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

Abstract

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.