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 (EPS_E1) strains, both consist of a repeating unit with a backbone composed of four α-L-rhamnose units, with alternate 2- and 3-linkages, and a β-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 EPS_E1 showed variation in the glucosylation level that is non-stochiometric in EPS_35193.R. gnavus strains and their purified EPS induced strain-specific production of cytokines and chemokines in bone-marrow derived dendritic cells and NF-κB 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 EPS_E1 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.