Gut microbiota and sepsis: mechanisms, clinical correlations, and therapeutic prospects

Sepsis is a life-threatening organ dysfunction triggered by a dysregulated host response to infection. According to the Global Burden of Disease Study, this condition affects over 50 million people annually and causes approximately 5.3 million deaths, with fatality rates varying significantly across populations and healthcare settings, ranging from about 20% to 50%, representing a major challenge in critical care medicine. In recent years, the gut microbiota, as the largest microbial ecosystem in the human body, has increasingly demonstrated a central role. It is not only essential for maintaining intestinal barrier integrity, immune homeostasis, and metabolic balance but also actively participates in the pathogenesis, progression, and outcomes of sepsis through modulating immune responses, influencing the production of key metabolites, and mediating gut-organ axes. This article systematically reviews the characteristics of sepsis-induced gut microbiota dysbiosis, delves into the molecular mechanisms by which dysbiosis drives immune disorders, metabolic disturbances, and multi-organ injury, evaluates the clinical potential and current limitations of microbiome-associated biomarkers, and summarizes recent advances and controversies in microbiota-targeted therapeutic strategies, including probiotics, fecal microbiota transplantation, precision nutrition, and antibiotic stewardship. This review aims to analyze the shortcomings and translational challenges in current research, providing a theoretical basis and forward-looking perspective for developing precise microbiome-based individualized management strategies for sepsis.