Multi-omics analysis provides new insights into molecular mechanisms for waterfowl fatty liver formation.

Waterfowl fatty liver has high nutritional value and offers benefits to human health. While previous research on fatty liver has focused on individual organs, this study explored fatty liver by examining the cecum, serum metabolites, and liver gene expression. This study integrated transcriptomic, metabolomic, and 16S rRNA microbiome analyses to analyze the molecular mechanism of waterfowl fatty liver formation. We identified seven core genes, five core metabolites, and three core microorganisms, which were significantly correlated. Overfeeding increased the abundance of Mucispirillum in the cecum, while Prevotella and Olsenella decreased. These microbial shifts, mediated by metabolites such as phthalic acid, influenced lipid metabolism, which induced changes in liver gene expression, including upregulation of ACBD4 and downregulation of HSP90B1 and HSPA5, thereby supporting fatty liver development. Additionally, ABC transporters, protein processing in the endoplasmic reticulum, and amino acid metabolism were important in fatty liver development. Our research findings provide new insights into the molecular mechanism of fatty liver with overfeeding in waterfowl from the perspective of the gut-liver axis.