Causal effects of gut microbiota in the development of lung cancer and its histological subtypes: A Mendelian randomization study

Abstract

Background: Numerous studies have characterized the gut microbiome (GM) in lung cancer (LC). Yet, the causality between GM and LC and its subtypes remain uncharacterized. Methods: Two-sample Mendelian randomization (MR) was designed to investigate the causal relationship between the GM and LC and its subtypes, using publicly available summary data of genome-wide association studies. The researchers ran two groups of MR analyses, including the genome-wide statistical significance threshold (5 × 10−8) and the locus-wide significance level (1 × 10−5). Results: Using MR analysis, we ascertained 42 groups of GM that are intimately linked to LC and its subtypes at the locus-wide significance level. Of the 42 groups, 12 were in LC, nine in non-small cell lung cancer (NSCLC), six in small cell lung cancer (SCLC), two in lung adenocarcinomas, and 13 in lung squamous carcinomas. After false discovery rate correction, we still found a remarkable causal interaction between the Eubacterium ruminantium group and SCLC. Moreover, five groups of GM closely linked to LC and its subtypes were recognised at the genome-wide statistical significance threshold. This finding included one group each in LC, NSCLC and SCLC, two groups in lung adenocarcinoma and none in lung squamous carcinoma. None of the foregoing findings were heterogeneous or horizontal pleiotropy. Reverse MR revealed that genetic susceptibility to LC and its subtypes caused significant changes in three groups of GM. Conclusion: Our findings substantiate the causality between GM and LC and its subtypes. This study offers fresh insights into the function of GM in mediating the progression of LC.