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GAMES SIGNED

Gut Microbiota in Nervous System Autoimmunity: Molecular Mechanisms of Disease Initiation and Regulation

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Project "GAMES" data sheet

The following table provides information about the project.

Coordinator
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV 

Organization address
address: HOFGARTENSTRASSE 8
city: Munich
postcode: 80539
website: www.mpg.de

contact info
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name: n.a.
surname: n.a.
function: n.a.
email: n.a.
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fax: n.a.

 Coordinator Country Germany [DE]
 Project website https://www.biochem.mpg.de/krishnamoorthy
 Total cost 1˙499˙946 €
 EC max contribution 1˙499˙946 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-06-01   to  2020-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV DE (Munich) coordinator 1˙499˙946.00

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 Project objective

Multiple Sclerosis (MS), an autoimmune demyelinating disease affecting the central nervous system (CNS), causes tremendous disability in young adults and inflicts huge economic burden on the society. The incidence of MS is steadily increasing in many countries arguing for environmental factors driven changes in disease induction. How and which environmental factors contribute to disease initiation and progression is unknown. Using a spontaneous mouse model of MS, we have shown that the gut microbiota is essential in triggering CNS autoimmunity. In contrast to the mice housed in conventional housing conditions, germ free (GF) mice, devoid of gut bacteria, were protected from spontaneous experimental autoimmune encephalomyelitis (sEAE). Re-colonization of GF mice with a complex regular gut flora derived from specific pathogen free (SPF) mice resulted in sEAE within 2-3 months. The re-colonization also triggered pro-inflammatory T and B cell responses. However, colonization of GF mice with a reduced gut flora failed to induce sEAE during our observation period suggesting a “specific” rather than a “broader” microbial trigger. In this proposal, I want to study the role of gut microbiota in CNS autoimmunity with the following aims:

Aim 1: CNS autoimmunity triggering/protecting gut microbes and host immune responses I want to study how and which gut bacterial species are modulating CNS autoimmunity to better understand the origin of autoimmune responses and their relation to host immune responses. Aim 2: Molecular mechanisms of sensing of gut microbiota and microbial metabolites during CNS autoimmunity I want to identify the molecular pathways that are involved in sensing the gut microbiota and its metabolites which are relevant to CNS autoimmunity. Aim 3: Therapeutic application of gut microbiota for CNS autoimmunity I want to identify therapeutic strategies targeting gut microbiota to limit the development of inflammatory processes during CNS autoimmunity.

 Publications

year authors and title journal last update
List of publications.
2018 Mathangi Janakiraman, Gurumoorthy Krishnamoorthy
Emerging Role of Diet and Microbiota Interactions in Neuroinflammation
published pages: 2067, ISSN: 1664-3224, DOI: 10.3389/fimmu.2018.02067
Frontiers in Immunology 9 2020-01-29
2019 Marsilius Mues, Gurumoorthy Krishnamoorthy
B ReDi mouse: A novel transgenic mouse strain to track and deplete B cells
published pages: 500-503, ISSN: 0014-2980, DOI: 10.1002/eji.201847930
European Journal of Immunology 49/3 2020-01-29
2018 Kerstin Berer, Inés Martínez, Alesia Walker, Birgit Kunkel, Philippe Schmitt-Kopplin, Jens Walter, Gurumoorthy Krishnamoorthy
Dietary non-fermentable fiber prevents autoimmune neurological disease by changing gut metabolic and immune status
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-018-28839-3
Scientific Reports 8/1 2019-04-18
2017 Kerstin Berer, Lisa Ann Gerdes, Egle Cekanaviciute, Xiaoming Jia, Liang Xiao, Zhongkui Xia, Chuan Liu, Luisa Klotz, Uta Stauffer, Sergio E. Baranzini, Tania Kümpfel, Reinhard Hohlfeld, Gurumoorthy Krishnamoorthy, Hartmut Wekerle
Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice
published pages: 10719-10724, ISSN: 0027-8424, DOI: 10.1073/pnas.1711233114
Proceedings of the National Academy of Sciences 114/40 2019-06-04

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