[1]王禹捷 吴璨 武楷文 孙晓滨.基于孟德尔随机化探索肠道菌群和血液代谢物与高血压及其并发症之间的因果关系[J].心血管病学进展,2024,(11):1039.[doi:10.16806/j.cnki.issn.1004-3934.2024.11.017]
　WANG Yujie,WU Can,WU Kaiwen,et al.Exploring the Causal Relationship Between Gut Microbiota and Blood Metaboliteson on Hypertension and Hypertension- Related Complications Based on Mendelian Randomization[J].Advances in Cardiovascular Diseases,2024,(11):1039.[doi:10.16806/j.cnki.issn.1004-3934.2024.11.017]
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基于孟德尔随机化探索肠道菌群和血液代谢物与高血压及其并发症之间的因果关系()
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《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2024年11期
页码:
1039
栏目:
论著
出版日期:
2024-11-25

文章信息/Info

Title:
Exploring the Causal Relationship Between Gut Microbiota and Blood Metaboliteson on Hypertension and Hypertension- Related Complications Based on Mendelian Randomization
作者:
王禹捷1; 2 吴璨1; 2 武楷文2 孙晓滨1; 2
(1. 西南医科大学附属医院消化内科,四川 泸州 646000;2. 成都市第三人民医院消化内科,四川 成都 610031)
Author(s):
WANG Yujie1; 2; WU Can1; 2; WU Kaiwen2; SUN Xiaobin 1; 2
(1.Department of Gastroenterology,The Affiliated Hospital of Southwest Medical University,Luzhou 646000,Sichuan,China; 2.Department of Gastroenterology,The Third People’s Hospital of Chengdu, Chengdu 610031,Sichuan,China)
关键词:
孟德尔随机化; 肠道微生物; 血液代谢物; 高血压; 并发症
Keywords:
Mendelian randomization; Gut microbiota; Blood metabolite; Hypertension;  Complication
DOI:
10.16806/j.cnki.issn.1004-3934.2024.11.017
摘要:
目的 使用孟德尔随机化方法探究肠道菌群和血液代谢物与高血压及其并发症之间的因果关系。方法 从MiBioGen联盟和大型全基因组关联分析中获取肠道微生物和血液代谢物的汇总数据并获取与其显著相关的遗传变异作为工具变量。高血压、高血压心脏病、高血压肾病和卒中的汇总数据来自于芬兰基因组研究和其他大型全基因组关联分析。使用两样本孟德尔随机化分析探究肠道微生物和血液代谢物与高血压、高血压心脏病和高血压肾病之间的潜在关联，使用中介孟德尔随机化探究体重指数在其中的潜在效应。结果 研究结果表明，当使用P＜5×10?8筛选暴露的工具变量时，共有4种肠道微生物与高血压具有因果关系，3种与高血压心脏病相关。共有13种血液代谢物与高血压及其并发症具有因果关系，其中family Streptococcaceae（OR=2.446 5，P=0.045 5）和genus Streptococcus（OR=2.446 5，P=0.045 5）可能是高血压和高血压心脏病的共同危险因素。当阈值设置为P＜5×10?5时，经过P值校正，分别有8种肠道微生物和10种血液代谢物与高血压及其并发症存在因果关系，其中family Bacteroidaceae（OR=0.935，P=0.005）对高血压具有保护作用，class Betaproteobacteria（OR=0.940，P=0.008）可能会导致卒中发生风险的降低。结论 遗传预测的多种特定肠道微生物和血液代谢物与高血压及其并发症之间具有因果关系，这些菌群和血液代谢物可能成为新的生物标志物，为高血压及其并发症的预防、早期筛查和治疗提供新的思路，未来需更多的基础和临床研究进行验证。
Abstract:
Objective To explore the causal relationship between gut microbiota and circulating blood metabolites and hypertension and its complications using Mendelian randomization method. Methods Collect summary statistical data on gut microbiota and circulating blood metabolites from the MiBioGen consortium and large-scale genome-wide association studies,and obtain genetic variations significantly associated with them as instrumental variables. The summary statistical data for hypertension,hypertensive heart disease,hypertensive kidney disease,and stroke were obtained from the Finnish Genome Research Project and other large-scale genome-wide association studies. Exploring the potential association between gut microbiota and blood metabolites with hypertension,hypertensive heart disease,and hypertensive kidney disease using two sample Mendelian randomization analysis,and investigating the potential effects of body mass index using mediation Mendelian randomization. Results The research results indicate that when using P＜5×10?8 to screen for exposed instrumental variables,a total of 4 gut microbiota have a causal relationship with hypertension,and 3 are associated with hypertensive heart disease. There are a total of 13 blood metabolites that have a causal relationship with hypertension and its complications,among which family Streptococcaceae (OR=2.4465,P=0.0455) may be common risk factors for hypertension and hypertensive heart disease. When the threshold is set to P＜5×10?5, after P-value correction,there are causal relationships between 8 gut microbiota and 10 circulating blood metabolites and hypertension and its complications, respectively. Among them,family Bacteroidaceae ( OR=0.935,P=0.005) has a protective effect on hypertension,while class Betaproteobacteria (OR=0.940,P=0.008) may lead to a reduced risk of stroke. Conclusion There is a causal relationship between various specific gut microbiota and circulating blood metabolites predicted by genetics and hypertension and its complications. These microbiota and circulating blood metabolites may become new biomarkers,providing new ideas for the prevention,early screening,and treatment of hypertension and its complications. More basic and clinical research is needed to verify this in the future

