This document discusses the interaction between nutrients and genes in Celiac Disease from a nutrigenomic perspective. It describes how Celiac Disease has transitioned from a rare childhood disorder to a common autoimmune disease triggered by gluten in genetically susceptible individuals. It discusses how omics sciences can help elucidate relationships between bioactive molecules like gluten, genetic polymorphisms, and the human gut and immune system. Specifically, it focuses on how recent proteomic developments have furthered understanding of gluten toxicity and the roles of genes and the microbiome in disease risk.

1. Interaction between nutrients and genes in Celiac Disease: a nutrigenomic approach 2nd International Conference on FOOD-OMICS A science for nutrition, health and wellness in the post-genomic era Cesena (Italy), June 22-24, 2011 Interaction between nutrients and genes in Celiac Disease: a nutrigenomic approach

2. FoodOmics 2011 Celiac Disease … .. from a rare disorder typical of infancy … Interaction between nutrients and genes in Celiac Disease: a nutrigenomic approach

3. FoodOmics 2011 Interaction between nutrients and genes in Celiac Disease: a nutrigenomic approach Cinderella ………… . to a common auto-immune inflammatory disease of the small intestine . It is mainly triggered and maintained by the storage proteins (gluten) of wheat, rye and barley, in genetically susceptible individuals . Catassi C & Fasano A, Curr Opin Gastroenterol. 24(6):687-91; 2008 Greetje JT et al., Nature Reviews Gastroenterology and Hepatology 7, 204; 2011 Gluten sensitivity Sapone A et al., BMC Med. 9:23 2011

4. FoodOmics 2011 Associated diseases Type 1 diabetes, vitiligo, primary biliary cirrhosis Fasano A, Le Scienze 494, 2009 Greetje J et al., Nature: Gastr & Hepat 7:204, 2010 The causes Trigger Genes Leaky small intestine + + Interaction between nutrients and genes in Celiac Disease: a nutrigenomic approach The clinical spectrum Typical symptoms Abdominal distension, diarrhoea, vomiting, weight loss, fatigue Extraintestinal symptoms Alopecia, arthritis, ataxia, epilepsy, dental enamel hypoplasia, infertility, osteoporosis

5. Omic Sciences provide powerful approaches to elucidate the complex relationships between bioactive molecules , genetic polymorphisms and a biological system and can give rise to personalised nutrition and dietary recommendations. V. García-Cañas et al., J Phar Biom Analy 51:2 290, 2010 FoodOmics 2011 Interaction between nutrients and genes in Celiac Disease: a nutrigenomic approach

6. FoodOmics 2011 Bioactive molecule - Gluten Recent developments in proteomics have provided an important contribution to the understanding of the biochemical and immunological aspects and the toxicity mechanism of prolamins. Manone G et al., Expert Rev Proteomics 8(1):95, 2011 Interaction between nutrients and genes in Celiac Disease: a nutrigenomic approach gliadins glutenins gluten Secalins Rye + Hordeins Barley + Avenins Oats ? Zeins Maize - Oryzins Rice - Kafirins Millet, Sorghum -

7. FoodOmics 2011 Bioactive molecule - Gliadins cytotoxic activity Maiuri L.et al. Scand J Gastroent 31:247, 1996 Interaction between nutrients and genes in Celiac Disease: a nutrigenomic approach CXCR3-dependent IL8 release Lammer s KM et al, Immunology 132(3): 432, 2011 immunomodulatory activity Shan L et al, Science 297: 2275, 2002 Zonulin release and gut permeating activity Lammers K et al, Gastroenterology 135:194, 2008

8. FoodOmics 2011 non-HLA genes Genetic Polymorphisms - Genes 40 Interaction between nutrients and genes in Celiac Disease: a nutrigenomic approach Human Genome (inherited from both parents, stable, never changes in its composition) HLA-DQ2 and/or HLA-DQ8 Microbiome ( Inherited from the mother, changes from individual to individual and in the same individual over time ) 300 billion bacteria

9. FoodOmics 2011 Genetic Polymorphisms - Genes Pop Classical Jazz Interaction between nutrients and genes in Celiac Disease: a nutrigenomic approach A Tag–single nucleotide polymorphism (SNPs) approach is very usefull to integrate or replace classic HLA typing in at high-risk groups (first-degree relatives), for research purposes or in population screening programs. S. Vatta et al., Human Immunology 72(6):499, 2011 new

10. FoodOmics 2011 Biological system - Gut Interaction between nutrients and genes in Celiac Disease: a nutrigenomic approach

11. FoodOmics 2011 Biological system - Gut Interaction between nutrients and genes in Celiac Disease: a nutrigenomic approach Gluten Zonulin Innate Immune events Adaptive Immune events

12. Nutrigenomic Nutrigenetic prolamins human gut human genome FoodOmics 2011 Interaction between nutrients and genes in Celiac Disease: a nutrigenomic approach

13. Dottoressa Letizia SATURNI Dottore in Ricerca e Specialista in Scienze dell’Alimentazione Tutor Master Internazionale di Dietetica e Nutrizione Foodblogger – http://notonlyglutenfree.org E-mail: [email_address] FoodOmics 2011 Interaction between nutrients and genes in Celiac Disease: a nutrigenomic approach