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Training Network for the Development of Bacterial ExoPolysaccharides for the treatment of Inflammatory Conditions

Final Report Summary - TEAM-EPIC (Training Network for the Development of Bacterial ExoPolysaccharides for the treatment of Inflammatory Conditions)

It is now widely accepted that the bacteria, which colonise the human body (i.e. the microbiota), is important for optimal host development and for ongoing immune homeostasis. The microbiota aids in the digestion of foods and nutrient absorption, protects against colonization by pathogens, degrades mucin and promotes the differentiation and function of mucosal immune networks, in particular the induction of immune tolerance. Accumulating evidence suggests that certain bacterial strains may provide protective signals while other bacterial strains may stimulate aggressive and damaging immune responses. Thus, the activity of the mammalian immune system seems to be governed by the balance between symbiotic and pathogenic factors derived from our microbial inhabitants. This raises the possibility that dysbiosis can lead to inappropriate inflammatory responses and may contribute to the dramatic increase in several immune-mediated disorders observed in recent decades, including allergy and asthma. Bifidobacterium longum 35624 (B. longum 35624) is a commensal micro-organism, originally isolated from human gastrointestinal tissue, which has demonstrated unique properties in human clinical studies. It induces potent immunoregulatory networks in vivo, which are associated with the positive health benefits of the bacterium.

The TEAM-EPIC consortium are exploring the precise mechanisms by which one such ‘effective’ commensal microbe, B.longum 35624, confers protection against inflammatory disease through the identification and characterisation of the signalling molecules and pathways mediating communication between this bacterium and its human host. It is believed that particular cellular components, in particular polysaccharide molecules, are behind the host response observed in human clinical trials. Although there is evidence to suggest that bacterial components may be involved in the efficacy of probiotic bacteria, there are no products on the market that exploit probiotic bacterial cellular components. Therefore, the overall goal of this project is to identify and develop a number of well defined polysaccharide molecules and investigate the clinical benefits that derive from purified components of B. longum 35624.

The TEAM-EPIC consortium consists of a multidisciplinary team of five prestigious European partners: Alimentary Health Ltd (expert in developing probiotic products), Alimentary Health Pharma Davos AG (expert in developing drugs from different components of probiotics ), Swiss Institute for Asthma and Allergy Research (Coordinator and expert in immune-regulation), Vienna Institute of Biotechnology at Universität für Bodenkultur (expert in glycobiology) and University College Cork, Alimentary Pharmabiotics Centre and Department of Microbiology (expert in bioinformatics and glycobiology assembly in probiotic bacteria). Each partner provides unique critical expertise, through knowledge, personnel and facilities which have been complementary and additive and have provided the synergistic expertise required to successfully deliver on the goal of this project and forge a long-lasting relationship.

The TEAM-EPIC partners completed the project in line with the original project plan. The main significant scientific achievements of the project include:
The development of a method for the commercial isolation and purification of polysaccharides from B. longum 35624;
The identification of protective immune responses, and associated molecular mechanisms, which are induced by these polysaccharides;
The generation and analysis of genetically modified B. infantis 35624 variants, that no longer make cell surface polysaccharides;
The determination of the polysaccharide composition and putitive chemical structures.

In addition to the scientific successes of this project, the partners have trained nine researchers during the course of this program. Four researchers were recruited and five researchers have been seconded to the collaborating institutions. Three events open to the public and one workshop at an international scientific meeting have been organized and were well attended by external researchers.

A new patent application was submitted in August 2015 and three manuscripts, focused on the research carried out by the TEAM-EPIC partners, have been submitted for publication.

The end result of this project is in line with the goal originally stated in the grant application: a unique opportunity for cross-sector state-of-the-art knowledge transfer and dissemination, through the identification of molecules from B. longum 35624 with proven efficacy in the treatment of IBS and other inflammatory conditions – expected to have major commercialization, economic and health implications.

For further information, please contact the project coordinator Dr. Liam O'Mahony, Swiss Institute of Allergy and Asthma Research, University of Zürich, Obere strasse 22, 7270 Davos Platz, Switzerland (e-mail: liam.omahony@siaf.uzh.ch).

Project website: www.team-epic.ch