Gut microbiota, immune cells, and postpartum depression: A mediation Mendelian randomization study
Bo Zhou1, Jingcheng Guo1, Xuanxuan Peng1
1Department of Anesthesiology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.
Background:
Recent studies suggest links between the gut microbiome, immune cells, and postpartum depression (PPD), but causal relationships are unclear. This study employed the Mendelian randomization (MR) to explore the causal relationship and mediating effect among the three factors.
Methods:
Summary data from genome-wide association studies were analyzed using MR techniques, including inverse variance weighted, weighted median, MR-Egger, simple mode, and weighted mode. Mediation analysis was conducted to assess the roles of immune cells and gut microbiota in PPD. Sensitivity tests were performed to verify the stability of the findings.
Results:
The analysis results showed that there were 26 positive correlations (risk factors) (OR > 1, p < 0.05) and 19 negative correlations (protective factors) (OR < 1, p < 0.05) between immune cell traits and PPD. In addition, there were 13 positive correlations (OR > 1, p < 0.05) and 20 negative correlations (OR < 1, p < 0.05) between gut microbiota and PPD. Additionally, 6 relationships were identified with the gut microbiota serving as mediators, among them, "GCA-900066755" increased the risk of PPD via "CD45RA- CD4+ T cell %T cell" (9.4 %). With immune cells acting as mediators, "CD4+ CD8dim T cell Absolute Count" was found to reduce the risk of "Holdemania sp900120005" on PPD (25.8 %). Sensitivity tests corroborated the reliability of the findings.
Conclusion:
This MR study indicates a causal relationship among immune cells, gut microbiota, and PPD. It clarifies the mediating roles of immune cells and gut microbiota in PPD, offering new insights into the underlying mechanisms for PPD.
Insights
This study used Mendelian randomization to find causal links between gut bacteria, immune cells, and postpartum depression (PPD). It identified specific gut microbes and immune cells that mediate the risk of developing PPD.
Area of Science:
- Neuroscience
- Immunology
- Microbiology
Background:
- Emerging evidence suggests a connection between the gut microbiome, immune system, and postpartum depression (PPD).
- However, the causal pathways underlying these associations remain largely uncharacterized.
Purpose of the Study:
- To investigate the potential causal relationships between gut microbiota, immune cell traits, and PPD using Mendelian randomization.
- To elucidate the mediating roles of gut microbiota and immune cells in the development of PPD.
Main Methods:
- Utilized Mendelian randomization (MR) with summary data from genome-wide association studies.
- Employed various MR techniques including inverse variance weighted, weighted median, MR-Egger, simple mode, and weighted mode.
- Conducted mediation analysis and sensitivity tests to confirm findings.
Main Results:
- Identified numerous significant correlations between immune cell traits and PPD (26 risk factors, 19 protective factors).
- Found significant associations between gut microbiota and PPD (13 risk factors, 20 protective factors).
- Revealed 6 instances where gut microbiota mediated PPD risk and identified immune cells as mediators in other pathways.
Conclusions:
- This MR study provides evidence for a causal interplay between immune cells, gut microbiota, and PPD.
- The findings clarify the mediating roles of the gut microbiome and immune system in PPD pathogenesis.
- Offers novel insights into the biological mechanisms underlying PPD.
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