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MODulATE SIGNED

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

Total Cost €

EC-Contrib. €

Partnership

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MODulATE project word cloud

Explore the words cloud of the MODulATE project. It provides you a very rough idea of what is the project "MODulATE" about.

follow societal direct inflammation epithelial cutting metabolites impaired disease beside mediated acid aryl decipher indoleamine components metabolite data trp molecules cells inflammatory edge biochemical scientific suggests modulating intestinal mammalian immune amino fungi hydrocarbon gastrointestinal precursor roles metabolism relevance kynurenin suggest effect least medicine patients mice biosynthesis technologies pathogenesis hydroxylase enterochromaffin reciprocal preliminary impacted metabolic play functions bowel ligands phenomena dioxygenase serotonin microorganisms disciplinary tract modulation tryptophan therapeutic microbiology human diseases equilibrium strategies bacteria gut involve unmet translational protein physiology receptor microbiota multiple

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 SORBONNE UNIVERSITE Organization address address: 21 RUE DE L'ECOLE DE MEDECINE city: PARIS postcode: 75006 website: n.a. contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	FR (PARIS)	coordinator	533˙816.00
2	UNIVERSITE PIERRE ET MARIE CURIE - PARIS 6 UNIVERSITE PIERRE ET MARIE CURIE - PARIS 6 Organization address address: Place Jussieu 4 city: PARIS postcode: 75252 website: www.upmc.fr contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	FR (PARIS)	coordinator	0.00
3	INSTITUT NATIONAL DE RECHERCHE POUR L'AGRICULTURE, L'ALIMENTATION ET L'ENVIRONNEMENT INSTITUT NATIONAL DE RECHERCHE POUR L'AGRICULTURE, L'ALIMENTATION ET L'ENVIRONNEMENT Organization address address: Rue De L'Universite 147 city: PARIS CEDEX 07 postcode: 75338 website: www.inra.fr contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	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

List of publications.
year	authors and title	journal	last update
2018	Michela Miani, Julie Le Naour, Emmanuelle Waeckel-EnÃ©e, Subash chand Verma, MarjolÃ¨ne Straube, Patrick Emond, Bernhard Ryffel, Peter van Endert, Harry Sokol, Julien Diana Gut Microbiota-Stimulated Innate Lymphoid Cells Support Î²-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, JosÃ© 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, ChloÃ© 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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The information about "MODULATE" are provided by the European Opendata Portal: CORDIS opendata.