Gut barrier-microbiota crosstalk in sepsis: from pathogenesis to potential therapies

Sepsis is a systemic inflammatory response syndrome triggered by infection, frequently complicated by severe organ dysfunction and high mortality rates. Recent studies of intestinal epithelial function and the gut microbiota have highlighted their pivotal roles in the pathogenesis of sepsis. However, the precise mechanisms governing the interaction between the intestinal epithelium and gut microbiota, and how this interaction drives sepsis progression, still need to be elucidated. In this review, the functions of the intestinal epithelial barrier are first outlined, and the clinical significance of its altered permeability during sepsis is highlighted. Then, the physiological roles of the gut microbiota are further explored, detailing how dysbiosis and microbial metabolites influence disease progression and trigger both localized and systemic immune responses. Based on this, a logical framework for gut-originated systemic inflammation is proposed, and the potential adverse effects of current clinical supportive therapies on intestinal integrity are further discussed. Finally, the emerging sepsis treatment strategies that target gut function are summarized, aiming to provide novel insights and therapeutic directions for clinical practice.