Gut microecology in critical illness: mechanisms, biomarkers, and therapeutic strategies - a critical appraisal.

Authors

Liang Tian, Shanshan Xu, Xueping Xie, Man Wang, Lina Huang

Published in

Frontiers in gastroenterology (Lausanne, Switzerland). Volume 5. Pages 1902608. Epub Aug 05, 2026.

Abstract

Critical illness is associated with a predictable ecological collapse of the gut microbiome. Within 48 hours of ICU admission, three convergent selective pressures-luminal oxygen enrichment from mucosal inflammation, nitrate provision by iNOS, and antibiotic-mediated niche clearance-drive a phase transition from obligate-anaerobe-dominated communities to pathogen-dominated monocultures, compromising barrier integrity and immune homeostasis. Multi-omics integration recasts this as a cross-kingdom phenomenon encompassing fungi, bacteriophages, and the metabolite networks linking them to host immunity. Whether this collapse directly causes organ dysfunction or merely marks disease severity remains the central unresolved question. This critical review examines evidence across six domains: the healthy microbiota as an ecological benchmark; patterns and temporal dynamics of ICU dysbiosis; molecular mechanisms across four gut-organ axes; clinical consequences including sepsis, nosocomial infection, acute gastrointestinal injury, and multiple organ dysfunction syndrome (MODS); biomarkers and machine-learning predictive models; and therapeutic strategies evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Only early enteral nutrition (GRADE: HIGH) and antimicrobial stewardship (GRADE: MODERATE-HIGH) have Phase III evidence supporting routine ICU use. The repeated failures of probiotic trials reflect design limitations-lack of patient stratification, strain mismatch, and soft endpoints-though biological efficacy limitations cannot be excluded. We conclude that ICU dysbiosis is best understood as ecosystem collapse driven by convergent selective pressures, not random taxonomic disturbance. Therapeutic strategies should target functional outputs-SCFAs, bile acids, indole derivatives-rather than species composition. The resilient minority (15-20% of patients who maintain diversity) holds keys to prevention science. A clinically actionable platform requires three components: rapid ecological risk assessment, endotype classification, and mortality-powered randomized controlled trials targeting functional restoration.

PMID:
42621893
Bibliographic data and abstract were imported from PubMed on 20 Aug 2026.

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