Genes & Nutrition

, 9:378 | Cite as

Consensus statement understanding health and malnutrition through a systems approach: the ENOUGH program for early life

  • Jim Kaput
  • Ben van Ommen
  • Bas Kremer
  • Corrado Priami
  • Jacqueline Pontes Monteiro
  • Melissa Morine
  • Fre Pepping
  • Zoey Diaz
  • Michael Fenech
  • Yiwu He
  • Ruud Albers
  • Christian A. Drevon
  • Chris T. Evelo
  • Robert E. W. Hancock
  • Carel IJsselmuiden
  • L. H. Lumey
  • Anne-Marie Minihane
  • Michael Muller
  • Chiara Murgia
  • Marijana Radonjic
  • Bruno Sobral
  • Keith P. WestJr.


Nutrition research, like most biomedical disciplines, adopted and often uses experimental approaches based on Beadle and Tatum’s one gene—one polypeptide hypothesis, thereby reducing biological processes to single reactions or pathways. Systems thinking is needed to understand the complexity of health and disease processes requiring measurements of physiological processes, as well as environmental and social factors, which may alter the expression of genetic information. Analysis of physiological processes with omics technologies to assess systems’ responses has only become available over the past decade and remains costly. Studies of environmental and social conditions known to alter health are often not connected to biomedical research. While these facts are widely accepted, developing and conducting comprehensive research programs for health are often beyond financial and human resources of single research groups. We propose a new research program on essential nutrients for optimal underpinning of growth and health (ENOUGH) that will use systems approaches with more comprehensive measurements and biostatistical analysis of the many biological and environmental factors that influence undernutrition. Creating a knowledge base for nutrition and health is a necessary first step toward developing solutions targeted to different populations in diverse social and physical environments for the two billion undernourished people in developed and developing economies.


Systems nutrition research Malnutrition Health Essential nutrients for optimal Underpinning of growth and health 


  1. Al Aama J, Smith TD, Lo A et al (2011) Initiating a Human Variome Project Country Node. Hum Mutat 32:501–506. doi:10.1002/humu.21463 CrossRefGoogle Scholar
  2. Afacan NJ, Fjell CD, Hancock REW (2012) A systems biology approach to nutritional immunology: focus on innate immunity. Mol Aspects Med 33:14–25. doi:10.1016/j.mam.2011.10.013 PubMedCrossRefGoogle Scholar
  3. Berry EM (2011) The role of the sociotype in managing chronic disease: integrating bio-psycho-sociology with systems biology. Med Hypotheses 77:610–613. doi:10.1016/j.mehy.2011.06.046 PubMedCrossRefGoogle Scholar
  4. Bhan A, Singh J, Upshur R et al (2007) Grand challenges in global health: engaging civil society organizations in biomedical research in developing countries. PLoS Med 4:e272. doi:10.1371/journal.pmed.0040272 PubMedCentralPubMedCrossRefGoogle Scholar
  5. Brabin B, Combs G Jr, Abbe MRL, et al (2011) Executive summary: biomarkers of nutrition for development: building a consensus 1–3. doi:10.3945/ajcn.110.008227.Am
  6. Braddick O, Atkinson J, Wattam-Bell J (2011) VERP and brain imaging for identifying levels of visual dorsal and ventral stream function in typical and preterm infants. Prog Brain Res 189:95–111. doi:10.1016/B978-0-444-53884-0.00020-8 PubMedCrossRefGoogle Scholar
