The human gut symbiont Ruminococcus gnavus displays strain-specific exopolysaccharides modulating the host immune response

Ruminococcus gnavus is a prevalent member of the human gut microbiota and over-represented in inflammatory bowel diseases. R. gnavus ATCC 29149 was previously shown to produce a pro-inflammatory exopolysaccharide (EPS) referred to here as glucorhamnan-I or EPS29149. Here, we determined the structure of the polysaccharides from R. gnavus ATCC 35913 (EPS35193) and E1 (EPSE1) strains, both consist of a repeating unit with a backbone composed of four alpha-L-rhamnose units, with alternate 2- and 3-linkages, and a beta-d-glucose residue linked to O-2 of one 3-Rha as side branch. This structure differs from EPS29149 and is referred to as glucorhamnan-II. EPS35193 and EPSE1 showed variation in the glucosylation level that is non-stochiometric in EPS35193. R. gnavus strains and their purified EPS induced strain-specific production of cytokines and chemokines in bone-marrow derived dendritic cells and NF-kappa B activation in reporter cells. R. gnavus ATCC 35913 was the most immunogenic strain, likely due to the absence of an additional capsular polysaccharide layer as shown by TEM, while EPS29149, EPS35193 and EPSE1 showed activation of TLR4 reporter cells. These strain-specific differences in R. gnavus cell surface glycosylation and host response underscore the importance of studying R. gnavus-host interaction at the strain level.