Role of CD64 on CD14+ CD16+ Monocytes in Mediating the Effect of genus Collinsella on Nonalcoholic Fatty Liver Disease

Objective Previous Mendelian randomization (MR) studies have explored the association between gut microbiota and nonalcoholic fatty liver disease (NAFLD), but the role of monocytes in this relationship remains unclear. Methods We performed a bidirectional and mediation Mendelian randomization(MR) study using summary statistics from the genome-wide association studies of gut microbial taxa (Dutch Microbiome Project, n = 7738), immune cells (GWAS Catalog, (accession numbers from GCST0001391 to GCST0002121, n = 3757), and NAFLD (the FinnGen study, 2568 cases and 409613 controls). We utilized two-sample MR analysis to assess the association between gut microbes and NAFLD and calculated the mediating effects of immune cells on this association. The primary methods for causal inference were Inverse Variance Weighting (IVW) test and Bayesian Weighted Mendelian Randomization (BWMR). A sensitivity analysis was also conducted to ensure the robustness of our results. Results genus Collinsella is the most significant taxon causally associated with NAFLD among five microbial taxa [odds ratio = 1.453, 95% confidence interval (CI) = 1.120–1.883, P-value = 0.0048]. The BWMR analysis confirmed this causal relationship. The univariable MR analysis showed that CD64 on CD14 + CD16 + monocyte was causal immune cell for NAFLD. (OR = 1.227, 95% CI = 1.036–1.453, P = 0.018). The mediation MR analysis showed that CD64 on CD14 + CD16 + monocyte mediated the causal effects of genus Collinsella on NAFLD (proportion mediated = 13.5%, 95% CI = 1.4–30.8%). Conclusion Our study identified a causal relationship between genus Collinsella and NAFLD, with a proportion of the effect mediated by a specific monocyte.