The Gut–lung Axis in Severe Viral and Bacterial Pneumonia: Microbiota Dysbiosis, Host Defense, and Translational Priorities

Abstract

Severe viral and bacterial pneumonia is frequently complicated by acute lung injury, secondary bacterial infection, and systemic organ dysfunction. The gut–lung axis has emerged as a biologically plausible framework linking intestinal microbial ecology, microbial metabolites, barrier integrity, and pulmonary immune defence. This narrative review synthesises clinical and experimental evidence on how dysbiosis may modulate host responses during severe pneumonia. A targeted narrative search of PubMed/MEDLINE, Scopus, Web of Science, the Cochrane Library, and African Journals Online was used to identify literature published from January 2016 to July 2026; landmark earlier studies were retained when directly relevant, and Google Scholar was used only as a supplementary citation-tracking tool. Evidence was narratively organised around short-chain fatty acid (SCFA) signalling, lung-to-gut injury, gut-to-lung translocation, viral–bacterial superinfection, and microbiome-targeted interventions. Observational human cohorts, particularly in coronavirus disease 2019 (COVID-19), report associations between severe respiratory infection, reduced abundance of selected commensal taxa, and systemic inflammatory markers. Experimental studies support mechanisms whereby altered microbial metabolite availability can influence alveolar macrophage activity, tonic interferon signalling, and susceptibility to secondary bacterial pneumonia. Severe illness and antibiotic exposure may also impair intestinal colonisation resistance and barrier function, potentially facilitating systemic exposure to microbial products. However, causal inference in humans remains limited by confounding, heterogeneous sequencing methods, and the predominance of animal models. Microbiome-directed treatment therefore remains investigational. In particular, safety findings from live-probiotic trials in predicted severe acute pancreatitis should not be extrapolated as direct evidence in pneumonia. Prospective human multi-omics cohorts and rigorously designed, condition-specific trials are needed before targeted postbiotic or other microbiome-based therapies can be incorporated into routine critical care.