Elevated levels of colonic interleukin-1beta and interleukin-8 in isolated REM sleep behavior disorder without associated changes in permeability

Abstract Some recent studies suggest that gastrointestinal inflammation could play a role in the development of Parkinson’s disease (PD) by increasing intestinal permeability and triggering early neuropathological changes in the gut. Therefore, we set out to analyze gut inflammation as well as intestinal barrier function and integrity in patients with isolated REM sleep behavior disorder (iRBD), a prodromal stage of PD. Sigmoid colon biopsy specimens from patients with iRBD (n = 20), patients with PD (n = 34) and controls (n = 20) were analyzed by qPCR to measure the expression levels of proinflammatory cytokines and enteric glial markers. Fecal calprotectin levels were also measured to further assess gastrointestinal inflammation. Gut permeability was evaluated in biopsies mounted in Ussing chambers, and the integrity of the intestinal epithelial barrier was assessed by analyzing the expression of tight junction proteins by western blot. We found that the mRNA expression levels of interleukin-1β and interleukin-8 were increased in both patients with iRBD and PD relative to controls; the expression of TNF-α was also higher in PD but not in iRBD patients. We did not observe any differences in colonic permeability, tight junction proteins expression and calprotectin levels between iRBD, PD and control participants. Our study is the first to characterize the inflammatory profile in the gut in iRBD. As a whole, our findings provide evidence that enteric inflammation is present at a moderate level in prodromal PD, not higher than in individuals with established PD, and without concurrent changes in intestinal permeability.