Integrated multi-omics reveals Enterococcus faecalis JM263 alleviates high-concentrate diet-induced hepatic injury via the gut-liver axis in goats

BACKGROUND: In intensive ruminant production, long-term high-concentrate diets (HCD) are employed to increase short-term growth but frequently cause systemic inflammation, oxidative stress, and multiorgan damage, posing significant challenges to the sustainability of the goat industry. This study investigated the potential regulatory mechanisms of Enterococcus faecalis JM263, a strain isolated from yak gut contents, in mitigating HCD-induced inflammation and oxidative stress via the gut-liver axis. Twenty-four male Yudong black goats were randomly assigned to four groups: a control group (CON) and three treatment groups supplemented with 0.1, 0.5, or 1.0 g/kg E. faecalis JM263 (HCD1, HCD2, and HCD3, respectively) for 60 days. RESULTS: E. faecalis JM263 supplementation significantly attenuated intestinal and hepatic injury caused by systemic inflammation and oxidative stress, thereby enhancing growth performance and immune function. Mechanistically, E. faecalis JM263 mitigated systemic inflammation by reinforcing intestinal barrier function and remodeling the gut microbiota, which was associated with increased relative abundances of Muribaculaceae and Acetatifactor. Furthermore, E. faecalis JM263 reduced hepatic oxidative stress, accompanied by coordinated changes in the Nrf2/Keap1 signaling pathway and antioxidant enzyme activity. Integrated proteomics and metabolomics analyses revealed that E. faecalis JM263 was associated with changes in hepatic inflammatory responses and apoptosis, potentially through the regulation of arachidonic acid metabolism. Correlation analysis further showed close associations among the gut microbiota, arachidonic acid-related proteins/metabolites, and host phenotypic indices. CONCLUSIONS: In summary, E. faecalis JM263 alleviates HCD-induced multiorgan damage and functional dysfunction by synergistically improving the intestinal barrier, suppressing systemic inflammation, and reducing oxidative stress. These findings highlight the efficacy of E. faecalis JM263 in promoting growth performance and maintaining health in ruminants via the gut-liver axis. Video Abstract.