Linking Strain Engraftment in Fecal Microbiota Transplantation With Maintenance of Remission in Crohn’s Disease

An original immuno-regulatory strategy against inflammatory bowel diseases based on the use of 28 kDa glutathione S-transferase (P28GST), a unique schistosome protein, was recently proposed. Improvement of intestinal inflammation occurs through restoration of the immunological balance between pro-inflammatory T-helper 1 (Th1) responses and both T-helper 2 (Th2) and regulatory responses. However, detailed mechanisms explaining how P28GST prevents colitis and promotes gut homeostasis remain unknown. Considering the complex interplay between the adaptive and innate immune system and the intestinal microbiota, we raised the question of the possible role of the microbial ecosystem in the anti-inflammatory effects mediated by the helminth-derived P28GST protein. We first analyzed, by 16S rRNA sequencing, the bacterial profiles of mice fecal microbiota at several time points of the P28GST-immunomodulation period prior to trinitrobenzene sulfonic acid (TNBS)-colitis. The influence of gut microbiota in the P28GST-mediated anti-inflammatory effects was then assessed by fecal microbiota transplantation experiments from P28GST-immunized mice to either conventional or microbiota depleted naïve recipient mice. Finally, the experimental data were supplemented by the temporal fecal microbiota compositions of P28GST-treated Crohn’s disease patients from a pilot clinical study (NCT02281916). The P28GST administration slightly modulated the diversity and composition of mouse fecal microbiota while it significantly reduced experimental colitis in mice. Fecal microbiota transplantation experiments failed to restore the P28GST-induced anti-inflammatory effects. In Crohn’s disease patients, P28GST also induced slight changes in their overall fecal bacterial composition. Collectively, these results provide key elements in both the anti-inflammatory mechanisms and the safe therapeutic use of immunomodulation with such promising helminth-derived molecules.

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Fecal microbiota transplantation to maintain remission in Crohn’s disease: a pilot randomized controlled study

Microbiome ◽

10.1186/s40168-020-0792-5 ◽

2020 ◽

Vol 8 (1) ◽

Cited By ~ 22

Author(s):

Harry Sokol ◽

◽

Cecilia Landman ◽

Philippe Seksik ◽

Laurence Berard ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Randomized Controlled Study ◽

Controlled Study ◽

Randomized Controlled

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P168 WHERE WILL FECAL MICROBIOTA TRANSPLANTATION FIT IN THE TREATMENT ALGORITHMS FOR CROHN’S DISEASE AND ULCERATIVE COLITIS: A SYNTHESIS OF COMPLETED, ONGOING AND FUTURE TRIALS

Inflammatory Bowel Diseases ◽

10.1093/ibd/izy037.041 ◽

2018 ◽

Vol 24 (suppl_1) ◽

pp. S63-S63

Author(s):

Yiran Song ◽

Peiqi Wang ◽

Alyssa Parian ◽

Gongying Chen ◽

Sharon Dudley-Brown ◽

...

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Treatment Algorithms

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When to Start a Second Fecal Microbiota Transplantation in Patients with Active Crohn’s Disease

Gastroenterology ◽

10.1016/s0016-5085(17)32216-3 ◽

2017 ◽

Vol 152 (5) ◽

pp. S623-S624

Author(s):

Faming Zhang ◽

Pan Li ◽

Bota Cui ◽

Ting Zhang

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota

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Fecal Microbiota Transplantation is a Promising Switch Therapy for Patients with Prior Failure of Infliximab in Crohn’s Disease

Frontiers in Pharmacology ◽

10.3389/fphar.2021.658087 ◽

2021 ◽

Vol 12 ◽

Author(s):

Qianqian Li ◽

Xiao Ding ◽

Yujie Liu ◽

Cicilia Marcella ◽

Min Dai ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Remission ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Clinical Factors ◽

