Gut microbiota in combination with blood metabolites and inflammatory cytokines reveals characteristics of hypertrophic cardiomyopathy: a Mendelian randomization study

Background and purpose: Hypertrophic cardiomyopathy (HCM) is the most prevalent form of cardiomyopathy and the leading cause of sudden cardiac death in young individuals. However, research on the precise intervention targets for this condition remains limited. This study investigated the causal relationships between the gut microbiota (GM) and HCM, as well as potential mediators, using Mendelian randomization. Methods: Two-sample Mendelian randomization was conducted to explore the causal relationships among the GM, blood metabolites, inflammatory factors, and HCM. Two-step and multivariate Mendelian analyses were employed to assess the mediating roles of blood metabolites and inflammatory factors in the relationship between GMs and HCM. Additionally, Bayesian model mean multivariate Mendelian randomization (MR-BMA) analysis was performed to identify blood metabolites and inflammatory factors with the most significant intermediary effects. Results: A total of 18 GM, 49 blood metabolites, and five inflammatory factors were identified as having significant causal relationships with HCM. Further multivariate Mendelian randomization (MVMR) analysis confirmed that the serum metabolites C-glycosyltryptophan and X-12740 are significant mediators associated with HCM. After MR-BMA validation, C-glycosyltryptophan levels were found to significantly mediate the relationships between the classes Methanobacteria, family Methanobacteria, and order Methanobacteria and HCM, with mediated proportions of 7.79%, 5.08%, and 5.08% (P = 0.01), respectively. Conclusions: This study used Mendelian randomization to identify the GM, blood metabolites, and inflammatory factors associated with HCM, providing evidence for potential mediating metabolites and inflammatory cytokines. These findings offer valuable insights for identifying biomarkers of HCM and potential therapeutic targets.