Liver fibrosis, a common pathological outcome of chronic liver injury, is a key precursor to cirrhosis and hepatocellular carcinoma. Despite its clinical importance, no effective antifibrotic therapies are currently available.

Increasing evidence indicates that the gut microbiota and their metabolites play critical roles in shaping hepatic inflammation and tissue remodeling through gut–liver metabolic communication. However, the specific microbial species and metabolites that confer protection against fibrotic progression remain poorly understood.

A recent study published in Life Metabolism by researchers from the Affiliated Hospital of Nantong University has identified the gut commensal bacterium Akkermansia muciniphila (AKK) as a potent modulator of liver fibrosis (Figure 1). The study reveals that AKK alleviates hepatic fibrosis by promoting propionate-driven antioxidant defense across the gut–liver axis, thereby offering new mechanistic insights and therapeutic opportunities for chronic liver disease.

Using a carbon tetrachloride–induced mouse model, the researchers found that oral administration of live AKK markedly reduced collagen deposition, inflammation, and hepatocellular injury. Mechanistic analyses demonstrated that AKK reshaped the gut microbiota, restored intestinal barrier integrity, and enhanced the transport of the short-chain fatty acid, propionic acid, from the gut to the liver. Elevated hepatic propionate levels suppressed activation of hepatic stellate cells and inhibited the TGF-β/SMAD fibrotic signaling cascade. Notably, supplementation with propionic acid alone recapitulated the benefits of AKK—improving liver function, reducing extracellular matrix accumulation, and activating the Keap1–Nrf2 antioxidant pathway to counter oxidative stress.

Together, these findings position AKK as a next-generation probiotic capable of modulating systemic metabolism and redox homeostasis. By reinforcing metabolic and signaling crosstalk along the gut–liver axis, this study establishes a foundation for microbiota-based therapeutic strategies to combat liver fibrosis and related chronic liver disorders.
DOI：10.1093/lifemeta/loaf036