Capsular polysaccharide correlates with immune response to the human gut microbe <i>Ruminococcus gnavus</i>

Abstract

Active inflammatory bowel disease (IBD) often coincides with increases of <i>Ruminococcus gnavus</i>, a gut microbe found in nearly everyone. It was not known how, or if, this correlation contributed to disease. We investigated clinical isolates of <i>R. gnavus</i> to identify molecular mechanisms that would link <i>R. gnavus</i> to inflammation. Here, we show that only some isolates of <i>R. gnavus</i> 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 <i>R. gnavus</i> 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 <i>R. gnavus</i> could drive the inflammatory responses that characterize IBD.