参考文献/References:

[1].NCD Risk Factor Collaboration(NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019:a pooled analysis of 1201 population-representative studies with 104 million participants[J]. Lancet,2021,398(10304):957-980.
[2].Ren Y,Tong E,Di C,et al. Association between ABCA1 gene polymorphisms and the risk of hypertension in the Chinese Han population[J]. Front Public Health,2022,10:878610.
[3].Marques FZ,Mackay CR,Kaye DM. Beyond gut feelings:how the gut microbiota regulates blood pressure[J].?Nat Rev Cardiol,2018,15(1):20-32.
[4].Muralitharan RR,Jama HA,Xie L,et al. Microbial peer pressure:the role of the gut microbiota in hypertension and its complications[J]. Hypertension,2020,76(6):1674-1687.
[5].Chen BY,Li YL,Lin WZ,et al. Integrated omic analysis of human plasma metabolites and microbiota in a hypertension cohort[J]. Nutrients,2023,15(9):2074.
[6].Larsson SC,Butterworth AS,Burgess S. Mendelian randomization for cardiovascular diseases:principles and applications[J]. Eur Heart J,2023,44(47):4913-4924.
[7].Liu JZ,van Sommeren S,Huang H,et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations[J]. Nat Genet,2015,47(9):979-986.
[8].Shin SY,Fauman EB,Petersen AK,et al. An atlas of genetic influences on human blood metabolites[J]. Nat Genet,2014,46(6):543-550.
[9].Lawlor DA,Harbord RM,Sterne JA,et al. Mendelian randomization:using genes as instruments for making causal inferences in epidemiology[J]. Stat Med,2008,27(8):1133-1163.
[10].Bahls M,Leitzmann MF,Karch A,et al. Physical activity,sedentary behavior and risk of coronary artery disease,myocardial infarction and ischemic stroke:a two-sample Mendelian randomization study[J]. Clin Res Cardiol,2021,110(10):1564-1573.
[11].Wu K,Luo Q,Liu Y,et al. Causal relationship between gut microbiota and gastrointestinal diseases:a Mendelian randomization study[J]. J Transl Med,2024,22(1):92.
[12].Emdin CA,Khera AV,Kathiresan S. Mendelian randomization[J]. JAMA,2017,318(19):1925-1926.
[13].Tang J,Wei Y,Pi C,et al. The therapeutic value of bifidobacteria in cardiovascular disease[J]. NPJ Biofilms Microbiomes,2023,9(1):82.
[14].Cai M,Lin L,Jiang F,et al. Gut microbiota changes in patients with hypertension:a systematic review and meta-analysis [J]. J Clin Hypertens(Greenwich),2023,25(12):1053-1068.
[15].Luo L,Yin H,Gou D. Gut microbiota and metabolome changes in three pulmonary hypertension rat models[J]. Microorganisms,2023,11(2):472.
[16].Barbadoro P,Ponzio E,Coccia E,et al. Association between hypertension,oral microbiome and salivary nitric oxide:a case-control study [J]. Nitric Oxide,2021,106:66-71.
[17].Bian CF,Wang Y,Yu A,et al. Gut microbiota changes and biological mechanism in hepatocellular carcinoma after transarterial chemoembolization treatment[J].?Front Oncol,2022,12:1002589.
[18].Onyszkiewicz M,Gawrys-Kopczynska M,Sa?agaj M,et al. Valeric acid lowers arterial blood pressure in rats[J]. Eur J Pharmacol,2020,877:173086.
[19].Luo X,Han Z,Kong Q,et al.Clostridium butyricum?prevents dysbiosis and the rise in blood pressure in spontaneously hypertensive rats[J]. Int J Mol Sci,2023,24(5):4955.
[20].Li P,Wang H,Guo L,et al. Association between gut microbiota and preeclampsia-eclampsia:a two-sample Mendelian randomization study[J]. BMC Med,2022,20(1):443.
[21].Yang F,Chen H,Gao Y,et al. Gut microbiota-derived short-chain fatty acids and hypertension:Mechanism and treatment[J]. Biomed Pharmacother,2020,130:110503.
[22].Hu T,Wu Q,Yao Q,et al. Short-chain fatty acid metabolism and multiple effects on cardiovascular diseases[J]. Ageing Res Rev,2022,81:101706.
[23].Farook VS,Reddivari L,Chittoor G,et al. Metabolites as novel biomarkers for childhood obesity-related traits in Mexican-American children[J]. Pediatr Obes,2015,10(4):320-327.
[24].Jarrell ZR,Smith MR,Hu X,et al. Plasma acylcarnitine levels increase with healthy aging[J].?Aging(Albany NY),2020,12(13):13555-13570.
[25].Huang K,Li Z,He X,et al. Gut microbial co-metabolite 2-methylbutyrylcarnitine exacerbates thrombosis via binding to and activating integrin α2β1[J]. Cell Metab,2024,36(3):598-616.e9.

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更新日期/Last Update: 2024-12-02