Objective: To evaluate, in an integrated manner, changes in faecal microbiota composition, morpho-functional alterations of the colonic mucosal barrier and changes of inflammatory markers in blood and stools of PD patients.

Background: Changes in gut microbiota composition, enteric inflammation, impairments of the intestinal epithelial barrier (IEB) and enteric neuro-immune system have been reported in Parkinson’s disease (PD) patients and could contribute to the onset of both neurological and gastrointestinal symptoms [1,2]. However, most of this evidence has been reported in the form of distinct and separate determinants, but their mutual interplay has rarely been investigated.

Method: 19 PD patients (14 males and 5 females, mean age 70,7 ± 1,2 years) and 19 asymptomatic subjects comparable by age (67,5±2,2 years) and sex were enrolled. Blood lipopolysaccharide binding protein (LBP, marker of altered intestinal permeability) and Interleukin-1β (IL-1β), as well as stool IL-1β and tumour necrosis factor (TNF) levels, were evaluated. Gut microbiota analysis was performed. Epithelial mucins, collagen fibres, Claudin-1 and S-100 positive glial cells as markers of an impairment of the intestinal barrier and mucosal remodelling were evaluated on colonic mucosal specimens collected during colonoscopy.

Results: Faecal microbiota analysis revealed a significant difference in the a-diversity in PD patients compared to controls, while no differences were found in the beta diversity. [fig.1] Compared with controls, PD patients showed a significant increase in plasma LBP (34.4 ± 3.4 vs 22.4 ± 1.5 ng/mL), as well as faecal TNF (95.9 ± 12.3 vs 59.3 ± 10.4 pg/mg stool) and IL-1β (17.4 ± 2.4 vs 7.7 ± 0.8 pg/mg stool) levels. In addition, the histological analysis showed a decrease in epithelial neutral mucins and claudin-1 expression, and an increased expression of acidic mucins, collagen fibres and S-100 positive glial cells [fig.2] [fig.3].

Conclusion: PD patients are characterized by intestinal inflammation and increased intestinal epithelial barrier permeability, as well as colonic mucosal barrier remodeling, associated with changes in gut microbiota composition. Further studies are needed to establish whether such alterations are a pathogenetic factor or a mere consequence of the disease.

References: 1. Pellegrini C, Antonioli L, Colucci R, Blandizzi C, Fornai M. Interplay among gut microbiota, intestinal mucosal barrier and enteric neuro-immune system: a common path to neurodegenerative diseases? Acta Neuropathol. 2018;136(3):345-361. doi:10.1007/s00401-018-1856-5

2. Mrabet S, Ben Ali N, Achouri A, et al. Gastrointestinal Dysfunction and Neuropathologic Correlations in Parkinson Disease. J Clin Gastroenterol [online serial]. 2016;50:e85–e90. Accessed at: https://journals.lww.com/00004836-201610000-00003.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/molecular-alterations-and-pathological-remodeling-of-colonic-wall-in-patients-with-parkinsons-disease/