Causal effects and immune cells mediators between gut microbiota and sicca syndrome: A Mendelian randomization study

This study sought to investigate the causal relationship between gut microbiota (GM) and sicca syndrome (SS), as well as to identify and quantify potential immune cell traits as mediators in this association. The analysis incorporated data from genome-wide association studies, encompassing 473 GM variables, 731 immune cell traits, and SS. The primary method of analysis was inverse variance weighting. Sensitivity analyses, such as Cochran Q test, Mendelian randomization pleiotropy RESidual sum and outlier test, Mendelian randomization-Egger regression intercept, and leave-one-out analysis, were conducted to assess the stability and reliability of the results. Notably, our mediation analysis identified 8 immune cell traits that act as mediators in the causal association between GM and SS. Specifically, Bacteroides A abundance in stool, Bifidobacteriaceae abundance in stool, CAG-776 sp000438195 abundance in stool, and CAG-81 sp000435795 abundance in stool were found to be causally linked to SS. The corresponding immune cell mediators involved in these relationships are forward scatter-area on human leukocyte antigen (HLA) DR+ T cell, CD14+ CD16- monocyte %monocyte, TD CD8br AC, and CD33dim HLA DR+ CD11b+ %CD33dim HLA DR+, respectively. The mediation effect proportions for these associations were determined as -2.35%, -3.57%, -7.5%, and -5.4%, respectively. Moreover, Clostridium M clostridioforme abundance in stool was associated with SS and mediated by 2 immune cell traits: CD45 on HLA DR+ CD8br and CD4RA on TD CD4+. The mediation effect proportions for these associations were -3.9% and 3.7%, respectively. Similarly, Pandoraea abundance in stool was associated with SS and mediated by 2 immune cell traits: CD3 on CD4 regulatory T cell and CD28 on CD39+ secreting regulatory T cell. The mediation effect proportions for these associations were -15.7% and 8.5%, respectively. In conclusion, this study provides evidence for a causal relationship between GM and SS, demonstrating the role of immune cell traits as mediators in this causal association.