains unknown whether alcoholism is involved in changes in gut microbiota and its underlying mechanism is also not clear. Here, we tested the gut microbiota of patients with alcoholism and conducted fecal microbiota transplantation (FMT) from patients with alcoholism to C57BL/6J mice whose gut microbiota had been sharply suppressed with antibiotics (ABX). Then we evaluated their alcohol preference degree, anxiety, and depression-like behaviors and social interaction behaviors, together with molecular changes in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Our data indicated that the gut microbiota of patients with alcoholism was drastically different from those of the healthy adults. The abundance of p_Firmicutes was significantly increased whereas p_Bacteroidetes was decreased. Compared to mice transplanted with fecal microbiota from healthy male adults, the mice accepting fecal microbiota from patients with alcoholism showed (a) anxiety-like and depression-like behaviors, (b) decreased social interaction behaviors, (c) spontaneous alcohol preference, and (d) decreased brain-derived neurotrophic factor (BDNF), alpha 1 subunit of GABA type A receptor (α1GABAA R) in mPFC and decreased metabotropic glutamate receptors 1 (mGluR1), protein kinase C (PKC) ε in NAc. Overall, our results suggest that fecal microbiota from patients with alcoholism did induce a status like alcohol dependence in C57BL/6J mice. The decreased expression of BDNF, α1GABAA R, and mGluR1/ PKC ε may be the underlying mechanism.}, }
@article {pmid31516555, year = {2019}, author = {Wu, X and Dai, M and Buch, H and Bai, J and Long, W and Long, C and Tang, X and Tu, H and Zhang, R and Zhu, C and Yang, S and Cui, B and Ji, G and Zhang, F}, title = {The recognition and attitudes of postgraduate medical students toward fecal microbiota transplantation: a questionnaire study.}, journal = {Therapeutic advances in gastroenterology}, volume = {12}, number = {}, pages = {1756284819869144}, pmid = {31516555}, issn = {1756-283X}, abstract = {Background: Physicians and medical students in the world do not have high awareness of fecal microbiota transplantation (FMT). This study aimed to explore the recognition and attitude of postgraduate medical students towards FMT and to create awareness for it.<br><br>Methods: A self-administered questionnaire was distributed to first-year Chinese postgraduate medical students across six medical universities. Basic descriptive statistical analyses were performed.<br><br>Results: A total of 1828 eligible questionnaires were included into analysis. 47.76% of students did not know FMT prior to this survey. Respondents with a high-level recognition of FMT were more willing to donate feces or receive FMT therapy than those with a low-level recognition (80.26% vs. 69.62%, p = 0.000 and 56.80% vs. 41.45%, p = 0.000). The respondents from a leading institution of FMT in China showed better awareness compared with others, and 42.26% of them knew about FMT from medical lectures. The main reasons for respondents not supporting FMT were: limited reported clinical evidence (67.94%), raw technology (42.56%), and lack of analysis of patient willingness or cost-effectiveness (36.71%). However, the life-saving value (84.41%), the automatic purification system (38.68%), low expenses (36.00%), and convenient delivering ways (35.67%) were the major considerations for supporting FMT.<br><br>Conclusions: This study revealed the low recognition level of postgraduate medical students about FMT. Therefore, medical education should not neglect the knowledge of FMT. Studies of FMT and standardized FMT should be carried out to promote its development.}, }
@article {pmid31512505, year = {2019}, author = {Schepici, G and Silvestro, S and Bramanti, P and Mazzon, E}, title = {The Gut Microbiota in Multiple Sclerosis: An Overview of Clinical Trials.}, journal = {Cell transplantation}, volume = {28}, number = {12}, pages = {1507-1527}, pmid = {31512505}, issn = {1555-3892}, abstract = {Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, and degenerative disease that affects the central nervous system. A recent study showed that interaction between the immune system and the gut microbiota plays a crucial role in the development of MS. This review reports the clinical studies carried out in recent years that aimed to evaluate the composition of the microbiota in patients with relapsing-remitting MS (RR-MS). We also report what is available in the literature regarding the effectiveness of fecal microbiota transplantation and the role of the diet in restoring the intestinal bacterial population. Studies report that patients with RR-MS have a microbiota that, compared with healthy controls, has higher amounts of Pedobacteria, Flavobacterium, Pseudomonas, Mycoplana, Acinetobacter, Eggerthella, Dorea, Blautia, Streptococcus and Akkermansia. In contrast, MS patients have a microbiota with impoverished microbial populations of Prevotella, Bacteroides, Parabacteroides, Haemophilus, Sutterella, Adlercreutzia, Coprobacillus, Lactobacillus, Clostridium, Anaerostipes and Faecalibacterium. In conclusion, the restoration of the microbial population in patients with RR-MS appears to reduce inflammatory events and the reactivation of the immune system.}, }
