Ningxiang pig-derived Enterococcus hirae protects against E. coli-induced gut dysbiosis and inflammation via acetate/propionate-MyD88-NF-κB axis in piglets

Abstract Background Intestinal inflammation, often driven by microbial dysbiosis and infections, remains a significant health challenge with limited effective treatments. Identifying probiotic strains with anti-inflammatory properties and elucidating their mechanisms is essential for developing novel therapeutic strategies. This study investigates the molecular mechanisms by which E. hirae—a lactic acid bacterium (LAB) isolated from Ningxiang piglets with low diarrhea incidence—alleviates E. coli-induced intestinal inflammation. Results In the present study, comparative analysis showed that Ningxiang piglets exhibited a significantly lower incidence of diarrhea and reduced E. coli abundance compared to Yorkshire piglets. Notably, E. hirae was more abundant in Ningxiang piglets and correlated with elevated secretory IgA levels. Additionally, in vitro antagonism assays found that E. hirae effectively inhibited E. coli growth. In vivo supplementation of E. hirae in E. coli-infected piglets restored intestinal microbial balance, increased levels of short-chain fatty acids (SCFAs) such as acetate and propionate, and mitigated E. coli colonization. Further analyses suggested that acetate and propionate downregulated the MyD88/NF-κB signaling pathway, thereby reducing pro-inflammatory cytokine expression. Molecular docking and MyD88 − / − experiments verified that MyD88 is involved in SCFA-mediated protection against E. coli-induced inflammation. Furthermore, analyses of public human datasets revealed that Crohn’s disease patients exhibited a similar reduction in SCFA levels and MyD88–NF-κB pathway activation, suggesting potential clinical relevance. Conclusion Token together, our results reveal that Ningxiang pig-derived E. hirae alleviates E. coli-induced gut dysbiosis and inflammation potentially through the acetate/propionate–MyD88–NF-κB axis. This work provides mechanistic insights for further exploration of probiotic and postbiotic approaches against bacterial-induced intestinal inflammation. Video Abstract