Probiotic Clostridium butyricum CB-a alleviates intestinal inflammation through targeted modulation of the microbiome metabolome axis
ABSTRACT 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. IMPORTANCE Severe gut inflammation, such as inflammatory bowel disease, is often driven by a breakdown in our natural gut bacteria. Although probiotics are popular treatments, how they actually repair the gut remains largely unknown. Our study highlights the remarkable healing ability of Clostridium butyricum CB-a, a natural bacterium isolated from the environment. We discovered that this microbe acts as an ecological engineer for the digestive system. It actively rescues the damaged gut by promoting the growth of beneficial bacteria and suppressing harmful ones. This positive shift triggers the release of natural, healing molecules that calm the immune system and rebuild the protective gut lining. By uncovering the exact steps this bacterium takes to restore digestive harmony, our work provides a powerful blueprint for designing highly targeted, natural probiotic therapies to combat severe intestinal diseases. Severe gut inflammation, such as inflammatory bowel disease, is often driven by a breakdown in our natural gut bacteria. Although probiotics are popular treatments, how they actually repair the gut remains largely unknown. Our study highlights the remarkable healing ability of Clostridium butyricum CB-a, a natural bacterium isolated from the environment. We discovered that this microbe acts as an ecological engineer for the digestive system. It actively rescues the damaged gut by promoting the growth of beneficial bacteria and suppressing harmful ones. This positive shift triggers the release of natural, healing molecules that calm the immune system and rebuild the protective gut lining. By uncovering the exact steps this bacterium takes to restore digestive harmony, our work provides a powerful blueprint for designing highly targeted, natural probiotic therapies to combat severe intestinal diseases.