@article {pmid31510101, year = {2019}, author = {Prochazkova, P and Roubalova, R and Dvorak, J and Tlaskalova-Hogenova, H and Cermakova, M and Tomasova, P and Sediva, B and Kuzma, M and Bulant, J and Bilej, M and Hrabak, P and Meisnerova, E and Lambertova, A and Papezova, H}, title = {Microbiota, Microbial Metabolites, and Barrier Function in A Patient with Anorexia Nervosa after Fecal Microbiota Transplantation.}, journal = {Microorganisms}, volume = {7}, number = {9}, pages = {}, pmid = {31510101}, issn = {2076-2607}, support = {17-28905A//MINISTRY OF HEALTH OF THE CZECH REPUBLIC/ ; }, abstract = {The change in the gut microbiome and microbial metabolites in a patient suffering from severe and enduring anorexia nervosa (AN) and diagnosed with small intestinal bacterial overgrowth syndrome (SIBO) was investigated. Microbial gut dysbiosis is associated with both AN and SIBO, and therefore gut microbiome changes by serial fecal microbiota transplantation (FMT) is a possible therapeutic modality. This study assessed the effects of FMT on gut barrier function, microbiota composition, and the levels of bacterial metabolic products. The patient treatment with FMT led to the improvement of gut barrier function, which was altered prior to FMT. Very low bacterial alpha diversity, a lack of beneficial bacteria, together with a great abundance of fungal species were observed in the patient stool sample before FMT. After FMT, both bacterial species richness and gut microbiome evenness increased in the patient, while the fungal alpha diversity decreased. The total short-chain fatty acids (SCFAs) levels (molecules presenting an important source of energy for epithelial gut cells) gradually increased after FMT. Contrarily, one of the most abundant intestinal neurotransmitters, serotonin, tended to decrease throughout the observation period. Overall, gut microbial dysbiosis improvement after FMT was considered. However, there were no signs of patient clinical improvement. The need for an in-depth analysis of the donor´s stool and correct selection pre-FMT is evident.}, }
@article {pmid31504398, year = {2019}, author = {Hata, T and Miyata, N and Takakura, S and Yoshihara, K and Asano, Y and Kimura-Todani, T and Yamashita, M and Zhang, XT and Watanabe, N and Mikami, K and Koga, Y and Sudo, N}, title = {The Gut Microbiome Derived From Anorexia Nervosa Patients Impairs Weight Gain and Behavioral Performance in Female Mice.}, journal = {Endocrinology}, volume = {160}, number = {10}, pages = {2441-2452}, doi = {10.1210/en.2019-00408}, pmid = {31504398}, issn = {1945-7170}, mesh = {Adult ; Animals ; Anorexia Nervosa/*microbiology ; *Behavior, Animal ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Mice ; Mice, Inbred BALB C ; *Weight Gain ; Young Adult ; }, abstract = {Anorexia nervosa (AN) results in gut dysbiosis, but whether the dysbiosis contributes to AN-specific pathologies such as poor weight gain and neuropsychiatric abnormalities remains unclear. To address this, germ-free mice were reconstituted with the microbiota of four patients with restricting-type AN (gAN mice) and four healthy control individuals (gHC mice). The effects of gut microbes on weight gain and behavioral characteristics were examined. Fecal microbial profiles in recipient gnotobiotic mice were clustered with those of the human donors. Compared with gHC mice, gAN mice showed a decrease in body weight gain, concomitant with reduced food intake. Food efficiency ratio (body weight gain/food intake) was also significantly lower in gAN mice than in gHC mice, suggesting that decreased appetite as well as the capacity to convert ingested food to unit of body substance may contribute to poor weight gain. Both anxiety-related behavior measured by open-field tests and compulsive behavior measured by a marble-burying test were increased only in gAN mice but not in gHC mice. Serotonin levels in the brain stem of gAN mice were lower than those in the brain stem of gHC mice. Moreover, the genus Bacteroides showed the highest correlation with the number of buried marbles among all genera identified. Administration of Bacteroides vulgatus reversed compulsive behavior but failed to exert any substantial effect on body weight. Collectively, these results indicate that AN-specific dysbiosis may contribute to both poor weight gain and mental disorders in patients with AN.}, }
