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Intestinal histomorphological and molecular alterations in patients with Parkinson’s disease

Eur J Neurol. 2022 Oct 20. doi: 10.1111/ene.15607. Online ahead of print.

ABSTRACT

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. However, their mutual interplay has rarely been investigated. This study evaluated, 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.

METHODS: 19 PD patients and 19 asymptomatic subjects 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 α-diversity in PD patients compared to controls, while no differences were found in the beta diversity. Compared to controls, PD patients showed a significant increase in plasma LBP, as well as faecal TNF and IL-1β levels. 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.

CONCLUSIONS: PD patients are characterized by intestinal inflammation and increased IEB permeability, as well as colonic mucosal barrier remodeling, associated with changes in gut microbiota composition.

PMID:36263629 | DOI:10.1111/ene.15607

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