Nutrigenomics NEW ZEALAND Interventional clinical trial results, and the value of genetic and genomic studies Lynnette Ferguson and Gareth Marlow, The University of Auckland Nutrigenomics or Nutrigenetics? Nutrigenetics Nutrigenomics What is Nutrigenetics? • The study of how individual genetic differences can affect the way we respond to nutrients in the foods we eat • The use of genetic characterisation in the the interpretation of clinical trial data In real terms LR Ferguson, 2012, Nature reviews Fat mass and obesity associated (FTO) 'Fatso' gene has clear link to obesity, say scientists NZ Herald 5:00AM Saturday April 14, 2007 Scientists have discovered the clearest link yet between genes and obesity in a study that opens the way to explaining why some people put on weight while others remain slim. The researchers have identified a genetic variation that gives a child a 70 per cent higher risk of developing obesity compared with a child who has not inherited the genetic variant. Tayside Schools Intensive phenotyping study Eating behaviour and food choice. Resting and total energy expenditure Courtesy of Colin Palmer N=100 FTO-targeted: Satiety-enhanced Foods The Development, Instrumental and Sensory Evaluation of a Gel-Based Model Food of Varying Textural Complexity. Danaé Larsen, Jingyuan Tang, Lynnette Ferguson, Marco Morgenstern and Bryony James Submitted Paper An eczema-related gene target of probiotics Differential modification of genetic susceptibility to childhood eczema by two probiotics Angharad R. Morgan, Dug Yeo Han, Kristin Wickens, Christine Barthow, Edwin A. Mitchell, Thorsten V. Stanley, James Dekker, Julian Crane and Lynnette R. Ferguson DOI: 10.1111/cea.12394 Just Published Unsuccessful Nutrigenetic Companies • Sciona Inc. was founded in 2000. • Provided gene-based personalised health and nutrition analysis and recommendations based on individual diet, lifestyle, and genetic profile. • It also offered genetic testing products, which addressed personal wellness, fitness, and nutritional issues. • Sciona Inc. went out of business in 2009. Unsuccessful Nutrigenetic Companies • MyGene specialised in the development of genetic tests and interpretive reports that assessed the genetic contribution of personal response to diet, also known as nutrigenetics. • In 2011 MyGene brought to market a nutrigenetic dietary program to optimise weight loss that was composed of a genetic test, a genetically allocated meal replacement formulation and 12- week dietary program (MyGene Weightloss Complete®). • Founded in 2007, the company has now been dissolved. Successful Nutrigenetic Companies International Science Advisory Board Nutrigenomix Inc. is a University Ben van Lynn Ahmed El- David of Toronto start-up biotechnology Ommen Ferguson Sohemy Jenkins company that moves genetic studies from the laboratory into the clinic. Working with our International Science Advisory Board, consisting of global leaders in the field of nutrigenomics, we have developed a panel of 7 genetic tests that enable your registered David Jose Bruce Bénédicte dietitian to provide you with Castle Ordovas German Fontaine-Bisson personalized nutritional recommendations based on your DNA. Nutrigenetics • Still viable, as a means of stratifying human populations for response to novel foods • BUT, single gene-functional food interactions are probably not of primary importance in all diseases. • May be more applicable to diseases such as IBD and metabolic syndrome • We have developed the appropriate methods, and could apply these where wanted So attention is turning to nutrigenomics: The study of how foods affect our genes Why Nutrigenomics? • To understand mechanisms whereby nutrition affects metabolic health • To optimise personal health/nutrition • To provide evidence for “functional food” health claims Two Strategies Afman & Muller J Am Diet Assoc 2006; 106:569-576 Will Nutrigenomics provide answers? You need to ask the right Questions Complex Nutrition + Complex Genotypes + Complex lifestyles + Omics Technologies Nutrigenomic Considerations? • Why do you need nutrigenomics? • What are the most suitable tools for your research and how to apply them? • What is healthy and how do you quantify? • What is the impact of nutrigenomics for the food industry? 1. In vitro studies e.g. Du Pont work on mechanism of action of a novel oil… Figure 1. Research Development Introduction Maturation Future Re-invent product in “4P” paradigm of “Personal Nutrition” Nutrigenomic Tool Kit • Transcriptomic profiling • Nuclear receptor profiling Decline • Lipidomics • Toxicogenomics • Genotyping Multi-level, multi-media, science-driven networking to engage thought-leaders and empowered consumers Return on Investment Investment on Return Research provides critical “Proof of Principle” underpinning product differentiation and patent estate to protect return on investment Time 2. In vivo studies Aim: validate use of nutrigenomics in small dietary intervention study • 30 healthy volunteers • Any gender, ethnicity, age, non-smokers • 6 week Mediterranean-style dietary intervention • 2 interventions; High or Low Traditional Biomarkers C-Reactive Protein Micronuclei Mean levels of C-reactive protein, Micronuclei scored in 1100 measured from serum samples of all cytokinesis-blocked cells for each subjects, before and after the dietary participant. Illustrated are the intervention. mean for each group. Transcriptomics • Input RNA required: 50–500 ng • Sensitivity: ≥1:100,000 • Detectable fold change: ≥2.0 fold • Dynamic range: ≥3log • Probe length: 25-mer • Probe Number: 530,000 • Transcripts: 36,000 • Represents: >20,000 genes Microarray Data How do we make sense of >30,000 data points? Statistical Pathway Heatmaps Analysis Analysis Statistical Analysis Raw Data: 30,000 transcripts Changed with inflammation: ~1,000 transcripts Non-hypothesis based study endpoint • Focus on those genes. • Search published literature, to learn about what they do in cells. • Put together a story that explains why they might be relevant to the change in diet. Differential Expression of top 150 Genes in High Intervention Diet (p<10-8) Week 1 Week 6 Pathways affected by dietary intervention Adding in metabolomics studies • To test for compliance • To discover biomarkers – Effects of foods on metabolism – Metabolite markers showing effects of foods on health Value of Nutrigenomics • Add to the understanding of the mechanism of nutrition • Aid in the development of personalised nutrition • Identify biomarkers and improve diagnostics for nutrition related diseases Value of Nutrigenomics to Industry • Support the development of functional foods – Demonstrate efficacy of the food-health claim in a cost-effective manner – Provide scientific validation for food health claims Nutrigenomics NEW ZEALAND Acknowledgements • Stephanie Ellett • Amalini Jesuthasan • Isobel Ferguson • Nishi Karunasinghe • William Zhu .