Gut microbiota-derived 9-OxoODE impaired hepatic energy metabolism and feed conversion ratio via RAB7A-mediated mitochondrial dysfunction

Enhancing the feed conversion ratio (FCR) is pivotal for achieving cost-effective and sustainable animal production. This study elucidated the interplay between gut microbiota-derived metabolites, particularly 9-Oxo-10,12-octadecadienoic acid (9-OxoODE) and their regulation of hepatic mitochondrial function, which impacts FCR in avian models. 9-OxoODE, a metabolite in ducks with low FCR, disrupted mitochondrial ultrastructure and fusion processes in vivo in pseudo-germ-free duck and mouse models. This disruption impaired oxidative phosphorylation and energy metabolism through Ras-related protein Rab-7a (RAB7A)-mediated mitochondrial fusion, activated by PGC-1α/MFN1 signaling in in vitro cultures of duck primary hepatocytes. However, a curcumin and resveratrol combination effectively inhibited 9-lipoxygenase activity and production of 9-OxoODE in an in vitro gut microbiome model, and it enhanced mitochondrial fusion and FCR in an in vivo duck model. The gut gut-liver-mitochondria axis could be a novel strategy to improve both feed efficiency and productivity in economically important animals.