Exploring the metabolic patterns and response mechanisms of bile acids during fasting: A study with poultry as an example

Fasting is beneficial to alleviate fatty liver, lose weight and improve reproductive function. However, previous studies have shown that, during fasting, disorders of bile acid metabolism were strongly associated with intestinal inflammation. The physiological and biochemical parameters and gene expression of multiple tissues of chickens at every critical time node were measured by ELISA and qPCR. In addition, association analysis was performed based on liver transcriptome sequencing and cecum metabolome data. At the cellular level, the regulatory effects of cecal metabolites on host bile acid metabolism were verified. During fasting, hepatic FXR-SHP-CYP7A1 and ileum-hepatic FXR-SHP-FGF15/19-FGFR4-CYP7A1 negative feedback pathways were activated to inhibit hepatic bile acid synthesis. The ileum FXR-SHP-ASBT pathways are activated, hindered the ileal bile reflux. At the same time, it promotes the secretion of bile acids and cholesterol in the liver, accelerates the utilization of H₂O and CO₂, to maintain liver homeostasis during fasting. In addition, enhanced gallbladder contraction and increased hunger were observed in laying hens during fasting. At the cellular level, the correlation between CYP7A1 and L-valine was verified, revealing that cecal metabolites of laying hens was enabled to regulate host bile acid metabolism. This study explored the metabolic patterns of bile acids during fasting and identified the main reasons for the accumulation of bile acids in the cecum, which provides a basis for fasting research and offers a reference for the formulation of fasting protocols.