Dissecting Causal Relationships Between Gut Microbiota, Blood Metabolites, and Stroke: A Mendelian Randomization Study

被引：55

作者：

Wang, Qi ^{[1
,2
]}

Dai, Huajie ^{[1
,2
]}

Hou, Tianzhichao ^{[1
,2
]}

Hou, Yanan ^{[1
,2
]}

Wang, Tiange ^{[1
,2
]}

Lin, Hong ^{[1
,2
]}

Zhao, Zhiyun ^{[1
,2
]}

Li, Mian ^{[1
,2
]}

Zheng, Ruizhi ^{[1
,2
]}

Wang, Shuangyuan ^{[1
,2
]}

Lu, Jieli ^{[1
,2
]}

Xu, Yu ^{[1
,2
]}

Liu, Ruixin ^{[1
,2
]}

Ning, Guang ^{[1
,2
]}

Wang, Weiqing ^{[1
,2
]}

Bi, Yufang ^{[1
,2
]}

Zheng, Jie ^{[1
,2
,3
]}

Xu, Min ^{[1
,2
]}

机构：

[1] Shanghai Jiao Tong Univ, Shanghai Inst Endocrine & Metab Dis, Ruijin Hosp, Dept Endocrine & Metab Dis,Sch Med, Shanghai, Peoples R China

[2] Shanghai Jiao Tong Univ, Shanghai Natl Clin Res Ctr Metab Dis,Ruijin Hosp, Sch Med,Key Lab Endocrine & Metab Dis,Natl Hlth C, Shanghai Key Lab Endocrine Tumor,State Key Lab Me, Shanghai, Peoples R China

[3] Univ Bristol, Bristol Med Sch, MRC Integrat Epidemiol Unit, Bristol, Avon, England

来源：

JOURNAL OF STROKE | 2023年 / 25卷 / 03期

基金：

中国国家自然科学基金;

关键词：

Gastrointestinal microbiome; Stroke; Metabolomics; Mendelian randomization analysis; GENETIC-VARIANTS; INSTRUMENTS; RISK; BIAS;

D O I：

10.5853/jos.2023.00381

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). Methods We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. Results Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. Conclusion The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

引用

页码：350 / 360

页数：11

共 45 条

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