Dynamics of the gut and lung microbiota in severe infections: from observational studies to therapeutic strategies

BACKGROUND: Severe infections and sepsis are characterized by a disruption of intestinal and respiratory microbial communities. Loss of obligate gut anaerobes and depletion of immunomodulatory metabolites disrupt mucosal integrity, impair immune homeostasis, and increase susceptibility to secondary infection and organ failure. OBJECTIVES: To summarize the current understanding of gut and lung microbiome dynamics during severe infections, describe immunometabolic crosstalk along the gut-lung axis, and identify microbiome-targeted strategies to improve outcomes. SOURCES: Peer-reviewed preclinical and clinical studies on microbiota composition, metabolite signalling, and therapeutic modulation in severe infections published up to October 2025. CONTENT: In health, obligate anaerobes such as Faecalibacterium and Blautia species are thought to support mucosal homeostasis through short-chain fatty acids, secondary bile acids, and tryptophan-derived indoles that calibrate systemic immunity and suppress overgrowth of opportunistic pathogens. Sepsis-associated inflammation, hypoperfusion, and antibiotic exposure deplete obligate anaerobes, shifting the gut ecosystem towards Enterococcus, Enterobacterales, and Candida species, accompanied by disruption of metabolite-mediated immune homeostasis. The lungs, which contain their own low-biomass microbiota, similarly undergo a loss of diversity with overrepresentation of Proteobacteria during critical illness, a pattern that has been linked to impaired alveolar immunity and adverse outcomes. Experimental studies indicate that gut-derived metabolites and migrating immune cells shape pulmonary responses, and loss of gut-lung compartmentalization may permit bacterial translocation and contribute to systemic inflammation. Defined live anaerobic consortia and postbiotics represent promising experimental strategies to restore microbial balance during severe infections, but the most immediate opportunity lies in antibiotic stewardship that limits unnecessary anaerobe-active coverage. IMPLICATIONS: The obligately anaerobic microbiome is central to host-pathogen interactions in severe infection. Preserving and restoring anaerobic and pulmonary microbial communities through rational antimicrobial use and mechanistically informed microbiome-based interventions may improve outcomes and recovery after critical illness.