@article {pmid31501716, year = {2019}, author = {Lee, H and Kim, J and An, J and Lee, S and Choi, D and Kong, H and Song, Y and Park, IH and Lee, CK and Kim, K}, title = {Downregulation of IL-18 Expression in the Gut by Metformin-induced Gut Microbiota Modulation.}, journal = {Immune network}, volume = {19}, number = {4}, pages = {e28}, pmid = {31501716}, issn = {1598-2629}, abstract = {IL-18 is a crucial pro-inflammatory cytokine that mediates chronic intestinal inflammation. Metformin, an anti-diabetic drug, was reported to have ameliorative effects on inflammatory bowel disease. Recently, the mechanism of action of metformin was explained as a modulation of gut microbiota. In this study, fecal microbiota transplantation (FMT) using fecal material from metformin-treated mice was found to upregulate the expression of GLP-1 and pattern-recognition receptors TLR1 and TLR4 for the improvement in hyperglycemia caused by a high-fat diet. Further, FMT downregulated the expression of the inflammatory cytokine IL-18. Within the genera Akkermansia, Bacteroides, and Butyricimonas, which were promoted by metformin therapy, Butyricimonas was found to be consistently abundant following FMT. Our findings suggest that modulation of gut microbiota is a key factor for the anti-inflammatory effects of metformin which is used for the treatment of hyperglycemia.}, }
@article {pmid31496843, year = {2019}, author = {Philips, CA and Augustine, P and Yerol, PK and Rajesh, S and Mahadevan, P}, title = {Severe alcoholic hepatitis: current perspectives.}, journal = {Hepatic medicine : evidence and research}, volume = {11}, number = {}, pages = {97-108}, pmid = {31496843}, issn = {1179-1535}, abstract = {Severe acute alcoholic hepatitis (AH) is a catastrophic disease in the natural history of alcoholic liver disease with a very high 180-day mortality. It can present as acute on chronic liver failure with worse prognosis in the presence of infections and higher grades of liver disease severity. The clinical scenario involves a patient with a recent history of heavy alcohol consumption within three months of presentation with jaundice and characteristic liver enzyme elevation pattern with coagulopathy, hepatic encephalopathy, variceal bleeding and sepsis that results in extrahepatic organ failures. Several liver disease severities and therapy response indicators are in clinical use. Even though not approved, the only recommended treatment option for patients with severe AH is corticosteroids, which is without long term survival benefit. Novel efficacious treatment options awaiting high-quality multi-center studies include liver transplantation (involves strict selection criteria), growth factor therapy and fecal microbiota transplantation. In this exhaustive review, we discuss the definitions, disease severity, histopathology, and treatment options - past, present, and future, in patients with severe alcoholic hepatitis.}, }
@article {pmid31496168, year = {2019}, author = {Hu, Y and Lyu, B}, title = {[Development and prospects of fecal microbiota transplantation].}, journal = {Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences}, volume = {48}, number = {3}, pages = {342-346}, pmid = {31496168}, issn = {1008-9292}, mesh = {*Fecal Microbiota Transplantation/standards/trends ; Humans ; Treatment Outcome ; }, }
@article {pmid31493500, year = {2020}, author = {Madoff, SE and Urquiaga, M and Alonso, CD and Kelly, CP}, title = {Prevention of recurrent Clostridioides difficile infection: A systematic review of randomized controlled trials.}, journal = {Anaerobe}, volume = {61}, number = {}, pages = {102098}, doi = {10.1016/j.anaerobe.2019.102098}, pmid = {31493500}, issn = {1095-8274}, abstract = {Recurrent Clostridioides (formerly Clostridium) difficile infection (rCDI) is common, and patients who have had one recurrence are more likely to have multiple recurrences. Frequent recurrences have been associated with increased morbidity and mortality, high healthcare costs, and lower quality of life. In this review, we compare the efficacy of interventions designed to prevent rCDI. We performed a systematic review of the English literature, including randomized controlled trials (RCTs) that evaluated rCDI as an outcome. Studies were included irrespective of patient demographics, disease severity, type of intervention, comparator used, or time-point of outcome evaluation. We performed a comprehensive literature search