The gut microbiota metabolite propionate ameliorates intestinal epithelial barrier dysfunction-mediated Parkinson's disease via the AKT signaling pathway.

Abstract

Parkinson's disease is a common neurodegenerative disease. Here, we investigated the protective effect and potential mechanisms of propionate on the intestinal epithelial barrier in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease. Gas chromatography was used to determine short-chain fatty acids (SCFA) concentrations in the fecal samples of Parkinson's disease patients and healthy controls. The stepping test was used to analyze forelimb akinesia, whisker test was used to analyze sensorimotor injury, cylinder test was used to analyze sensorimotor function, and Western blotting was used to analyze protein expression. The concentrations of SCFAs, including acetate, butyrate and propionate, were significantly downregulated in the fecal samples of Parkinson's disease patients, and among the SCFAs, propionate decreased the most. Propionate administration improved the stepping test score, whisker test score and cylinder test score of MPTP-induced Parkinson's disease mice. Additionally, propionate administration increased the protein expression of zonula occludens-1 and occludin. Moreover, the effects of propionate on motor behavior and the intestinal epithelial barrier were dependent on the proteirrserinc-threonine kinases (AKT) signaling pathway. More importantly, treatment with SC79, a specific AKT agonist, abolished the effects of propionate on the intestinal epithelial barrier and motor behavior. Our results demonstrated that propionate, which was decreased in the fecal samples of Parkinson's disease patients, exerted beneficial effects on intestinal epithelial barrier function and improved motor behavior in MPTP-induced Parkinson's disease mice through the AKT signaling pathway.