The fecal metabolome as a functional readout of the gut microbiome

The human gut microbiome plays a key role in human health1, but 16S characterization lacks quantitative functional annotation2. The fecal metabolome provides a functional readout of microbial activity and could be used as an intermediate phenotype mediating these interactions3. In the first comprehensive description of the fecal metabolome, examining 1116 metabolites of 786 individuals from a population-based twin study (TwinsUK), the fecal metabolome was found to be only modestly influenced by host genetics (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, illustrating potential mechanisms underlying the well-established microbial influence on abdominal obesity. Fecal metabolic profiling appears as a novel tool to explore links between microbiome composition, host phenotypes, and heritable complex traits.