PRJNA454325
Bacteroides ovatus ATCC 8483 Monotherapy is Sufficient to Suppress Intestinal Inflammation in a Murine Colitis Model
Background: Fecal Microbiome Transplant (FMT) therapy has shown inconsistent efficacy in the treatment of human Inflammatory Bowel Disease (IBD). However, the fecal microbiome is a vastly complex and dynamic community that is highly variable between, and even within, donors. This variability can confound dissection of the key therapeutic attributes of a successful FMT. The goal of our study was to determine if defined Bacteroides-based bacteriotherapy could be an effective and consistent alternative to FMT in a murine model of IBD.Results: 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. 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 combination of strains, in preventing weight loss, decreasing histological damage, dampening inflammatory response, and stimulating epithelial recovery. Irrespective of treatment group, overall Bacteroides abundance associated with treatment success and decreased cytokine production while 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 is 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, on-going human study, this therapy may be repurposed for the management of IBD in a clinically expedient timeline.