Sands, B. E. | bioRxiv Science

bioRxiv2018

Inflammatory bowel disease microbiotas alter gut CD4 T-cell homeostasis and drive colitis in mice

To examine the functional contribution of Inflammatory Bowel Disease (IBD) microbes to immune homeostasis and colitis, we colonized unchallenged and colitis-susceptible germ-free mice with over twenty human intestinal microbiotas from healthy and IBD donors. Compared to healthy microbiotas, IBD microbiotas led to expanded ROR{gamma}t+Th17 cells and reduced ROR{gamma}t+Treg in the gut of unchallenged gnotobiotic mice and increased disease severity in colitis-susceptible mice. The proportions of ROR{gamma}t+Th17 and ROR{gamma}t+Treg induced by each microbiota were highly predictive of the human disease status and strongly correlated with disease severity in colitis-susceptible mice colonized with the same human microbiotas. The transmittable functional potential of IBD microbes suggests a mechanism for a microbial contribution to IBD pathogenesis and a potential route for its treatment and prevention.

immunology↗

bioRxiv2018

Microbial Engraftment and Efficacy of Fecal Microbiota Transplant for Clostridium difficile Patients With and Without IBD

Background & AimsRecurrent and refractory Clostridium difficile infections (CDI) are effectively treated with fecal microbiota transplant (FMT). Uncertainty exists regarding the effectiveness of FMT for CDI with underlying inflammatory bowel disease (IBD), its effects on disease activity and its effectiveness transferring the donor microbiome to patients with and without IBD. This study aims to determine FMTs effectiveness in subjects with and without IBD, its impact on IBD activity, the level of microbiome engraftment, and predictors of CDI recurrence.\n\nMethodsSubjects with and without IBD who underwent FMT for recurrent or refractory CDI between 2013 and 2016 at The Mount Sinai Hospital were followed for up to 6 months. The primary outcome was CDI recurrence 6 months after FMT. Secondary outcomes were (1) CDI recurrence 2 months after FMT; (2) Frequency of IBD flare after FMT; (3) Microbiome engraftment after FMT; (4) Predictors of CDI recurrence.\n\nResultsOverall, 134 patients, 46 with IBD, were treated with FMT. There was no difference in recurrence in patients with and without IBD at 2 months (22.5% vs 17.9%; p=0.63) and 6 months (38.7% vs 36.5%; p>0.99). Proton pump inhibitor use, severe CDI, and comorbid conditions were predictors of recurrence. The pre-FMT microbiome was not predictive of CDI recurrence. Subjects with active disease requiring medication escalation had reduced engraftment. There was no difference in engraftment based on IBD endoscopic severity at FMT.\n\nConclusionsIBD did not affect CDI recurrence rates 6 months after FMT. Pre-FMT microbiome was not predictive of recurrence, and microbial engraftment was dependent on IBD treatment escalation but not on underlying disease severity.

microbiology↗