with the assistance of a research librarian. Two reviewers independently extracted data and assessed risk of bias. Our search yielded 38 RCTs (8,102 participants). Nineteen RCTs (3,743 subjects) evaluated antibiotics, eight fecal microbiota transplantation (FMT) (582 subjects), three monoclonal antibodies (MAbs) (2,805 subjects), and eight probiotics, prebiotics, or non-antibiotic polymers (972 subjects). The antibiotic and FMT therapies that demonstrated efficacy in rCDI prevention included: fidaxomicin (when compared to a ten-day vancomycin course) and FMT administered by nasogastric tube (when compared to a fourteen-day vancomycin course and a fourteen-day vancomycin course plus bowel lavage). Actoxumab (MAb against C. difficile toxin A; CDA1) plus bezlotoxumab (MAb against C. difficile toxin B; CDB1) in combination or bezlotoxumab alone appeared to be more effective in preventing rCDI compared to actoxumab alone. Of the prebiotics, probiotics, and nonantibiotic polymers, oligofructose, Saccharomyces boulardii, and the nontoxigenic C. difficile strain M3 were the most efficacious for rCDI prevention. Thirty-eight RCTs (>8,000 participants) evaluating treatment modalities for CDI were examined for efficacy in prevention of rCDI. Several CDI-specific antibiotics, FMT modalities, monoclonal antibodies, and various prebiotics and probiotics demonstrated a reduction in risk of rCDI with the greatest risk reduction observed with FMT and monoclonal antibody therapy. It is notable that the comparators in these studies were very different from one another and the relative risk reduction of rCDI may not be directly comparable from one study to the next.}, }
@article {pmid31493042, year = {2019}, author = {Luo, Y and Lucas, AL and Grinspan, AM}, title = {Fecal Transplants by Colonoscopy and Capsules Are Cost-Effective Strategies for Treating Recurrent Clostridioides difficile Infection.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-019-05821-1}, pmid = {31493042}, issn = {1573-2568}, abstract = {BACKGROUND: Recurrent Clostridioides difficile infections (CDIs) occur frequently and pose a substantial economic burden on the US healthcare system. The landscape for the treatment of CDI is evolving.<br><br>AIM: To elucidate the most cost-effective strategy for managing recurrent CDI.<br><br>METHODS: A decision tree analysis was created from a modified third-party payer's perspective to compare the cost-effectiveness of five strategies for patients experiencing their first CDI recurrence: oral vancomycin, fidaxomicin, fecal microbiota transplant (FMT) via colonoscopy, FMT via oral capsules, and a one-time infusion of bezlotoxumab with vancomycin. Effectiveness measures were quality-adjusted life years (QALY). A willingness-to-pay (WTP) threshold of $100,000 per QALY was set. One-way and probabilistic sensitivity analyses were performed.<br><br>RESULTS: Base-case analysis showed that FMT via colonoscopy was associated with the lowest cost at $5250 and that FMT via capsules was also a cost-effective strategy with an incremental cost-effectiveness ratio (ICER) of $31205/QALY. Sensitivity analyses demonstrated that FMT delivered by oral capsules and colonoscopy was comparable cost-effective modalities. At its current cost and effectiveness, bezlotoxumab was not a cost-effective strategy.<br><br>CONCLUSIONS: FMT via oral capsules and colonoscopy is both cost-effective strategies to treat the first recurrence of CDI. Further real-world economic studies are needed to understand the cost-effectiveness of all available strategies.}, }
@article {pmid31492463, year = {2020}, author = {Chong, PP and Koh, AY}, title = {The gut microbiota in transplant patients.}, journal = {Blood reviews}, volume = {39}, number = {}, pages = {100614}, pmid = {31492463}, issn = {1532-1681}, support = {R01 AI123163/AI/NIAID NIH HHS/United States ; }, abstract = {Solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients are at increased risk for developing infections due to underlying immunosuppression. Antibiotic use, and in HSCT recipients, the use of preparative regimens prior to transplantation can deplete gut commensal bacteria, resulting in intestinal dysbiosis. Emerging evidence in transplant patients, particularly HSCT, suggest that disturbances in gut microbiota populations are associated with a number of adverse outcomes. Here, we review the outcomes of HSCT and SOT recipients with gut microbiota imbalance or dysbiosis, explore the nascent field of gut microbiome therapeutic approaches including fecal microbiota transplantation and the use of precision probiotics in HSCT and SOT recipients.}, }
