Microbiome-associated metabolite pools aid discovery of novel functions.

Guilt-by-association approaches identify microbial derivatives of standard metabolites.

Machine learning approaches predict metabolites from metagenomes.

Computational and in vitro tools are emerging to study chemically mediated roles of the microbiome.

The metabolome lies at the interface of host–microbiome crosstalk. Previous work has established links between chemically diverse microbial metabolites and a myriad of host physiological processes and diseases. Coupled with scalable and cost-effective technologies, metabolomics is thus gaining popularity as a tool for characterization of microbial communities, particularly when combined with metagenomics as a window into microbiome function. A systematic interrogation of microbial community metabolomes can uncover key microbial compounds, metabolic capabilities of the microbiome, and also provide critical mechanistic insights into microbiome-linked host phenotypes. In this review, we discuss methods and accompanying resources that have been developed for these purposes. The accomplishments of these methods demonstrate that metabolomes can be used to functionally characterize microbial communities, and that microbial properties can be used to identify and investigate chemical compounds.

© 2022 Published by Elsevier Ltd.