Daily, Oral FMT for Long-Term Maintenance Therapy in Ulcerative Colitis: Results of a Single-Center, Prospective, Randomized Pilot Study.

Abstract This randomized study was designed to assess the safety and feasibility of long-term fecal microbiota transplantation (FMT) in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT). FMT induction was implemented by colonoscopy, followed by 12 weeks of daily oral administration of frozen encapsulated cFMT. Ribosomal 16S bacterial sequencing was used to assess donor-induced changes in the gut microbiota. Changes in T regulatory (Treg) and mucosal associated invariant T (MAIT) cell populations were evaluated as an exploratory endpoint. Twelve subjects with active UC were randomized: 6 subjects completed the full 12-week course of FMT plus cFMT, and 6 subjects received sham treatment by colonic installation and longitudinal oral treatment. Chronic administration of cFMT was found to be safe and well-tolerated. Protocol adherence was high, and none of the study subjects experienced FMT-associated treatment emergent adverse events. While n-values were too small to draw firm conclusions, 3/6 subjects that received cFMT exhibited multiple signs of clinical improvement. These pilot data suggest that daily encapsulated cFMT may extend the durability of index FMT-induced changes in gut bacterial community structure and that an association between MAIT cell cytokine production and clinical response to FMT may exist in UC populations. Oral frozen encapsulated cFMT is a promising FMT delivery system and may be preferred for longterm treatment strategies in UC and other chronic diseases but further evaluations will have to address home storage concerns. Larger trials should be done to explore the benefits of cFMT and to determine its long-term impacts on the colonic microbiome. Trial registration: ClinicalTrials.gov (NCT02390726). Registered 17 March 2015, https://clinicaltrials.gov/ct2/show/NCT02390726?term=NCT02390726&draw=2&rank=1.

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Daily, Oral FMT for Longterm Maintenance Therapy in Ulcerative Colitis: Results of a single-center, prospective, randomized pilot study.

10.21203/rs.3.rs-62372/v2 ◽

2021 ◽

Author(s):

Jessica Wood Crothers ◽

Nathaniel D. Chu ◽

Le Thanh Tu Nguyen ◽

Magen Phillips ◽

Cheryl Collins ◽

...

Keyword(s):

Cytokine Production ◽

Fecal Microbiota Transplantation ◽

Oral Treatment ◽

Randomized Study ◽

Fecal Microbiota ◽

Microbial Composition ◽

Induced Changes ◽

Cell Cytokine Production ◽

Mait Cell

Abstract BackgroundFecal microbiota transplantation (FMT) is a promising new strategy in the treatment of Inflammatory Bowel Disease, but long-term delivery systems are lacking. This randomized study was designed as a safety and feasibility study of long-term fecal microbiota transplantation (FMT) in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT). MethodsSubjects were randomized 1:1 to receive FMT induction by colonoscopy, followed by 12 weeks of daily oral administration of frozen encapsulated cFMT or sham therpay. Subjects were followed for 36 weeks and longitudenal clinical assessments included multiple subjective and objective markers of disease severity. Ribosomal 16S bacterial sequencing was used to assess donor-induced changes in the gut microbiota. Changes in T regulatory (Treg) and mucosal associated invariant T (MAIT) cell populations were evaluated by flow cytometry as an exploratory endpoint. ResultsTwelve subjects with active UC were randomized: 6 subjects completed the full 12-week course of FMT plus cFMT, and 6 subjects received sham treatment by colonic installation and longitudinal oral treatment. Chronic administration of cFMT was found to be safe and well-tolerated but home storage concerns exist. Protocol adherence was high, and none of the study subjects experienced FMT-associated treatment emergent adverse events. Two subjects that received cFMT achieved clinical remission versus none in the placebo group (95% CI = 0.38-infinity, p = 0.45). cFMT was associated with sustained donor-induced shifts in fecal microbial composition. Changes in MAIT cell cytokine production were observed in cFMT recipients and correlated with treatment response. ConclusionThese pilot data suggest that daily encapsulated cFMT may extend the durability of index FMT-induced changes in gut bacterial community structure and that an association between MAIT cell cytokine production and clinical response to FMT may exist in UC populations. Oral frozen encapsulated cFMT is a promising FMT delivery system and may be preferred for longterm treatment strategies in UC and other chronic diseases but further evaluations will have to address home storage concerns. Larger trials should be done to explore the benefits of cFMT and to determine its long-term impacts on the colonic microbiome. Trial registration: ClinicalTrials.gov (NCT02390726). Registered 17 March 2015, https://clinicaltrials.gov/ct2/show/NCT02390726?term=NCT02390726&draw=2&rank=1.