@article {pmid31487251, year = {2019}, author = {Martínez, JV and Raush, A and Efrón, ED and Zubiaurre, I and Pinoni, MV and Giorgio, PL and Eusebio, MJ and Verbanaz, SC and Jordan, R}, title = {[Refractory colitis by Clostridium difficile treated with fecal microbiota transplant].}, journal = {Medicina}, volume = {79}, number = {4}, pages = {291-294}, pmid = {31487251}, issn = {1669-9106}, mesh = {Aged, 80 and over ; Clostridium Infections/complications/*therapy ; *Clostridium difficile ; Diarrhea/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Treatment Outcome ; }, abstract = {Clostridium difficile infection is an increasingly recognized cause of diarrhea in inpatients, frequently associated to high mortality. Vancomycin is the treatment of choice for all Clostridium difficile- associated diarrheas, with different degrees of severity. However, some patients develop refractory forms to that treatment and there are no alternative antibiotic schemes recommended for these cases. Fecal microbiota transplantation has been shown to be successful in a series of cases of severe diarrhea associated with this organism. We present a case of refractory C. difficile infection successfully treated with fecal microbiota transplantation.}, }
@article {pmid31482438, year = {2020}, author = {Mishima, Y and Sartor, RB}, title = {Manipulating resident microbiota to enhance regulatory immune function to treat inflammatory bowel diseases.}, journal = {Journal of gastroenterology}, volume = {55}, number = {1}, pages = {4-14}, pmid = {31482438}, issn = {1435-5922}, abstract = {Altered intestinal microbial composition (dysbiosis) and metabolic products activate aggressive mucosal immune responses that mediate inflammatory bowel diseases (IBD). This dysbiosis impairs the function of regulatory immune cells, which normally promote mucosal homeostasis. Normalizing and maintaining regulatory immune cell function by correcting dysbiosis provides a promising approach to treat IBD patients. However, existing microbe-targeted therapies, including antibiotics, prebiotics, probiotics, and fecal microbial transplantation, provide variable outcomes that are not optimal for current clinical application. This review discusses recent progress in understanding the dysbiosis of IBD and the basis for therapeutic restoration of homeostatic immune function by manipulating an individual patient's microbiota composition and function. We believe that identifying more precise therapeutic targets and developing appropriate rapid diagnostic tools will guide more effective and safer microbe-based induction and maintenance treatments for IBD patients that can be applied in a personalized manner.}, }
@article {pmid31476300, year = {2019}, author = {Monaghan, TM and Pučić-Baković, M and Vučković, F and Lee, C and Kao, D and , }, title = {Decreased Complexity of Serum N-glycan Structures Associates with Successful Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.}, journal = {Gastroenterology}, volume = {157}, number = {6}, pages = {1676-1678.e3}, doi = {10.1053/j.gastro.2019.08.034}, pmid = {31476300}, issn = {1528-0012}, support = {/DH_/Department of Health/United Kingdom ; }, mesh = {Adult ; Aged ; Clostridium Infections/blood/microbiology/*therapy ; Clostridium difficile/*pathogenicity ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Glycosylation ; Humans ; Male ; Middle Aged ; Polysaccharides/*blood/metabolism ; Randomized Controlled Trials as Topic ; Retrospective Studies ; Treatment Outcome ; }, }
@article {pmid31472233, year = {2019}, author = {Tan, X and Johnson, S}, title = {Fecal microbiota transplantation (FMT) for C. difficile infection, just say 'No'.}, journal = {Anaerobe}, volume = {60}, number = {}, pages = {102092}, doi = {10.1016/j.anaerobe.2019.102092}, pmid = {31472233}, issn = {1095-8274}, abstract = {Despite lack of regulatory approval, fecal microbiota transplantation (FMT) is widely performed to manage C. difficile infection (CDI), particularly recurrent CDI. Herein, we critically review the available randomized controlled trials of FMT and address the following questions: Is FMT better than drug management of recurrent CDI?; Is FMT treatment per se or adjunctive treatment to antibiotics for CDI?; and, Is FMT safe? Finally, we elaborate non-FMT options for the management of recurrent CDI. Although promising, FMT should be reserved for patients who have failed appropriate antibiotic management of recurrent CDI.}, }
