Peptidoglycan from Bifidobacterium adolescentis enhances IL-10 production in regulatory B cells to alleviate gut inflammation.

The mechanisms by which gut microbiota modulate host immune responses remain incompletely understood. Here, we screened Lactobacillus and Bifidobacterium strains isolated from healthy individuals to identify symbionts capable of suppressing gut inflammation. Among them, Bifidobacterium adolescentis (Bifi-94) induced IL-10 production in mononuclear cells in vitro. Oral administration of Bifi-94 to mice treated with dextran sulfate sodium attenuated weight loss and reduced colonic inflammation scores. In wild-type C57BL/6 mice, Bifi-94 increased IL-10 levels in colonic tissue homogenates without altering the frequency of regulatory T cells. Instead, CD19+CD11b+ regulatory B (Breg) cells emerged as the primary source of IL-10, with their numbers significantly increasing in the peritoneal cavity (PEC) after treatment. IL-10 secretion by PEC cells was robustly activated by live, heat-killed, and formalin-fixed Bifi-94. Bifi-94-derived peptidoglycan (PG) selectively stimulated IL-10 production in CD19⁺CD11b⁺ Breg cells, and multi-omics analyses showed that Bifi-94 exhibits increased expression of PG biosynthetic enzymes (MurE, MurD, Alr, UppP) relative to the type strain. Mechanistically, Bifi-94-derived PG promoted TLR2-dependent activation of ERK and p38 MAPK signaling in Breg cells. Notably, PG similarly enhanced IL-10 production in CD19+ B cells from human colonic tissue. These findings demonstrate that Bifi-94-derived PG promotes IL-10 production in Breg cells via TLR2-mediated signaling, thereby contributing to the attenuation of gut inflammation.