Objective To assess any potential associations between lung cancer and gut microbiota. Methods Mendelian randomization (MR) analysis was carried out by utilizing summary data from genome-wide association studies (GWAS) of the gut microbiota and lung cancer. The gut microbiota served as an exposure. Instrumental ariables (IVs) were identified from the GWAS of 18340 participants. The GWAS study of lung cancer from Europe served as an outcome, including 29 266 lung cancer patients and 56450 controls. We used the inverse-variance weighted (IVW) method as the primary analysis. Sensitivity analysis was used to test the reliability of MR analysis results. Results IVW results showed that Genus Parabacteroides (OR=1.258, 95%CI 1.034 to 1.531, P=0.022) and Phylum Bacteroidetes (OR=1.192, 95%CI 1.001 to 1.419, P=0.048) had a positive causal association with lung cancer, and there was a negative causal association between family Bifidobacteriaceae (OR=0.845, 95%CI 0.721 to 0.989, P=0.037) and order Bifidobacteriales (OR=0.865, 95%CI 0.721 to 0.989, P=0.037) with lung cancer. Sensitivity analysis showed no evidence of reverse causality, pleiotropy, and heterogeneity. Conclusion This study demonstrates that Genus Parabacteroides and Phylum Bacteroidetes are related to an increased risk of lung cancer, family Bifidobacteriaceae and order Bifidobacteriales can reduce the risk of lung cancer. Our thorough investigations provide evidence in favor of a potential causal relationship between a number of gut microbiota-taxa and lung cancer. To demonstrate how gut microbiota influences the development of lung cancer, further research is necessary.
ObjectiveTo investigate the causal relationship between gut microbiota and idiopathic pulmonary fibrosis (IPF). MethodsGenome-wide association studies (GWAS) data of gut microbiota and IPF were obtained from MiBioGen and IEU OpenGWAS, respectively. Instrumental variables were screened by means of significance, linkage disequilibrium, weak instrumental variable screening, and removal of confounding factors (genetics, smoking, host characteristics). Inverse variance weighted (IVW) was used as the main Mendelian randomization (MR) analysis method, and the weighted median, simple mode, MR-Egger, and weighted mode were used to perform MR to reveal the causal effect of gut microbiota and IPF. The Cochrane's Q, leave-one-out, MR-Egger-intercept, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) and Steiger tests were used to analyze the heterogeneity, horizontal pleiotropy, outliers, and directionality, respectively. ResultsIVW analysis results showed that Actinobacteria [OR=1.773, 95%CI (1.323, 2.377), P<0.001], Erysipelatoclostridium [OR=2.077, 95%CI (1.107, 3.896), P=0.023], and Streptococcus [OR=1.35, 95%CI (1.100, 1.657), P=0.004] could increase the risk of IPF. Bifidobacterium [OR=0.668, 95%CI (0.620, 0.720), P<0.001], Ruminococcus [OR=0.434, 95%CI (0.222, 0.848), P=0.015], and Tyzzerella [OR=0.479, 95%CI (0.304, 0.755), P=0.001] could reduce the risk of IPF. No significant heterogeneity, horizontal pleiotropy, outliers, and reverse causality were found. ConclusionActinobacteria, Erysipelatoclostridium and Streptococcus may increase the risk of IPF, while Bifidobacterium, Ruminococcus and Tyzzerella may reduce the risk of IPF. Regulation of the above gut microbiota may become a new direction in the study of the pathogenesis of IPF.