@article {pmid31471351, year = {2020}, author = {Kim, MS and Kim, Y and Choi, H and Kim, W and Park, S and Lee, D and Kim, DK and Kim, HJ and Choi, H and Hyun, DW and Lee, JY and Choi, EY and Lee, DS and Bae, JW and Mook-Jung, I}, title = {Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer's disease animal model.}, journal = {Gut}, volume = {69}, number = {2}, pages = {283-294}, doi = {10.1136/gutjnl-2018-317431}, pmid = {31471351}, issn = {1468-3288}, mesh = {Alzheimer Disease/metabolism/*microbiology/*therapy ; Animals ; Behavior, Animal ; Chronic Disease ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammation/microbiology ; Intestines/microbiology ; Memory, Short-Term ; Mice, Transgenic ; Permeability ; Plaque, Amyloid/microbiology/pathology ; Spatial Learning ; tau Proteins/analysis ; }, abstract = {OBJECTIVE: Cerebral amyloidosis and severe tauopathy in the brain are key pathological features of Alzheimer's disease (AD). Despite a strong influence of the intestinal microbiota on AD, the causal relationship between the gut microbiota and AD pathophysiology is still elusive.<br><br>DESIGN: Using a recently developed AD-like pathology with amyloid and neurofibrillary tangles (ADLPAPT) transgenic mouse model of AD, which shows amyloid plaques, neurofibrillary tangles and reactive gliosis in their brains along with memory deficits, we examined the impact of the gut microbiota on AD pathogenesis.<br><br>RESULTS: Composition of the gut microbiota in ADLPAPT mice differed from that of healthy wild-type (WT) mice. Besides, ADLPAPT mice showed a loss of epithelial barrier integrity and chronic intestinal and systemic inflammation. Both frequent transfer and transplantation of the faecal microbiota from WT mice into ADLPAPT mice ameliorated the formation of amyloid β plaques and neurofibrillary tangles, glial reactivity and cognitive impairment. Additionally, the faecal microbiota transfer reversed abnormalities in the colonic expression of genes related to intestinal macrophage activity and the circulating blood inflammatory monocytes in the ADLPAPT recipient mice.<br><br>CONCLUSION: These results indicate that microbiota-mediated intestinal and systemic immune aberrations contribute to the pathogenesis of AD in ADLPAPT mice, providing new insights into the relationship between the gut (colonic gene expression, gut permeability), blood (blood immune cell population) and brain (pathology) axis and AD (memory deficits). Thus, restoring gut microbial homeostasis may have beneficial effects on AD treatment.}, }
@article {pmid31468999, year = {2019}, author = {Yoon, YK and Suh, JW and Kang, EJ and Kim, JY}, title = {Efficacy and safety of fecal microbiota transplantation for decolonization of intestinal multidrug-resistant microorganism carriage: beyond Clostridioides difficile infection.}, journal = {Annals of medicine}, volume = {51}, number = {7-8}, pages = {379-389}, doi = {10.1080/07853890.2019.1662477}, pmid = {31468999}, issn = {1365-2060}, abstract = {Persistent reservoirs of multidrug-resistant microorganisms (MDRO) that are prevalent in hospital settings and communities can lead to the spread of MDRO. Currently, there are no effective decolonization strategies, especially non-pharmacological strategies without antibiotic regimens. Our aim was to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for the eradication of MDRO. A systematic literature search was performed to identify studies on the use of FMT for the decolonization of MDRO. PubMed, EMBASE, Web of Science, and Cochrane Library were searched from inception through January 2019. Of the 1395 articles identified, 20 studies met the inclusion and exclusion criteria. Overall, the efficacy of FMT for the eradication of each MDRO was 70.3% (102/146) in 121 patients from the 20 articles. The efficacy rates were 68.2% (30/44) for gram-positive bacteria and 70.6% (72/102) for gram-negative bacteria. Minor adverse events, including vomiting, diarrhea, abdominal pain, and ileus, were reported in patients who received FMT. FMT could be a promising strategy to eradicate MDRO in patients. Further studies are needed to confirm these findings and establish a comprehensive FMT protocol for standardized treatment.Key messagesThe development of new antibiotics lags behind the emergence of multidrug-resistant microorganisms (MDRO). New strategies are needed.Theoretically, fecal microbiota transplantation (FMT) might recover the diversity and function of commensal microbiota from dysbiosis in MDRO carriers and help restore colonization resistance to pathogens.A literature review indicated that FMT could be a promising strategy to eradicate MDRO in patients.}, }