  7. Breuer K, Foroushani AK, Laird MR et al (2012) InnateDB: systems biology of innate immunity and beyond–recent updates and continuing curation. Nucleic Acids Res. doi:10.1093/nar/gks1147 PubMedCentralPubMedGoogle Scholar
  8. Bures J, Cyrany J, Kohoutova D et al (2010) Small intestinal bacterial overgrowth syndrome. World J Gastroenterol 16:2978–2990PubMedCentralPubMedCrossRefGoogle Scholar
  9. Cohen ER, Masum H, Berndtson K et al (2008) Public engagement on global health challenges. BMC Public Health 8:168. doi:10.1186/1471-2458-8-168 PubMedCentralPubMedCrossRefGoogle Scholar
  10. Consortium T 100 GP (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491:56–65. doi:10.1038/nature11632 CrossRefGoogle Scholar
  11. Daar AS, Berndtson K, Persad DL, Singer PA (2007) How can developing countries harness biotechnology to improve health? BMC Public Health 7:346. doi:10.1186/1471-2458-7-346 PubMedCentralPubMedCrossRefGoogle Scholar
  12. Darnton-hill I, Schultink W, Shrimpton R et al (2009) Multiple Micronutrient Supplementation During Pregnancy in Developing Country Settings. In: Dalmiya N, Darnton-Hill I, Schultink W, Shrimpton R (eds) Food Nutr. Bull. pp 1–100Google Scholar
  13. Dewey KG, Begum K (2011) Long-term consequences of stunting in early life. Matern Child Nutr 7(Suppl 3):5–18. doi:10.1111/j.1740-8709.2011.00349.x PubMedCrossRefGoogle Scholar
  14. Dominguez-Salas P, Moore SE, Cole D et al (2013) DNA methylation potential : dietary intake and blood concentrations of one-carbon metabolites and cofactors in rural African women. Am J Clin Nutr 97:1217–1227. doi:10.3945/ajcn.112.048462.The PubMedCentralPubMedCrossRefGoogle Scholar
  15. Fairweather-Tait SJ (2003) Human nutrition and food research: opportunities and challenges in the post-genomic era. Philos Trans R Soc L B Biol Sci 358:1709–1727CrossRefGoogle Scholar
  16. Fenech M (2004) Genome health nutrigenomics: nutrition and the science of optimal genome maintenance. Asia Pac J Clin Nutr 13:S15Google Scholar
  17. Fenech MF (2010) Dietary reference values of individual micronutrients and nutriomes for genome damage prevention : current status and a road map to the. Am J Clin Nutr 91:1438–1454. doi:10.3945/ajcn.2010.28674D.1 CrossRefGoogle Scholar
  18. Fu W, Stromberg A, Viele K et al (2011) NStatistics and bioinformatics in nutritional scienes: analysis of complex data in the era of systems biology. J Nutr Biochem 21:561–572. doi:10.1016/j.jnutbio.2009.11.007.Statistics CrossRefGoogle Scholar
  19. Gardy JL, Lynn DJ, Brinkman FSL, Hancock REW (2009) Enabling a systems biology approach to immunology: focus on innate immunity. Trends Immunol 30:249–262. doi:10.1016/ PubMedCrossRefGoogle Scholar
  20. Glenn D (2006) Blood feud: a controversy over South American DNA samples held in North American laboratories ripples through anthropology. Chron High Educ 52(A14–6):A18Google Scholar
  21. Gordon JI, Dewey KG, Mills D a, Medzhitov RM (2012) The human gut microbiota and undernutrition. Sci Transl Med 4:137ps12. doi:10.1126/scitranslmed.3004347
  22. De Graaf AA, Freidig AP, De Roos B et al (2009) Nutritional systems biology modeling: from molecular mechanisms to physiology. PLoS Comput Biol 5:e1000554PubMedCentralPubMedCrossRefGoogle Scholar
  23. Van der Greef J, van Wietmarschen H, Schroën J et al (2010) Systems biology-based diagnostic principles as pillars of the bridge between Chinese and Western medicine. Planta Med 76:2036–2047. doi:10.1055/s-0030-1250450 PubMedCrossRefGoogle Scholar
