Background

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.

Methods

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).

Results

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.

Limitations

The use of summary-level data, the risk of sample overlap and low statistical power are the major limiting factors.

Conclusions

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.

中文翻译：

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肠道微生物群和重度抑郁症：双向孟德尔随机化

背景

观察性研究表明肠道菌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的组成与重度抑郁症 (MDD) 之间是否存在双向因果关系，并探索肠道微生物群在降低 MDD 风险中的作用。

方法

我们的两样本孟德尔随机化 (MR) 研究从公开可用的全基因组关联研究 (GWAS) 中获得了与肠道微生物群组成 (n = 18,340) 和 MDD (n = 480,359) 相关的顶级 SNP。使用逆方差加权荟萃分析汇总 SNP 估计值，并进行敏感性分析——加权中位数、MR Egger 和 MR Pleiotropy Residual Sum and Outlier (PRESSO)。

结果

放线菌类对MDD 具有保护性因果影响（OR 0.88，95%CI 0.87 至 0.9）。进一步发现双歧杆菌（OR 0.89，95 %CI 0.88 至 0.91）具有与放线菌类相似的作用。Ruminococcus1属对 MDD 具有保护作用（OR 0.88，95%CI 0.76 至 0.99），而链球菌科及其属对 MDD 具有抗保护作用（OR 1.07，95%CI 1.01 至 1.13），但这些发现MR-Egger 分析不支持。双向 MR 显示 MDD 对肠道微生物群组成没有影响。

限制

摘要级数据的使用、样本重叠的风险和低统计功效是主要的限制因素。

结论

我们的 MR 分析显示放线菌、双歧杆菌和瘤胃球菌的保护作用以及链球菌对 MDD 发病机制的潜在抗保护作用。需要进一步的研究将研究结果转化为实践。