No abstract

Background and aims: Bacteriotherapy aimed at addressing dysbiosis may be therapeutic for Inflammatory Bowel Diseases (IBDs). We sought to determine if defined Bacteroides-based bacteriotherapy could be an effective and consistent alternative to fecal microbiota transplantation (FMT) in a murine model of IBD. Methods: We induced experimental colitis in 8-12-week-old C57BL/6 mice using 2-3% dextran sodium sulfate. Mice were simultaneously treated by oral gavage with a triple-Bacteroides cocktail, individual Bacteroides strains, FMT using stool from healthy donor mice, or their own stool as a control. Survival, weight loss and markers of inflammation (histology, serum amyloid A, cytokine production) were correlated to 16S rRNA gene profiling of fecal and mucosal microbiomes. Results: Triple-Bacteroides combination therapy was more protective against weight loss and mortality than traditional FMT therapy. B. ovatus ATCC8483 was more effective than any individual strain, or a combination of strains, in preventing weight loss, decreasing histological damage, dampening inflammatory response, and stimulating epithelial recovery. Irrespective of the treatment group, overall Bacteroides abundance associated with treatment success and decreased cytokine production while the presence of Akkermansia correlated with treatment failure. However, the therapeutic benefit associated with high Bacteroides abundance was negated in the presence of Streptococcus. Conclusions: Bacteroides ovatus monotherapy was more consistent and effective than traditional FMT at ameliorating colitis and stimulating epithelial recovery in a murine model of IBD. Given the tolerability of Bacteroides ovatus ATCC 8483 in an active, ongoing human study, this therapy may be repurposed for the management of IBD in a clinically expedient timeline.

Background Children with inflammatory bowel disease (IBD) are disproportionally affected by recurrent Clostridioides difficile infection (rCDI). Although fecal microbiota transplantation (FMT) has been used with good efficacy in adults with IBD, little is known about outcomes associated with FMT in pediatric IBD. Methods We performed a retrospective review of FMT at 20 pediatric centers in the United States (US) from March 2012-March 2020. Children with and without IBD were compared to determine differences in the efficacy of FMT for rCDI. In addition, children with IBD with and without a successful outcome were compared to determine predictors of success. Safety data and IBD-specific outcomes were obtained. Results A total of 396 pediatric patients, including 148 with IBD, were included. Children with IBD were no less likely to have a successful first FMT then the non-IBD affected cohort (76% vs 81%, P=0.17). Among children with IBD, patients were more likely to have a successful FMT if they received FMT with fresh stool (P=0.03), were without diarrhea prior to FMT (P=0.03), or had a shorter time from rCDI diagnosis until FMT (P=0.04). Children with a failed FMT were more likely to have clinically active IBD post-FMT (P=0.002) and 19 (13%) patients had an IBD-related hospitalization in the 3 month follow-up. Conclusions Based on the findings from this large US multi-center cohort, the efficacy of FMT for the treatment of rCDI did not differ in children with IBD. Failed FMT among children with IBD was possibly related to the presence of clinically active IBD.