Mechanism of Bao Gan Ning decoction in attenuating hepatic fibrosis via modulation of the gut microbiome and PPAR/CYP7A1-mediated bile acid metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Timely intervention in hepatic fibrosis (HF) is imperative to reduce mortality associated with cirrhosis and prevent progression to hepatocellular carcinoma. Bao Gan Ning Decoction (BGN), a Traditional Chinese Medicine formula, demonstrates therapeutic efficacy against HF. However, its mechanism of action remains incompletely defined.

AIM OF THE STUDY: To elucidate the mechanistic role of BGN in attenuating HF through modulation of specific gut microbiota taxa and bile acid (BA) metabolism.

MATERIALS AND

METHODS

HF was induced in mice using CCl4. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Hepatic BA profiles were quantified using LC-MS/MS, targeting 53 specific BA in negative ion mode through multiple reaction monitoring. Complementary histopathological, molecular, and functional analyses were performed.

RESULTS

The findings indicate that BGN mediates remodelling of the gut microbiota by enriching probiotic taxa (Lactobacillus, Bifidobacterium) and depleting pathobionts. Furthermore, BGN attenuates fibrosis by increasing anti-fibrotic BA levels (e.g., ursodeoxycholic acid) while reducing hepatotoxic BA; it activates the PPARα/CYP7A1 signalling axis to upregulate hepatointestinal BA transporters (Slc10a1/NTCP, ABCB11/BSEP, OSTα/β, Slc10a2/ASBT).

CONCLUSIONS

BGN alleviates HF through gut microbiota-dependent restoration of BA homeostasis and activation of the PPARα/CYP7A1 pathway. This study provides novel mechanistic insights into BGN's anti-fibrotic activities, positioning it as a microbiota-modulating therapeutic candidate for HF management.