<i>Bacteroides ovatus</i> ATCC 8483 monotherapy is superior to traditional fecal transplant and multi-strain bacteriotherapy in a murine colitis model

Abstract

<b>Background and aims</b>: Bacteriotherapy aimed at addressing dysbiosis may be therapeutic for Inflammatory Bowel Diseases (IBDs). We sought to determine if defined <i>Bacteroides</i>-based bacteriotherapy could be an effective and consistent alternative to fecal microbiota transplantation (FMT) in a murine model of IBD. <b>Methods</b>: 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-<i>Bacteroides</i> cocktail, individual <i>Bacteroides</i> 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 <i>16S rRNA</i> gene profiling of fecal and mucosal microbiomes. <b>Results</b>: Triple-<i>Bacteroides</i> combination therapy was more protective against weight loss and mortality than traditional FMT therapy. <i>B. ovatus</i> 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 <i>Bacteroides</i> abundance associated with treatment success and decreased cytokine production while the presence of <i>Akkermansia</i> correlated with treatment failure. However, the therapeutic benefit associated with high <i>Bacteroides</i> abundance was negated in the presence of <i>Streptococcus</i>. <b>Conclusions</b>: <i>Bacteroides ovatus</i> 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 <i>Bacteroides ovatus</i> ATCC 8483 in an active, on-going human study, this therapy may be repurposed for the management of IBD in a clinically expedient timeline.