Nanocellulose Alleviates Intrahepatic Cholestasis of Pregnancy via Gut Microbiota-Mediated Bile Acid Homeostasis.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorder characterized by elevated maternal serum total bile acid (TBA) and increased risk of adverse fetal outcomes, yet current therapies and preventive strategies remain suboptimal. Here, we present a preclinical investigation of nanocellulose as a gut microbiota-targeted dietary intervention to restore bile acid homeostasis. We demonstrate that nanocellulose, particularly cellulose nanofibers (CNF), administered prophylactically, attenuated maternal TBA and improved offspring survival in a rat ICP model by enriching probiotic microbial taxa while suppressing bile acid-transforming bacteria. These microbial shifts promoted the accumulation of fecal primary bile acids and activation of gut-liver farnesoid X receptor (FXR) signaling. This cascade reduced intestinal reabsorption and hepatic synthesis of bile acids while promoting their excretion in feces. Collectively, pre-gestational CNF effectively lowered systemic bile acid burden and mitigated the ICP phenotype. Our findings identify CNF as a biosafe, microbiota-responsive dietary fiber with translational potential for early preventive management of bile acid-related disorders during pregnancy.