1<br />Our other genome - the foundation for new approaches in medicine<br />S. Dusko Ehrlich, INRA, MetaHIT coordinator<b...
The human intestinal metagenome<br />3.3 million bacterial gene catalog 150-fold human genome<br />85% of abundant gut  ge...
The MetaHIT (Metagenomics of the Human Intestinal Tract) Consortium<br /><ul><li>European Commission FP7 project, coordina...
12 European and 1 Chinese Institutions; 9 public,  4 private
21.2 M € /4 yrs (11.4 M € from the EC); 100 scientists
Started on March 2008
 clinicians
 microbiologists
 immunologists
 genomics
 bioinformatics
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05 rencontres biomédicale LIR Dusko Ehrlich

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2ND INTERNATIONAL RESEARCH MEETING
4 JUNE 2010- HÔTEL DE MARIGNY PARIS

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05 rencontres biomédicale LIR Dusko Ehrlich

  1. 1. 1<br />Our other genome - the foundation for new approaches in medicine<br />S. Dusko Ehrlich, INRA, MetaHIT coordinator<br />Paris, June 4, 2010<br />
  2. 2. The human intestinal metagenome<br />3.3 million bacterial gene catalog 150-fold human genome<br />85% of abundant gut genes from a cohort of 124 Europeans<br />70-86% of genes from the US & Japanese studies<br />March 2010<br />Major media, week of 4 Mar – 10 Mar (Nature Author & Referee Services): <br />ABC News; Boston Globe; CBC (Canada); FOX News; MSNBC/NBC; <br />New York Times; San Francisco Chronicle; Washington Post ; BBC News; Independent ; AP ; AFP (France); Reuters; ABC (Australia) ; The Australian <br />Spiegel (Germany); Le Monde; Le Figaro; Dagens Nyheter (Sweden)….<br />
  3. 3. The MetaHIT (Metagenomics of the Human Intestinal Tract) Consortium<br /><ul><li>European Commission FP7 project, coordinated by INRA (S. Dusko Ehrlich)
  4. 4. 12 European and 1 Chinese Institutions; 9 public, 4 private
  5. 5. 21.2 M € /4 yrs (11.4 M € from the EC); 100 scientists
  6. 6. Started on March 2008
  7. 7. clinicians
  8. 8. microbiologists
  9. 9. immunologists
  10. 10. genomics
  11. 11. bioinformatics
  12. 12. stakeholders</li></li></ul><li>The human intestinal microbiota is a forgotten organ…<br /><ul><li>100 trillion microorganisms ; 10-fold more cells than the human body; 2 kg of mass!
  13. 13. Interface between food and epithelium
  14. 14. In contact with the 1st pool of immune cells and the 2nd pool of neural cells of the body</li></ul>…with a major role in health & disease ! <br />
  15. 15. Perturbation of intestinal microbiota in many pathologies<br />Frailty in seniors Van Tongeren et al., 2005<br />Crohn Seksik et al., 2003; Sokol et al., 2006, 2008, 2009<br />Ulcerative colitis Sokol et al., 2008; Martinez et al., 2008<br />Pouchitis Lim et al., 2009, Kühbacher et al., 2006<br />Obesity Ley et al., 2007; Kalliomäki et al., 2008<br />Type-2 diabetes Cani and Delzenne, 2009<br />Type-1 diabetes Dessein et al., 2009; Wen et al., 2008<br />Coeliac disease Nadal et al., 2007; Collado et al., 2009<br />Allergy Kirjavainen et al., 2002; Björkstén, 2009<br />Autism Finegold et al., 2002; Paracho et al., 2005<br />Colorectal cancer Mai et al., 2007; Scanlan et al., 2008 <br />HIV infection Gori et al., 2008<br />* Indications from animal models, effects of antibiotics or probiotics, clinical studies; courtesy of Joël Doré<br />
  16. 16. The MetaHIT approach to relation between microbes & us <br />Establish a reference gene set by metagenomic & genomic sequencing of the Human GI tract microbes <br />Develop generic tools for profiling the GI tract microbiota genes : arrays and high throughput DNA sequencing<br />Use the profiling tools to search association of microbial genes and disease in Inflammatory Bowel Diseases and Obesity <br />Carry out function analysis to go from associations to mechanisms<br />Bioinformatics overlays all activities<br />
  17. 17. The MetaHIT barcode<br />Obesitystudy, 80 individuals<br />Three clinical studies<br />(in progress; unpublished)<br />Obesity<br />177 Danes<br />lean: n = 67 ; obese: n = 110<br />IBD – Crohn Disease <br />21 Spaniards<br />patients: n = 8 ; healthy: n = 13<br />IBD – Ulcerative Colitis<br />24 Spaniards<br />patients: n = 12; healthy: n = 12<br />4firmicutespecies<br />19<br />60 million sequences per individual are used to establish bacterial gene profiles<br />19<br />42<br />BMI <br />
  18. 18. Bacterial Species are Associated to Chronic Disease<br />Five species discriminant for Crohn<br />Four species discriminant for obesity<br />Healthy<br />Patients<br />Lean<br />Obese<br />Three species discriminant for UC<br />Healthy<br />Patients<br />For 45% of individuals four firmicute species discriminate obesity with 81 % accuracy <br />A small number of species fully discriminate the IBD phenotypes <br />Causal agents? Contributors? Consequence? <br />
  19. 19. Where do these studies lead to and when?<br />Diagnostic & prognostic tests - soon<br /> - arrays, sequencing, Q-PCR; immunomarkers (?)<br />Better treatments - next<br /><ul><li> personalized medicine </li></ul> Responders/non-responders<br />Novel treatments – last: target our other genome! <br /><ul><li> modulation of microbiota </li></ul>Promoters (pre-biotics: FOS, others?)<br />Inhibitors (“soft” AB-like?? “Re-purposing”?)<br /><ul><li> transplantation of microbiota; biobanking</li></li></ul><li>Let’s go there together–France is the place to do it!!<br /><ul><li>The world-wide leadership in the field exists & the necessary expertise can easily be networked (clinicians, microbiologists, genomics, bio-informatics...)
  20. 20. The tools are available and can easily be strengthened (cohorts for different diseases, gene profiling techniques, informatics, function analysis...)
  21. 21. Motivation is high and will rise even further with new discoveries – the field is ripe ! </li></ul>(scientists, research institutions, government...)<br />Target Inflammation!?<br />
  22. 22. 11<br />We can build together new approaches in medicine, targeting<br />our other genome<br />Work<br />Network<br />Leadership<br />Improve health and well-being of many<br />

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