Department of colorectal diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
J Affect Disord. 2022 Nov 1;316:187-193. doi: 10.1016/j.jad.2022.08.012. Epub 2022 Aug 10.
Observational studies showed an association between gut microbiota and depression, but the causality relationship between them is unclear. We aimed to determine whether there is a bidirectional causal relationship between the composition of gut microbiota and major depressive disorders (MDD) and explore the role of gut microbiota in decreasing the risk of MDD.
Our two-sample Mendelian randomization (MR) study acquired top SNPs associated with the composition of gut microbiota (n = 18,340) and with MDDs (n = 480,359) from publicly available genome-wide association studies (GWAS). The SNPs estimates were pooled using inverse-variance weighted meta-analysis, with sensitivity analyses-weighted median, MR Egger, and MR Pleiotropy Residual Sum and Outlier (PRESSO).
The Actinobacteria class had protective causal effects on MDD (OR 0.88, 95%CI 0.87 to 0.9). The Bifidobacterium (OR 0.89, 95%CI 0.88 to 0.91) were further found to have similar effects as the Actinobacteria class. The genus Ruminococcus1 had a protective effect on MDD (OR 0.88, 95%CI 0.76 to 0.99) while the Streptococcaceae family and its genus had an anti-protective effect on MDD (OR 1.07, 95%CI 1.01 to 1.13), but these findings were not supported by the MR-Egger analysis. Bidirectional MR showed no effect of MDD on gut microbiota composition.
The use of summary-level data, the risk of sample overlap and low statistical power are the major limiting factors.
Our MR analysis showed a protective effect of Actinobacteria, Bifidobacterium, and Ruminococcus and a potentially anti-protective effect of Streptococcaceae on MDD pathogenesis. Further studies are needed to transform the findings into practice.
观察性研究表明肠道微生物群与抑郁症之间存在关联，但它们之间的因果关系尚不清楚。我们旨在确定肠道微生物群组成与重度抑郁症（MDD）之间是否存在双向因果关系，并探讨肠道微生物群在降低 MDD 风险中的作用。
我们的两样本孟德尔随机化（MR）研究从公开的全基因组关联研究（GWAS）中获得了与肠道微生物群组成（n=18340）和 MDD（n=480359）相关的顶级 SNP。使用逆方差加权荟萃分析对 SNP 估计值进行汇总，敏感性分析包括加权中位数、MR Egger 和 MR 偏倚残留和异常值（PRESSO）。
厚壁菌门对 MDD 有保护作用（OR 0.88，95%CI 0.87 至 0.9）。双歧杆菌（OR 0.89，95%CI 0.88 至 0.91）被进一步发现与厚壁菌门有相似的作用。瘤胃球菌属对 MDD 有保护作用（OR 0.88，95%CI 0.76 至 0.99），而链球菌科及其属对 MDD 有抗保护作用（OR 1.07，95%CI 1.01 至 1.13），但这些发现并未得到 MR-Egger 分析的支持。双向 MR 分析显示 MDD 对肠道微生物群组成没有影响。
使用汇总数据、样本重叠风险和低统计能力是主要的限制因素。
我们的 MR 分析表明厚壁菌门、双歧杆菌和瘤胃球菌属具有保护作用，链球菌科及其属可能具有抗保护作用，这可能有助于 MDD 的发病机制。需要进一步的研究将这些发现转化为实践。
