1 Our other genome - the foundation for new approaches in medicine S. Dusko Ehrlich, INRA, MetaHIT coordinator Paris, June 4, 2010
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)….
The MetaHIT (Metagenomics of the Human Intestinal Tract) Consortium
European Commission FP7 project, coordinated by INRA (S. Dusko Ehrlich)
12 European and 1 Chinese Institutions; 9 public, 4 private
21.2 M € /4 yrs (11.4 M € from the EC); 100 scientists
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 !
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
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
The MetaHIT barcode Obesitystudy, 80 individuals Three clinical studies (in progress; unpublished) Obesity 177 Danes lean: n = 67 ; obese: n = 110 IBD – Crohn Disease 21 Spaniards patients: n = 8 ; healthy: n = 13 IBD – Ulcerative Colitis 24 Spaniards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
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?
Where do these studies lead to and when? Diagnostic & prognostic tests - soon - arrays, sequencing, Q-PCR; immunomarkers (?) Better treatments - next
Responders/non-responders Novel treatments – last: target our other genome!