Changes in the gut microbiome during fasting‐induced molting and its effects on gut–liver function

Fasting‐induced molting (FIM) rejuvenates the laying cycle in hens; however, the fasting process may result in intestinal dysbiosis, which compromises host immunity and disrupts the intestine‐liver function. Consequently, investigating the changes in gut microbiota during FIM and its impacts on gut‐liver metabolic homeostasis is crucial for enhancing the efficiency of FIM in laying hens. Here, a total of 90 laying hens, aged 60 weeks, were selected for the FIM. Samples were collected at four time points: the day before fasting, the 15th day of fasting, the 5th day of refeeding, and the 47th day of refeeding. Metagenomic sequencing and non‐targeted metabolomics were employed to investigate the roles of the gut microbiota and metabolites in the remodeling of gut–liver function, focusing on intestinal injury‐repair mechanisms and changes in liver function. During the fasting period, the abundance of harmful microbiota and metabolites increase, leading to intestinal injury. This process activates the TGF‐beta signaling pathway, promoting intestinal stem cell proliferation. Simultaneously, liver function dysfunction as evidenced by elevated bile acid levels in the liver and serum and activation of the non‐classical bile acid synthesis pathway. During the refeeding period, the previously observed effects were reversed, leading to the remodeling of the intestinal microbiota and gut‐liver function. We identified key microorganisms ( Liquorilactobacillus mali and Tissierellia bacterium KA00581) and functional metabolites ( d ‐Panthenol and 3‐hydroxyanthranilic acid (3‐HAA)) involved in intestinal‐liver function during FIM. Notably, d ‐Panthenol promotes chicken small intestinal organoid branching and growth, enhances barrier function, and reduces inflammation. Our study underscores the role of gut microbiota in gut‐liver injury during FIM in laying hens, suggesting potential probiotic‐ or metabolite‐based interventions to mitigate gut‐liver injury and facilitate recovery.