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05 rencontres biomédicale LIR Dusko Ehrlich

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2ND INTERNATIONAL RESEARCH MEETING …

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

Published in: Technology, Health & Medicine

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

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