Guangxi University of Chinese Medicine, Nanning, 530200, China.
Yongning District Traditional Chinese Medicine Hospital, Nanning, 530299, China.
Exp Gerontol. 2024 Oct 1;195:112530. doi: 10.1016/j.exger.2024.112530. Epub 2024 Jul 29.
The gut microbiota (GM) plays an important role in the development of immune-related diseases, and the immune response is one of the pathomechanisms of depression (Dep); whether the effect of GM on Dep is mediated by immune cells (ImC) is unclear.
ImC may mediate the effect of GM on Dep. Our aim is to identify and quantify the role of immune characteristics as potential mediators.
Pooled statistics for GM (n = 7738) and ImC (n = 3757) were obtained from publicly available genome-wide association studies (GWAS), and for Dep (n = 47,696) from the Finnish database R10. We used a mediated Mendelian randomization (MR) study to investigate the causal relationship between GM and Dep and the mediating role of ImC between GM and Dep associations.
The results showed that the genetically predicted GM was significantly correlated with both ImC as well as Dep. MR analysis identified five microbiomes that had significant causal effects on Dep (Methionine biosynthesis III, PWY-6737-Starch degradation V, Parasutterella excrementihominis, Parasutterella, and Lysine biosynthesis I). In addition, five of the 26 ImC trait significantly associated with GM were most closely associated with Dep (T cell %lymphocyte、CD28-CD127-CD25++CD8br AC、CD28-CD8br AC、CD27 receptor on peripheral blood plasma cells (CD27 on PB/PC) and CD11b receptor on mononuclear myeloid-derived suppressor cells (CD11b on Mo MDSC)). This mediated MR illustrates the causal role of methionine biosynthesis III on Dep (IVW: OR = 1.08, 95%CI [1.04,1.14], P = 0.001). And there was no strong evidence for a causal effect of depression on methionine biosynthesis III. In the B cell group, the proportion of CD27 on PB/PC mediated was 7.88 %(95%CI [-0.04,0.03]) of the total effect. This study further suggests that Dep patients should actively seek immunologic intervention therapy.
This MR study found that GM may play a causal role in Dep by mediating ImC. Our findings will help to understand the pathogenic mechanism of GM in Dep and the risk of immune mediation.
肠道微生物群（GM）在免疫相关疾病的发展中起着重要作用，而免疫反应是抑郁症（Dep）的发病机制之一；GM 对 Dep 的影响是否通过免疫细胞（ImC）介导尚不清楚。
ImC 可能介导 GM 对 Dep 的影响。我们的目的是确定和量化免疫特征作为潜在介质的作用。
从公开的全基因组关联研究（GWAS）中获得 GM（n=7738）和 ImC（n=3757）的汇总统计数据，以及芬兰数据库 R10 中 Dep（n=47696）的汇总统计数据。我们使用中介孟德尔随机化（MR）研究来调查 GM 与 Dep 之间的因果关系以及 GM 与 Dep 关联之间 ImC 的中介作用。
结果表明，遗传预测的 GM 与 ImC 和 Dep 均呈显著相关。MR 分析确定了五个对 Dep 具有显著因果影响的微生物组（蛋氨酸生物合成 III、PWY-6737-淀粉降解 V、Parasutterella excrementihominis、Parasutterella 和赖氨酸生物合成 I）。此外，与 GM 显著相关的 26 个 ImC 特征中有五个与 Dep 最密切相关（T 细胞%淋巴细胞、CD28-CD127-CD25++CD8br AC、CD28-CD8br AC、CD27 受体在外周血浆细胞（CD27 on PB/PC）和单核髓样来源的抑制性细胞上的受体（CD11b on Mo MDSC））。这种中介 MR 说明了蛋氨酸生物合成 III 对 Dep 的因果作用（IVW：OR=1.08，95%CI [1.04，1.14]，P=0.001）。Dep 对蛋氨酸生物合成 III 没有明显的因果影响。在 B 细胞组中，CD27 on PB/PC 介导的比例为总效应的 7.88%（95%CI [-0.04，0.03]）。本研究进一步表明，Dep 患者应积极寻求免疫干预治疗。
这项 MR 研究发现，GM 可能通过调节 ImC 对 Dep 产生因果作用。我们的研究结果将有助于了解 GM 在 Dep 中的发病机制和免疫介导的风险。
