PT - JOURNAL ARTICLE AU - Justin P. Shaffer AU - Louis-Félix Nothias AU - Luke R. Thompson AU - Jon G. Sanders AU - Rodolfo A. Salido AU - Sneha P. Couvillion AU - Asker D. Brejnrod AU - Shi Huang AU - Franck Lejzerowicz AU - Holly L. Lutz AU - Qiyun Zhu AU - Cameron Martino AU - James T. Morton AU - Smruthi Karthikeyan AU - Mélissa Nothias-Esposito AU - Kai Dührkop AU - Sebastian Böcker AU - Hyunwoo Kim AU - Alexander A. Aksenov AU - Wout Bittremieux AU - Jeremiah J. Minich AU - Clarisse Marotz AU - MacKenzie M. Bryant AU - Karenina Sanders AU - Tara Schwartz AU - Greg Humphrey AU - Yoshiki Vásquez-Baeza AU - Anupriya Tripathi AU - Laxmi Parida AU - Anna Paola Carrieri AU - Niina Haiminen AU - Kristen L. Beck AU - Promi Das AU - Antonio González AU - Daniel McDonald AU - Søren M. Karst AU - Mads Albertsen AU - Gail Ackermann AU - Jeff DeReus AU - Torsten Thomas AU - Daniel Petras AU - Ashley Shade AU - James Stegen AU - Se Jin Song AU - Thomas O. Metz AU - Austin D. Swafford AU - Pieter C. Dorrestein AU - Janet K. Jansson AU - Jack A. Gilbert AU - Rob Knight AU - the Earth Microbiome Project 500 (EMP500) Consortium TI - Multi-omics profiling of Earth’s biomes reveals that microbial and metabolite composition are shaped by the environment AID - 10.1101/2021.06.04.446988 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.06.04.446988 4099 - http://biorxiv.org/content/early/2021/06/06/2021.06.04.446988.short 4100 - http://biorxiv.org/content/early/2021/06/06/2021.06.04.446988.full AB - Microbes produce an array of secondary metabolites that perform diverse functions from communication to defense1. These metabolites have been used to benefit human health and sustainability2. In their analysis of the Genomes from Earth’s Microbiomes (GEM) catalog3, Nayfach and co-authors observed that, whereas genes coding for certain classes of secondary metabolites are limited or enriched in certain microbial taxa, “specific chemistry is not limited or amplified by the environment, and that most classes of secondary metabolites can be found nearly anywhere”. Although metagenome mining is a powerful way to annotate biosynthetic gene clusters (BCGs), chemical evidence is required to confirm the presence of metabolites and comprehensively address this fundamental hypothesis, as metagenomic data only identify metabolic potential. To describe the Earth’s metabolome, we use an integrated omics approach: the direct survey of metabolites associated with microbial communities spanning diverse environments using untargeted metabolomics coupled with metagenome analysis. We show, in contrast to Nayfach and co-authors, that the presence of certain classes of secondary metabolites can be limited or amplified by the environment. Importantly, our data indicate that considering the relative abundances of secondary metabolites (i.e., rather than only presence/absence) strengthens differences in metabolite profiles across environments, and that their richness and composition in any given sample do not directly reflect those of co-occurring microbial communities, but rather vary with the environment.Competing Interest StatementS.B. and K.D. are co-founders of Bright Giant GmbH.