enhances dextran sulfate sodium-induced colitis by promoting nf-κB-NLRP3-Dependent macrophage pyroptosis.

Evidence indicates that gut microbiota is crucial in ulcerative colitis (UC) development. Increased species abundance is linked to UC, but its role and mechanisms in intestinal inflammation are not well understood. This study used a dextran sulfate sodium (DSS)-induced colitis model in mice, and different bacterial strains were administered via gavage. We assessed clinical manifestations, colonic barrier function, gut microbiota composition, and levels of inflammatory cytokines, NOD-like receptor family pyrin domain-containing 3 (NLRP3) signaling molecules, and pyroptosis-related proteins. Mouse bone marrow-derived macrophages (BMDMs) were infected with at different time points and multiplicities of infection (MOI). Cell viability and the expression of NLRP3 signaling molecules and pyroptosis-associated proteins were assessed. The inhibitors C29, TAK-242, and MCC950 were employed for Toll-like receptor (TLR) and NLRP3 signaling pathways. It was observed that exacerbated intestinal inflammation and barrier injury in DSS-induced colitis in mice. Additionally, contributed to gut microbiota dysbiosis during colitis progression. induced the expression of NLRP3 signaling molecules and pyroptosis-associated proteins in mouse colitis tissues. assays demonstrated that activated NLRP3 inflammasome and evoked gasdermin D-mediated pyroptosis and interleukin (IL)-1β secretion in macrophages. Furthermore, TLR2 and TLR4 were identified as key mediators of -induced macrophage pyroptosis via activation of the Nuclear Factor-kappa B (NF-κB)-NLRP3 pathway. In conclusion, promotes macrophage pyroptosis and IL-1β secretion through the TLR2/4-NF-κB-NLRP3 signaling axis, thereby aggravating colitis. may represent a potential risk factor for UC development.