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Microbial-host co-metabolites are prodromal markers predicting phenotypic heterogeneity in behavior, obesity and impaired glucose tolerance

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Title: Microbial-host co-metabolites are prodromal markers predicting phenotypic heterogeneity in behavior, obesity and impaired glucose tolerance
Authors: Dumas, M
Rothwell, AR
Hoyles, L
Aranias, T
Chilloux, J
Calderari, S
Noll, EM
Péan, N
Boulange, CL
Blancher, C
Barton, RH
Gu, Q
Fearnside, JF
Deshayes, C
Hue, C
Scott, J
Nicholson, JK
Gauguier, D
Item Type: Journal Article
Abstract: The influence of the gut microbiome on metabolic and behavioral traits is now 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 behaviorial (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, whilst 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.
Issue Date: 5-Jul-2017
Date of Acceptance: 13-Jun-2017
URI: http://hdl.handle.net/10044/1/49234
DOI: https://dx.doi.org/10.1016/j.celrep.2017.06.039
ISSN: 2211-1247
Publisher: Elsevier (Cell Press)
Start Page: 136
End Page: 148
Journal / Book Title: Cell Reports
Volume: 20
Issue: 1
Copyright Statement: © 2017 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Sponsor/Funder: Wellcome Trust
Commission of the European Communities
Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: 066786/A/02/Z
305312
MR/L01632X/1
MR/L01632X/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
TRIMETHYLAMINE-N-OXIDE
HUMAN GUT MICROBIOME
HIGH-FAT DIET
ENDOPLASMIC-RETICULUM STRESS
CONTAINING MONOOXYGENASE 3
UNFOLDED PROTEIN RESPONSE
INSULIN-RESISTANT MICE
L-CARNITINE
BACTERIAL METABOLITES
CHEMICAL CHAPERONES
TMAO
anxiety
endoplasmic reticulum stress
impaired glucose tolerance
insulin secretion
metabolome
microbiome
natural phenotypic variation
obesity
transcriptome
trimethylamine-N-oxide
Publication Status: Published
Appears in Collections:Division of Surgery
Faculty of Medicine



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