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Background  Untargeted metabolomics of host-associated samples has yielded insights into mechanisms by which microbes modulate health. However, data interpretation is challenged by the complexity of origins of the small molecules measured, which can come from the host, microbes that live within the host, or from other exposures such as diet or the environment.    Results  We address this challenge through development of AMON: Annotation of Metabolite Origins via Networks. AMON is an open-source bioinformatics application that can be used to annotate which compounds in the metabolome could have been produced by bacteria present or the host, to evaluate pathway enrichment of host verses microbial metabolites, and to visualize which compounds may have been produced by host versus microbial enzymes in KEGG pathway maps.    Conclusions  AMON empowers researchers to predict origins of metabolites via genomic information and to visualize potential host:microbe interplay. Additionally, the evaluation of enrichment of pathway metabolites of host versus microbial origin gives insight into the metabolic functionality that a microbial community adds to a host:microbe system. Through integrated analysis of microbiome and metabolome data, mechanistic relationships between microbial communities and host phenotypes can be better understood.

AMON: annotation of metabolite origins via networks to integrate microbiome and metabolome data