Intestinal barrier dysfunction plays an integral role in arthritis pathology and can be targeted to ameliorate disease.

Animals Arthritis, Rheumatoid / metabolism Dysbiosis / metabolism Gastrointestinal Microbiome Humans Inflammation / metabolism Intestinal Diseases / metabolism Intestinal Mucosa / metabolism Mice
arthritis gut mucosa gut permeability inflammation therapy

Journal

Med (New York, N.Y.)
ISSN: 2666-6340
Titre abrégé: Med
Pays: United States
ID NLM: 101769215

Informations de publication

Date de publication:
09 07 2021
Historique:
received: 04 02 2020
revised: 22 02 2021
accepted: 15 04 2021
entrez: 23 7 2021
pubmed: 24 7 2021
medline: 24 7 2021
Statut: ppublish

Résumé

Evidence suggests an important role for gut-microbiota dysbiosis in the development of rheumatoid arthritis (RA). The link between changes in gut bacteria and the development of joint inflammation is missing. Here, we address whether there are changes to the gut environment and how they contribute to arthritis pathogenesis. We analyzed changes in markers of gut permeability, damage, and inflammation in peripheral blood and serum of RA patients. Serum, intestines, and lymphoid organs isolated from K/BxN mice with spontaneous arthritis or from wild-type, genetically modified interleukin (IL)-10R RA patients display increased levels of serum markers of gut permeability and We suggest that breakdown of gut-barrier integrity contributes to arthritis development and propose restoration of gut-barrier homeostasis as a new therapeutic approach for RA. Funded by Versus Arthritis (21140 and 21257) and UKRI/MRC (MR/T000910/1).

Sections du résumé

BACKGROUND
Evidence suggests an important role for gut-microbiota dysbiosis in the development of rheumatoid arthritis (RA). The link between changes in gut bacteria and the development of joint inflammation is missing. Here, we address whether there are changes to the gut environment and how they contribute to arthritis pathogenesis.
METHODS
We analyzed changes in markers of gut permeability, damage, and inflammation in peripheral blood and serum of RA patients. Serum, intestines, and lymphoid organs isolated from K/BxN mice with spontaneous arthritis or from wild-type, genetically modified interleukin (IL)-10R
FINDINGS
RA patients display increased levels of serum markers of gut permeability and
CONCLUSIONS
We suggest that breakdown of gut-barrier integrity contributes to arthritis development and propose restoration of gut-barrier homeostasis as a new therapeutic approach for RA.
FUNDING
Funded by Versus Arthritis (21140 and 21257) and UKRI/MRC (MR/T000910/1).

Identifiants

DOI: 10.1016/j.medj.2021.04.013 PMID: 34296202 PMC: PMC8280953
pubmed: 34296202
doi: 10.1016/j.medj.2021.04.013
pii: S2666-6340(21)00162-8
pmc: PMC8280953
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Pagination

864-883.e9

Subventions

Organisme : Versus Arthritis
ID : 21140
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T000910/1
Pays : United Kingdom

Informations de copyright

© 2021 The Author(s).

Déclaration de conflit d'intérêts

A.F. is co-founder and stockholder of Alba Therapeutics, a company developing treatments complementary to the gluten-free diet by exploiting gut permeability.

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Auteurs

Diana E Matei (DE)

Centre for Rheumatology, Division of Medicine and Division of Infection and Immunity and Transplantation, University College London, London WC1E 6JF, UK.

Madhvi Menon (M)

Centre for Rheumatology, Division of Medicine and Division of Infection and Immunity and Transplantation, University College London, London WC1E 6JF, UK.
Evergrande Center for Immunologic Diseases, Harvard Medical School, Boston, MA 02115, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Lydia Becker Institute of Immunology and Inflammation, Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester M13 9PL, UK.

Dagmar G Alber (DG)

Infection, Immunity and Inflammation Programme, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.

Andrew M Smith (AM)

Eastman Dental Institute, School of Life and Medical Sciences, UCL, London WC1X 8LD, UK.

Bahman Nedjat-Shokouhi (B)

Eastman Dental Institute, School of Life and Medical Sciences, UCL, London WC1X 8LD, UK.
Centre for Molecular Medicine, Division of Medicine, UCL, London WC1E 6BT, UK.

Alessio Fasano (A)

MassGeneral Hospital for Children, Boston, MA 02114, USA.

Laura Magill (L)

Centre for Rheumatology, Division of Medicine and Division of Infection and Immunity and Transplantation, University College London, London WC1E 6JF, UK.

Amanda Duhlin (A)

Centre for Rheumatology, Division of Medicine and Division of Infection and Immunity and Transplantation, University College London, London WC1E 6JF, UK.

Samuel Bitoun (S)

Rheumatology Department, Bicêtre Hospital AP-HP, Université Paris-Saclay and INSERM UMR 1184 IMVA 78 Avenue du Général Leclerc, 94270 Le Kremlin Bicêtre, France.

Aude Gleizes (A)

Université de Paris, CNRS, INSERM, UTCBS, Unité des Technologies Chimiques et Biologiques pour la Santé, 75006 Paris, France.
Clinical Immunology Laboratory, Groupe Hospitalier Universitaire Paris-Sud, Hôpital Kremlin-Bicêtre, Assistance Publique-Hôpitaux de Paris, 94270 Le-Kremlin-Bicêtre, France.

Salima Hacein-Bey-Abina (S)

Université de Paris, CNRS, INSERM, UTCBS, Unité des Technologies Chimiques et Biologiques pour la Santé, 75006 Paris, France.
Assistance Publique - Hôpitaux Paris Saclay, Clinical Immunology Laboratory, Hôpital Bicêtre, 94275 Le-Kremlin-Bicêtre, France.

Jessica J Manson (JJ)

Department of Rheumatology, University College London Hospital, London NW1 2BU, UK.

Elizabeth C Rosser (EC)

Centre for Rheumatology, Division of Medicine and Division of Infection and Immunity and Transplantation, University College London, London WC1E 6JF, UK.
Centre for Adolescent Rheumatology Versus Arthritis at UCL, UCLH and GOSH, London WC1E 6JF, UK.

Nigel Klein (N)

Infection, Immunity and Inflammation Programme, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.

Paul A Blair (PA)

Centre for Rheumatology, Division of Medicine and Division of Infection and Immunity and Transplantation, University College London, London WC1E 6JF, UK.

Claudia Mauri (C)

Centre for Rheumatology, Division of Medicine and Division of Infection and Immunity and Transplantation, University College London, London WC1E 6JF, UK.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Intestinal barrier dysfunction plays an...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Polyarthrite rhumatoïde › Intestinal barrier dysfunction plays an...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Dysbiose › Intestinal barrier dysfunction plays an...
questionsmedicales.fr › Environnement et santé publique › Environnement › Écosystème › Biodiversité › Biote › Microbiote › Microbiome gastro-intestinal › Intestinal barrier dysfunction plays an...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Intestinal barrier dysfunction plays an...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Intestinal barrier dysfunction plays an...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Intestinal barrier dysfunction plays an...
questionsmedicales.fr › Tissus › Membranes › Muqueuse › Muqueuse intestinale › Intestinal barrier dysfunction plays an...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Intestinal barrier dysfunction plays an...