H2020Индивидуална стипендия2017–2020

MaRiA · Microbiota and Resolvins in Arthritis

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2017-09-21 → 2020-02-21
Финансиране от ЕС: 195 455 €
Участници: 1
Схема: MSCA-IF-EF-RI

Линиите свързват координатора с партньорите.

Накратко на български

Бактериите P. gingivalis и P. copri се изследват за това как влияят върху защитната бариера на червата и веществата, които спират възпалението при ревматоиден артрит. Разбирането на този процес помага за търсенето на начини да се предотврати влошаването на ставното заболяване.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Microbiota and Resolvins in Arthritis

Rheumatoid arthritis (RA), a chronic inflammatory disease, affects primarily the joints. Its cause remains unknown. Treatments are limited to the maintenance of symptoms, hampered by side effects, such as immunosuppression. Together, the disease and side effects carry a significant burden for the patient and society. Two types of bacteria, Porphyromonas gingivalis and Prevotella copri, exist in large parts of the population without causing harm, yet in RA patients they have been linked to joint disease, although the reason is unclear. My preliminary work had shown that infection with these bacteria worsened arthritis and decreased the amounts of lipid mediators that normally resolve inflammation and prevent chronicity of disease. This project investigated if these bacteria deregulate the production of pro-resolving lipid mediators, thus causing the worsening of joint disease. Objectives: - Determine how P.gingivalis and P.copri regulate pro-resolving lipid mediators, affect gut bacteria and the function of the gut barrier, which prevents invasion of gut bacteria into the tissues. - Assess whether the communities of bacteria living in RA patients’ intestines, which are known to differ from the communities in intestines of healthy people, negatively affect joint disease and pro-resolving lipid mediators. - Determine whether and how treatment with pro-resolving lipid mediators can prevent worsening of joint disease caused by bacteria such as P.gingivalis and P.copri. Main discoveries: During arthritis reduced levels of pro-resolving mediator RvD5n-3 DPA in the gut were linked with a weakened gut barrier. In this environment, P.gingivalis caused further breakdown of gut barrier function, invasion and spread of gut bacteria and the worsening of joint disease. If mice were given RVD5n-3 DPA, the function of the gut barrier was restored and P. gingivalis could no longer exert its detrimental actions, preventing both invasion of gut bacteria as well as the worsening of joint inflammation.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

QUEEN MARY UNIVERSITY OF LONDON · LONDONКоординаторОбединеното кралство