Genetic Insights into the Gut-Lung Axis: Mendelian Randomization Analysis on Gut Microbiota, Lung Function, and COPD.

Background: Chronic obstructive pulmonary disease (COPD) is a respiratory disorder with a complex etiology involving genetic and environmental factors. The dysbiosis of gut microbiota has been implicated in COPD. Mendelian Randomization (MR) provides a tool to investigate causal links using genetic variants as instrumental variables. This study aims to employ MR analysis to explore the causal relationship between gut microbiota, lung function, and COPD. Methods: We utilized genome-wide association study (GWAS) data from MiBioGen, UK Biobank and FinnGen, which were related to gut microbial taxa, lung function parameters including forced vital capacity in one second (FEV1), forced vital capacity (FVC), and percentage of predicted FEV1 (FEV1%pred), as well as GWAS data for COPD. MR analysis was conducted to assess the causal effects of gut microbiota on lung function and the risk of COPD. Sensitivity analysis was utilized to examine the stability of the causal relationships. Multiple testing and reverse analysis were employed to evaluate the robustness of these relationships. Results: Using the IVW method, 64 causal correlations were identified. Through conducting sensitivity analysis, multiple testing, and reverse analysis, we identified 14 robust and stable causal relationships. The bacterial taxa that showed a positive association with lung function included Desulfovibrionaceae, Erysipelotrichales, Desulfovibrionales, Clostridiales, Clostridia, Deltaproteobacteria and Erysipelotrichia, while Selenomonadales and Negativicutes showed a negative association with lung function. The abundance of Holdemanella were positively correlated with the risk of COPD, while FamilyXIII exhibited a negative correlation with the risk of COPD. Conclusion: Several microbial taxa were discovered to have a positive causal correlation with lung function, offering potential insights into the development of probiotics. The presence of microbial taxa negatively correlated with lung function and positively correlated with COPD emphasized the potential impact of gut microbiota dysbiosis on respiratory health.

Genetic evidence on the causality between gut microbiota and various asthma phenotypes: a two-sample Mendelian randomization study.

Introduction: Asthma is a multifarious disease that manifests in various phenotypes. Among the various factors that contribute to the development of asthma, the gut microbiota has recently emerged as a compelling area of investigation. This study aims to investigate the causal relationships between gut microbiota and distinct asthma phenotypes. Methods: The genome-wide association study (GWAS) summary statistics for 211 gut microbial taxa were used as study exposure. Five traits pertaining to various asthma phenotypes (asthma, allergic asthma, childhood asthma, suggestive for eosinophilic asthma and obesity-related asthma) were included as study outcome. We conducted Mendelian randomization (MR) analysis and sensitivity analysis for each bacterial taxa and asthma phenotypes. Result: We discovered a total of 58 associations that exhibited evidence of causality. Out of these, 4 associations remained significant even after applying multiple correction. An increased risk of asthma was causally associated with higher abundance of genus Holdemanella (OR = 1.11; CI: 1.05-1.17; p = 0.027), genus Oxalobacter (OR = 1.09; CI: 1.04-1.15; p = 0.025) and genus Butyricimonas (OR = 1.14; CI: 1.06-1.22; p = 0.027). Order NB1n was causally linked with an increased risk of obesity-related asthma (OR = 1.17; CI: 1.07-1.29; p = 0.015). There was limited overlap among the taxa that exhibited potential causal relationships with distinct asthma phenotypes. Conclusion: Our research has provided genetic evidence that establishes multiple causal relationships between the gut microbiota and distinct asthma phenotypes, supporting the role of the gut microbiota in various asthma phenotypes. It is possible that different taxa play a role in the development of distinct asthma phenotypes. The causal relationships identified in this study require further investigation.