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      The gut microbiome in atherosclerotic cardiovascular disease

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      Nature Communications
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          Abstract

          The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular health. Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort. We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.

          Abstract

          The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease.

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          Most cited references15

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Human metabolic phenotype diversity and its association with diet and blood pressure.

            Metabolic phenotypes are the products of interactions among a variety of factors-dietary, other lifestyle/environmental, gut microbial and genetic. We use a large-scale exploratory analytical approach to investigate metabolic phenotype variation across and within four human populations, based on 1H NMR spectroscopy. Metabolites discriminating across populations are then linked to data for individuals on blood pressure, a major risk factor for coronary heart disease and stroke (leading causes of mortality worldwide). We analyse spectra from two 24-hour urine specimens for each of 4,630 participants from the INTERMAP epidemiological study, involving 17 population samples aged 40-59 in China, Japan, UK and USA. We show that urinary metabolite excretion patterns for East Asian and western population samples, with contrasting diets, diet-related major risk factors, and coronary heart disease/stroke rates, are significantly differentiated (P < 10(-16)), as are Chinese/Japanese metabolic phenotypes, and subgroups with differences in dietary vegetable/animal protein and blood pressure. Among discriminatory metabolites, we quantify four and show association (P < 0.05 to P < 0.0001) of mean 24-hour urinary formate excretion with blood pressure in multiple regression analyses for individuals. Mean 24-hour urinary excretion of alanine (direct) and hippurate (inverse), reflecting diet and gut microbial activities, are also associated with blood pressure of individuals. Metabolic phenotyping applied to high-quality epidemiological data offers the potential to develop an area of aetiopathogenetic knowledge involving discovery of novel biomarkers related to cardiovascular disease risk.
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              A Sparse-Group Lasso

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                Author and article information

                Contributors
                jiahuijue@genomics.cn
                hekl301@aliyun.com
                kk@bio.ku.dk
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                10 October 2017
                10 October 2017
                2017
                : 8
                : 845
                Affiliations
                [1 ]ISNI 0000 0001 2034 1839, GRID grid.21155.32, BGI-Shenzhen, ; Shenzhen, 518083 China
                [2 ]China National Genebank, Shenzhen, 518120 China
                [3 ]ISNI 0000 0001 2034 1839, GRID grid.21155.32, Shenzhen Key Laboratory of Human Commensal Microorganisms and Health Research, BGI-Shenzhen, ; Shenzhen, 518083 China
                [4 ]ISNI 0000 0004 1760 3705, GRID grid.413352.2, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, , Guangdong Cardiovascular Institute, ; Guangzhou, 510080 China
                [5 ]GRID grid.410643.4, Medical Research Center of Guangdong General Hospital, , Guangdong Academy of Medical Sciences, ; Guangzhou, 510080 China
                [6 ]Shenzhen Engineering Laboratory of Detection and Intervention of Human Intestinal Microbiome, Shenzhen, 518083 China
                [7 ]ISNI 0000 0001 0674 042X, GRID grid.5254.6, Department of Biology, Laboratory of Genomics and Molecular Biomedicine, , University of Copenhagen, ; Universitetsparken 13, 2100 Copenhagen, Denmark
                [8 ]BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, 518083 China
                [9 ]ISNI 0000 0004 1764 3838, GRID grid.79703.3a, School of Bioscience and Biotechnology, , South China University of Technology, ; Guangzhou, 510006 China
                [10 ]ISNI 0000 0004 1761 8894, GRID grid.414252.4, Beijing Key Laboratory for Precision Medicine of Chronic Heart Failure, , Chinese PLA General Hospital, ; Beijing, 100853 China
                [11 ]James D. Watson Institute of Genome Sciences, Hangzhou, 310000 China
                [12 ]Macau University of Science and Technology, Macau, 999078 China
                [13 ]ISNI 0000 0000 9889 6335, GRID grid.413106.1, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, , Chinese Academy of Medical Sciences and Peking Union Medical College, ; Beijing, 100730 China
                [14 ]ISNI 0000 0004 0428 2404, GRID grid.419612.9, National Institute of Nutrition and Seafood Research, (NIFES), ; Postboks 2029, Nordnes, N-5817 Bergen, Norway
                [15 ]ISNI 0000 0001 2181 8870, GRID grid.5170.3, Department of Biotechnology and Biomedicine, , Technical University of Denmark (DTU), ; 2800 Kongens Lyngby, Denmark
                [16 ]ISNI 0000 0004 0368 8293, GRID grid.16821.3c, Department of Endocrinology and Metabolism, State Key Laboratory of Medical Genomes, National Clinical Research Center for Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, , Shanghai Jiao Tong University School of Medicine, ; Shanghai, 200025 China
                [17 ]Department of Human Microbiome, School of Stomatology, Shandong University, Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, 250012 China
                [18 ]ISNI 0000 0001 2355 7002, GRID grid.4367.6, Present Address: Center for Genome Sciences & Systems Biology, , Washington University School of Medicine, St. Louis, ; MO, 63110 USA
                [19 ]iCarbonX, Shenzhen, 518053 China
                Author information
                http://orcid.org/0000-0001-9512-1750
                http://orcid.org/0000-0001-6784-1873
                http://orcid.org/0000-0003-2261-3150
                http://orcid.org/0000-0001-8775-1699
                http://orcid.org/0000-0003-4468-1947
                http://orcid.org/0000-0001-8951-6705
                http://orcid.org/0000-0003-3256-2940
                http://orcid.org/0000-0002-0420-0726
                http://orcid.org/0000-0002-3592-126X
                Article
                900
                10.1038/s41467-017-00900-1
                5635030
                29018189
                f78ba82c-96f4-4d7f-a57f-d89ec47288cd
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 9 February 2017
                : 2 August 2017
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