NLRP3 deficiency alleviates colitis in association with short-chain fatty acid–producing bacteria

The NLRP3 inflammasome is an important susceptibility factor in inflammatory bowel disease (IBD), yet its specific mechanisms in modulating gut microbiota during intestinal inflammation remain unclear. This study observed significant upregulation of NLRP3 inflammasome in colonic tissues from patients with active ulcerative colitis and a murine dextran sulfate sodium (DSS)-induced colitis model. Nlrp3 deletion markedly attenuated disease severity, evidenced by improved histopathology, reduced pro-inflammatory cytokines, and increased microbial alpha diversity. Notably, Nlrp3 deficiency mitigated the depletion of beneficial SCFA-producing taxa, specifically enriching Dubosiella and Rikenellaceae_RC9_gut_group, which was associated with the restoration of fecal propionate and butyrate levels. Furthermore, treatment with the SCFA-producing probiotic Clostridium butyricum alleviated colitis in wild-type mice but provided no additional benefit in Nlrp3 - deficient mice and failed to reduce inflammation in mice treated with the NLRP3 activator nigericin. Collectively, these results suggest that the therapeutic efficacy of C. butyricum may be influenced by the activation status of host NLRP3, underscoring the complex relationship between NLRP3 signaling and microbiota-mediated regulation in IBD pathogenesis.