Investigating the causal relationship between the plasma lipidome and cholangiocarcinoma mediated by immune cells: a mediation Mendelian randomization study

The plasma lipidome and immune cells are instrumental in shaping the health profile of an organism, and their influence on diseases is profound. However, the intricate interactions between cholangiocarcinoma (CCA) and these physiological components have yet to be comprehensively explored. Employing Mendelian randomization (MR), our study delved into the causal links among immune cells, the lipidome, and CCA. The research design meticulously considered both the direct associations and the mediating roles of immune cells within the complex interplay between the lipidome and CCA. Our analysis uncovered significant correlations between the levels of Sphingomyelin (d34:1), Phosphatidylcholine (0-16:0, 22:5) and Sterol ester (27:1/16:0) and CCA. Moreover, we have pinpointed various immune cells that play a mediating role in the impact of the lipidome on CCA. For example, Sphingomyelin (d34:1) can impact CCA through the IgD on IgD+ CD38- unswitched memory (unsw mem) B cell (B cell panel), IgD on unsw mem (B cell panel) and Naive CD4+ %CD4+ (maturation stages of T cell). The proportion of mediating effects further sheds light on the intricate interplay among the lipidome, immune cells, and their cumulative influence on CCA. Our study illuminates the intricate relationship among the lipidome, immune cells, and CCA. These findings suggest that the lipidome could serve as a promising and potentially effective therapeutic target in the treatment of CCA.