Probiotic Clostridium butyricum CB-a alleviates intestinal inflammation through targeted modulation of the microbiome metabolome axis

This study investigated the capacity of Clostridium butyricum CB-a, a novel environmental isolate with unique ecological adaptability, to restore host-microbiome homeostasis in a dextran sodium sulfate (DSS)-induced murine model of intestinal dysbiosis. Integrated 16S rRNA gene sequencing and untargeted LC-MS/MS metabolomics revealed that CB-a (1 × 10⁸ CFU/mL, administered orally) fundamentally restructured the colonic microbial architecture. Specifically, it enriched beneficial, short-chain fatty acid (SCFA)-producing consortia (e.g., Lactobacillus , Bacteroides , and Alloprevotella ) while suppressing opportunistic pathobionts ( Escherichia-Shigella ) and mitigating excessive mucin-degrading bacteria ( Akkermansia ). This ecological shift was accompanied by a pronounced metabolic reconfiguration, highlighted by the significant restoration of fecal SCFA pools, predominantly butyrate ( P < 0.05). Mechanistically, multi-omics correlation potential that the CB-a-driven microbial remodeling alleviates mucosal inflammation through SCFA-linked host-microbe signaling. This pathway explicitly involves the upregulation of G-protein-coupled receptors (GPR41, GPR43, and GPR109A), the inhibition of histone deacetylases (HDAC1/2), and the subsequent reinforcement of epithelial tight junction proteins (ZO-1, Occludin). Furthermore, CB-a significantly attenuated systemic pro-inflammatory cytokine expression while restoring superoxide dismutase (SOD) antioxidant capacity. These findings provide mechanistic insights into how this specific environmental isolate modulates the intestinal microenvironment, offering a robust theoretical basis for deploying C. butyricum in functional interventions targeting microbiota-associated inflammatory disruptions.