Gut microbiota, immune cells, and postpartum depression: A mediation Mendelian randomization study.

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. 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. 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. 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.