Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

A reference map of potential determinants for the human serum metabolome

Research output: Contribution to journalJournal articleResearchpeer-review

  1. The power of genetic diversity in genome-wide association studies of lipids

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Combinatorial, additive and dose-dependent drug–microbiome associations

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. A roadmap for the Human Developmental Cell Atlas

    Research output: Contribution to journalReviewResearchpeer-review

  4. Genetic insights into biological mechanisms governing human ovarian ageing

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Origins of SARS-CoV-2: window is closing for key scientific studies

    Research output: Contribution to journalComment/debateResearchpeer-review

  1. The power of genetic diversity in genome-wide association studies of lipids

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Combinatorial, additive and dose-dependent drug–microbiome associations

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Airway hyperresponsiveness to inhaled mannitol identifies a cluster of non-eosinophilic asthma patients with high symptom burden

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Noam Bar
  • Tal Korem
  • Omer Weissbrod
  • David Zeevi
  • Daphna Rothschild
  • Sigal Leviatan
  • Noa Kosower
  • Maya Lotan-Pompan
  • Adina Weinberger
  • Caroline I. Le Roy
  • Cristina Menni
  • Alessia Visconti
  • Mario Falchi
  • Tim D. Spector
  • Henrik Vestergaard
  • Manimozhiyan Arumugam
  • Torben Hansen
  • Kristine Allin
  • Tue Hansen
  • Mun Gwan Hong
  • Jochen Schwenk
  • Ragna Haussler
  • Matilda Dale
  • Toni Giorgino
  • Marianne Rodriquez
  • Mandy Perry
  • Rachel Nice
  • Timothy McDonald
  • Andrew Hattersley
  • Angus Jones
  • Ulrike Graefe-Mody
  • Patrick Baum
  • Rolf Grempler
  • Cecilia Engel Thomas
  • Federico De Masi
  • Caroline Anna Brorsson
  • Gianluca Mazzoni
  • Rosa Allesøe
  • Simon Rasmussen
  • Valborg Gudmundsdóttir
  • Agnes Martine Nielsen
  • Karina Banasik
  • Konstantinos Tsirigos
  • Birgitte Nilsson
  • Helle Pedersen
  • Søren Brunak
  • Tugce Karaderi
  • Agnete Troen Lundgaard
  • Martin Ridderstråle
  • Line Engelbrechtsen
  • The IMI DIRECT consortium
View graph of relations

The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.

Original languageEnglish
JournalNature
Volume588
Issue number7836
Pages (from-to)135-140
Number of pages6
ISSN0028-0836
DOIs
Publication statusPublished - 3 Dec 2020

Bibliographical note

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.

ID: 69062233