Hyperuricemia drives intestinal barrier dysfunction by regulating gut microbiota.

BACKGROUND

Hyperuricemia elevates gut permeability; however, the risk of its influence on the compromised intestinal barrier is poorly understood.

AIMS

This study was carried out, aiming to elucidate the orchestrators and disruptors of intestinal barrier in hyperuricemia.

METHODS

A mouse model of hyperuricemia was induced by administering adenine and oteracil potassium to mice. Allopurinol was used to decrease uric acid level, and antibiotics were administered to mice to deplete gut microbiota. Intestinal permeability was assessed using FITC-labeled dextran. Changes in gut microbial community were analyzed through 16S rRNA sequencing. IL-1β and TNF-α levels were quantified using ELISA. The expression of tight junction protein genes, , and , was determined with Q-PCR and Western blotting.

RESULTS

Allopurinol treatment effectively reduced intestinal permeability and serum TNF-α levels. Antibiotic treatment alleviated but not abolished intestinal permeability. Uric acid alone was insufficient to increase Coca2 monolayer permeability. Allopurinol treatment altered microbial composition and suppressed opportunistic infections. Re-establishing hyperuricemia in a germfree mouse model protected mice from intestinal injury. Allopurinol and antibiotic treatments reduced and expressions, increased and expressions but suppressed NF-ĸB p65 signaling. However, removing gut microbiota aggravated lipid metabolic dysfunction.

CONCLUSION

Gut microbiota is a direct and specific cause for intestinal barrier dysfunction.