Influence of the microbiome, diet and genetics on inter-individual variation in the human plasma metabolome
The levels of the thousands of metabolites in the human plasma metabolome are strongly influenced by an individual’s genetics and the composition of their diet and gut microbiome. Here, by assessing 1,183 plasma metabolites in 1,368 extensively phenotyped individuals from the Lifelines DEEP and Geno...
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| Published in: | Nature medicine Vol. 28; no. 11; pp. 2333 - 2343 |
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| Main Authors: | , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
New York
Nature Publishing Group US
01.11.2022
Nature Publishing Group |
| Subjects: | |
| ISSN: | 1078-8956, 1546-170X, 1546-170X |
| Online Access: | Get full text |
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| Abstract | The levels of the thousands of metabolites in the human plasma metabolome are strongly influenced by an individual’s genetics and the composition of their diet and gut microbiome. Here, by assessing 1,183 plasma metabolites in 1,368 extensively phenotyped individuals from the Lifelines DEEP and Genome of the Netherlands cohorts, we quantified the proportion of inter-individual variation in the plasma metabolome explained by different factors, characterizing 610, 85 and 38 metabolites as dominantly associated with diet, the gut microbiome and genetics, respectively. Moreover, a diet quality score derived from metabolite levels was significantly associated with diet quality, as assessed by a detailed food frequency questionnaire. Through Mendelian randomization and mediation analyses, we revealed putative causal relationships between diet, the gut microbiome and metabolites. For example, Mendelian randomization analyses support a potential causal effect of
Eubacterium rectale
in decreasing plasma levels of hydrogen sulfite—a toxin that affects cardiovascular function. Lastly, based on analysis of the plasma metabolome of 311 individuals at two time points separated by 4 years, we observed a positive correlation between the stability of metabolite levels and the amount of variance in the levels of that metabolite that could be explained in our analysis. Altogether, characterization of factors that explain inter-individual variation in the plasma metabolome can help design approaches for modulating diet or the gut microbiome to shape a healthy metabolome.
The influence of an individual’s genetics, diet and gut microbiome on their plasma metabolome was studied in 1,368 individuals and Mendelian randomization and mediation analyses were used to unveil causal relationships between diet, the gut microbiome and the metabolome. |
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| AbstractList | The levels of the thousands of metabolites in the human plasma metabolome are strongly influenced by an individual’s genetics and the composition of their diet and gut microbiome. Here, by assessing 1,183 plasma metabolites in 1,368 extensively phenotyped individuals from the Lifelines DEEP and Genome of the Netherlands cohorts, we quantified the proportion of inter-individual variation in the plasma metabolome explained by different factors, characterizing 610, 85 and 38 metabolites as dominantly associated with diet, the gut microbiome and genetics, respectively. Moreover, a diet quality score derived from metabolite levels was significantly associated with diet quality, as assessed by a detailed food frequency questionnaire. Through Mendelian randomization and mediation analyses, we revealed putative causal relationships between diet, the gut microbiome and metabolites. For example, Mendelian randomization analyses support a potential causal effect of
Eubacterium rectale
in decreasing plasma levels of hydrogen sulfite—a toxin that affects cardiovascular function. Lastly, based on analysis of the plasma metabolome of 311 individuals at two time points separated by 4 years, we observed a positive correlation between the stability of metabolite levels and the amount of variance in the levels of that metabolite that could be explained in our analysis. Altogether, characterization of factors that explain inter-individual variation in the plasma metabolome can help design approaches for modulating diet or the gut microbiome to shape a healthy metabolome.
