ENDOTARGET – Systemic Endotoxemia as a driver of chronic inflammation: Biomarkers and novel therapeutic targets for Arthritis
Rheumatic diseases (RDs) affect more than 40% of Europe’s population and cause significant disability, pain, reduced lifespan, and a very high economic burden. But by now it is unclear, which mechanisms and triggers are responsible for the onset of RDs.
It is suggested that chronic systemic inflammations are caused by the intestinal microorganisms (gut microbiota), or rather by bacterial derived compounds, which activate the immune system. Due to an increased gut permeability, these compounds are able to move from the gut into the blood, reaching systemic circulation and causing local inflammations (systemic endotoxemia).
The EU funded project ENDOTARGET aims to explore the relationship between gut microbiota, gut permeability, and systemic endotoxemia with a special focus on the three most abundant rheumatic diseases (RDs): osteoarthritis, rheumatoid arthritis and spondylarthritis. The events leading to disease onset will be studied by geographically diverse cohorts (blood and feces samples), OMICS-based analyses, clinical studies, in vitro mechanistic studies (tissue cultures, organ on chip models) and proof of concept studies focusing on diet, fecal transplantation, and drugs influencing gut permeability. The aim is to clarify (1) the role of the three factors gut microbiota, gut permeability and systemic endotoxemia in RD onset and pathogenesis, (2) which events and mechanisms are responsible for the origin of RDs, and (3) the influence of the gut microbiota on joint inflammation.
Based on the gained knowledge, new biomarkers (measurable parameters) for risk assessment will be identified and a Rheumatic disease risk prediction tool (RDPT) will be developed to support clinicians in the classification of patients and to treat RDs preventively. This tool will help to reduce the risk of RD onset and/or to reduce disease activity.
The EU has awarded the ENDOTARGET project with 7 million EUR and an additional 1.8 million EUR has been granted by the Swiss State Secretariat for Education, Research and Innovation (SERI). The Consortium, which starts its work in January 2023, consists of 14 Partners from 8 countries: Helsingin ja Uudenmaan sairaanhoitopiiri (Hospital District of Helsinki and Uusimaa) (Finland), Tartu Ulikool (University of Tartu) (Estonia), Universita degli studi della Campania Luigi Vanvitelli (University of Campania Luigi Vanvitelli) (Italy), Instituto de Medicina Molecular Joao Lobo Antunes (Institute of Molecular Medicine) (Portugal), Servizio Gelago de Saude (Galician Health Service) (Spain), Fundacion Instituto de Investigacion Sanitaria de Santiage de Compostela (Health Research Institute of Santiage de Compostela) (Spain), Helsingin Yliopisto (University of Helsinki) (Finland), Technische Universität Wien (Vienna University of Technology) (Austria), NEC Laboratories Europe GmbH (Germany), NEC Italie SPA (Italy), Steinbeis 2i GmbH (Gemany), Fondazione Ebris (European Biomedical Research Institute of Salerno) (Italy), SIB Swiss Institute of Bioinformatics (Switzerland), Eidgenössische Technische Hochschule Zürich (Swiss Federal Institute of Technology in Zürich) (Switzerland).