Abstract
BACKGROUND: Inflammatory bowel disease (IBD) is closely associated with intestinal microbiota dysbiosis and metabolic dysfunction. The aim of this study was to explore the protective effects and mechanisms of the probiotic Bacillus velezensis MZ09, which produces branched-chain short-chain fatty acids (BSCFAs), against the dextran sulfate sodium (DSS)-induced colitis in piglets. RESULTS: In this study, a DSS-induced piglet colitis model was established to explore the impact of MZ09. Pretreatment with MZ09 significantly alleviated the symptoms of colitis in piglets. For example, the disease activity index (DAI) score decreased, the length of the colon was restored, and splenomegaly was alleviated. MZ09 enhanced intestinal barrier integrity by upregulating the expression of tight junction proteins such as Claudin-1, Occludin, and ZO-1. Using 16S rRNA analysis, we found that MZ09 could remodel the intestinal microbiota. MZ09 increased the abundance of beneficial bacteria such as Firmicutes and Lactobacillus while suppressing the growth of harmful bacteria such as Proteobacteria and Escherichia-Shigella. MZ09 also increased the levels of short-chain fatty acids (SCFAs) in the colon. The increased SCFA content activated G-protein-coupled receptor 43 (GPR43), which increased the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and promoted the production of the anti-inflammatory cytokine interleukin-10 (IL-10). Mechanistically, MZ09 mitigated mitochondrial damage via the STAT3/hypoxia-inducible factor 1α (HIF-1α) axis. This action inhibits nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome-mediated pyroptosis, thus reducing the release of the proinflammatory cytokines IL-1β and IL-18. CONCLUSIONS: B. velezensis MZ09 alleviates DSS-induced colitis in piglets through multiple pathways, including gut microbiota remodeling, SCFAs-GPR43-STAT3 axis activation, and NLRP3 inflammasome-mediated pyroptosis suppression. These findings provide a new theoretical basis for the development of targeted intervention strategies for IBD, suggesting that MZ09 represents a potentially promising therapeutic agent for IBD treatment.