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Connection between BMI-Related Plasma Metabolite Profile and Gut Microbiota

Ottosson, Filip LU ; Brunkwall, Louise LU ; Ericson, Ulrika LU ; Nilsson, Peter M. LU ; Almgren, Peter LU ; Fernandez, Céline LU ; Melander, Olle LU orcid and Orho-Melander, Marju LU (2018) In Journal of Clinical Endocrinology and Metabolism 103(4). p.1491-1501
Abstract

Context Emerging evidence has related the gut microbiome and circulating metabolites to human obesity. Gut microbiota is responsible for several metabolic functions, and altered plasma metabolome might reflect differences in the gut microbiome. Objective To identify a plasma metabolite profile associated with body mass index (BMI) in a general population and investigate whether such metabolite profile is associated with distinct composition of the gut microbiota. Design Targeted profiling of 48 plasma metabolites was performed in a population of 920 Swedish adults (mean age, 39 years; 53% women) from the ongoing Malmö Offspring Study using targeted liquid chromatography-mass spectrometry. Gut microbiota was analyzed by sequencing the... (More)

Context Emerging evidence has related the gut microbiome and circulating metabolites to human obesity. Gut microbiota is responsible for several metabolic functions, and altered plasma metabolome might reflect differences in the gut microbiome. Objective To identify a plasma metabolite profile associated with body mass index (BMI) in a general population and investigate whether such metabolite profile is associated with distinct composition of the gut microbiota. Design Targeted profiling of 48 plasma metabolites was performed in a population of 920 Swedish adults (mean age, 39 years; 53% women) from the ongoing Malmö Offspring Study using targeted liquid chromatography-mass spectrometry. Gut microbiota was analyzed by sequencing the 16S ribosomal RNA gene (V1-V3 region) in fecal samples of 674 study participants. Results BMI was associated with 19 metabolites (P < 0.001 for all), of which glutamate provided the strongest direct association (P = 5.2e-53). By orthogonal partial least squares regression, a metabolite principal component predictive of BMI was constructed (PC BMI). In addition to glutamate, PC BMI was dominated by branched-chain amino acids (BCAAs) and related metabolites. Four gut microbiota genera (Blautia, Dorea, Ruminococcus, and SHA-98) were associated with both BMI and PC BMI (P < 8.0e-4 for all). When simultaneously regressing PC BMI and metabolite-associated gut bacteria against BMI, only PC BMI remained statistically significant. Conclusions We discovered associations between four gut microbiota genera (Blautia, Dorea, Ruminococcus, and SHA-98) and BMI-predictive plasma metabolites, including glutamate and BCAAs. Thus, these metabolites could be mediators between gut microbiota and obesity, pointing to potential future opportunities for targeting the gut microbiota in prevention of obesity.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Endocrinology and Metabolism
volume
103
issue
4
pages
11 pages
publisher
Oxford University Press
external identifiers
  • pmid:29409054
  • scopus:85045473744
ISSN
0021-972X
DOI
10.1210/jc.2017-02114
language
English
LU publication?
yes
id
2a36c1bf-9bb3-4633-b6e3-083ca1ce9d2c
date added to LUP
2018-04-26 14:42:30
date last changed
2024-04-15 06:06:38
@article{2a36c1bf-9bb3-4633-b6e3-083ca1ce9d2c,
  abstract     = {{<p>Context Emerging evidence has related the gut microbiome and circulating metabolites to human obesity. Gut microbiota is responsible for several metabolic functions, and altered plasma metabolome might reflect differences in the gut microbiome. Objective To identify a plasma metabolite profile associated with body mass index (BMI) in a general population and investigate whether such metabolite profile is associated with distinct composition of the gut microbiota. Design Targeted profiling of 48 plasma metabolites was performed in a population of 920 Swedish adults (mean age, 39 years; 53% women) from the ongoing Malmö Offspring Study using targeted liquid chromatography-mass spectrometry. Gut microbiota was analyzed by sequencing the 16S ribosomal RNA gene (V1-V3 region) in fecal samples of 674 study participants. Results BMI was associated with 19 metabolites (P &lt; 0.001 for all), of which glutamate provided the strongest direct association (P = 5.2e-53). By orthogonal partial least squares regression, a metabolite principal component predictive of BMI was constructed (PC BMI). In addition to glutamate, PC BMI was dominated by branched-chain amino acids (BCAAs) and related metabolites. Four gut microbiota genera (Blautia, Dorea, Ruminococcus, and SHA-98) were associated with both BMI and PC BMI (P &lt; 8.0e-4 for all). When simultaneously regressing PC BMI and metabolite-associated gut bacteria against BMI, only PC BMI remained statistically significant. Conclusions We discovered associations between four gut microbiota genera (Blautia, Dorea, Ruminococcus, and SHA-98) and BMI-predictive plasma metabolites, including glutamate and BCAAs. Thus, these metabolites could be mediators between gut microbiota and obesity, pointing to potential future opportunities for targeting the gut microbiota in prevention of obesity.</p>}},
  author       = {{Ottosson, Filip and Brunkwall, Louise and Ericson, Ulrika and Nilsson, Peter M. and Almgren, Peter and Fernandez, Céline and Melander, Olle and Orho-Melander, Marju}},
  issn         = {{0021-972X}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{4}},
  pages        = {{1491--1501}},
  publisher    = {{Oxford University Press}},
  series       = {{Journal of Clinical Endocrinology and Metabolism}},
  title        = {{Connection between BMI-Related Plasma Metabolite Profile and Gut Microbiota}},
  url          = {{http://dx.doi.org/10.1210/jc.2017-02114}},
  doi          = {{10.1210/jc.2017-02114}},
  volume       = {{103}},
  year         = {{2018}},
}