Role of CD25 on resting Treg immune cell in Mediating the Effect of stearate biosynthesis microbiome pathway on lung adenocarcinoma

Abstract Background Gut microbiota (GM) often influences the development of diseases by regulating the immune system. The causal relationship between GM and lung adenocarcinoma (LUAD) and whether it can be mediated by immune cells remains unclear. Methods We conducted two-step, two-sample Mendelian randomization (MR) analyses. The data of GM, LUAD and immune cells for analysis were derived from publicly available genetic data. The causal relationship between GM and LUAD, as well as the mediation effect of immune cells in the association between GM and LUAD were estimated using inverse variance weighted (IVW), MR-Egger and weighted median. Sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO. Results MR analyses determined the protective effects of PWY-5989 (stearate biosynthesis II bacteria and plants) on LUAD. In addition, CD25 on resting Treg was negatively correlated with LUAD. Of note, the mediation MR illustrated that in the presence of CD25 on resting Treg, PWY-5989 can promote the risk of LUAD by inhibiting the expression of CD25 on resting Treg. Conclusion The study suggested a causal relationship between PWY-5989 and LUAD, which may be mediated by CD25 on resting Treg.