The influence of an individual’s genetics, diet and gut microbiome on their plasma metabolome was studied in 1,368 individuals and Mendelian randomization and mediation analyses were used to unveil causal relationships between diet, the gut microbiome and the metabolome. The levels of the thousands of metabolites in the human plasma metabolome are strongly influenced by an individual’s genetics and the composition of their diet and gut microbiome. Here, by assessing 1,183 plasma metabolites in 1,368 extensively phenotyped individuals from the Lifelines DEEP and Genome of the Netherlands cohorts, we quantified the proportion of inter-individual variation in the plasma metabolome explained by different factors, characterizing 610, 85 and 38 metabolites as dominantly associated with diet, the gut microbiome and genetics, respectively. Moreover, a diet quality score derived from metabolite levels was significantly associated with diet quality, as assessed by a detailed food frequency questionnaire. Through Mendelian randomization and mediation analyses, we revealed putative causal relationships between diet, the gut microbiome and metabolites. For example, Mendelian randomization analyses support a potential causal effect of Eubacterium rectale in decreasing plasma levels of hydrogen sulfite—a toxin that affects cardiovascular function. Lastly, based on analysis of the plasma metabolome of 311 individuals at two time points separated by 4 years, we observed a positive correlation between the stability of metabolite levels and the amount of variance in the levels of that metabolite that could be explained in our analysis. Altogether, characterization of factors that explain inter-individual variation in the plasma metabolome can help design approaches for modulating diet or the gut microbiome to shape a healthy metabolome. The levels of the thousands of metabolites in the human plasma metabolome are strongly influenced by an individual's genetics and the composition of their diet and gut microbiome. Here, by assessing 1,183 plasma metabolites in 1,368 extensively phenotyped individuals from the Lifelines DEEP and Genome of the Netherlands cohorts, we quantified the proportion of inter-individual variation in the plasma metabolome explained by different factors, characterizing 610, 85 and 38 metabolites as dominantly associated with diet, the gut microbiome and genetics, respectively. Moreover, a diet quality score derived from metabolite levels was significantly associated with diet quality, as assessed by a detailed food frequency questionnaire. Through Mendelian randomization and mediation analyses, we revealed putative causal relationships between diet, the gut microbiome and metabolites. For example, Mendelian randomization analyses support a potential causal effect of Eubacterium rectale in decreasing plasma levels of hydrogen sulfite-a toxin that affects cardiovascular function. Lastly, based on analysis of the plasma metabolome of 311 individuals at two time points separated by 4 years, we observed a positive correlation between the stability of metabolite levels and the amount of variance in the levels of that metabolite that could be explained in our analysis. Altogether, characterization of factors that explain inter-individual variation in the plasma metabolome can help design approaches for modulating diet or the gut microbiome to shape a healthy metabolome.The levels of the thousands of metabolites in the human plasma metabolome are strongly influenced by an individual's genetics and the composition of their diet and gut microbiome. Here, by assessing 1,183 plasma metabolites in 1,368 extensively phenotyped individuals from the Lifelines DEEP and Genome of the Netherlands cohorts, we quantified the proportion of inter-individual variation in the plasma metabolome explained by different factors, characterizing 610, 85 and 38 metabolites as dominantly associated with diet, the gut microbiome and genetics, respectively. Moreover, a diet quality score derived from metabolite levels was significantly associated with diet quality, as assessed by a detailed food frequency questionnaire. Through Mendelian randomization and mediation analyses, we revealed putative causal relationships between diet, the gut microbiome and metabolites. For example, Mendelian randomization analyses support a potential causal effect of Eubacterium rectale in decreasing plasma levels of hydrogen sulfite-a toxin that affects cardiovascular function. Lastly, based on analysis of the plasma metabolome of 311 individuals at two time points separated by 4 years, we observed a positive correlation between the stability of metabolite levels and the amount of variance in the levels of that metabolite that could be explained in our analysis. Altogether, characterization of factors that explain inter-individual variation in the plasma metabolome can help design approaches for modulating diet or the gut microbiome to shape a healthy metabolome. The levels of the thousands of metabolites in the human plasma metabolome are strongly influenced by an individual's genetics and the composition of their diet and gut microbiome. Here, by assessing 1,183 plasma metabolites in 1,368 extensively phenotyped individuals from the Lifelines DEEP and Genome of the Netherlands cohorts, we quantified the proportion of inter-individual variation in the plasma metabolome explained by different factors, characterizing 610, 85 and 38 metabolites as dominantly associated with diet, the gut microbiome and genetics, respectively. Moreover, a diet quality score derived from metabolite levels was significantly associated with diet quality, as assessed by a detailed food frequency questionnaire. Through Mendelian randomization and mediation analyses, we revealed putative causal relationships between diet, the gut microbiome and metabolites. For example, Mendelian randomization analyses support a potential causal effect of Eubacterium rectale in decreasing plasma levels of hydrogen sulfite-a toxin that affects cardiovascular function. Lastly, based on analysis of the plasma metabolome of 311 individuals at two time points separated by 4 years, we observed a positive correlation between the stability of metabolite levels and the amount of variance in the levels of