双歧杆菌属与抑郁症的因果关联：一项孟德尔随机化研究

Causal association between Bifidobacterium and major depressive disorder： a Mendelian randomization study

中文关键词:  双歧杆菌属  抑郁症  因果效应  孟德尔随机化

英文关键词:Bifidobacterium  Major depressive disorder  Causal effect  Mendelian randomization

中文摘要:

      背景 抑郁症是一种常见的精神疾病，其核心特征包括持续的情绪低落、注意力难以集中、对日常活动失去兴趣、食欲减退以及出现睡眠障碍。既往关于双歧杆菌属改善抑郁症状的随机对照试验（RCT）结果不一致。目的 采用孟德尔随机化（MR）方法，探究双歧杆菌属与抑郁症的因果关联，以期为抑郁症的发病风险及机制研究提供遗传学证据支持。方法 基于全基因组关联研究（GWAS）的汇总数据，将双歧杆菌属、抑郁症分别作为暴露因素和结局变量，采用逆方差加权法、加权中位数法、MR-Egger回归法、加权众数法及简单众数法对双歧杆菌属与抑郁症之间的因果关联进行分析，使用MR-Egger回归检验、MR-PRESSO检验、留一法进行敏感性分析。结果 逆方差加权法结果显示，双歧杆菌属与抑郁症存在因果关联（OR=1.018，95% CI：1.001~1.035，P=0.035），且不存在反向因果关联（OR=0.603，95% CI：0.116~3.130，P=0.547）。结论 双歧杆菌属是抑郁症的危险因素，双歧杆菌属可能会增加抑郁症的发病风险。

英文摘要:

      Background Major depressive disorder （MDD）， a prevalent mental disorder， is characterized by persistent depressed mood， impaired concentration， loss of interest in daily activities， decreased appetite， and sleep disturbances. Randomized controlled trials （RCTs） indicate potential benefits of Bifidobacterium supplementation for MDD， but the evidence base remains insufficient to draw definitive conclusions.Objective To explore the causal association between Bifidobacterium and MDD through a Mendelian randomization （MR） approach， with the hope of providing genetic evidence to elucidate the etiological mechanisms and risk factors underlying MDD.Methods Summary-level data from genome-wide association studies （GWAS） was conducted， specifying Bifidobacterium as the exposure variable and MDD as the outcome variable， to rigorously investigate the causal association between Bifidobacterium and MDD. Multiple complementary analytical approaches were employed， including inverse-variance weighted， weighted median estimator， MR-Egger regression， weighted mode and simple mode， to derive robust causal estimates. Furthermore， to ensure the robustness and validity of the findings， a series of comprehensive sensitivity analysis were systematically performed， encompassing MR-Egger regression test， MR-PRESSO test and leave-one-out analysis.Results Inverse-variance weighted revealed a causal link from Bifidobacterium to MDD （OR=1.018， 95% CI： 1.001–1.035， P=0.035）， whereas no evidence of reverse causality was observed （OR=0.603， 95% CI： 0.116–3.130， P=0.547）.Conclusion Bifidobacterium is a risk factor for MDD， and its presence may increase the risk of MDD onset.