A Bidirectional Mendelian Randomization reveals the association between the abundance of Gut Microbiota and multiple subtypes of Lung Cancer

Abstract

Abstract Background: Using Mendelian randomization research, several specialists are now curious to learn more about the association between gut bacteria and lung cancer and its subtypes. However, their GWAS summary statistics and statistical methodologies are outdated and constrained. Methods: A two-sample bidirectional Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest genome-wide meta-analysis conducted by the MiBioGen. The summary statistics of lung cancer were extracted from the largest lung cancer GWAS meta-analysis.Inverse variance weighted (multiplicative random effects), MR-Egger regression, weighted median, weighted model and MR-PRESSO were used to examine the causal relationship. Reverse MR analysis was also performed on the lung cancer and its subtypes and microbiota. Result:Inverse variance weighted(IVW) estimates suggested that we identified 2 bacterial taxon that were causally associated with lung cancer, 1 bacterial taxon with Lung Adenocarcinoma (LUAD), 3 bacterial taxon with Small Cell Lung Carcinoma (SCLC),1 bacterial taxon with Lung cancer in never smokers (LCNS) and 3 bacterial taxon with Lung cancer in ever smokers (LCES).Also in the reverse MR analysis,we identified 1 bacterial taxon that were causally associated with lung cancer, 5 bacterial taxon with Squamous Cell Lung Carcinoma (LUSC), 1 bacterial taxon with LCNS and 5 bacterial taxon with LCES. Conclusion: In summary, this two-sample MR study found that several gut microbiota taxon was causally associated with lung cancer and its subtypes. Further studies are needed to clarify the effect of gut microbiota on them, including their specific mechanism.