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Microbial-Host Co-metabolites Are Prodromal Markers Predicting Phenotypic Heterogeneity in Behavior, Obesity, and Impaired Glucose Tolerance

Microbial-Host Co-metabolites Are Prodromal Markers Predicting Phenotypic Heterogeneity in Behavior, Obesity, and Impaired Glucose Tolerance

Authors :
Dumas, Marc-Emmanuel
Rothwell, Alice R.
Hoyles, Lesley
Aranias, Thomas
Chilloux, Julien
Calderari, Sophie
Noll, Elisa M.
Péan, Noémie
Boulangé, Claire L.
Blancher, Christine
Barton, Richard H.
Gu, Quan
Fearnside, Jane F.
Deshayes, Chloé
Hue, Christophe
Scott, James
Nicholson, Jeremy K.
Gauguier, Dominique
Source :
Cell Reports; July 2017, Vol. 20 Issue: 1 p136-148, 13p
Publication Year :
2017

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 1H-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.

Details

Language :
English
ISSN :
22111247
Volume :
20
Issue :
1
Database :
Supplemental Index
Journal :
Cell Reports
Publication Type :
Periodical
Accession number :
ejs42681088
Full Text :
https://doi.org/10.1016/j.celrep.2017.06.039