Bacteroides ovatusATCC 8483 monotherapy is superior to traditional fecal transplant and multi-strain bacteriotherapy in a murine colitis model

ABSTRACTBackground and aimsBacteriotherapy 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.MethodsWe 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-Bacteroidescocktail, individual Bacteroidesstrains, 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 rRNAgene profiling of fecal and mucosal microbiomes.ResultsTriple-Bacteroidescombination therapy was more protective against weight loss and mortality than traditional FMT therapy. B. ovatusATCC8483 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 Bacteroidesabundance associated with treatment success and decreased cytokine production while the presence of Akkermansiacorrelated with treatment failure. However, the therapeutic benefit associated with high Bacteroidesabundance was negated in the presence of Streptococcus.ConclusionsBacteroides ovatusmonotherapy 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 ovatusATCC 8483 in an active, on-going human study, this therapy may be repurposed for the management of IBD in a clinically expedient timeline.