Targeting zonulin and intestinal epithelial barrier function to prevent onset of arthritis.
Nat Commun
; 11(1): 1995, 2020 04 24.
Article
in En
| MEDLINE
| ID: mdl-32332732
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligopeptides
/
Arthritis, Rheumatoid
/
Protein Precursors
/
Haptoglobins
/
Cell Membrane Permeability
/
Dysbiosis
/
Intestinal Mucosa
Type of study:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2020
Document type:
Article
Affiliation country:
Germany
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM