Coprophagy prevention interfered with intestinal barrier, lipid metabolism, and immune performance in rabbits via microbe-gut-liver axis

Coprophagy (CP) is a critical physiological behavior in rabbits and some rodents. This study used 16 S rRNA and ITS sequencing, LC-MS/MS, gene expression profiling, and histological observation to investigate the effects of coprophagy prevention (CP) on the cecal microbiota and its links to immune function and liver lipid metabolism in rabbits. Results showed that CP reduced the richness and diversity of bacterial and fungal communities in the cecal contents, significantly changing 15 bacterial genera (P < 0.05) and 116 metabolites (P < 0.05). Akkermansia and Subdoligranulum exhibited the strongest associations with lipids and lipid-related molecules (P < 0.05). CP also damaged the cecal and colonic barriers, affecting the sacculus rotundus and vermiform appendix in rabbits by upregulating IFN-γ and RLA-A3 gene expression (P < 0.05) in both tissues, while downregulating LYG2, MUC13, and REG-3G (P < 0.05) in the vermiform appendix and reducing goblet cell counts in the sacculus rotundus. CP reduced serum TG and TCHO levels while downregulating key lipid metabolism genes (APOB100, FFAR2, FXR, P < 0.05), thereby negatively affecting rabbit weight. In short, CP disrupts both microbial balance and physical barriers in the cecum, subsequently compromising hepatic lipid metabolic balance through gut-liver axis, ultimately resulting in reduced growth performance and impaired immune function in rabbits. These findings provide valuable insights into animal physiology, nutrition, and microbiota-host interactions.