Corticosterone disrupts the temporal coordination of the gut–liver bile acid axis in broiler chickens

This is the authors' abstract. We don't add key points for this paper.

Elevated corticosterone levels resulting from chronic stress impair metabolic balance in broilers, frequently culminating in lipid dysregulation. While bile acids (BAs) are essential for managing lipid metabolism, how chronic stress alters BA dynamics and drives metabolic failure across the gut-liver axis is not fully understood. To address this, we developed a chronic corticosterone-exposure model in broilers (divided into control and stressed groups) to mimic prolonged stress. We evaluated temporal changes across two zeitgeber time (ZT) points (ZT2 and ZT14) using transcriptomics for both the liver and ileum, alongside ZT2 hepatic metabolomics and ZT14 ileal metabolomics paired with ileal microbiota analysis. The stress model exhibited retarded growth, hepatic fat accumulation, and hyperlipidemia. Crucially, corticosterone disrupted the diurnal differences of BAs in a highly time- and tissue-dependent manner. During the day (ZT2), hepatic dysfunction was most pronounced, marked by the suppression of BA synthesis (cytochrome P450 family 7 subfamily A member 1, CYP7A1) and conjugation (bile acid-CoA:amino acid N-acyltransferase, BAAT ), reduced fatty acid oxidation, and a lower conjugated-to-unconjugated BA ratio. In contrast, nocturnal (ZT14) impairments were localized to the ileum, where decreased expression of intestinal barrier components and BA transporters (organic solute transporter beta, OSTβ ) resulted in the buildup of total and free BAs. Our findings reveal the spatiotemporal specificity of gut–liver bile acid axis dysregulation under chronic stress, and establish a robust theoretical foundation for precision temporal bile acid interventions to alleviate stress-induced metabolic disorders in yellow-feathered broiler production.