Disentangling the Immune Cell-Mediated Causal Effects of Gut Microbiota on Inflammatory Bowel Disease via Mendelian Randomization

Introduction: Inflammatory Bowel Disease (IBD), including Crohn's Disease and Ulcerative Colitis, is a chronic intestinal inflammation that significantly impacts patients' quality of life. Recently, studies have highlighted that the gut microbiota can influence the pathogenesis of IBD by mediating immune cells. Methods :We used a two-sample bidirectional Mendelian Randomization (MR) analysis on genetically predicted gut microbiota and IBD. Additionally, a two-step MR approach was applied to quantify the mediating effect of HLA DR on monocytes on the influence of gut microbiota on IBD. Results :The results indicate that Alistipes shahii significantly reduces the risk of developing IBD (IVW odds ratio [OR] per SD increase in IBD =0.8917/ 0.5944 P =0.0373/0.0389），HLA-DR on monocyte, as the intermediary factor between Alistipes shahii and IBD, can strengthen the protective effect of Alistipes shahii on IBD, and the proportion of mediation effect accounted for 13.9% Conclusion :In summary, our study found that the protective effect of HLA DR On monocytes enhanced the protective effect of Alistipes shahii on IBD in Finland. However, most of the mechanisms by which Alistipes shahii affects IBD on monocytes via HLA DR are unknown.Further research is needed to explore other risk factors as potential mediators.