  24. Guerrant RL, Deboer MD, Moore SR et al (2012) The impoverished gut-a triple burden of diarrhoea, stunting and chronic disease. Nat Rev Gastroenterol Hepatol. doi:10.1038/nrgastro.2012.239 PubMedCentralPubMedGoogle Scholar
  25. Hammond RA, Dubé L (2012) A systems science perspective and transdisciplinary models for food and nutrition security. Proc Natl Acad Sci USA 109:12356–12363. doi:10.1073/pnas.0913003109 PubMedCentralPubMedCrossRefGoogle Scholar
  26. Hood L, Heath JR, Phelps ME, Lin B (2004) Systems biology and new technologies enable predictive and preventative medicine. Science (80) 306:640–643CrossRefGoogle Scholar
  27. Horowitz CR, Robinson M, Seifer S (2009) Community-based participatory research from the margin to the mainstream: are researchers prepared? Circulation 119:2633–2642. doi:10.1161/CIRCULATIONAHA.107.729863 PubMedCentralPubMedCrossRefGoogle Scholar
  28. Huber M, Knottnerus JA, Green L et al (2011) How should we define health? BMJ 343:d4163. doi:10.1136/bmj.d4163 PubMedCrossRefGoogle Scholar
  29. Kaput J, Astley S, Renkema M et al (2006) Harnessing Nutrigenomics: development of web-based communication, databases, resources, and tools. Genes Nutr 1:5–11. doi:10.1007/BF02829931 PubMedCentralPubMedCrossRefGoogle Scholar
  30. Kaput J, Ordovas JM, Ferguson L et al (2005) The case for strategic international alliances to harness nutritional genomics for public and personal health. Br J Nutr 94:623–632PubMedCrossRefGoogle Scholar
  31. Khulan B, Cooper WN, Skinner BM et al (2012) Periconceptional maternal micronutrient supplementation is associated with widespread gender related changes in the epigenome: a study of a unique resource in the Gambia. Hum Mol Genet 21:2086–2101. doi:10.1093/hmg/dds026 PubMedCrossRefGoogle Scholar
  32. Kibbe WA (2006) The Informatics and Bioinformatics Infrastructure of a Nutrigenomics Database. In: Kaput Rodriguez, R.L. J (ed) Nutr. Genomics. Discov. Path to Pers. Nutr. Wiley, Hoboken, NJ, pp 353–374Google Scholar
  33. Korpe PS, Petri WA (2012) Environmental enteropathy: critical implications of a poorly understood condition. Trends Mol Med 18:328–336. doi:10.1016/j.molmed.2012.04.007 PubMedCentralPubMedCrossRefGoogle Scholar
  34. Levine MM (2010) Immunogenicity and efficacy of oral vaccines in developing countries: lessons from a live cholera vaccine. BMC Biol 8:129. doi:10.1186/1741-7007-8-129 PubMedCentralPubMedCrossRefGoogle Scholar
  35. Lynn DJ, Chan C, Naseer M et al (2010) Curating the innate immunity interactome. BMC Syst Biol 4:117. doi:10.1186/1752-0509-4-117 PubMedCentralPubMedCrossRefGoogle Scholar
  36. MacLellan WR, Wang Y, Lusis AJ (2012) Systems-based approaches to cardiovascular disease. Nat Rev Cardiol 9:172–184. doi:10.1038/nrcardio.2011.208 PubMedCrossRefGoogle Scholar
  37. Maggini S, Wintergerst ES, Beveridge S, Hornig DH (2007) Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses. Br J Nutr 98(Suppl 1):S29–S35. doi:10.1017/S0007114507832971 PubMedGoogle Scholar
  38. Mayer ML, Blohmke CJ, Falsafi R et al (2013) Rescue of dysfunctional autophagy attenuates hyperinflammatory responses from cystic fibrosis cells. J Immunol 190:1227–1238. doi:10.4049/jimmunol.1201404 PubMedCrossRefGoogle Scholar
  39. McCabe-Sellers B, Lovera D, Nuss H et al (2008) Personalizing nutrigenomics research through community based participatory research and omics technologies. OMICS 12:263–272. doi:10.1089/omi 2008.0041PubMedCrossRefGoogle Scholar
