Chlorogenic acid modulates gut microbiota and metabolites to alleviate intrahepatic cholestasis of pregnancy: Insights from 16S rRNA sequencing and metabolomics

Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder marked by impaired bile flow, elevated serum bile acids, and pruritus, posing significant risks to maternal and fetal health. Current treatments, including ursodeoxycholic acid, have shown limited efficacy, underscoring the need for more effective therapies. Chlorogenic acid (CGA), a polyphenolic compound with antioxidant, anti-inflammatory, and hepatoprotective properties, has shown promise in managing liver diseases, but its role in ICP remains poorly understood. This study investigated the therapeutic effects of CGA in a rat model of ICP induced by 17α-ethinylestradiol. CGA treatment significantly reduced liver enzyme levels, total bile acids, and bilirubin, while improving histopathological liver damage. CGA also modulated key proteins involved in bile acid synthesis and transport, including FXR, CYP7A1, NTCP, and BSEP. Additionally, CGA treatment improved intestinal barrier function by upregulating tight junction proteins, including ZO-1. Metabolomics and 16S rRNA gene sequencing revealed that CGA treatment restored gut microbiota balance in ICP rats. CGA demonstrated a dose-dependent response, with higher doses providing more pronounced therapeutic effects. These findings suggest that CGA alleviates ICP by regulating bile acid metabolism, improving liver function, and modulating the gut microbiome, highlighting its potential as an effective therapeutic option for managing ICP. • Chlorogenic acid alleviates liver injury and improves pregnancy outcomes in ICP rats. • CGA restores bile acid metabolism by upregulating key proteins in ICP treatment. • CGA treatment protects intestinal barrier function, improving gut-liver axis integrity. • CGA modulates gut microbiota, restoring microbial diversity in ICP rat models. • Dose-dependent therapeutic effects of CGA highlight its potential for ICP management.