that metabolite that could be explained in our analysis. Altogether, characterization of factors that explain inter-individual variation in the plasma metabolome can help design approaches for modulating diet or the gut microbiome to shape a healthy metabolome. The levels of the thousands of metabolites in the human plasma metabolome are strongly influenced by an individual’s genetics and the composition of their diet and gut microbiome. Here, by assessing 1,183 plasma metabolites in 1,368 extensively phenotyped individuals from the Lifelines DEEP and Genome of the Netherlands cohorts, we quantified the proportion of inter-individual variation in the plasma metabolome explained by different factors, characterizing 610, 85 and 38 metabolites as dominantly associated with diet, the gut microbiome and genetics, respectively. Moreover, a diet quality score derived from metabolite levels was significantly associated with diet quality, as assessed by a detailed food frequency questionnaire. Through Mendelian randomization and mediation analyses, we revealed putative causal relationships between diet, the gut microbiome and metabolites. For example, Mendelian randomization analyses support a potential causal effect of Eubacterium rectale in decreasing plasma levels of hydrogen sulfite—a toxin that affects cardiovascular function. Lastly, based on analysis of the plasma metabolome of 311 individuals at two time points separated by 4 years, we observed a positive correlation between the stability of metabolite levels and the amount of variance in the levels of that metabolite that could be explained in our analysis. Altogether, characterization of factors that explain inter-individual variation in the plasma metabolome can help design approaches for modulating diet or the gut microbiome to shape a healthy metabolome. The influence of an individual’s genetics, diet and gut microbiome on their plasma metabolome was studied in 1,368 individuals and Mendelian randomization and mediation analyses were used to unveil causal relationships between diet, the gut microbiome and the metabolome. |
| Author | Wijmenga, Cisca Fu, Jingyuan Kurilshikov, Alexander Vich Vila, Arnau Augustijn, Hannah E. Weersma, Rinse K. Netea, Mihai G. Kuipers, Folkert Medema, Marnix H. Andreu-Sánchez, Sergio Zhernakova, Daria V. Zhernakova, Alexandra Chen, Lianmin Wang, Daoming |
| Author_xml | – sequence: 1 givenname: Lianmin orcidid: 0000-0003-0660-3518 surname: Chen fullname: Chen, Lianmin organization: Department of Genetics, University of Groningen, University Medical Center Groningen, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Department of Cardiology, Nanjing Medical University, The First Affiliated Hospital of Nanjing Medical University, Cardiovascular Research Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University – sequence: 2 givenname: Daria V. orcidid: 0000-0001-6531-3890 surname: Zhernakova fullname: Zhernakova, Daria V. organization: Department of Genetics, University of Groningen, University Medical Center Groningen, Laboratory of Genomic Diversity, Center for Computer Technologies, ITMO University – sequence: 3 givenname: Alexander orcidid: 0000-0003-2541-5627 surname: Kurilshikov fullname: Kurilshikov, Alexander organization: Department of Genetics, University of Groningen, University Medical Center Groningen – sequence: 4 givenname: Sergio orcidid: 0000-0002-3503-9971 surname: Andreu-Sánchez fullname: Andreu-Sánchez, Sergio organization: Department of Genetics, University of Groningen, University Medical Center Groningen, Department of Pediatrics, University of Groningen, University Medical Center Groningen – sequence: 5 givenname: Daoming orcidid: 0000-0003-4623-8527 surname: Wang fullname: Wang, Daoming organization: Department of Genetics, University of Groningen, University Medical Center Groningen – sequence: 6 givenname: Hannah E. surname: Augustijn fullname: Augustijn, Hannah E. organization: Department of Genetics, University of Groningen, University Medical Center Groningen, Bioinformatics Group, Wageningen University – sequence: 7 givenname: Arnau orcidid: 0000-0003-4691-5583 surname: Vich Vila fullname: Vich Vila, Arnau organization: Department of Genetics, University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen – sequence: 9 givenname: Rinse K. surname: Weersma fullname: Weersma, Rinse K. organization: Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen – sequence: 10 givenname: Marnix H. orcidid: 0000-0002-2191-2821 surname: Medema fullname: Medema, Marnix H. organization: Bioinformatics Group, Wageningen University – sequence: 11 givenname: Mihai G. orcidid: 0000-0003-2421-6052 surname: Netea fullname: Netea, Mihai G. organization: Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn – sequence: 12 givenname: Folkert orcidid: 0000-0003-2518-737X surname: Kuipers fullname: Kuipers, Folkert organization: Department of Pediatrics, University of Groningen, University Medical Center Groningen, European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen – sequence: 13 givenname: Cisca orcidid: 0000-0002-5635-1614 surname: Wijmenga fullname: Wijmenga, Cisca organization: Department of Genetics, University of Groningen, University Medical Center Groningen – sequence: 14 givenname: Alexandra orcidid: 0000-0002-4574-0841 surname: Zhernakova fullname: Zhernakova, Alexandra organization: Department of Genetics, University of Groningen, University Medical Center Groningen – sequence: 15 givenname: Jingyuan orcidid: 0000-0001-5578-1236 surname: Fu fullname: Fu, Jingyuan email: j.fu@umcg.nl organization: Department of Genetics, University of Groningen, University Medical Center Groningen, Department of Pediatrics, University of Groningen, University Medical Center Groningen |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36216932$$D View this record in MEDLINE/PubMed |
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| Copyright_xml | – notice: The Author(s) 2022 – notice: 2022. The Author(s). – notice: The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
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| Title | Influence of the microbiome, diet and genetics on inter-individual variation in the human plasma metabolome |
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