Exploring Gut Microbe-Host Genes in Postpartum Depression: Mendelian Randomization and Transcriptomic Analysis
Ting Cong1,2, Jing Liu3, Li Yuan1,2
1Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People's Republic of China.
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.
Insights
Gut bacteria may influence postpartum depression (PPD) risk. Certain microbes like Veillonellaceae may decrease PPD, while Alphaproteobacteria and Family XIII AD3011 group may increase PPD risk.
Area of Science:
- Microbiome research
- Genetics
- Mental health
Background:
- Postpartum depression (PPD) is a significant mental health concern affecting women after childbirth.
- The role of the gut microbiome in PPD is increasingly recognized but requires further investigation.
- Identifying specific microbial taxa and host genes involved could offer new therapeutic avenues.
Purpose of the Study:
- To investigate the potential causal relationship between gut microbial composition and the risk of developing PPD.
- To identify specific gut microbiota-host genes associated with PPD susceptibility.
- To explore novel biomarkers and therapeutic targets for PPD prevention and intervention.
Main Methods:
- A two-sample Mendelian randomization (MR) study utilizing genome-wide association studies (GWAS) data for 196 gut microbial taxa and PPD.
- Employing various statistical approaches including inverse variance weighted (IVW), MR-Egger, weighted mode, and weighted median for causal inference.
- Conducting pleiotropy and heterogeneity tests (Cochran's Q, MR-Egger intercept, MR-PRESSO, leave-one-out analysis) and applying FDR correction.
- Analyzing a microarray dataset (GSE45603) to identify microbiota-host gene interactions.
Main Results:
- The IVW analysis indicated that the bacterial family Veillonellaceae is associated with a reduced risk of PPD (OR=0.82, q=0.030).
- Conversely, the class Alphaproteobacteria (OR=1.22, q=0.074) and the genus Family XIII AD3011 group (OR=1.24, q=0.065) were linked to an increased incidence of PPD.
- Four potential gut microbiota-host genes (AQP9, ALDH1A2, DGUOK, STAMBP) were identified in relation to the Family XIII AD3011 group.
Conclusions:
- The study provides genetically supported evidence for a causal link between gut microbiota and PPD.
- Identified microbiota-host genes represent potential targets for PPD diagnostics or therapeutics.
- These findings contribute to a better understanding of PPD etiology and inform prevention strategies.
