World journal of critical care medicineDec 11, 2025

The Gut's Role in Sepsis and Organ Dysfunction

Abstract

Sepsis is a serious condition that can lead to multiple organ failures and is a major cause of illness and death worldwide. Recent research shows that the gut microbiome, which is the collection of bacteria in our intestines, plays a crucial role in how our immune system responds during sepsis. This paper reviews how problems in the gut can affect other organs like the liver, lungs, kidneys, brain, and heart during sepsis. We discuss how substances produced by gut bacteria can worsen inflammation and organ damage. We also look at potential treatments that target the gut microbiome, such as prebiotics and probiotics, which might help in managing sepsis. However, there are still challenges to overcome, such as differences between patients and safety concerns. Overall, this review highlights the importance of the gut in sepsis and suggests that targeting gut bacteria could be a promising approach in treating this condition.

Simplified

Sepsis remains a leading cause of morbidity and mortality worldwide, driven by a dysregulated host immune response to infection that culminates in multi-organ dysfunction. Recent advances highlight the gut microbiota's pivotal role in modulating immune responses and influencing the pathophysiology of sepsis through the organ-gastrointestinal tract axis. This review synthesizes current evidence on the bidirectional interplay between gut dysbiosis and the dysfunction of major organ systems-liver, lungs, kidneys, brain, and heart-during sepsis. We explore how gut-derived factors such as microbial translocation, endotoxins, and altered metabolite production exacerbate systemic inflammation and organ injury. In particular, we emphasize the roles of short-chain fatty acids, uremic toxins, bile acids, and trimethylamine-N-oxide in mediating immune dysfunction across the gut-organ axes. Therapeutic strategies targeting the gut microbiota- including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation- show promise in preclinical and early clinical settings. However, challenges related to patient heterogeneity, safety, and the lack of precise biomarkers persist. This review consolidates disparate findings to underscore the gut as a central modulator in sepsis and advocates for microbiota-based interventions as adjunctive therapies in sepsis management.

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Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

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