Immune cells appraising the causal effect of gut microbiota on endometrial cancer: A Mendelian randomization analysis

The intricate relationship between the gut microbiota (GM) and immune-mediated diseases deserves deep exploration. Our study focused on investigating the potential causal link between the recently discovered 885 GM and endometrial cancer (EC), as well as determining the role of immune cells in mediating this relationship. Causal relationship between GM and EC was firstly investigated using a 2-sample Mendelian randomization (MR) analysis. Subsequently, a 2-step MR study was conducted to provide evidence for a mediating role of immune traits in this causal pathway. MR analyses revealed genus Bacillus and Bacillaceae A had a protective effect on EC, while Fusobacterium A and GCA-900199385 sp900320755 showed a positive correlation with EC. Mediation analyses indicated that these GM components influence EC through various immune cell traits as mediators, including IgD+ CD38br %lymphocytes and transitional AC on the B cell panel, DP (CD4+CD8+) % leukocytes on the TBNK panel, and CD25 on memory B cells. Our study suggested added genetic evidence support the causal relationship between GM and EC, with a partial contributing role of immune cells in mediating such effects. Further in-depth functional research is warranted to fully explore the mechanisms of intermediation behind this intricate association.