Xenometabolite signatures in the UC Davis type 2 diabetes mellitus rat model revealed using a metabolomics platform enriched with microbe-derived metabolites.
diabetes
metabolomics
microbiota
xenometabolites
Journal
American journal of physiology. Gastrointestinal and liver physiology
ISSN: 1522-1547
Titre abrégé: Am J Physiol Gastrointest Liver Physiol
Pays: United States
ID NLM: 100901227
Informations de publication
Date de publication:
01 08 2020
01 08 2020
Historique:
pubmed:
9
6
2020
medline:
21
10
2020
entrez:
9
6
2020
Statut:
ppublish
Résumé
The gut microbiome has the potential to create or modify xenometabolites (i.e., nonhost-derived metabolites) through de novo synthesis or modification of exogenous and endogenous compounds. While there are isolated examples of xenometabolites influencing host health and disease, wide-scale characterization of these metabolites remains limited. We developed a metabolomics platform ("XenoScan") using liquid chromatography-mass spectrometry to characterize a range of known and suspected xenometabolites and their derivatives. This assay currently applies authentic standards for 190 molecules, enriched for metabolites of microbial origin. As a proof-of-principle, we characterized the cecal content xenometabolomics profile in adult male lean Sprague-Dawley (LSD) and University of California, Davis type 2 diabetes mellitus (UCD-T2DM) rats at different stages of diabetes. These results were correlated to specific bacterial species generated via shotgun metagenomic sequencing. UCD-T2DM rats had a unique xenometabolite profile compared with LSD rats, regardless of diabetes status, suggesting that at least some of the variation is associated with host genetics. Furthermore, modeling approaches revealed that several xenometabolites discriminated UCD-T2DM rats at early stages of diabetes versus those at 3 mo postdiabetes onset. Several xenometabolite hubs correlated with specific bacterial species in both LSD and UCD-T2DM rats. For example, indole-3-propionic acid negatively correlated with species within the
Identifiants
pubmed: 32508155
doi: 10.1152/ajpgi.00105.2020
pmc: PMC7500265
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
G157-G169Subventions
Organisme : HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ID : RC1DK087307
Pays : International
Organisme : U.S. Department of Agriculture (USDA)
ID : 6026-51000-010-05S
Pays : International
Organisme : NHLBI NIH HHS
ID : R01 HL121324
Pays : United States
Organisme : HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)
ID : R01HL107256
Pays : International
Organisme : HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ID : R01DK095060
Pays : International
Organisme : HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ID : U24DK092933
Pays : International
Organisme : HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)
ID : R01HL091333
Pays : International
Organisme : HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)
ID : RO1HL121324
Pays : International
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