  40. McKay S, Gaudier E, Campbell D, Prentice A (2010) Environmental enteropathy: new targets for nutritional interventions. Int Health 2:172–180PubMedCrossRefGoogle Scholar
  41. Merched AJ, Chan L (2013) Nutrigenetics and nutrigenomics of atherosclerosis. Curr Atheroscler Rep 15:328. doi:10.1007/s11883-013-0328-6 PubMedCentralPubMedCrossRefGoogle Scholar
  42. Moretti D, Zimmermann MB, Wegmuller R et al (2006) Iron status and food matrix strongly affect the relative bioavailability of ferric pyrophosphate in humans. Am J Clin Nutr 83:632–638PubMedGoogle Scholar
  43. Morine MJ, McMonagle J, Toomey S et al (2010) Bi-directional gene set enrichment and canonical correlation analysis identify key diet-sensitive pathways and biomarkers of metabolic syndrome. BMC Bioinformatics 11:499. doi:10.1186/1471-2105-11-499 PubMedCentralPubMedCrossRefGoogle Scholar
  44. Morine MJ, Priami C (2013) Analysis of biological systems. Imperial College Press, London (in press)Google Scholar
  45. Morine MJ, Tierney AC, van Ommen B et al (2011) Transcriptomic coordination in the human metabolic network reveals links between n-3 fat intake, adipose tissue gene expression and metabolic health. PLoS Comput Biol 7:e1002223. doi:10.1371/journal.pcbi.1002223 PubMedCentralPubMedCrossRefGoogle Scholar
  46. Morine MJ, Toomey S, McGillicuddy FC et al (2012) Network analysis of adipose tissue gene expression highlights altered metabolic and regulatory transcriptomic activity in high-fat-diet-fed IL-1RI knockout mice. J Nutr Biochem. doi:10.1016/j.jnutbio.2012.04.012 Google Scholar
  47. Norheim F, Gjelstad IMF, Hjorth M et al (2012) Molecular nutrition research: the modern way of performing nutritional science. Nutrients 4:1898–1944. doi:10.3390/nu4121898 PubMedCentralPubMedCrossRefGoogle Scholar
  48. Office for Human Research Protections (2012) International compilation of human research standards. 114Google Scholar
  49. Palsson BO (2006) Systems biology: properties of reconstructed networks. 322Google Scholar
  50. Patrinos G, Al Aama J, Al Aqeel A et al (2010) Recommendations for genetic variation data capture in developing countries to ensure a comprehensive worldwide data collection. Hum Mutat 31:1–8CrossRefGoogle Scholar
  51. Rozenblit L, Keil F (2002) The misunderstood limits of folk science: an illusion of explanatory depth. Cogn Sci 26:521–562. doi:10.1207/s15516709cog2605_1 PubMedCentralPubMedCrossRefGoogle Scholar
  52. Savy M, Edmond K, Fine PEM et al (2009) Landscape analysis of interactions between nutrition and vaccine responses in children. J Nutr 139:2154S–2218S. doi:10.3945/jn.109.105312.research PubMedCrossRefGoogle Scholar
  53. Scrimshaw N, Taylor C, Gordon J (1959) Interactions of nutrition and infection. Am J Med Sci 237:367–403PubMedCrossRefGoogle Scholar
  54. Séguin B, Hardy B-J, Singer PA, Daar AS (2008) Genomics, public health and developing countries: the case of the Mexican National Institute of Genomic Medicine (INMEGEN). Nat Rev Genet 9(Suppl 1):S5–S9. doi:10.1038/nrg2442 PubMedCrossRefGoogle Scholar
  55. Seguin B, Hardy BJ, Singer PA, Daar AS (2008) Genomic medicine and developing countries: creating a room of their own. Nat Rev Genet 9:487–493. doi:10.1038/nrg2379 PubMedCrossRefGoogle Scholar
  56. Singer PA, Daar AS (2001) Harnessing genomics and biotechnology to improve global health equity. Science (80) 294:87–89CrossRefGoogle Scholar
