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Oral microbiome and risk of lung cancer: results from a two-sample mendelian randomization analysis

Chudong Wang,Biao Hu,Qiuyi Liang,Han Jiang,Lu Yuan,Shuben Li

Published 2025 in Translational Lung Cancer Research

ABSTRACT

Background Numerous studies have suggested that the oral microbiome may function as a biomarker for lung cancer screening. However, the relationship between oral microbiome and lung cancer has not been thoroughly investigated. Consequently, investigating the causal relationship between oral microbiome and lung cancer was the primary goal of this study. Methods We conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between the oral microbiome and lung cancer. Summary statistics for the oral microbiomes were obtained from large-scale metagenome-genome-wide association studies (mgGWAS), while genome-wide association study (GWAS) summary statistics for lung cancer were sourced from the IEU-OpenGWAS online platform. We employed inverse variance weighted (IVW) analysis and Wald ratio methods to evaluate the causal associations between the oral microbiome and lung cancer. Finally, we performed MR Steiger’s test to strengthen the validity of the causal associations. Results Three oral microbiomes were causally associated with lung cancer. Gemella haemolysans (pheno.388) from saliva and an unclassified species (pheno.844) of Clostridia from saliva were protective factors for lung cancer, and an unclassified species (pheno.1354) of Prevotella from tongue was a risk factor for lung cancer. And there is no bidirectional association of causality between oral microbiomes and lung cancer. Conclusions The oral microbiomes, Gemella haemolysans (pheno.388) from saliva, an unclassified species (pheno.844) of Clostridia from saliva and an unclassified species (pheno.1354) of Prevotella from tongue, were causally associated with lung cancer. Oral microbiology holds significant potential for clinical applications in etiologic exploration, early screening, prevention, and enhancing survival in lung cancer. Regarding treatment, personalized therapy based on oral flora may provide novel therapeutic strategies for lung cancer.

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