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

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.