  57. Slikker W Jr, Paule MG, Wright LK et al (2007) Systems biology approaches for toxicology. J Appl Toxicol 27:201–217. doi:10.1002/jat.1207 PubMedCrossRefGoogle Scholar
  58. Storlien L, Oakes ND, Kelley DE (2004) Metabolic flexibility. Proc Nutr Soc 63:363–368. doi:10.1079/PNS2004349 PubMedCrossRefGoogle Scholar
  59. Stumbo PJ, Weiss R, Newman JW et al (2010) Web-enabled and improved software tools and data are needed to measure nutrient intakes and physical activity for personalized health research. J Nutr 140:2104–2115. doi:10.3945/jn.110.128371 PubMedCentralPubMedCrossRefGoogle Scholar
  60. Taylor AD, Brook D, Watters D et al (2007) North–south partnerships–a study of Canadian firms. Nat Biotechnol 25:978–979. doi:10.1038/nbt0907-978 PubMedCrossRefGoogle Scholar
  61. Tindana PO, Singh JA, Tracy CS et al (2007) Grand challenges in global health: community engagement in research in developing countries. PLoS Med 4:e273. doi:10.1371/journal.pmed.0040273 PubMedCentralPubMedCrossRefGoogle Scholar
  62. Tucker KL, Smith CE, Lai C-Q, Ordovas JM (2013) Quantifying diet for nutrigenomic studies. Annu Rev Nutr 33:349–371. doi:10.1146/annurev-nutr-072610-145203 PubMedCrossRefGoogle Scholar
  63. United Nations Standing Committee on Nutrition (2012) What progress in nutrition? Nutr Rev 5:134. doi:10.1111/j.1753-4887.1947.tb04238.x Google Scholar
  64. Van Ommen B, Cavallieri D, Roche HM et al (2008a) The challenges for molecular nutrition research 4: the “nutritional systems biology level”. Genes Nutr 3:107–113. doi:10.1007/s12263-008-0090-5 PubMedCentralPubMedCrossRefGoogle Scholar
  65. Van Ommen B, Fairweather-Tait S, Freidig A et al (2008b) A network biology model of micronutrient related health. Br J Nutr 99(Suppl 3):S72–S80. doi:10.1017/S0007114508006922 PubMedGoogle Scholar
  66. Van Ommen B, Keijer J, Heil SG, Kaput J (2009) Challenging homeostasis to define biomarkers for nutrition related health. Mol Nutr Food Res 53:795–804. doi:10.1002/mnfr.200800390 PubMedCrossRefGoogle Scholar
  67. Van Ommen B, Bouwman J, Dragsted LO et al (2010a) Challenges of molecular nutrition research 6: the nutritional phenotype database to store, share and evaluate nutritional systems biology studies. Genes Nutr 5:189–203. doi:10.1007/s12263-010-0167-9 PubMedCentralPubMedCrossRefGoogle Scholar
  68. Van Ommen B, El-Sohemy A, Hesketh J et al (2010b) The micronutrient genomics project: creating a community driven knowledge base for micronutrient research. Genes Nutr 5:285–296PubMedCentralPubMedCrossRefGoogle Scholar
  69. Van Wietmarschen HA, Reijmers TH, van der Kooij AJ et al (2011) Sub-typing of rheumatic diseases based on a systems diagnosis questionnaire. PLoS One 6:e24846. doi:10.1371/journal.pone.0024846 PubMedCentralPubMedCrossRefGoogle Scholar
  70. Verkerke HP, Petri WA, Marie CS (2012) The dynamic interdependence of amebiasis, innate immunity, and undernutrition. Semin Immunopathol 34:771–785. doi:10.1007/s00281-012-0349-1 PubMedCentralPubMedCrossRefGoogle Scholar
  71. Von Bertalanffy L (1951) General system theory: a new approach to unity of science. Hum Biol 23:203–361Google Scholar
  72. Westerberg AC, Henriksen C, Ellingvåg A et al (2010) First year growth among very low birth weight infants. Acta Paediatr 99:556–562. doi:10.1111/j.1651-2227.2009.01667.x PubMedCrossRefGoogle Scholar
