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Dumas, M.-E., Rothwell, A.R., Hoyles, L. 
ORCID: 0000-0002-6418-342X, 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.,
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 | ||||||
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| 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 | ||||||
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| 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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