Objective The proposed work will investigate the regulation of pro-resolving lipid mediators (LM) by pathobionts and dysbiotic microbiota in rheumatoid arthritis (RA).RA is a chronic inflammatory disease with considerable socioeconomic impact. Most treatment options carry severe side effects including immunosuppression. Recent studies found associations between RA and dysbiosis of the microbiota, with the underlying mechanisms leading to this dysbiosis remaining of interest. In addition, I recently found that in both mice during pathobiont-driven inflammatory arthritis and in plasma from patients with RA the levels of a novel family of host protective LM, termed n-3 docosapentaenoic acid-derived Resolvins (RvDn-3 DPA), were significantly altered.The novel hypothesis of this action is that pathobionts and pathobiont-induced gut-dysbiosis trigger local inflammatory responses and impair the production of RvDn-3 DPA, resulting in exacerbation and chronicity of local inflammation.This novel hypothesis will be addressed using a multi-pronged approach to: 1) Characterise the role of Porphyromonas gingivalis and Prevotella copri in regulating RvDn-3 DPA, local inflammation and their effects on intestinal microbiota and gut barrier function.2) Assess the regulation of inflammatory arthritis and RvDn-3 DPA by RA patients’ microbiota.3) Establish the protective actions of RvDn-3 DPA in pathobiont-driven inflammatory arthritis.This will provide insights into mechanisms of pathobiont- and dysbiotic microbiota-triggered arthritic inflammation, the regulation of tissue LM profiles and identify potential novel diagnostic markers for early RA-detection. In addition, this work will establish the therapeutic potential of RvDn-3 DPA in regulating exacerbated inflammation and dysbiosis in inflammatory arthritis, providing novel therapeutic opportunities for RA treatment. Fields of science medical and health sciencesclinical medicinerheumatologymedical and health scienceshealth sciencesinflammatory diseasesnatural sciencesbiological sciencesbiochemistrybiomoleculeslipids Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2016 - Individual Fellowships Call for proposal H2020-MSCA-IF-2016 See other projects for this call Funding Scheme MSCA-IF-EF-RI - RI – Reintegration panel Coordinator QUEEN MARY UNIVERSITY OF LONDON Net EU contribution € 195 454,80 Address 327 MILE END ROAD E1 4NS London United Kingdom See on map Region London Inner London — East Tower Hamlets Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 195 454,80
