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肠道微生物群、血液代谢物与药物抗抑郁效应的因果关系研究
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| 篇名： | 肠道微生物群、血液代谢物与药物抗抑郁效应的因果关系研究 |
| TITLE： | Study on the causal relationship between gut microbiota，blood metabolites and antidepressant treatment response |
| 摘要： | 目的 从遗传学角度探究肠道微生物群、血液代谢物与抗抑郁效应之间的因果关系，并评估血液代谢物在其中可能发挥的中介作用。方法采用双样本孟德尔随机化（MR）分析，基于4个大规模的肠道微生物组全基因组关联研究（GWAS）数据集和2个血液代谢物GWAS数据集，以逆方差加权法作为主要分析方法，评估肠道微生物群、血液代谢物与抗抑郁效应之间的因果关系，通过多种敏感性分析评估结果的稳健性、遗传异质性与水平多效性，并采用错误发现率（FDR）校正多重假设检验带来的Ⅰ型错误。通过MR中介分析评价血液代谢物的中介效应。结果嗜胆菌属菌种与抗抑郁治疗有效呈显著负相关（P＝8.030×10－5，FDR校正后P＝0.033），而拟杆菌目菌科与抗抑郁治疗有效呈显著正相关（P＝3.275×10－4，FDR校正后P＝0.034）；筛选出百余个与抗抑郁效应相关的血液代谢物，但经FDR校正后显示，均无显著因果关系；血液代谢物在“肠道微生物群-血液代谢物-抗抑郁效应”路径中的中介效应比值的P均大于0.05。结论嗜胆菌属菌种可能是抗抑郁效应的危险性因素，拟杆菌目菌科则可能是抗抑郁效应的保护性因素。血液代谢物与抗抑郁效应的相关性不强，且尚无遗传学证据表明血液代谢物可在肠道微生物群与抗抑郁效应之间发挥关键中介作用。 |
| ABSTRACT： | OBJECTIVE To investigate the causal relationships between gut microbiota， blood metabolites and antidepressant treatment response from a genetic perspective， and to assess the potential mediating role of blood metabolites. METHODS This study utilized a two-sample Mendelian randomization （MR） design. Exposure data were derived from four large-scale gut microbiome genome-wide association study （GWAS） datasets and two blood metabolite GWAS datasets. The inverse variance weighted method was used as the primary method to evaluate the causal relationships between gut microbiota， blood metabolites and antidepressant effects. The robustness， heterogeneity and horizontal pleiotropy of the results were evaluated through various sensitivity analyses. Additionally， the false discovery rate （FDR） was applied to correct type Ⅰ errors caused by multiple hypothesis testing. Finally， MR mediation analysis was conducted to test the potential mediating effect of blood metabolites. RESULTS The s_ Bilophila was negatively associated with the effectiveness of antidepressant treatment （ P ＝8.030×10 －5 ， then P ＝0.033 after FDR correction）， and the f_Bacteroidales was positively associated with the effectiveness of antidepressant treatment （ P ＝3.275×10 －4 ， then P ＝0.034 after FDR correction）. Over a hundred blood metabolites were also screened out as being associated with antidepressant response， but after FDR correction， no significant causal relationship was observed. The P value of the mediation effect proportion of blood metabolites in the “gut microbiota-blood metabolites-antidepressant efficacy” pathway was greater than 0.05. CONCLUSIONS The s_ Bilophila may represent a risk factor for antidepressant effects， whereas the f_Bacteroidales may serve as a protective factor for antidepressant effects. The correlation between blood metabolites and antidepressant efficacy is not strong， and no genetic evidence is found to support that the investigated blood metabolites play a key mediating role between the gut microbiota and antidepressant response. |
| 期刊： | 2026年第37卷第06期 |
| 作者： | 娄琳琳；施玲怡；周湘君；蒋颖；朱浩浩 |
| AUTHORS： | LOU Linlin，SHI Lingyi，ZHOU Xiangjun，JIANG Ying，ZHU Haohao |
| 关键字： | 肠道微生物群；血液代谢物；抗抑郁效应；孟德尔随机化分析；中介分析 |
| KEYWORDS： | gut microbiota； blood metabolites； antidepressant |
| 阅读数： | 3 次 |
| 本月下载数： | 0 次 |
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