Role of CD40 on CD14- CD16+ monocyte in mediating the effect of Dialister on Depression
Description
Objective: To explore the cause-and-effect link between gut microbiota and depression, and to determine and measure the function of immune cells as possible intermediaries.Methods：This research involved conducting a dual-sample Mendelian randomization analysis (MR) on genetically forecasted gut microbiota (7,738 individuals) and depression (25,087 individuals and 92,695 controls), utilizing aggregate data from a genome-wide association study (GWAS). The primary MR analysis employed inverse variance-weighted (IVW), along with additional techniques, and we executed heterogeneity and level pleiotropy tests to corroborate the primary MR findings. Furthermore, genetic variations in immune cell signatures were extracted from an extensive, open-label genome-wide social study (GWAS) with 3757 participants, utilizing a two-phase MR analysis to ascertain and measure the impact of CD40 on the CD14-CD16+ monocyte-driven effects of Microbacterium on depression.Results: By MR analysis, five gut bacteria were associated with a reduced risk of depression: Butyrivibrio (OR=0.9922, 95%, CI=0.9864-0.9980, P=0.0084), Sutterellaceae (OR=0.9843, 95%CI=0.9732-0.9956, P=0.0067), Dialister (OR=0.9887, 95%CI=0.9775-1.0000, P=0.0497), Bacteroides (OR=0.9883, 95%CI=0.9768-1.0000, P=0.0476), Butyrivibrio_crossotus (OR=0.9933, 95%CI=0.9879-0.9988, P=0.0166), and there was no strong evidence of a causal relationship between depression and gut bacteria. The im-muno phenotype were identified as significantly associated with depression risk. In addition, we also found that the proportion of CD40 on CD14- CD16+ monocyte-mediated in genetically predicted Dialister on depression was 5.42%.Conclusions: Our study identified five gut microbiota that reduced the risk of depression, and twenty-seven immunophenotypes are significantly associated with depression. Of these, the CD40-mediated microbiota has small effect on CD14-CD16+ monocytes, but these effects are largely unknown and additional potential factors need to be investigated. Clinically, attention should be paid to the effects of the gut microbiome on depression.