<b>Peptidoglycan from</b> <i> <b>Bifidobacterium adolescentis</b> </i> <b>enhances IL-10 production in regulatory B cells to alleviate gut inflammation</b>

The mechanisms by which gut microbiota modulate host immune responses remain incompletely understood. Here, we screened <i>Lactobacillus</i> and <i>Bifidobacterium</i> strains isolated from healthy individuals to identify symbionts capable of suppressing gut inflammation. Among them, <i>Bifidobacterium adolescentis</i> (Bifi-94) induced IL-10 production in mononuclear cells <i>in vitro</i>. 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.