Bifidobacterium bifidum is recognized for its immunomodulatory potential, yet the specific components mediating its anti-inflammatory effects remain poorly defined. Here, we systematically dissected the role of B. bifidum-derived lipoteichoic acid (LTA) in modulating mucosal immunity and alleviating 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced acute colitis. Initial in vitro assays revealed that the IL-10-inducing activity of B. bifidum in mesenteric lymph node cells resides mainly in heat-resistant cell wall fractions, particularly LTA, acting through a TLR2-associated (and pharmacologically TLR2-sensitive) pathway. Comparative analyses among multiple B. bifidum strains demonstrated that LTA immunostimulatory potency strongly predicted protective efficacy against colitis, with FJSWX19M5 strain LTA exerting the most pronounced anti-inflammatory effects in both conventional and germ-free mouse models. In vivo, mice received LTA by oral gavage (0.2 mg/mouse, 200 μL) prior to TNBS challenge. LTA from FJSWX19M5 significantly improved survival, ameliorated colonic injury and inflammation, reduced IL-1β production, and modulated Treg cell distribution, outperforming other strain LTAs. Transcriptomic profiling showed that FJSWX19M5 LTA intervention prominently altered colonic gene expression, activating multiple immune- and inflammation-related signaling pathways, such as Jak-STAT, PI3K-Akt, and IL-17. Furthermore, FJSWX19M5 LTA enhanced both T and B lymphocyte proliferation and cellular immunity in healthy mice. Together, these results establish that the anti-colitis and immunoregulatory benefits of B. bifidum are largely attributable to strain-specific LTA, highlighting its mechanistic link to TLR2-involved mucosal immune modulation and supporting its potential as a defined immunomodulatory molecule for IBD-relevant intervention.
Qu et al. (Sun,) studied this question.