期刊
CELL REPORTS
卷 20, 期 1, 页码 136-148出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.06.039
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资金
- Wellcome Trust [06678, 057733]
- European Commission [FGENTCARD LSHG-CT-2006-037683, METACARDIS HEALTH-F4-2012-305312]
- Medical Research Council [MR/L01632X/1]
- MRC Intermediate Research Fellowship in Data Science (UK MED-BIO) [MR/L01632X/1]
- Nestle [RDLS015375]
- MRC [MR/L01632X/1] Funding Source: UKRI
- Medical Research Council [MR/L01632X/1] Funding Source: researchfish
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.
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