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

Publication date: May 13, 2021 DOI: https : //doi.org/10.1016/j.medj.2021.04.013

Explanation

The purpose of this study was to explain whether there are changes in the gut environment and how they contribute to the etiology of arthritis.

Changes in markers of intestinal permeability, damage, and inflammation in the peripheral blood and serum of RA patients were analyzed.

As a result, RA patients showed elevated levels of serum markers of intestinal permeability and damage, and cellular intestinal homing markers, both parameters positively correlated with disease severity.

Mice with arthritis show increased intestinal permeability, bacterial migration, inflammatory intestinal damage, increased interferon gamma (IFNγ)+ and decreased IL-10+ from the early stages of the disease.

Mechanistically, disruption of the integrity of the intestinal barrier requires both arthritis-inducing bacteria and leukocytes, and exposure of intestinal organoids to IFNγ reduced expression of IL-10R by epithelial cells, while mice lacking epithelial IL-10R showed increased intestinal permeability and worsened arthritis.

The conclusion of these analyses suggests that disruption of gut barrier integrity contributes to the development of arthritis and proposes the restoration of gut barrier homeostasis as a novel therapeutic approach for RA.