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MODulATE SIGNED

Gut microbiota-dependent tryptophan metabolism: role in disease pathogenesis and therapeutic target

Total Cost €

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EC-Contrib. €

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Partnership

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Project "MODulATE" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITE PIERRE ET MARIE CURIE - PARIS 6 

There are not information about this coordinator. Please contact Fabio for more information, thanks.

 Coordinator Country France [FR]
 Total cost 1˙495˙525 €
 EC max contribution 1˙495˙525 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-STG
 Funding Scheme ERC-STG
 Starting year 2017
 Duration (year-month-day) from 2017-03-01   to  2022-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    SORBONNE UNIVERSITE FR (PARIS) coordinator 533˙816.00
2    UNIVERSITE PIERRE ET MARIE CURIE - PARIS 6 FR (PARIS) coordinator 0.00
3    INSTITUT NATIONAL DE RECHERCHE POUR L'AGRICULTURE, L'ALIMENTATION ET L'ENVIRONNEMENT FR (PARIS CEDEX 07) participant 961˙708.00

Map

 Project objective

Tryptophan (Trp) is an essential amino acid required for protein biosynthesis and is also a biochemical precursor of metabolites which have major effects on mammalian physiology. In the gastrointestinal tract, Trp metabolism can follow three major pathways, all of which are under the control of the gut microbiota: (i) the kynurenin pathway in immune and epithelial cells via indoleamine 2,3-Dioxygenase 1, (ii) the serotonin production pathway in enterochromaffin cells via Trp hydroxylase 1 and (iii) the direct use of Trp by the microorganisms of the gut microbiota into several molecules including ligands of the Aryl Hydrocarbon Receptor. The end products of these pathways play key roles in modulating the immune response, intestinal and metabolic functions and behaviour. Several diseases which involve the gut microbiota in their pathogenesis are also impacted by Trp metabolite. This suggests that the effect of the microbiota in these diseases could be at least partially mediated by impaired Trp metabolism. We recently observed that impaired Trp metabolism by the gut microbiota is involved in inflammatory bowel disease pathogenesis and preliminary data suggest a potential role in other major human diseases. The aims of the current proposal are (i) to identify the components of the gut microbiota, including both bacteria and fungi, involved in the control of the 3 Trp metabolism pathways in the gut, (ii) to decipher the reciprocal equilibrium between the pathways and to evaluate the potential of its modulation as a therapeutic target, and finally (iii) to assess the relevance of these phenomena in human patients. This challenging project will involve multi-disciplinary aspects, from microbiology to metabolism, inflammation and medicine, the use of multiple cutting edge technologies and translational analysis from mice to human. Beside scientific importance, it will have societal impact by identifying new therapeutic strategies in several human diseases with unmet needs.

 Publications

year authors and title journal last update
List of publications.
2018 Michela Miani, Julie Le Naour, Emmanuelle Waeckel-Enée, Subash chand Verma, Marjolène Straube, Patrick Emond, Bernhard Ryffel, Peter van Endert, Harry Sokol, Julien Diana
Gut Microbiota-Stimulated Innate Lymphoid Cells Support β-Defensin 14 Expression in Pancreatic Endocrine Cells, Preventing Autoimmune Diabetes
published pages: 557-572.e6, ISSN: 1550-4131, DOI: 10.1016/j.cmet.2018.06.012
Cell Metabolism 28/4 2020-04-24
2018 Ludivine Laurans, Nicolas Venteclef, Yacine Haddad, Mouna Chajadine, Fawaz Alzaid, Sarvenaz Metghalchi, Bruno Sovran, Raphael G. P. Denis, Julien Dairou, Marina Cardellini, Jose-Maria Moreno-Navarrete, Marjolene Straub, Sarah Jegou, Claire McQuitty, Thomas Viel, Bruno Esposito, Bertrand Tavitian, Jacques Callebert, Serge H. Luquet, Massimo Federici, José Manuel Fernandez-Real, Remy Burcelin, Jean-Marie Launay, Alain Tedgui, Ziad Mallat, Harry Sokol, Soraya Taleb
Genetic deficiency of indoleamine 2,3-dioxygenase promotes gut microbiota-mediated metabolic health
published pages: 1113-1120, ISSN: 1078-8956, DOI: 10.1038/s41591-018-0060-4
Nature Medicine 24/8 2020-04-24
2018 Jane M. Natividad, Allison Agus, Julien Planchais, Bruno Lamas, Anne Charlotte Jarry, Rebeca Martin, Marie-Laure Michel, Caroline Chong-Nguyen, Ronan Roussel, Marjolene Straube, Sarah Jegou, Claire McQuitty, Maude Le Gall, Gregory da Costa, Emmanuelle Lecornet, Chloé Michaudel, Morgane Modoux, Jeremy Glodt, Chantal Bridonneau, Bruno Sovran, Louise Dupraz, Andre Bado, Mathias L. Richard, Philippe Langella, Boris Hansel, Jean-Marie Launay, Ramnik J. Xavier, Henri Duboc, Harry Sokol
Impaired Aryl Hydrocarbon Receptor Ligand Production by the Gut Microbiota Is a Key Factor in Metabolic Syndrome
published pages: , ISSN: 1550-4131, DOI: 10.1016/j.cmet.2018.07.001
Cell Metabolism 2020-04-24
2018 Bruno Lamas, Jane M. Natividad, Harry Sokol
Aryl hydrocarbon receptor and intestinal immunity
published pages: 1024-1038, ISSN: 1933-0219, DOI: 10.1038/s41385-018-0019-2
Mucosal Immunology 11/4 2020-04-24
2018 Allison Agus, Julien Planchais, Harry Sokol
Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease
published pages: 716-724, ISSN: 1931-3128, DOI: 10.1016/j.chom.2018.05.003
Cell Host & Microbe 23/6 2020-04-24

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