Li Hui, Meng Hongyan, Dang Chunxiao, Liu Pengfei, Liu Jinxing, Yu Xiao, Wang Zhonglin, Sui Xiaohui
Shandong University of Traditional Chinese Medicine, Jingshi Road, Jinan, Shandong, 250014, China.
Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jingshi Road, Jinan, Shandong, 250014, China.
BMC Pregnancy Childbirth. 2025 Feb 17;25(1):177. doi: 10.1186/s12884-025-07304-w.
Recent studies have suggested a potential correlation between ecological dysregulation of the gut microbiota (GM) and the onset and development of postpartum depression (PPD). In addition, inflammatory factors (IFs) have been reported to play an important role in the development of PPD. However, the causal connections among GM, IFs, and PPD remain to be understood.
This study sought to determine if genetically predicted GM and IFs exert a causal effect on PPD and to study whether IFs mediate the causal effect of GM on PPD.
Two-step and two-sample Mendelian randomization (MR) analyses, primarily employing the inverse variance weighted (IVW) method, were conducted to evaluate the causal relationship between GM, IFs, and PPD, and to assess potential mediating effects. Heterogeneity and horizontal pleiotropy tests were performed to evaluate the robustness of the findings and the strength of the causal associations.
Class Alphaproteobacteria, genus Family XIII AD3011 group exhibited a positive association with PPD risk; whereas, the family Clostridiales vadin BB60 group, family Veillonellaceae, genus Ruminococcaceae UCG011, and the inflammatory factors C-C motif chemokine ligand 5 (CCL5) and C-C motif chemokine ligand 3 (CCL3) demonstrated negative correlations with PPD risk. IFs did not exhibit a mediating role. No heterogeneity or horizontal pleiotropy was observed.
Our MR study offered genetic evidence that GM and IFs contribute to the pathogenesis of PPD, with no mediating effect of IFs. This enhances our understanding of PPD's pathological mechanisms and offers new perspectives for developing novel preventative and therapeutic strategies.
近期研究表明，肠道微生物群（GM）的生态失调与产后抑郁症（PPD）的发生和发展之间可能存在关联。此外，据报道炎症因子（IFs）在PPD的发展中起重要作用。然而，GM、IFs和PPD之间的因果关系仍有待明确。
本研究旨在确定基因预测的GM和IFs是否对PPD产生因果效应，并研究IFs是否介导GM对PPD的因果效应。
进行两步和两样本孟德尔随机化（MR）分析，主要采用逆方差加权（IVW）方法，以评估GM、IFs和PPD之间的因果关系，并评估潜在的中介效应。进行异质性和水平多效性检验，以评估研究结果的稳健性和因果关联的强度。
α-变形菌纲、XIII AD3011菌群家族与PPD风险呈正相关；而梭菌目vadin BB60菌群家族、韦荣氏菌科、瘤胃球菌科UCG011属以及炎症因子C-C基序趋化因子配体5（CCL5）和C-C基序趋化因子配体3（CCL3）与PPD风险呈负相关。IFs未表现出中介作用。未观察到异质性或水平多效性。
我们的MR研究提供了基因证据，表明GM和IFs促成了PPD的发病机制，且IFs无中介作用。这增强了我们对PPD病理机制的理解，并为开发新的预防和治疗策略提供了新的视角。
