Noncanonical Surface Glycoconjugates from Bacteroides stercoris DSM 19555 Reprogram Innate Immune Responses

Deciphering the role(s) of surface glycoconjugates in gut microbiota-immune interactions is essential for improving human health. This study shows that Bacteroides stercoris DSM 19555 produces two previously undescribed surface glycoconjugates: an atypical rough-type lipopolysaccharide (R-LPS) and a positively charged capsular polysaccharide (CPS). Structural analysis revealed an R-LPS featuring a 2-aminoethyl phosphate-substituted 2-keto-3-deoxy-d-manno-octulosonic acid (Kdo) bearing a phosphodiester-linked hexose, a fucose-lacking core oligosaccharide, and a highly heterogeneous mono-phosphorylated, hypoacylated lipid A. In parallel, a branched, galacto-configured, and amino sugar-rich cationic CPS is also identified. Both glycoconjugates promote anti-inflammatory IL-10 production while limiting classical pro-inflammatory outputs, with CPS exhibiting the strongest immunomodulatory activity. In an inflamed epithelial-immune coculture model, both glycoconjugates shape cytokine responses toward an IL-10-associated, low-inflammatory profile. These findings uncover a structurally and functionally distinct glycan repertoire in B. stercoris DSM 19555 and support the emerging view that gut Bacteroidales surface glycans behave as active modulators of innate immune responses rather than as simple inflammatory triggers.