A review of gut failure as a cause and consequence of critical illness

• Published in: Critical care (London, England) Vol. 29; no. 1; p. 91
• Main Authors: Soranno, Danielle E., Coopersmith, Craig M., Brinkworth, Jessica F., Factora, Faith N. F., Muntean, Julia H., Mythen, Monty G., Raphael, Jacob, Shaw, Andrew D., Vachharajani, Vidula, Messer, Jeannette S.
• Format: Journal Article
• Language: English
• Published: London BioMed Central 26.02.2025; BioMed Central Ltd
• Subjects: Apoptosis; Bacteria; Blood vessels; Cell death; Colon; Consensus; Consensus Article; Critical Care Medicine; Critical Illness - therapy; Disease susceptibility; Dysbiosis - physiopathology; Emergency Medicine; Esophagus; Gastrointestinal Diseases - physiopathology; Gastrointestinal Microbiome - physiology; Gastrointestinal Tract - physiopathology; Health aspects; Humans; Illnesses; Infection; Intensive; Kinases; Lymphatic system; Medicine; Medicine & Public Health; Microbiota; Motility; Multiple Organ Failure - etiology; Multiple Organ Failure - physiopathology; Permeability; Small intestine; Stem cells; Supplies; Taxonomy; Veins & arteries
• ISSN: 1364-8535; 1466-609X; 1364-8535; 1466-609X; 1366-609X
• DOI: 10.1186/s13054-025-05309-7

In critical illness, all elements of gut function are perturbed. Dysbiosis develops as the gut microbial community loses taxonomic diversity and new virulence factors appear. Intestinal permeability increases, allowing for translocation of bacteria and/or bacterial products. Epithelial function is altered at a cellular level and homeostasis of the epithelial monolayer is compromised by increased intestinal epithelial cell death and decreased proliferation. Gut immunity is impaired with simultaneous activation of maladaptive pro- and anti-inflammatory signals leading to both tissue damage and susceptibility to infections. Additionally, splanchnic vasoconstriction leads to decreased blood flow with local ischemic changes. Together, these interrelated elements of gastrointestinal dysfunction drive and then perpetuate multi-organ dysfunction syndrome. Despite the clear importance of maintaining gut homeostasis, there are very few reliable measures of gut function in critical illness. Further, while multiple therapeutic strategies have been proposed, most have not been shown to conclusively demonstrate benefit, and care is still largely supportive. The key role of the gut in critical illness was the subject of the tenth Perioperative Quality Initiative meeting, a conference to summarize the current state of the literature and identify key knowledge gaps for future study. This review is the product of that conference. Key points The healthy gut maintains an epithelial barrier that simultaneously cooperates with and contains gut microbes. In critical illness, blood is diverted away from the gut, gut integrity is compromised by intestinal epithelial cell death and failure of intercellular junctions, and the microbial community undergoes taxonomic and functional remodeling. Gut barrier failure leads to translocation of live microbes, microbial components, or microbial products into host tissues where they elicit local and systemic inflammatory and immune responses. Diagnosing gastrointestinal (GI) failure is challenging due to a lack of gut specific diagnostic tests. Therapeutic interventions are in development for nearly all aspects of GI failure, but none have yet shown efficacy in large clinical trials. Ultimately, there is an urgent need to identify key molecular mechanisms that lead to gut barrier failure, develop diagnostics to detect their activation, and create therapeutic strategies to counteract them.