Switch Therapy ◽

Treatment Stage ◽

One Year

Background: How to handle patients with anti-tumor necrosis factor (anti-TNF) failure was a common challenge to clinicians in Crohn’s disease (CD). The present study is dedicated to clarifying whether fecal microbiota transplantation (FMT) could be a switch therapy for patients with prior failure of infiiximab (IFX) in CD in a long-term observation.Methods: Thirty-six patients with CD who had prior failure of IFX were recruited from January 2013 to December 2019. The “one-hour FMT protocol” was followed in all patients. All patients received the first course of FMT through gastroscopy or mid-gut transendoscopic enteral tubing. After April 2014, the methodology of FMT was coined as washed microbiota transplantation (WMT), substituting for the manual methods, which is dependent on the automatic microbiota purification system and the washing process. The primary endpoint of this study was the clinical remission at one month and one year after FMT. The secondary endpoint was the safety of FMT in the short and long term, and clinical factors as predictors for long-term efficacy of FMT. Clinical factors as independent predictors of efficacy from FMT were isolated using univariable and multivariable logistic regression analysis.Results: There was no significant difference in the rates of clinical response and remission between IFX treatment stage and FMT treatment stage (at one month, three months and six months after administration) (p > 0.05). Compared with those of 19 patients who achieved clinical remission at one month after FMT, the rates of clinical relapse were significantly higher in 18 patients who achieved clinical remission at one month after IFX [log-rank test p = 0.0009 HR = 3.081 (95% CI 1.43–6.639)]. Multivariate analysis revealed that the gender of donor (95% CI: 0.001–0.72; p = 0.031) was an independent predictor of efficacy at one year after FMT. No serious adverse events (AEs) associated with FMT were observed during and after FMT. The rate of AEs was significantly lower in group FMT than that in group IFX (p = 0.002).Conclusion: The present findings first time provided the evidence for clinicians to consider FMT into practice as an alternative switch therapy for patients with prior loss of response or intolerance to IFX in CD.Clinical Trial Registration:https://clinicaltrials.gov, identifier NCT01793831

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Inflammatory Bowel Disease Outcomes Following Fecal Microbiota Transplantation for Recurrent C. difficile Infection

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa283 ◽

2020 ◽

Author(s):

Jessica R Allegretti ◽

Colleen R Kelly ◽

Ari Grinspan ◽

Benjamin H Mullish ◽

Jonathan Hurtado ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Bowel Disease ◽

De Novo ◽

Fecal Microbiota Transplantation ◽

Prospective Trial ◽

Fecal Microbiota ◽

Inflammatory Bowel

Abstract Background Recurrent Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is a clinical challenge. Fecal microbiota transplantation (FMT) has emerged as a recurrent CDI therapy. Anecdotal concerns exist regarding worsening of IBD activity; however, prospective data among IBD patients are limited. Methods Secondary analysis from an open-label, prospective, multicenter cohort study among IBD patients with 2 or more CDI episodes was performed. Participants underwent a single FMT by colonoscopy (250 mL, healthy universal donor). Secondary IBD-related outcomes included rate of de novo IBD flares, worsening IBD, and IBD improvement—all based on Mayo or Harvey-Bradshaw index (HBI) scores. Stool samples were collected for microbiome and targeted metabolomic profiling. Results Fifty patients enrolled in the study, among which 15 had Crohn’s disease (mean HBI, 5.8 ± 3.4) and 35 had ulcerative colitis (mean partial Mayo score, 4.2 ± 2.1). Overall, 49 patients received treatment. Among the Crohn’s disease cohort, 73.3% (11 of 15) had IBD improvement, and 4 (26.6%) had no disease activity change. Among the ulcerative colitis cohort, 62% (22 of 34) had IBD improvement, 29.4% (11 of 34) had no change, and 4% (1 of 34) experienced a de novo flare. Alpha diversity significantly increased post-FMT, and ulcerative colitis patients became more similar to the donor than Crohn’s disease patients (P = 0.04). Conclusion This prospective trial assessing FMT in IBD-CDI patients suggests IBD outcomes are better than reported in retrospective studies.

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