Gut Microbial Associations to Plasma Metabolites Linked to Cardiovascular Phenotypes and Risk

Author:

Kurilshikov Alexander1,van den Munckhof Inge C.L.2,Chen Lianmin13,Bonder Marc J.1,Schraa Kiki2,Rutten Joost H.W.2,Riksen Niels P.2,de Graaf Jacqueline2,Oosting Marije2,Sanna Serena1,Joosten Leo A.B.2,van der Graaf Marinette4,Brand Tessa2,Koonen Debby P.Y.3,van Faassen Martijn5,Slagboom P. Eline6,Xavier Ramnik J.78910,Kuipers Folkert35,Hofker Marten H.3,Wijmenga Cisca111,Netea Mihai G.21213,Zhernakova Alexandra1,Fu Jingyuan13,

Affiliation:

1. From the Department of Genetics (A.K., L.C., M.J.B., S.S., C.W., A.Z., J.F.), University of Groningen, University Medical Center Groningen, the Netherlands

2. Department of Internal Medicine and Radboud Center for Infectious Diseases (I.C.L.v.d.M., K.S., J.H.W.R., N.P.R., J.d.G., M.O., L.A.B.J., T.B., M.G.N.), Radboud University Medical Center, Nijmegen, the Netherlands

3. Department of Pediatrics (L.C., D.P.Y.K., F.K., M.H.H., J.F.), University of Groningen, University Medical Center Groningen, the Netherlands

4. Department of Radiology and Nuclear Medicine (M.v.d.G.), Radboud University Medical Center, Nijmegen, the Netherlands

5. Department of Laboratory Medicine (M.v.F., F.K.), University of Groningen, University Medical Center Groningen, the Netherlands

6. Section of Molecular Epidemiology, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, the Netherlands (P.E.S.)

7. Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston (R.J.X.)

8. Broad Institute of MIT and Harvard, Cambridge, MA (R.J.X.)

9. Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Harvard Medical School, Boston (R.J.X.)

10. Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge (R.J.X.)

11. Department of Immunology, K.G. Jebsen Coeliac Disease Research Centre, University of Oslo, Norway (C.W.)

12. Department for Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Germany (M.G.N.)

13. Human Genomics Laboratory, Craiova University of Medicine and Pharmacy, Romania (M.G.N.).

Abstract

Rationale: Altered gut microbial composition has been linked to cardiovascular diseases (CVDs), but its functional links to host metabolism and immunity in relation to CVD development remain unclear. Objectives: To systematically assess functional links between the microbiome and the plasma metabolome, cardiometabolic phenotypes, and CVD risk and to identify diet-microbe-metabolism-immune interactions in well-documented cohorts. Methods and Results: We assessed metagenomics-based microbial associations between 231 plasma metabolites and microbial species and pathways in the population-based LLD (Lifelines DEEP) cohort (n=978) and a clinical obesity cohort (n=297). After correcting for age, sex, and body mass index, the gut microbiome could explain ≤11.1% and 16.4% of the variation in plasma metabolites in the population-based and obesity cohorts, respectively. Obese-specific microbial associations were found for lipid compositions in the VLDL, IDL, and LDL lipoprotein subclasses. Bacterial L-methionine biosynthesis and a Ruminococcus species were associated to cardiovascular phenotypes in obese individuals, namely atherosclerosis and liver fat content, respectively. Integration of microbiome-diet-inflammation analysis in relation to metabolic risk score of CVD in the population cohort revealed 48 microbial pathways associated to CVD risk that were largely independent of diet and inflammation. Our data also showed that plasma levels rather than fecal levels of short-chain fatty acids were relevant to inflammation and CVD risk. Conclusions: This study presents the largest metagenome-based association study on plasma metabolism and microbiome relevance to diet, inflammation, CVD risk, and cardiometabolic phenotypes in both population-based and clinical obesity cohorts. Our findings identified novel bacterial species and pathways that associated to specific lipoprotein subclasses and revealed functional links between the gut microbiome and host health that provide a basis for developing microbiome-targeted therapy for disease prevention and treatment.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine,Physiology

Cited by 146 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3