Gut microbiota influence the risk of inflammatory bowel disease through regulation of immune cells: a mediated Mendelian study

Objective To analyze the causal relationship between gut flora, immune cells and inflammatory bowel disease (IBD) through Mediated Mendelian Randomization Analysis.Methods Obtain data related to gut flora, immune cells and IBD through publicly available genome-wide association study (GWAS) data sets. MR analysis was performed on the data using the random effects inverse variance weighting method (IVW), weighted median method (WME), MR-Egger regression method and MR-PRESSO method. Cochran’s Q statistic and leave-one-out (LOO) method were used to test for heterogeneity. Visualize the results by plotting a forest plot.Results Through multiple MR analyses, 5 types of bacterial groups were found to be significantly related to IBD; IBD was significantly related to 27 types of immune cells; UC was significantly related to 22 types of immune cells; CD was significantly related to 26 types of immune cells. There is a significant causal relationship between 12 types of immune cells and 5 types of gut flora. Mediated MR analysis found that Bacteroidales (o_Bacteroidales.f_Rikenellaceae) and Rikenellaceae (f_Rikenellaceae.g_Alistipes) exert their effects on IBD through Sw mem % lymphocytes and CD25++ CD8br %CD8br cells.Conclusion This study verifies that gut flora, immune cells, and IBD have a significant causal relationship, and provides certain guidance for future research on IBD in the direction of flora and immunity. These gut flora, immune cells, and phenotypes are expected to become the future Potential targets for the treatment of IBD in clinical and scientific research.