mouse gut metagenome Genome sequencing
Salmonella Typhimurium (S. typhimurium), a zoonotic pathogen inflicting substantial health and economic burdens on humans and animals. Dietary docosahexaenoic acid (DHA) has various roles in inflammation inhibition and disease risk reduction, but the influence of DHA-microbiota interaction on liver injury caused by S. typhimurium is largely unknown. In this study, we found that dietary DHA alleviates S. typhimurium-induced hepatic damage in mice by reshaping gut microbiota composition and promoting Kupffer cell (KC) polarization toward an anti-inflammatory M2 phenotype. Furthermore, fecal microbiota transplantation (FMT) from DHA-treated mice replicated these protective effects, confirming gut microbiota dependency. 16S rRNA sequencing and metagenomic analysis have demonstrated that Blautia coccoides (B. coccoides) as a pivotal mediator contributing to DHA alleviate liver injury. Mechanistically, intervention with B. coccoides promote KC conversion from M1 to M2 phenotype through secreted extracellular vesicles (EVs) to alleviate liver injury, and macrophage depletion abolished these benefits, underscoring KCs as indispensable mediators. These findings establish a novel gut-liver axis mechanism wherein DHA enriches B. coccoides, whose EVs drive KC reprogramming to resolve infection-induced inflammation. This work highlights the therapeutic potential of combining dietary DHA with probiotic or EV-based strategies to combat enteric pathogen-associated liver injury.