@article {pmid31467881, year = {2019}, author = {Zhou, Y and Xu, H and Huang, H and Li, Y and Chen, H and He, J and Du, Y and Chen, Y and Zhou, Y and Nie, Y}, title = {Are There Potential Applications of Fecal Microbiota Transplantation beyond Intestinal Disorders?.}, journal = {BioMed research international}, volume = {2019}, number = {}, pages = {3469754}, pmid = {31467881}, issn = {2314-6141}, mesh = {Clostridium Infections/microbiology/pathology/therapy ; Clostridium difficile/pathogenicity ; Fecal Microbiota Transplantation/*trends ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Intestinal Diseases/microbiology/pathology/*therapy ; Intestines/microbiology ; Irritable Bowel Syndrome/microbiology/*therapy ; }, abstract = {Intestinal microbial dysbiosis is associated with various intestinal and extraintestinal disorders. Fecal microbiota transplantation (FMT), a type of fecal bacteriotherapy, is considered an effective therapeutic option for recurrent Clostridium difficile infection (rCDI) and also has important value in other intestinal diseases including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). The purpose of this review is to discuss promising therapeutic value in extraintestinal diseases associated with gut microbial dysbiosis, including liver, metabolic, chronic kidney, neuropsychiatric, allergic, autoimmune, and hematological diseases as well as tumors.}, }
@article {pmid31465241, year = {2019}, author = {Liu, Z and Li, N and Fang, H and Chen, X and Guo, Y and Gong, S and Niu, M and Zhou, H and Jiang, Y and Chang, P and Chen, P}, title = {Enteric dysbiosis is associated with sepsis in patients.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {33}, number = {11}, pages = {12299-12310}, pmid = {31465241}, issn = {1530-6860}, abstract = {Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to microbial infection. For decades, the potential role of gut microbiota in sepsis pathogenesis has been revealed. However, the systemic and functional link between gut microbiota and sepsis has remained unexplored. To address this gap in knowledge, we carried out systematic analyses on clinical stool samples from patients with sepsis, including 16S rDNA sequencing, metabolomics, and metaproteomics analyses. In addition, we performed fecal microbiota transplantation from human to mice to validate the roles of gut microbiota on sepsis progression. We found that the composition of gut microbiota was significantly disrupted in patients with sepsis compared with healthy individuals. Besides, the microbial functions were significantly altered in septic feces as identified by metabolomics and metaproteomics analyses. Interestingly, mice that received septic feces exhibited more severe hepatic inflammation and injury than mice that received healthy feces after cecal ligation and puncture. Finally, several strains of intestinal microbiota and microbial metabolites were corelated with serum total bilirubin levels in patients with sepsis. Taken together, our data indicated that sepsis development is associated with the disruption of gut microbiota at both compositional and functional levels, and such enteric dysbiosis could promote organ inflammation and injury during sepsis.-Liu, Z., Li, N., Fang, H., Chen, X., Guo, Y., Gong, S., Niu, M., Zhou, H., Jiang, Y., Chang, P., Chen, P. Enteric dysbiosis is associated with sepsis in patients.}, }
@article {pmid31462301, year = {2019}, author = {Zhong, S and Zeng, J and Deng, Z and Jiang, L and Zhang, B and Yang, K and Wang, W and Zhang, T}, title = {Fecal microbiota transplantation for refractory diarrhea in immunocompromised diseases: a pediatric case report.}, journal = {Italian journal of pediatrics}, volume = {45}, number = {1}, pages = {116}, pmid = {31462301}, issn = {1824-7288}, abstract = {BACKGROUND: Immunocompromised (IC) patients have an increased risk of refractory diarrhea. Fecal microbiota transplantation (FMT) is a safe and effective therapy for infection-related diarrhea which are mainly mediated by the loss of the microbial colonization, although there is concern that IC patients may be at higher risk of infectious complications related to FMT. And reports of FMT in IC children are limited.<br><br>CASE PRESENTATION: We describe two cases of FMT in IC children with refractory diarrhea. One IC child had polyendocrinopathy, enteropathy, X-linked syndrome and the other child had graft-versus-host disease. Both of the children had a long course of diarrhea and no response to traditional treatment. FMT was performed on both patients via nasojejunal tubes under guidance of gastroduodenoscopy. After FMT, the patients achieved remission of symptoms and neither of them had related infectious complications. Microbiota analysis showed that FMT resulted in reconstruction of a diverse microbiota.<br><br>CONCLUSIONS: Use of FMT is safe and effective in treatment of refractory diarrhea in IC children with a damaged microbiota.}, }
