Microbial-Host Co-metabolites Are Prodromal Markers Predicting Phenotypic Heterogeneity in Behavior, Obesity, and Impaired Glucose Tolerance

被引：79

作者：

Dumas, Marc-Emmanuel ^{[1
]}

Rothwell, Alice R. ^{[2
]}

Hoyles, Lesley ^{[1
]}

Aranias, Thomas ^{[3
,4
]}

Chilloux, Julien ^{[1
]}

Calderari, Sophie ^{[3
,4
]}

Noll, Elisa M. ^{[1
]}

Pean, Noemie ^{[3
,4
]}

Boulange, Claire L. ^{[1
]}

Blancher, Christine ^{[2
]}

Barton, Richard H. ^{[1
]}

Gu, Quan ^{[1
]}

Fearnside, Jane F. ^{[2
]}

Deshayes, Chloe ^{[1
]}

Hue, Christophe ^{[3
,4
]}

Scott, James ^{[5
]}

Nicholson, Jeremy K. ^{[1
]}

Gauguier, Dominique ^{[1
,2
,3
,4
]}

机构：

[1] Imperial Coll London, Div Computat & Syst Med, Dept Surg & Canc, Fac Med, Sir Alexander Fleming Bldg,Exhibit Rd, London SW7 2AZ, England

[2] Univ Oxford, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England

[3] Univ Paris 06, INSERM, UMR S 1138, Cordeliers Res Ctr, 15 Rue Ecole Med, F-75084 Paris, France

[4] Sorbonne Univ, Sorbonne Paris Cite, Univ Paris Descartes, 15 Rue Ecole Med, F-75084 Paris, France

[5] Imperial Coll London, Dept Med, Du Cane Rd, London W12 0NN, England

来源：

CELL REPORTS | 2017年 / 20卷 / 01期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

TRIMETHYLAMINE-N-OXIDE; ENDOPLASMIC-RETICULUM STRESS; CONTAINING MONOOXYGENASE 3; UNFOLDED PROTEIN RESPONSE; HIGH-FAT DIET; GUT MICROBIOTA; L-CARNITINE; BACTERIAL METABOLITES; MOUSE MODEL; GENE;

D O I：

10.1016/j.celrep.2017.06.039

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 H-1-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.

引用

页码：136 / 148

页数：13

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