Exploring Gut Microbe-Host Genes in Postpartum Depression: Mendelian Randomization and Transcriptomic Analysis

Abstract

Purpose: To suggest a potential causal role of gut microbiota in Postpartum depression (PPD) and identify susceptible microbiota-host genes. Patients and Methods: The two-sample Mendelian randomization (MR) study was carried out with the genome-wide association studies (GWAS) data of 196 gut microbial taxa and PPD. Causal relationships were evaluated with inverse variance weighted (IVW), MR‒Egger, weighted mode, and weighted median approaches. Cochran’s Q test, the MR‒Egger intercept test, the MR-PRESSO test, and leave-one-out analysis were performed for assessing pleiotropy and heterogeneity. Additionally, false discovery rate (FDR) correction was completed via q-value method. A microarray dataset was carried out to identify susceptible microbiota-host genes. Results: IVW suggested that the family Veillonellaceae [odds ratio (OR) = 0.82, 95% confidence interval (CI) = 0.71–0.94, p = 0.004, q = 0.030] decreased the PPD risk, but the class Alphaproteobacteria (OR = 1.22, 95% CI = 1.01–1.47, p = 0.041, q = 0.074) and the genus Family XIII AD3011 group (OR = 1.24, 95% CI = 1.04–1.48, p = 0.019, q = 0.065) increased the incidence of PPD. Additionally, we extracted SNP-related genes from the Family XIII AD3011 group and identified four gut microbe-host genes (AQP9, ALDH1A2, DGUOK, and STAMBP) in combination with the transcriptome dataset GSE45603. Conclusion: The findings support the genetically predicted causal relationship of gut microbiota with PPD and identify susceptible microbiota-host genes as potential therapeutic targets or diagnostic biomarkers, providing new insights into the prevention and intervention of PPD.