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.