Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis

Tajik N, Frech M, Schulz O, Schälter F, Lucas S, Azizov V, Dürholz K, Steffen F, Omata Y, Rings A, Bertog M, Rizzo A, Iljazovic A, Basic M, Kleyer A, Culemann S, Krönke G, Luo Y, Überla K, Gaipl U, Frey B, Strowig T, Sarter K, Bischoff SC, Wirtz S, Cañete JD, Ciccia F, Schett G, Zaiss M (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 11

Article Number: 1995

Journal Issue: 1

DOI: 10.1038/s41467-020-15831-7

Abstract

Gut microbial dysbiosis is associated with the development of autoimmune disease, but the mechanisms by which microbial dysbiosis affects the transition from asymptomatic autoimmunity to inflammatory disease are incompletely characterized. Here, we identify intestinal barrier integrity as an important checkpoint in translating autoimmunity to inflammation. Zonulin family peptide (zonulin), a potent regulator for intestinal tight junctions, is highly expressed in autoimmune mice and humans and can be used to predict transition from autoimmunity to inflammatory arthritis. Increased serum zonulin levels are accompanied by a leaky intestinal barrier, dysbiosis and inflammation. Restoration of the intestinal barrier in the pre-phase of arthritis using butyrate or a cannabinoid type 1 receptor agonist inhibits the development of arthritis. Moreover, treatment with the zonulin antagonist larazotide acetate, which specifically increases intestinal barrier integrity, effectively reduces arthritis onset. These data identify a preventive approach for the onset of autoimmune disease by specifically targeting impaired intestinal barrier function.

Authors with CRIS profile

Michael Frech Department of Medicine 3 – Rheumatology and Immunology Sébastien Lucas Department of Medicine 3 – Rheumatology and Immunology Vugar Azizov Lehrstuhl für Biochemie und Pathobiochemie Kerstin Dürholz Department of Medicine 3 – Rheumatology and Immunology Marko Bertog Lehrstuhl für Physiologie (Vegetative Physiologie) Arnd Kleyer Department of Medicine 3 – Rheumatology and Immunology Gerhard Krönke Department of Medicine 3 – Rheumatology and Immunology Klaus Überla Lehrstuhl für Klinische und Molekulare Virologie Udo Gaipl Department of Radiation Oncology Benjamin Frey Department of Radiation Oncology Kerstin Sarter-Zaiss Department of Medicine 3 – Rheumatology and Immunology Stefan Wirtz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Georg Schett Lehrstuhl für Innere Medizin III Mario Zaiss Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Universität Hohenheim DE Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Hospital Clínic de Barcelona ES Spain (ES) West China Medical Center of Sichuan University / 四川大学华西医学中心 CN China (CN) Università degli Studi di Palermo IT Italy (IT) Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE)

How to cite

APA:

Tajik, N., Frech, M., Schulz, O., Schälter, F., Lucas, S., Azizov, V.,... Zaiss, M. (2020). Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis. Nature Communications, 11(1). https://dx.doi.org/10.1038/s41467-020-15831-7

MLA:

Tajik, Narges, et al. "Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis." Nature Communications 11.1 (2020).

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