The fecal metabolome as a functional readout of the gut microbiome
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, 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
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.
Conflict of interest statement
Competing financial interests
RPM is employee of Metabolon, Inc. TL and AT were employees of HLI, Inc. at the time this work was conducted. TDS is co-founder of MapMyGut Ltd. All other authors declare no competing financial interests.
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References
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