Dumas, M.-E., Rothwell, A.R., Hoyles, L. et al. (15 more authors) (2017) Microbial-Host Co-metabolites Are Prodromal Markers Predicting Phenotypic Heterogeneity in Behavior, Obesity, and Impaired Glucose Tolerance. Cell Reports, 20 (1). pp. 136-148. ISSN 2211-1247
Abstract
The influence of the gut microbiome on metabolic and behavioral traits is widely accepted, though the microbiome-derived metabolites involved remain unclear. We carried out untargeted urine 1 H-NMR spectroscopy-based metabolic phenotyping in an isogenic C57BL/6J mouse population (n = 50) and show that microbial-host co-metabolites are prodromal (i.e., early) markers predicting future divergence in metabolic (obesity and glucose homeostasis) and behavioral (anxiety and activity) outcomes with 94%– 100% accuracy. Some of these metabolites also modulate disease phenotypes, best illustrated by trimethylamine-N-oxide (TMAO), a product of microbial-host co-metabolism predicting future obesity, impaired glucose tolerance (IGT), and behavior while reducing endoplasmic reticulum stress and lipogenesis in 3T3-L1 adipocytes. Chronic in vivo TMAO treatment limits IGT in HFD-fed mice and isolated pancreatic islets by increasing insulin secretion. We highlight the prodromal potential of microbial metabolites to predict disease outcomes and their potential in shaping mammalian phenotypic heterogeneity.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | natural phenotypic; variationimpaired glucose tolerance; obesity; anxiety; microbiome; metabolome; transcriptome; trimethylamine-N-oxide; TMAO; endoplasmic reticulum stress; insulin secretion |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Health and Related Research (Sheffield) > ScHARR - Sheffield Centre for Health and Related Research |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 20 Sep 2017 11:34 |
Last Modified: | 20 Sep 2017 11:34 |
Published Version: | https://doi.org/10.1016/j.celrep.2017.06.039 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.celrep.2017.06.039 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:121386 |