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Daily, oral FMT for long-term maintenance therapy in ulcerative colitis: results of a single-center, prospective, randomized pilot study

BMC Gastroenterology ◽

10.1186/s12876-021-01856-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jessica W. Crothers ◽

Nathaniel D. Chu ◽

Le Thanh Tu Nguyen ◽

Magen Phillips ◽

Cheryl Collins ◽

...

Keyword(s):

Cytokine Production ◽

Fecal Microbiota Transplantation ◽

Randomized Study ◽

Treatment Strategies ◽

Chronic Administration ◽

Microbial Composition ◽

Induced Changes ◽

Cell Cytokine Production ◽

Mait Cell

Abstract Background Fecal microbiota transplantation (FMT) is a promising new strategy in the treatment of Inflammatory Bowel Disease, but long-term delivery systems are lacking. This randomized study was designed as a safety and feasibility study of long-term FMT in subjects with mild to moderate UC using frozen, encapsulated oral FMT (cFMT). Methods Subjects were randomized 1:1 to receive FMT induction by colonoscopy, followed by 12 weeks of daily oral administration of frozen encapsulated cFMT or sham therpay. Subjects were followed for 36 weeks and longitudenal clinical assessments included multiple subjective and objective markers of disease severity. Ribosomal 16S bacterial sequencing was used to assess donor-induced changes in the gut microbiota. Changes in T regulatory (Treg) and mucosal associated invariant T (MAIT) cell populations were evaluated by flow cytometry as an exploratory endpoint. Results Twelve subjects with active UC were randomized: 6 subjects completed the full 12-week course of FMT plus cFMT, and 6 subjects received sham treatment by colonic installation and longitudinal oral placebo capules. Chronic administration of cFMT was found to be safe and well-tolerated but home storage concerns exist. Protocol adherence was high, and none of the study subjects experienced FMT-associated treatment emergent adverse events. Two subjects that received cFMT achieved clinical remission versus none in the placebo group (95% CI = 0.38-infinity, p = 0.45). cFMT was associated with sustained donor-induced shifts in fecal microbial composition. Changes in MAIT cell cytokine production were observed in cFMT recipients and correlated with treatment response. Conclusion These pilot data suggest that daily encapsulated cFMT may extend the durability of index FMT-induced changes in gut bacterial community structure and that an association between MAIT cell cytokine production and clinical response to FMT may exist in UC populations. Oral frozen encapsulated cFMT is a promising FMT delivery system and may be preferred for longterm treatment strategies in UC and other chronic diseases but further evaluations will have to address home storage concerns. Larger trials should be done to explore the benefits of cFMT and to determine its long-term impacts on the colonic microbiome. Trial registration: ClinicalTrials.gov (NCT02390726). Registered 17 March 2015, https://clinicaltrials.gov/ct2/show/NCT02390726?term=NCT02390726&draw=2&rank=1.

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The microbial metabolite p-Cresol induces autistic-like behaviors in mice by remodeling the gut microbiota

Microbiome ◽

10.1186/s40168-021-01103-z ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Patricia Bermudez-Martin ◽

Jérôme A. J. Becker ◽

Nicolas Caramello ◽

Sebastian P. Fernandez ◽

Renan Costa-Campos ◽

...

Keyword(s):

Social Behavior ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Autism Spectrum ◽

Dopamine Neurons ◽

Therapeutic Interventions ◽

Microbiota Composition ◽

Microbial Metabolite ◽

Central Dopamine Neurons ◽

Induced Changes

Abstract Background Autism spectrum disorders (ASD) are associated with dysregulation of the microbiota-gut-brain axis, changes in microbiota composition as well as in the fecal, serum, and urine levels of microbial metabolites. Yet a causal relationship between dysregulation of the microbiota-gut-brain axis and ASD remains to be demonstrated. Here, we hypothesized that the microbial metabolite p-Cresol, which is more abundant in ASD patients compared to neurotypical individuals, could induce ASD-like behavior in mice. Results Mice exposed to p-Cresol for 4 weeks in drinking water presented social behavior deficits, stereotypies, and perseverative behaviors, but no changes in anxiety, locomotion, or cognition. Abnormal social behavior induced by p-Cresol was associated with decreased activity of central dopamine neurons involved in the social reward circuit. Further, p-Cresol induced changes in microbiota composition and social behavior deficits could be transferred from p-Cresol-treated mice to control mice by fecal microbiota transplantation (FMT). We also showed that mice transplanted with the microbiota of p-Cresol-treated mice exhibited increased fecal p-Cresol excretion, compared to mice transplanted with the microbiota of control mice. In addition, we identified possible p-Cresol bacterial producers. Lastly, the microbiota of control mice rescued social interactions, dopamine neurons excitability, and fecal p-Cresol levels when transplanted to p-Cresol-treated mice. Conclusions The microbial metabolite p-Cresol induces selectively ASD core behavioral symptoms in mice. Social behavior deficits induced by p-Cresol are dependant on changes in microbiota composition. Our study paves the way for therapeutic interventions targeting the microbiota and p-Cresol production to treat patients with ASD.