  73. Westerberg AC, Schei R, Henriksen C et al (2011) Attention among very low birth weight infants following early supplementation with docosahexaenoic and arachidonic acid. Acta Paediatr 100:47–52. doi:10.1111/j.1651-2227.2010.01946.x PubMedCrossRefGoogle Scholar
  74. Wintergerst ES, Maggini S, Hornig DH (2007) Contribution of selected vitamins and trace elements to immune function. Ann Nutr Metab 51:301–323. doi:10.1159/000107673 PubMedCrossRefGoogle Scholar
  75. Zhao L, Nicholson JK, Lu A et al (2012) Targeting the human genome-microbiome axis for drug discovery: inspirations from global systems biology and traditional Chinese medicine. J Proteome Res 11:3509–3519. doi:10.1021/pr3001628 PubMedCrossRefGoogle Scholar
  76. Zimmermann MB, Kohrle J (2002) The impact of iron and selenium deficiencies on iodine and thyroid metabolism: biochemistry and relevance to public health. Thyroid 12:867–878PubMedCrossRefGoogle Scholar
  77. Zimmermann MB, Muthayya S, Moretti D et al (2006) Iron fortification reduces blood lead levels in children in Bangalore, India. Pediatrics 117:2014–2021. doi:10.1542/peds.2005-2440 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Jim Kaput
    • 1
  • Ben van Ommen
    • 2
  • Bas Kremer
    • 2
  • Corrado Priami
    • 3
  • Jacqueline Pontes Monteiro
    • 4
  • Melissa Morine
    • 3
  • Fre Pepping
    • 5
  • Zoey Diaz
    • 6
  • Michael Fenech
    • 7
  • Yiwu He
    • 6
  • Ruud Albers
    • 8
    • 19
  • Christian A. Drevon
    • 9
  • Chris T. Evelo
    • 10
  • Robert E. W. Hancock
    • 11
  • Carel IJsselmuiden
    • 12
  • L. H. Lumey
    • 13
  • Anne-Marie Minihane
    • 14
  • Michael Muller
    • 15
  • Chiara Murgia
    • 16
  • Marijana Radonjic
    • 2
  • Bruno Sobral
    • 17
  • Keith P. WestJr.
    • 18
  1. 1.Clinical Translation UnitNestle Institute of Health SciencesLausanneSwitzerland
  2. 2.Research Group Microbiology and Systems BiologyTNOZeistThe Netherlands
  3. 3.Department of MathematicsUniversity of Trento and The Microsoft Research, University of Trento Centre for Computational and Systems BiologyRoveretoItaly
  4. 4.Department of Pediatrics, Faculty of MedicineUniversity of Sao PauloRibeirão PrêtoBrazil
  5. 5.Graduate School VLAGWageningen UniversityWageningenThe Netherlands
  6. 6.Bill and Melinda Gates FoundationSeattleUSA
  7. 7.Preventative Health FlagshipCSIROAdelaideAustralia
  8. 8.NutriLeadsRockanjeThe Netherlands
  9. 9.Department of Nutrition, Faculty of Medicine, Institute of Basic Medical SciencesUniversity of OsloOsloNorway
  10. 10.Department of BioinformaticsMaastricht UniversityMaastrichtThe Netherlands
  11. 11.Department of Microbiology and ImmunologyUniversity of British ColumbiaVancouverCanada
  12. 12.Council on Health Research for Economic DevelopmentGenevaSwitzerland
  13. 13.Department of Epidemiology, Mailman School of Public HealthColumbia UniversityNew YorkUSA
  14. 14.Nutrigenetics Program, Norwich Medical SchoolUniversity of East AngliaNorwichUK
  15. 15.Nutrition, Metabolism & Genomics GroupWageningen UniversityWageningenThe Netherlands
  16. 16.Nutritional ScienceInstitute Nazionale di Ricerca per gli Alimenti e la Nutrizione (INRAN)RomeItaly
  17. 17.BioSystem Informatics UnitNestle Institute of Health SciencesLausanneSwitzerland
  18. 18.Center for Human NutritionJohns Hopkins Bloomberg School of Public HealthBaltimoreUSA
  19. 19.Host Microbe Interactomics GroupWageningen UniversityWageningenThe Netherlands

Personalised recommendations