The composition alteration of gut microbiota in lung cancer: a systematic review and meta-analysis

The association between the gut microbiota and lung cancer remains understudied. In this study, we conducted a comprehensive systematic review and meta-analysis to quantitatively synthesize evidence from multiple cohorts to identify robust and consistent alterations in gut microbial diversity and taxonomy associated with lung cancer.

A systematic literature search was performed across PubMed, Cochrane Library, Embase, and Web of Science databases up to June 5, 2025. The analysis summarized key microbiota characteristics from the selected studies, including alpha diversity, beta diversity, and relative taxonomic abundance. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines.

Our systematic search identified 12,810 articles, out of which 27 studies comprising 2,263 individuals, involving 1,234 lung cancer patients and 1,029 non-cancer controls, were included for qualitative synthesis. Meta-analysis revealed a significant reduction in microbial alpha diversity of 25 studies in lung cancer patients. Significant decreases were indicated in the ACE index (SMD = -0.64, 95% CI: -1.14 to -0.13), Chao1 index (SMD = -0.31, 95% CI: -0.60 to -0.02), and Shannon index (SMD = -0.25, 95% CI: -0.57 to 0.08). Chinese cohorts showed significantly lower Chao1and Shannon by subgroup analysis. Twenty-seven studies assessed beta diversity, in which 20 studies (74.0%) reported a significant difference in overall microbial community structure between lung cancer patients and non-cancer controls. Quantitative meta-analysis by forest plot revealed, compared to non-cancer controls, lung cancer patients exhibited decreased relative abundances of phylum Firmicutes (SMD = -0.47, 95% CI: -0.91 to -0.02), and increased abundances of phylum Bacteroidetes (SMD = 0.53, 95% CI: 0.24 to 0.82). Furthermore, we observed a marked depletion of beneficial short-chain fatty acid producers of genus Lachnospira (SMD = -1.01, 95% CI: -1.29 to -0.73).

This meta-analysis demonstrates that lung cancer is consistently associated with gut microbiota dysbiosis characterized by reduced microbial diversity and reproducible taxonomic alterations. Clinically, these findings suggest that gut microbiota may serve as non-invasive biomarkers for lung cancer detection and patient stratification, and may also help predict immunotherapy response and inform future microbiota-targeted therapeutic strategies.

https://www.crd.york.ac.uk/PROSPERO/view/CRD42024537463, CRD42024537463.