Exploration of the microbiota and metabolites within body fluids could pinpoint novel disease mechanisms

Thanks to the emergence and recent advances in high‐throughput sequencing technologies, it is becoming more evident every day that changes in the microbiome composition are linked to a myriad of health conditions. Despite this, the mechanisms of host–microbiota signalling remain largely unknown. The microbiome has an extensive metabolic activity that leads to the generation of a large number of compounds that are likely to influence host health. Therefore, the microbiome–host cross‐talk is in part mediated by microbial‐derived metabolites. Unlike metagenomics, which only provides information about microbial genes and thus the microbiome functional potential, metabolic phenotyping is well suited to capture their actual metabolic activity. Here, we provide an overview of these approaches and propose an integration of metagenomics, as a microbiome compositional readout, with faecal and plasma/urine metabolomics, as a functional readout, to unravel novel mechanisms linking the microbiome to host health and disease.