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Nat Genet. 2018 Jun;50(6):790-795. doi: 10.1038/s41588-018-0135-7. Epub 2018 May 28.

The fecal metabolome as a functional readout of the gut microbiome.

Author information

1
Department for Twin Research & Genetic Epidemiology, King's College London, London, UK.
2
Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
3
Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY, USA.
4
NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London, UK.
5
Human Longevity, Inc, San Diego, CA, USA.
6
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
7
Metabolon, Inc, Durham, NC, USA.
8
NIHR Nottingham Biomedical Research Centre, Nottingham, UK.
9
School of Medicine, University of Nottingham, Nottingham, UK.
10
Department for Twin Research & Genetic Epidemiology, King's College London, London, UK. tim.spector@kcl.ac.uk.
11
Department for Twin Research & Genetic Epidemiology, King's College London, London, UK. cristina.menni@kcl.ac.uk.

Abstract

The human gut microbiome plays a key role in human health 1 , but 16S characterization lacks quantitative functional annotation 2 . The fecal metabolome provides a functional readout of microbial activity and can be used as an intermediate phenotype mediating host-microbiome interactions 3 . In this comprehensive description of the fecal metabolome, examining 1,116 metabolites from 786 individuals from a population-based twin study (TwinsUK), the fecal metabolome was found to be only modestly influenced by host genetics (heritability (H2) = 17.9%). One replicated locus at the NAT2 gene was associated with fecal metabolic traits. The fecal metabolome largely reflects gut microbial composition, explaining on average 67.7% (±18.8%) of its variance. It is strongly associated with visceral-fat mass, thereby illustrating potential mechanisms underlying the well-established microbial influence on abdominal obesity. Fecal metabolic profiling thus is a novel tool to explore links among microbiome composition, host phenotypes, and heritable complex traits.

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