Fecal microbiota transplantation reduces susceptibility to post-antibiotic CLP-induced sepsis by modulating the gut microbiota and its metabolites.

Sepsis remains a leading cause of mortality in intensive care units, and antibiotics continue to serve as the cornerstone of treatment. However, their potentially detrimental effects on gut health are often overlooked. Although antibiotic exposure may increase susceptibility to disease, its contribution to the progression of sepsis has not been fully elucidated. In this study, we investigated the effects of antibiotics on the gut microbiota, microbial metabolites, and intestinal barrier integrity in healthy mice, and further evaluated their impact on subsequent sepsis outcomes. Using a cecal ligation and puncture (CLP)-induced sepsis model, we demonstrated that antibiotic-induced gut dysbiosis exacerbated intestinal barrier damage and significantly increased mortality. In contrast, fecal microbiota transplantation (FMT) markedly improved survival and restored intestinal barrier function. Mechanistically, the protective effects of FMT were associated with modulation of the Hippo signaling pathway, which was accompanied by reduced intestinal permeability. Collectively, these findings highlight the critical role of antibiotic-induced gut dysbiosis in the pathogenesis of sepsis and support FMT as a potential therapeutic strategy to alleviate intestinal barrier damage and improve survival in sepsis.