Propionic acid secreted by Akkermansia muciniphila alleviates hepatic fibrosis by antioxidant regulation across the gut–liver axis

The gut commensal bacterium Akkermansia muciniphila (AKK) has emerged as a candidate for treating liver disorders, yet its therapeutic potential in liver fibrosis remains poorly defined. Here, using a carbon tetrachloride (CCl₄)-induced murine model, we show that AKK administration markedly attenuates collagen deposition, inflammation, and hepatic injury. AKK restored intestinal barrier integrity, reshaped microbial composition, and enhanced propionic acid transport from the gut to the liver, leading to suppression of hepatic stellate cell activation. Multi-omics profiling revealed that AKK enriched propionate-producing taxa and upregulated key metabolic enzymes, thereby elevating hepatic propionate levels. Supplementation with propionic acid alone recapitulated AKK's benefits, improving liver function, alleviating extracellular matrix accumulation, and activating the Keap1-Nrf2 antioxidant pathway. Together, our findings identify a microbiota-metabolite axis in which AKK counters liver fibrosis by enhancing propionate-mediated antioxidant regulation, highlighting its therapeutic promise for chronic liver disease.