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The gut microbiota-related metabolite phenylacetylglutamine associates with increased risk of incident coronary artery disease

Ottosson, Filip LU ; Brunkwall, Louise LU ; Smith, Einar LU ; Orho-Melander, Marju LU ; Nilsson, Peter M. LU ; Fernandez, Céline LU and Melander, Olle LU (2020) In Journal of Hypertension 38(12). p.2427-2434
Abstract

OBJECTIVE: The gut microbiota is increasingly being implicated in cardiovascular health. Metabolites produced by bacteria have been suggested to be mediators in the bacterial action on cardiovascular health. We aimed to identify gut microbiota-related plasma metabolites and test whether these metabolites associate with future risk of coronary artery disease (CAD). METHODS: Nontargeted metabolomics was performed using liquid chromatography-mass spectrometry in order to measure 1446 metabolite features in the Malmö Offspring Study (MOS) (N = 776). The gut microbiota was characterized using 16S rRNA sequencing. Gut bacteria-related metabolites were measured in two independent prospective cohorts, the Malmö Diet and Cancer - Cardiovascular... (More)

OBJECTIVE: The gut microbiota is increasingly being implicated in cardiovascular health. Metabolites produced by bacteria have been suggested to be mediators in the bacterial action on cardiovascular health. We aimed to identify gut microbiota-related plasma metabolites and test whether these metabolites associate with future risk of coronary artery disease (CAD). METHODS: Nontargeted metabolomics was performed using liquid chromatography-mass spectrometry in order to measure 1446 metabolite features in the Malmö Offspring Study (MOS) (N = 776). The gut microbiota was characterized using 16S rRNA sequencing. Gut bacteria-related metabolites were measured in two independent prospective cohorts, the Malmö Diet and Cancer - Cardiovascular Cohort (MDC-CC) (N = 3361) and the Malmö Preventive Project (MPP) (N = 880), in order to investigate the associations between gut bacteria-related metabolites and risk of CAD. RESULTS: In MOS, 33 metabolite features were significantly (P < 4.8e-7) correlated with at least one operational taxonomic unit. Phenylacetylglutamine (PAG) was associated with an increased risk of future CAD, using inverse variance weighted meta-analysis of age and sex-adjusted logistic regression models in MDC-CC and MPP. PAG remained significantly associated with CAD (OR = 1.17, 95% CI = 1.06-1.29, P = 1.9e-3) after adjustments for cardiovascular risk factors. CONCLUSION: The levels of 33 plasma metabolites were correlated with the gut microbiota. Out of these, PAG was associated with an increased risk of future CAD independently of other cardiovascular risk factors. Our results highlight a link between the gut microbiota and CAD risk and should encourage further studies testing if modification of PAG levels inhibits development of CAD.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Hypertension
volume
38
issue
12
pages
8 pages
publisher
Lippincott Williams & Wilkins
external identifiers
  • pmid:32665522
  • scopus:85095799417
ISSN
1473-5598
DOI
10.1097/HJH.0000000000002569
language
English
LU publication?
yes
id
7a66e8ed-55bf-4d61-ba34-fead70663742
date added to LUP
2020-12-09 15:09:12
date last changed
2021-06-08 06:09:23
@article{7a66e8ed-55bf-4d61-ba34-fead70663742,
  abstract     = {<p>OBJECTIVE: The gut microbiota is increasingly being implicated in cardiovascular health. Metabolites produced by bacteria have been suggested to be mediators in the bacterial action on cardiovascular health. We aimed to identify gut microbiota-related plasma metabolites and test whether these metabolites associate with future risk of coronary artery disease (CAD). METHODS: Nontargeted metabolomics was performed using liquid chromatography-mass spectrometry in order to measure 1446 metabolite features in the Malmö Offspring Study (MOS) (N = 776). The gut microbiota was characterized using 16S rRNA sequencing. Gut bacteria-related metabolites were measured in two independent prospective cohorts, the Malmö Diet and Cancer - Cardiovascular Cohort (MDC-CC) (N = 3361) and the Malmö Preventive Project (MPP) (N = 880), in order to investigate the associations between gut bacteria-related metabolites and risk of CAD. RESULTS: In MOS, 33 metabolite features were significantly (P &lt; 4.8e-7) correlated with at least one operational taxonomic unit. Phenylacetylglutamine (PAG) was associated with an increased risk of future CAD, using inverse variance weighted meta-analysis of age and sex-adjusted logistic regression models in MDC-CC and MPP. PAG remained significantly associated with CAD (OR = 1.17, 95% CI = 1.06-1.29, P = 1.9e-3) after adjustments for cardiovascular risk factors. CONCLUSION: The levels of 33 plasma metabolites were correlated with the gut microbiota. Out of these, PAG was associated with an increased risk of future CAD independently of other cardiovascular risk factors. Our results highlight a link between the gut microbiota and CAD risk and should encourage further studies testing if modification of PAG levels inhibits development of CAD.</p>},
  author       = {Ottosson, Filip and Brunkwall, Louise and Smith, Einar and Orho-Melander, Marju and Nilsson, Peter M. and Fernandez, Céline and Melander, Olle},
  issn         = {1473-5598},
  language     = {eng},
  month        = {12},
  number       = {12},
  pages        = {2427--2434},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Hypertension},
  title        = {The gut microbiota-related metabolite phenylacetylglutamine associates with increased risk of incident coronary artery disease},
  url          = {http://dx.doi.org/10.1097/HJH.0000000000002569},
  doi          = {10.1097/HJH.0000000000002569},
  volume       = {38},
  year         = {2020},
}