ENDOTARGET

Rheumatic diseases (RDs) affect more than 40% of Europe's population and cause significant disability, pain, reduced lifespan and a very high economic burden. In this project, we will explore the role of chronic systemic inflammation caused by intestinal microbiota derived immunologically active compounds, as a driver in the transition from health to disease, with a special focus on three RDs; osteoarthritis (OA), rheumatoid arthritis (RA), and spondylarthritis (SpA). We aim to explore the relationship between gut microbiota, intestinal permeability, and endotoxemia. We aim to understand their role as drivers of disease onset and disease activity in RA, SpA and OA, as well as targets of preventive and therapeutic approaches. We will study the events leading from health to disease onset by i) taking advantage of geographically diverse large cohorts of people with available blood and faeces samples, ii) search for novel risk biomarkers for RA, SpA, and OA by using high-throughput OMICS-based analyses iii) conducting targeted clinical studies, iv) performing in vitro mechanistic studies to explore the gut-joint axis using tissue explant cultures and organ-on-chip models v) conducting interventional proof of concept studies of diet, faecal transplantation and a gut permeability decreasing drug in RA and SpA patients, vi) exploring in vitro new potential drugs or nutraceuticals to cope with endotoxemia effects on target tissues. By combining all these results, machine learning and AI-informed rheumatic disease prediction tool will be developed for clinicians to help them identify patients with increased risk of developing the target diseases. It will thus assist in the choice of personalized blueprint intervention to reduce the risk of these diseases and disease activity in RA and SpA and to slow down the progression of OA.

2023

2026