학술논문
Microbial-Host Co-metabolites Are Prodromal Markers Predicting Phenotypic Heterogeneity in Behavior, Obesity, and Impaired Glucose Tolerance
Document Type
article
Author
Marc-Emmanuel Dumas; Alice R. Rothwell; Lesley Hoyles; Thomas Aranias; Julien Chilloux; Sophie Calderari; Elisa M. Noll; Noémie Péan; Claire L. Boulangé; Christine Blancher; Richard H. Barton; Quan Gu; Jane F. Fearnside; Chloé Deshayes; Christophe Hue; James Scott; Jeremy K. Nicholson; Dominique Gauguier
Source
Cell Reports, Vol 20, Iss 1, Pp 136-148 (2017)
Subject
Language
English
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 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.