Association between gut microbiota and chronic diseases in East Asian ethnicity: A two-sample Mendelian randomization study

The etiology and pathogenesis of chronic diseases (CDs) are complex and may result in a variety of symptoms that negatively affect patients’ daily lives. There is growing evidence that changes in the composition and function of the gut microbiota (GM) are linked to the onset and progression of CDs, but a causal relationship between them has not yet been demonstrated in the East Asian ethnicity. We sourced data from publicly available genome-wide association study summary statistics that focused on the composition of the GM and its association with 6 specific CDs: chronic obstructive pulmonary disease (COPD), Graves disease (GD), interstitial lung disease (ILD), periodontal disease (PD), peripheral arterial disease (PAD), and coronary artery disease (CAD). We then investigated the causal relationship between the GM and the 6 CDs using a two-sample Mendelian randomization approach. To assess these causal links, we applied multiple statistical methods, including MR-Egger regression, weighted median estimation, inverse-variance weighted analysis, as well as simple and weighted mode-based approaches. Among these, the inverse-variance weighted method was selected as the primary analytical strategy. To ensure the credibility and stability of our findings, we further conducted a comprehensive set of sensitivity analyses. We found that the genus Allisonella significantly increased the risk of COPD, whereas LachnospiraceaeNK4A136group decreased the risk of COPD; Anaerotruncus increased the risk of GD, whereas Lachnospiraceae UCG004 decreased the risk of GD; Catenibacterium and Bifidobacterium increased the risk of ILD, while Butyricicoccus decreased the risk of ILD; Catenibacterium and Olsenella increased the risk of PD, whereas Anaerostipes , LachnospiraceaeGroupNK4A136, Hungatella , and Lactococcus reduced the risk of PD; Parasutterella , CandidatusSoleaferrea , and Desulfovibrio increased the risk of PAD and Paraprevotella reduced the risk of PAD; Allisonella increased the risk of CAD and Senegalimassilia decreased the risk of CAD. No significant heterogeneity or polynomial estimates were found. Our research indicates a direct causal link between 19 specific types of GM and 6 chronic illnesses within East Asian populations. This contributes fresh understanding of how the composition of GM influences the development and progression of CDs.