Vitamin K₂ emerges as the key mediator: Cetobacterium somerae ZNN-1 increases muscle protein deposition and improves liver health in Nile tilapia (Oreochromis niloticus)

Background: Cetobacterium somerae (C. somerae) is a common indigenous bacterium in the intestine of freshwater fish. Studies have shown that it has the potential to promote protein deposition, but the underlying mechanisms remain unclear. Results: Nile tilapia were fed with C. somerae ZNN-1 (10⁸ CFU/g feed), which significantly increased the carcass ratio, reduced the hepatosomatic index, and decreased whole-body lipid content. Supplementation of C. somerae ZNN-1 significantly increased the crude protein content in muscle, promoted glucose uptake and utilization in muscle tissue, and activated the phosphorylation of S6K/S6 in muscle tissue. C. somerae ZNN-1 supplementation significantly decreased hepatic total lipid, triglyceride, and free fatty acid contents. Further analysis revealed that C. somerae ZNN-1 supplementation markedly activated the phosphorylation of hepatic AMPK and upregulated the expression of genes involved in hepatic lipolysis and fatty acid β-oxidation. Integrated serum metabolomic, bacterial genomic, and gut metagenomic analyses revealed that C. somerae ZNN-1 synthesized chorismate (CHA), which serves as a precursor for gut microbiota to produce vitamin K₂ (VK2). In vitro experiments demonstrated that VK2 activated the S6K/S6 pathway to promote protein synthesis, while stimulating AMPK phosphorylation and activating lipid catabolism to reduce fat accumulation. Conclusions: These findings provide a theoretical basis for the application of C. somerae ZNN-1 in enhancing edible protein content and reducing fat deposition of aquatic animals.