The international Human Microbiome Project [1,2] trumpeted the coming of age of the field of metagenomics, the study of entire communities of microbes and their contributions to health and disease. Metagenomic analyses are most often undertaken by sequencing the bacterial 16S ribosomal RNA (rRNA) subunit or by whole metagenome shotgun sequencing, typically on a massively parallel pyrosequencing platform. These technologies have expanded the scope of traditional culture-dependent microbiological methods and have enhanced our understanding of the rich microbial communities that inhabit the intestine, skin, oral cavity, and genitourinary tract and how these commensal microbes interact with both pathogen and host.
In parallel, the field of metabolomics emerged as the systematic, nonbiased analysis of all low-molecular-weight small molecules, or metabolites, produced by a system in response to an environmental stimulus. Metabolites are secreted into body fluids by host and microbial cells, measured by mass spectrometry–based approaches, and aligned against libraries of known biochemicals. These techniques have been used to gain insights into mechanisms of pathogenesis and to identify new biomarkers of disease. Metabolomics also offers clues to the presence and function of microbes living deep within the small bowel that are difficult to sample directly and highlights the complex relationship between resident microbes, host metabolism, pharmacotherapeutic action, and relative health or disease.
Metagenomics and metabolomics are the two most rapidly advancing “omics” technologies and lie at either end of the “omics cascade” [3]; the former identifies the genetic potential of a community, whereas the latter reports the actual biology that produces a phenotype. These fields have enabled discoveries pertinent to a number of human conditions—namely, acute gastroenteritis, antibiotic-associated diarrhea, inflammatory bowel disease, irritable bowel syndrome, liver disease, undernutrition, and obesity—and have begun to shed new light on multiple aspects of the neglected tropical diseases. Moreover, there are exciting opportunities to now pair metagenomic and metabolomic data in order to gain new and unprecedented insights into the host–parasite relationship. Here, we explore the nascent metagenomic and metabolomic contributions to the diagnosis, pathogenesis, treatment, and prevention (including vector control) of neglected tropical diseases. We then look ahead to the full potential of the postgenomics era and consider how metagenomics and metabolomics could help in the control and elimination of these diseases.
