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ERC

GAMES Report Summary

Project ID: 635617
Funded under: H2020-EU.1.1.

Periodic Reporting for period 1 - GAMES (Gut Microbiota in Nervous System Autoimmunity: Molecular Mechanisms of Disease Initiation and Regulation)

Reporting period: 2015-06-01 to 2016-11-30

Summary of the context and overall objectives of the project

Multiple Sclerosis (MS), an autoimmune disease, 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 mice, devoid of gut bacteria, were protected from spontaneous experimental autoimmune encephalomyelitis (sEAE). When such mice were treated with gut bacteria derived from specific pathogen free mice they developed the disease within 2-3 months. The GAMES project studies how and which gut bacteria influence autoimmune responses and which molecular pathways are involved in disease development. Knowing the basic processes leading to disease would aid the establishment of therapeutic strategies targeting gut microbiota to limit the development of inflammatory processes during CNS autoimmunity.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

During the first 1 ½ years GAMES researchers investigated the impact of gut microbes on CNS autoimmunity by combining germ free (GF) mouse models, knock out mouse strains, antibiotic treatments and dietary manipulation strategies to learn the mechanisms by which gut microbes impact CNS autoimmunity. They specifically worked towards defining minimal microbial flora that are essential for autoimmunity and also advanced an
approach to modulate microbiota using specific dietary interventions. This part of the work will be published soon.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Knowing the basic processes leading to disease would aid the establishment of therapeutic strategies targeting gut microbiota to limit the development of inflammatory processes during CNS autoimmunity.
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