The Human Microbial Metabolome Database (MiMeDB) (https://mimedb.org) is a comprehensive, multi-omic, microbiome resource that connects: (i) microbes to microbial genomes; (ii) microbial genomes to microbial metabolites; (iii) microbial metabolites to the human exposome and (iv) all of these ‘omes’ to human health. MiMeDB was established to consolidate the growing body of data connecting the human microbiome and the chemicals it produces to both health and disease. MiMeDB contains detailed taxonomic, microbiological and body-site location data on most known human microbes (bacteria and fungi). This microbial data is linked to extensive genomic and proteomic sequence data that is closely coupled to colourful interactive chromosomal maps. The database also houses detailed information about all the known metabolites generated by these microbes, their structural, chemical and spectral properties, the reactions and enzymes responsible for these metabolites and the primary exposome sources (food, drug, cosmetic, pollutant, etc.) that ultimately lead to the observed microbial metabolites in humans. Additional, extensively referenced data about the known or presumptive health effects, measured biosample concentrations and human protein targets for these compounds is provided. All of this information is housed in richly annotated, highly interactive, visually pleasing database that has been designed to be easy to search, easy to browse and easy to navigate. Currently MiMeDB contains data on 626 health effects or bioactivities, 1904 microbes, 3112 references, 22 054 reactions, 24 254 metabolites or exposure chemicals, 648 861 MS and NMR spectra, 6.4 million genes and 7.6 billion DNA bases. We believe that MiMeDB represents the kind of integrated, multi-omic or systems biology database that is needed to enable comprehensive multi-omic integration.

<b><i>Background:</i></b> For thousands of years, disabilities due to nutrient deficiencies have plagued humanity. Rickets, scurvy, anemia, stunted growth, blindness, and mental handicaps due to nutrient deficiencies affected up to 1/10 of the world’s population prior to 1900. The discovery of essential amino acids, vitamins, and minerals, in the early 1900s, led to a fundamental change in our understanding of food and a revolution in human health. Widespread vitamin and mineral supplementation, the development of recommended dietary allowances, and the implementation of food labeling and testing along with significant improvements in food production and food quality have meant that nutrient-related disorders have almost vanished in the developed world. The success of nutritional science in preventing disease at a population-wide level is one of the great scientific triumphs of the 20th century. The challenge for nutritional science in the 21st century is to understand how to use nutrients and other food constituents to enhance human health or prevent disease at a more personal level. This is the primary goal of precision nutrition. <b><i>Summary:</i></b> Precision nutrition is an emerging branch of nutrition science that aims to use modern omics technologies (genomics, proteomics, and metabolomics) to assess an individual’s response to specific foods or dietary patterns and thereby determine the most effective diet or lifestyle interventions to prevent or treat specific diseases in that individual. Metabolomics is vital to nearly every aspect of precision nutrition. It can be used to comprehensively characterize the thousands of chemicals in foods, to identify food byproducts in human biofluids or tissues, to characterize nutrient deficiencies or excesses, to monitor biochemical responses to dietary interventions, to track long-term or short-term dietary habits, and to guide the development of nutritional therapies. In this review, we will describe how metabolomics has been used to advance the field of precision nutrition by providing some notable examples or use cases. First, we will describe how metabolomics helped launch the field of precision nutrition through the diagnosis and dietary therapy of individuals with inborn errors of metabolism. Next, we will describe how metabolomics is being used to comprehensively characterize the full chemical complexity of many key foods, and how this is revealing much more about nutrients than ever imagined. Third, we will describe how metabolomics is being used to identify food consumption biomarkers and how this opens the door to a more objective and quantitative assessments of an individual’s diet and their response to certain foods. Finally, we will describe how metabolomics is being coupled with other omics technologies to develop custom diets and lifestyle interventions that are leading to positive health benefits. <b><i>Key Message:</i></b> Metabolomics is vital to the advancement of nutritional science and in making the dream of precision nutrition a reality.

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Conversion of native cellular prion protein (PrPc) from an α-helical structure to a toxic and infectious β-sheet structure (PrPSc) is a critical step in the development of prion disease. There are some indications that the formation of PrPSc is preceded by a β-sheet rich PrP (PrPβ) form which is non-infectious, but is an intermediate in the formation of infectious PrPSc. Furthermore the presence of lipid cofactors is thought to be critical in the formation of both intermediate-PrPβ and lethal, infectious PrPSc. We previously discovered that the endotoxin, lipopolysaccharide (LPS), interacts with recombinant PrPc and induces rapid conformational change to a β-sheet rich structure. This LPS induced PrPβ structure exhibits PrPSc-like features including proteinase K (PK) resistance and the capacity to form large oligomers and rod-like fibrils. LPS is a large, complex molecule with lipid, polysaccharide, 2-keto-3-deoxyoctonate (Kdo) and glucosamine components. To learn more about which LPS chemical constituents are critical for binding PrPc and inducing β-sheet conversion we systematically investigated which chemical components of LPS either bind or induce PrP conversion to PrPβ. We analyzed this PrP conversion using resolution enhanced native acidic gel electrophoresis (RENAGE), tryptophan fluorescence, circular dichroism, electron microscopy and PK resistance. Our results indicate that a minimal version of LPS (called detoxified and partially de-acylated LPS or dLPS) containing a portion of the polysaccharide and a portion of the lipid component is sufficient for PrP conversion. Lipid components, alone, and saccharide components, alone, are insufficient for conversion.