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

Dumas, M.-E. et al. (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. (doi: 10.1016/j.celrep.2017.06.039) (PMID:28683308)

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.

• Item Type: Articles
• Additional Information: This work was supported by grants from the Wellcome Trust (Functional Genomics Initiative grant Biological Atlas of Insulin Resistance 06678), the European Commission (FGENTCARD LSHG-CT-2006-037683 and METACARDIS HEALTH-F4- 2012-305312), and a Wellcome Trust Senior Fellowship in Basic Biomedical Science (057733) to D.G. This work used the computing resources of the UK MEDical BIOinformatics partnership—aggregation, integration, visualization, and analysis of large, complex data (UK MED-BIO), which is supported by the Medical Research Council (MR/L01632X/1). L.H. is in receipt of an MRC Intermediate Research Fellowship in Data Science (MR/L01632X/1, UK MED-BIO). C.L.B. was funded by Nestle´ (RDLS015375).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gu, Dr Quan
• Authors: 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.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Cell Reports
• Publisher: Elsevier (Cell Press)
• ISSN: 2211-1247
• ISSN (Online): 2211-1247
• Published Online: 05 July 2017
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Cell Reports 20(1): 136-148
• Publisher Policy: Reproduced under a Creative Commons license