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The fecal metabolome as a functional readout of the gut microbiome

Research output: Contribution to journalArticle

Jonas Zierer, Matthew A Jackson, Gabi Kastenmüller, Massimo Mangino, Tao Long, Amalio Telenti, Robert P Mohney, Kerrin S Small, Jordana T Bell, Claire J Steves, Ana M Valdes, Tim D Spector, Cristina Menni

Original languageEnglish
Pages (from-to)790-795
JournalNature Genetics
Volume50
Early online date28 May 2018
DOIs
Publication statusE-pub ahead of print - 28 May 2018

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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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