Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort

Abstract

Background

The gut microbiome is a complex and metabolically active community that directly influences host phenotypes. In this study, we profile gut microbiota using 16S rRNA gene sequencing in 531 well-phenotyped Finnish men from the Metabolic Syndrome In Men (METSIM) study.

Results

We investigate gut microbiota relationships with a variety of factors that have an impact on the development of metabolic and cardiovascular traits. We identify novel associations between gut microbiota and fasting serum levels of a number of metabolites, including fatty acids, amino acids, lipids, and glucose. In particular, we detect associations with fasting plasma trimethylamine N-oxide (TMAO) levels, a gut microbiota-dependent metabolite associated with coronary artery disease and stroke. We further investigate the gut microbiota composition and microbiota–metabolite relationships in subjects with different body mass index and individuals with normal or altered oral glucose tolerance. Finally, we perform microbiota co-occurrence network analysis, which shows that certain metabolites strongly correlate with microbial community structure and that some of these correlations are specific for the pre-diabetic state.

Conclusions

Our study identifies novel relationships between the composition of the gut microbiota and circulating metabolites and provides a resource for future studies to understand host–gut microbiota relationships.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-017-1194-2) contains supplementary material, which is available to authorized users.

Contributors

Elin Org: [phone] , [e-mail]

Yuna Blum: [e-mail]

Silva Kasela: [e-mail]

Margarete Mehrabian: [e-mail]

Johanna Kuusisto: [e-mail]

Antti J. Kangas: [e-mail]

Pasi Soininen: [e-mail]

Zeneng Wang: [e-mail]

Mika Ala-Korpela: [e-mail]

Stanley L. Hazen: [e-mail]

Markku Laakso: [e-mail]

Aldons J. Lusis: [phone] , [e-mail]

Journal

Journal ID (nlm-ta): Genome Biol

Journal ID (iso-abbrev): Genome Biol

Title: Genome Biology

Publisher: BioMed Central (London )

ISSN (Print): 1474-7596

ISSN (Electronic): 1474-760X

Publication date (Electronic): 13 April 2017

Publication date PMC-release: 13 April 2017

Publication date Collection: 2017

Volume: 18

Affiliations

[1 ]GRID grid.19006.3e, Department of Medicine, , University of California, Los Angeles, ; Los Angeles, CA 90095 USA

[2 ]GRID grid.10939.32, Estonian Genome Centre, , University of Tartu, ; Tartu, 51010 Estonia

[3 ]GRID grid.10939.32, , Institute of Molecular and Cell Biology, University of Tartu, ; Tartu, 51010 Estonia

[4 ]GRID grid.9668.1, , Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, ; Kuopio, Finland

[5 ]GRID grid.410705.7, , Kuopio University Hospital, ; Kuopio, Finland

[6 ]GRID grid.10858.34, Computational Medicine, Faculty of Medicine, , University of Oulu and Biocenter Oulu, ; Oulu, Finland

[7 ]GRID grid.9668.1, NMR metabolomics Laboratory, , School of Pharmacy, University of Eastern Finland, ; Kuopio, Finland

[8 ]GRID grid.239578.2, Department of Cellular and Molecular Medicine, , Cleveland Clinic, ; Cleveland, OH 44195 USA

[9 ]GRID grid.5337.2, Computational Medicine, School of Social and Community Medicine, , University of Bristol and Medical Research Council Integrative Epidemiology Unit at the University of Bristol, ; Bristol, UK

[10 ]GRID grid.19006.3e, Department of Human Genetics, , University of California, Los Angeles, ; Los Angeles, CA 90095 USA

[11 ]GRID grid.19006.3e, Department of Microbiology, Immunology and Molecular Genetics, , University of California, Los Angeles, ; Los Angeles, CA 90095 USA

Article

Publisher ID: 1194

DOI: 10.1186/s13059-017-1194-2

PMC ID: 5390365

Copyright statement: © The Author(s). 2017

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: HL028481

Award ID: HL30568

Award ID: DK094311

Award Recipient : Aldons J. Lusis

Funded by: FundRef http://dx.doi.org/10.13039/501100004963, Seventh Framework Programme;

Award ID: FP7-MC-IOF grant no 330381

Award Recipient : Elin Org

Categories

Subject: Research

Custom metadata

issue-copyright-statement © The Author(s) 2017