@article {pmid31456544, year = {2019}, author = {Fredericks, E and Hoosien, E and Brink, A}, title = {The case for stool banks in South Africa.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {109}, number = {8}, pages = {546-547}, doi = {10.7196/SAMJ.2019.v109i8.14169}, pmid = {31456544}, issn = {2078-5135}, mesh = {*Biological Specimen Banks ; Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Humans ; South Africa ; Tissue and Organ Procurement/standards ; }, }
@article {pmid31448542, year = {2020}, author = {Brüssow, H}, title = {Problems with the concept of gut microbiota dysbiosis.}, journal = {Microbial biotechnology}, volume = {13}, number = {2}, pages = {423-434}, pmid = {31448542}, issn = {1751-7915}, abstract = {The human microbiome research is with the notable exception of fecal transplantation still mostly in a descriptive phase. Part of the difficulty for translating research into medical interventions is due to the large compositional complexity of the microbiome resulting in datasets that need sophisticated statistical methods for their analysis and do not lend to industrial applications. Another part of the difficulty might be due to logical flaws in terminology particularly concerning 'dysbiosis' that avoids circular conclusions and is based on sound ecological and evolutionary reasoning. Many case-control studies are underpowered necessitating more meta-analyses that sort out consistent from spurious dysbiosis-disease associations. We also need for the microbiome a transition from statistical associations to causal relationships with diseases that fulfil a set of modified Koch's postulates for commensals. Disturbingly, the most sophisticated statistical analyses explain only a small percentage of the variance in the microbiome. Microbe-microbe interactions irrelevant to the host and stochastic processes might play a greater role than anticipated. To satisfy the concept of Karl Popper about conjectures and refutations in the scientific process, we should also conduct more experiments that try to refute the role of the commensal gut microbiota for human health and disease.}, }
@article {pmid31443761, year = {2019}, author = {Monif, GRG}, title = {Is ulcerative colitis a disease of a dysfunctional microbiota?.}, journal = {Medical hypotheses}, volume = {131}, number = {}, pages = {109300}, doi = {10.1016/j.mehy.2019.109300}, pmid = {31443761}, issn = {1532-2777}, mesh = {Adrenal Cortex Hormones/therapeutic use ; Anti-Bacterial Agents/adverse effects/therapeutic use ; Biological Products/therapeutic use ; Colitis, Ulcerative/classification/diet therapy/*microbiology/therapy ; Combined Modality Therapy ; Enema ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/physiology ; Humans ; }, abstract = {Using the gross pathology literature and the prior decoupling of Crohn's disease from inflammatory bowel disease, IDI's White Paper puts into question the current understanding of what ulcerative colitis is and how it can be therapeutically addressed. The pathology literature, when coupled with the ability of fecal enema therapy to achieve a remission rate significantly superior to those documented for biologics, puts focus on the dominant role of the gastrointestinal microbiota in both disease induction and its recovery. The concept of endogenous enterotoxogenesis is introduced.}, }
@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}, 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}, 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}, 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/ ; }, mesh = {Antimicrobial Cationic Peptides/*physiology ; Epithelium/*physiology ; Gastrointestinal Microbiome/*physiology ; Humans ; *Immunity, Innate ; Immunoglobulin A, Secretory/*physiology ; MicroRNAs/physiology ; Microvilli/physiology ; Mucus/*physiology ; Tight Junctions/physiology ; }, 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 {pmid31429237, year = {2019}, author = {Frøland, SS}, title = {Fecal transplantation and the microbiome.}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {139}, number = {11}, pages = {}, doi = {10.4045/tidsskr.19.0445}, pmid = {31429237}, issn = {0807-7096}, mesh = {Fecal Microbiota Transplantation/*classification ; Humans ; Norway ; Terminology as Topic ; *Translations ; }, }
@article {pmid31429236, year = {2019}, author = {Juul, FE and Valeur, J}, title = {F. E. Juul and J. Valeur respond.}, journal = {Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke}, volume = {139}, number = {11}, pages = {}, doi = {10.4045/tidsskr.19.0446}, pmid = {31429236}, issn = {0807-7096}, mesh = {*Electronic Nicotine Delivery Systems ; Fecal Microbiota Transplantation ; *Microbiota ; *Social Media ; }, }
@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 = {