The Food Metabolome


The food metabolome is the part of the human metabolome directly derived from the digestion and biotransformation of foods and their constituents. With over 25,000 compounds known in various foods, the food metabolome is extremely complex, with a composition varying widely according to the diet. This variability constitutes a unique and extremely rich source of information on the human diet, which can be used for pusposes such as accurate monitoring of dietary exposure and identification of foods that influence disease risks.

MetabolomeEarly metabolome studies allowed scientists to realize that the human metabolome was not as small or as simple as first imagined. In particular, noticeable differences in human metabolomes could be detected that appeared to depend strongly on diet, gender, health status, genetics, kinetics, physiology and age -- with diet being most important (, , , ). Though the dietary dependence was not unexpected, it was much more complicated than anticipated. This is largely due to the fact that unlike laboratory animals, humans are free-living omnivores who eat other metabolomes and are also exposed to a huge variety of chemical environments associated with the foods we consume. Thus, the human metabolome is not just a single entity but it consists of several components including: 1) the endogenous metabolome (consisting of chemicals needed for, or excreted from, cellular metabolism); 2) the food metabolome (consisting of essential and non-essential chemicals derived from foods after digestion and subsequent metabolism by the tissues and the microbiota); 3) other xenobiotics derived from drugs; and 4) xenobiotics derived from environmental or workplace chemicals.

This complexity makes the exact size and composition of these different human metabolomes is difficult to ascertain. It is believed to encompass at least 50,000 different detectable compounds (, ) but as instrument sensitivity and separation technologies improve, this number is expected to grow further. The plant kingdom, for example, is estimated to contain up to 200,000 different metabolites, with combinations of several hundreds of secondary metabolites characterizing each edible plant and thus entering the human food metabolome (, , ). Further complexity is introducted by the fact that metabolic transformation of compounds within the body means that composition often depends on the body compartment, tissue or biofluid. For instance, food and drug constituents found in the mouth or stomach are often chemically identical to the compounds isolated from the intact food or drug. On the other hand, food constituents found in blood, urine or other excreta are often metabolically transformed in the liver, kidney or intestine to metabolites that are very different from the parent compound. The importance of the gut microbiota in contributing metabolites to the human metabolome has also recently emerged (, ). Microbial metabolites are typically vitamins, certain essential amino acids, and a few fatty acids (about 100 compounds in total are known at this time). However, a large majority of the metabolites produced by the gut microbiota are derived from the biotransformation of both the endogenous metabolome and the food metabolome and are therefore an integral part of both these two metabolomes. These microbial metabolites include short chain fatty acids, secondary bile acids, protein and amino acid metabolites as well as plant polyphenol metabolites (). These factors add greatly to the diversity of the food metabolome.


References
For more information see: Scalbert A, Brennan L, Manach C, Andres-Lacueva C, Dragsted LO, Draper J, Rappaport SM, van der Hooft JJ, Wishart DS. The food metabolome: a window over dietary exposure. Am J Clin Nutr. 2014 Jun;99(6):1286-308. doi: 10.3945/ajcn.113.076133. Epub 2014 Apr 23. 24760973
  1. Holmes E, Loo RL, Stamler J, Bictash M, Yap IKS, Chan Q, Ebbels T, De Iorio M, Brown IJ, Veselkov KA, et al. Human metabolic phenotype diversity and its association with diet and blood pressure. Nature 2008;453:396 - 400.
  2. Slupsky CM, Rankin KN, Wagner J, Fu H, Chang D, Weljie AM, Saude EJ, Lix B, Adamko DJ, Shah S, et al. Investigations of the effects of gender, diurnal variation, and age in human urinary metabolomic profiles. Anal Chem 2007;79:6995-7004.
  3. Krug S, Kastenmueller G, Stueckler F, Rist MJ, Skurk T, Sailer M, Raffler J, Roemisch-Margl W, Adamski J, Prehn C, et al. The dynamic range of the human metabolome revealed by challenges. FASEB J 2012;26:2607-19.
  4. Heinzmann SS, Merrifield CA, Rezzi S, Kochhar S, Lindon JC, Holmes E, Nicholson JK. Stability and Robustness of Human Metabolic Phenotypes in Response to Sequential Food Challenges. J Proteome Res 2012;11:643-55.
  5. Wishart D, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, Djoumbou Y, Mandal R, Aziat F, Dong E, et al. HMDB 3.0 – The Human Metabolome Database in 2013. Nucleic Acids Res 2013:doi: 10.1093/nar/gks65.
  6. Smith CA, O'Maille G, Want EJ, Qin C, Trauger SA, Brandon TR, Custodio DE, Abagyan R, Siuzdak G. METLIN - A metabolite mass spectral database. Ther Drug Monit 2005;27:747-51.
  7. Manach C, Hubert J, Llorach R, Scalbert A. The complex links between dietary phytochemicals and human health deciphered by metabolomics. Mol Nutr Food Res 2009;53:1303 – 15.
  8. Fiehn O. Metabolomics--the link between genotypes and phenotypes. Plant Mol Biol 2002;48:155-71.
  9. Iijima Y, Nakamura Y, Ogata Y, Tanaka K, Sakurai N, Suda K, Suzuki T, Suzuki H, Okazaki K, Kitayama M, et al. Metabolite annotations based on the integration of mass spectral information. Plant J 2008;54:949-62.
  10. van der Werf MJ, Overkamp KM, Muilwijk B, Coulier L, Hankemeier T. Microbial metabolomics: toward a platform with full metabolome coverage. Anal Biochem 2007;370:17-25.
  11. Guo AC, Jewison T, Wilson M, Liu Y, Knox C, Djoumbou Y, Lo P, Mandal R, Krishnamurthy R, Wishart DS. ECMDB: The E-coli Metabolome Database. Nucleic Acids Res 2013;41:D625-30.
  12. Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S. Host-Gut Microbiota Metabolic Interactions. Science 2012;336:1262-7.