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Fecal Microbiota Transplant in Two Ulcerative Colitis Pediatric Cases: Gut Microbiota and Clinical Course Correlations

Microorganisms ◽

10.3390/microorganisms8101486 ◽

2020 ◽

Vol 8 (10) ◽

pp. 1486

Author(s):

Andrea Quagliariello ◽

Federica Del Chierico ◽

Sofia Reddel ◽

Alessandra Russo ◽

Andrea Onetti Muda ◽

...

Keyword(s):

Ulcerative Colitis ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Clinical Effects ◽

Phylogenetic Distance ◽

Fecal Microbiota Transplant ◽

Inflammatory Bowel ◽

Clinical Conditions ◽

And Control

Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts’ time-point profiles, donors and control cohorts’ baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient’s condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.

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Cultivation and Genomics Prove Long-Term Colonization of Donor’s Bifidobacteria in Recurrent Clostridioides difficile Patients Treated With Fecal Microbiota Transplantation

Frontiers in Microbiology ◽

10.3389/fmicb.2020.01663 ◽

2020 ◽

Vol 11 ◽

Author(s):

Hanne Jouhten ◽

Aki Ronkainen ◽

Juhani Aakko ◽

Seppo Salminen ◽

Eero Mattila ◽

...

Keyword(s):

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Clostridioides Difficile

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Precise quantification of bacterial strains after fecal microbiota transplantation delineates long-term engraftment and explains outcomes

Nature Microbiology ◽

10.1038/s41564-021-00966-0 ◽

2021 ◽

Author(s):

Varun Aggarwala ◽

Ilaria Mogno ◽

Zhihua Li ◽

Chao Yang ◽

Graham J. Britton ◽

...

Keyword(s):

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Bacterial Strains ◽

Precise Quantification

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Future Directions in Reducing Gastrointestinal Disorders in Children With ASD Using Fecal Microbiota Transplantation

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.630052 ◽

2021 ◽

Vol 11 ◽

Author(s):

Paulina Żebrowska ◽

Izabela Łaczmańska ◽

Łukasz Łaczmański

Keyword(s):

Pediatric Patients ◽

Fecal Microbiota Transplantation ◽

Neurodevelopmental Disorder ◽

Fecal Microbiota ◽

Autism Spectrum ◽

Long Term Effects ◽

Gi Symptoms ◽

Inflammatory Bowel ◽

Age Range

Research on the use of fecal microbiota transplantation (FMT) in the treatment of disorders related to digestive system ailments in children with autism spectrum disorders (ASDs) is a new attempt in a therapeutic approach. There are very little scientific evidences available on this emerging alternative method. However, it appears to be interesting not only because of its primary outcome, relieving the gastrointestinal (GI) symptoms, but also secondary therapeutic effect of alleviating autistic behavioral symptoms. FMT seems to be also promising method in the treatment of another group of pediatric patients, children with inflammatory bowel disease (IBD). The aim of this study is to discuss the potential use of FMT and modified protocols (MTT, microbiota transfer therapy) in the treatment of GI disorders in ASD children supported by reports on another disease, IBD concerning pediatric patients. Due to the few reports of the use of FMT in the treatment of children, these two patients groups were selected, although suffering from distant health conditions: neurodevelopmental disorder and gastrointestinal tract diseases, because of the the fact that they seem related in aspects of the presence of GI symptoms, disturbed intestinal microbiota, unexplained etiology of the condition and age range of patients. Although the outcomes for all are promising, this type of therapy is still an under-researched topic, studies in the group of pediatric patients are sparse, also there is a high risk of transmission of infectious and noninfectious elements during the procedure and no long-term effects on global health are known. For those reasons all obtained results should be taken with a great caution. However, in the context of future therapeutic directions for GI observed in neurodevelopmental disorders and neurodegenerative diseases, the topic seems worthy of attention.

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