Possible role of intestinal permeability and microbiota in the pathogenesis of Parkinson’s disease: preliminary results from a pilot study

Emerging data suggest that the gut-microbiota-brain axis may be involved in Parkinson's disease (PD) pathophysiology. Our aims were to evaluate the gut permeability and microbiota in patients with PD and REM sleep behavior disorder (RBD) compared to healthy controls (HCs). The study included 45 PD patients, divided in 22 PD body and 23 PD brain, 49 RBD patients and 16 HCs. Besides demographic data, all subjects were assessed according to the BSFS and Rome IV criteria to diagnose functional constipation (FC), and were given scales for clinical assessment (i.e., HADS, MoCA, SCOPA AUT-TOT/GI, MDS-UPDRS III, GIDS-PD/C/BI/UGI). Gut permeability was assessed with a serum ELISA assay for zonulin. The α- and β-diversity of gut microbiota was evaluated. Data were expressed as median (IQR) and compared using Kruskal-Wallis test with the Mann-Whitney test and Bonferroni correction. All four groups were comparable in age, gender, and BMI. Regarding clinical assessment, FC was more frequent in all three patient groups (p<0.001), RBD and PD body patients reported a greater prevalence of bowel irritability symptoms (p<0.001) and upper gastrointestinal symptoms (p<0.001). Zonulin levels were significantly increased only in PD body patients compared to those with RBD (p < 0.001). A partial segregation of the different study groups was observed at the beta-diversity analysis. PD patients showed significantly higher α-diversity compared to HCs, with intermediate values for the RBD group. Our findings suggest a predominant gastrointestinal pathogenesis for PD body and RBD patients, consistent with the ‘brain-first’ versus ‘body-first’ model.