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The causal effects between gut microbiota and hemorrhagic stroke: a bidirectional two-sample Mendelian randomization study.

作者信息

Shen Yingjie, Liu Hao, Meng Xiangyi, Gao Aili, Liu Yansong, Ma Wei, Liang Hongsheng, Hu Fulan

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Clinical Laboratory of Molecular Biology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Front Microbiol. 2023 Dec 22;14:1290909. doi: 10.3389/fmicb.2023.1290909. eCollection 2023.


DOI:10.3389/fmicb.2023.1290909
PMID:38188561
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10770845/
Abstract

BACKGROUND: Recent studies have suggested that the composition of gut microbiota (GM) may change after intracerebral hemorrhage. However, the causal inference of GM and hemorrhagic stroke is unknown. Mendelian Randomization (MR) is an effective research method that removes confounding factors and investigates the causal relationship between exposure and outcome. This study intends to explore the causal relationship between GM and hemorrhagic stroke with the help of MR. METHODS: Univariable and multivariable MR analyses were performed using summary statistics of the GM ( = 18,340) in the MiBioGen consortium vs. the FinnGen consortium R9 summary statistics (intracerebral hemorrhage, subarachnoid hemorrhage, and nontraumatic intracranial hemorrhage). Causal associations between gut microbiota and hemorrhagic stroke were analyzed using inverse variance weighted, MR-Egger regression, weighted median, weighted mode, simple mode, and MR-PRESSO. Cochran's statistic, MR-Egger regression, and leave-one-out analysis were used to test for multiplicity and heterogeneity of instrumental variables. Separate reverse MR analyses were performed for microbiota found to be causally associated with hemorrhagic stroke in the forward MR analysis. Also, multivariate MR analyses were conducted after incorporating common confounders. RESULTS: Based on the results of univariable and multivariate MR analyses, (OR, 0.80; 95%CI, 0.66-0.97; = 0.025) had a protective effect against hemorrhagic stroke, while (OR, 0.81; 95%CI, 0.67-0.99; = 0.039) had a potential protective effect. Furthermore, (OR, 1.77; 95%CI, 1.27-2.46; = 0.001), (OR, 1.24; 95%CI, 1.05-1.48; = 0.013) and (OR, 1.28; 95%CI, 1.01-1.62; = 0.041) acted as potential risk factors for hemorrhagic stroke. The abundance of (β, 0.05; 95%CI, 0.002 ~ 0.101; = 0.041) may increase, and that of (β, -0.072; 95%CI, -0.137 ~ -0.007; = 0.030) decreased after hemorrhagic stroke according to the results of reverse MR analysis. No significant pleiotropy or heterogeneity was detected in any of the MR analyses. CONCLUSION: There is a significant causal relationship between GM and hemorrhagic stroke. The prevention, monitoring, and treatment of hemorrhagic stroke through GM represent a promising avenue and contribute to a deeper understanding of the mechanisms underlying hemorrhagic stroke.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b3/10770845/e476d31fab85/fmicb-14-1290909-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b3/10770845/22327bd98804/fmicb-14-1290909-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b3/10770845/43d340953cd1/fmicb-14-1290909-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b3/10770845/c0148bd49382/fmicb-14-1290909-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b3/10770845/25b9c4ba5b05/fmicb-14-1290909-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b3/10770845/4023bb06c566/fmicb-14-1290909-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b3/10770845/2379c59f5a53/fmicb-14-1290909-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b3/10770845/6e687709da50/fmicb-14-1290909-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b3/10770845/e476d31fab85/fmicb-14-1290909-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b3/10770845/22327bd98804/fmicb-14-1290909-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b3/10770845/43d340953cd1/fmicb-14-1290909-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b3/10770845/c0148bd49382/fmicb-14-1290909-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b3/10770845/25b9c4ba5b05/fmicb-14-1290909-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b3/10770845/4023bb06c566/fmicb-14-1290909-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b3/10770845/2379c59f5a53/fmicb-14-1290909-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b3/10770845/6e687709da50/fmicb-14-1290909-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15b3/10770845/e476d31fab85/fmicb-14-1290909-g008.jpg

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[2]
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[6]
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本文引用的文献

[1]
Unlocking the Potential of Stroke Blood Biomarkers: Early Diagnosis, Ischemic vs. Haemorrhagic Differentiation and Haemorrhagic Transformation Risk: A Comprehensive Review.

Int J Mol Sci. 2023-7-17

[2]
2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

Stroke. 2023-7

[3]
Gut microbiome and risk of ischaemic stroke: a comprehensive Mendelian randomization study.

Eur J Prev Cardiol. 2023-5-9

[4]
Role of Inflammatory Processes in Hemorrhagic Stroke.

Stroke. 2023-2

[5]
Interplay between Gut Microbiota and NLRP3 Inflammasome in Intracerebral Hemorrhage.

Nutrients. 2022-12-9

[6]
Gut microbiota composition reflects disease progression, severity and outcome, and dysfunctional immune responses in patients with hypertensive intracerebral hemorrhage.

Front Immunol. 2022

[7]
Gut microbes in cerebrovascular diseases: Gut flora imbalance, potential impact mechanisms and promising treatment strategies.

Front Immunol. 2022

[8]
Association between gut microbiota and preeclampsia-eclampsia: a two-sample Mendelian randomization study.

BMC Med. 2022-11-15

[9]
Relationship between gut microbiota and lymphocyte subsets in Chinese Han patients with spinal cord injury.

Front Microbiol. 2022-9-26

[10]
Ferulic acid improves intestinal barrier function through altering gut microbiota composition in high-fat diet-induced mice.

Eur J Nutr. 2022-10

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