LAUSR

Significance Microbes shape human health and disease. Today, there are increasing correlations of gut microbes with specific diseases, but the underlying molecules and mechanism linking the two are not known. This stifles both the understanding of disease causation and the development of suitable treatments. We investigated a dozen patient isolates of Ruminococcus gnavus, a prevalent gut microbe linked to inflammatory bowel disease (IBD). We found that some isolates possess a protective capsule that encourages a symbiotic relationship with the host immune system, while others lack this protective capsule and elicit a robust inflammatory immune response. This work reveals a path by which R. gnavus could be connected to IBD and potential therapeutic interventions. Active inflammatory bowel disease (IBD) often coincides with increases of Ruminococcus gnavus, a gut microbe found in nearly everyone. It was not known how, or if, this correlation contributed to disease. We investigated clinical isolates of R. gnavus to identify molecular mechanisms that would link R. gnavus to inflammation. Here, we show that only some isolates of R. gnavus produce a capsular polysaccharide that promotes a tolerogenic immune response, whereas isolates lacking functional capsule biosynthetic genes elicit robust proinflammatory responses in vitro. Germ-free mice colonized with an isolate of R. gnavus lacking a capsule show increased measures of gut inflammation compared to those colonized with an encapsulated isolate in vivo. These observations in the context of our earlier identification of an inflammatory cell-wall polysaccharide reveal how some strains of R. gnavus could drive the inflammatory responses that characterize IBD.