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

Dumas, M-E, Rothwell, AR, Hoyles, L ORCID: https://orcid.org/0000-0002-6418-342X, Aranias, T, Chilloux, J, Calderari, S, Noll, EM, Péan, N, Boulangé, CL, Blancher, C, Barton, RH, Gu, Q, Fearnside, JF, Deshayes, C, Hue, C, Scott, J, Nicholson, JK and Gauguier, D, 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

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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.

Item Type:	Journal article
Publication Title:	Cell Reports
Creators:	Dumas, M.-E., Rothwell, A.R., Hoyles, L., Aranias, T., Chilloux, J., Calderari, S., Noll, E.M., Péan, N., Boulangé, C.L., Blancher, C., Barton, R.H., Gu, Q., Fearnside, J.F., Deshayes, C., Hue, C., Scott, J., Nicholson, J.K. and Gauguier, D.
Publisher:	Cell Press
Date:	5 July 2017
Volume:	20
Number:	1
ISSN:	2211-1247
Identifiers:	Number Type 10.1016/j.celrep.2017.06.039 DOI S2211124717308537 Publisher Item Identifier
Rights:	© 2017 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Divisions:	Schools > School of Science and Technology
Record created by:	Jill Tomkinson
Date Added:	09 Aug 2018 11:03
Last Modified:	09 Aug 2018 11:05
URI:	https://irep.ntu.ac.uk/id/eprint/34299

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