Gut permeability and neuroinflammation linked in Parkinson’s disease

A pilot study has found a significant relationship between gut permeability and neuroinflammation in patients with Parkinson’s disease. This association was demonstrated by the levels of serum inflammatory markers as well as the expression of procaspase-1, caspase-1, and CD68+ macrophages in colonic biopsies. Patients with rapid eye movement (REM) behaviour disorder, which often precedes the onset of Parkinson’s disease, alsocreased inflammatory markers.

A prospective study was conducted including 28 patients with Parkinson’s disease and 18 patients with REM behaviour disorder, all of whom reported gastrointestinal symptoms without serious organic diseases and were not receiving any therapies affecting gastrointestinal motility [1]. Additionally, 14 healthy controls were included for comparison. Serum ELISA assays measured levels of tumour necrosis factor (TNF), caspase-1, and lipopolysaccharide-binding protein (LBP). Colonic biopsies from 10 patients with Parkinson’s disease, 4 patients with REM behaviour disorder, and 9 healthy controls were also obtained to assess tissue expression of inflammatory markers via western blot (e.g. for caspase-1 and procaspase-1) and immunofluorescence (e.g. for CD68).

The primary endpoints included levels of systemic and colonic tissue inflammatory markers. All 3 groups were comparable regarding age and sex. Serum assays revealed significantly elevated LBP levels in patients with Parkinson's disease (35.0; P=0.002) and REM behaviour disorder (32.2; P=0.01) compared with healthy controls (23.1). TNF (0.1 vs 0.04; P=0.03) and caspase-1 (16.9 vs 9.9; P=0.04) levels were significantly increased only in the Parkinson's disease group compared with healthy controls. The western blot analysis showed higher procaspase-1 (157.3 vs 100.0; P=0.02) and caspase-1 (168.3 vs 83.5; P=0.03) in patients with Parkinson's disease compared with healthy controls. Finally, immunofluorescence indicated a qualitative increase in CD68+ macrophage infiltration and apoptosis-associated speck-like protein expression in both Parkinson's disease and REM behaviour disorder groups compared with healthy controls.

In conclusion, the study demonstrates increased gut inflammation in patients with Parkinson’s disease, evidenced by elevated levels of procaspase-1, caspase-1, CD68+ macrophages, and apoptosis-associated speck-like protein expression in colonic tissue. Patients with REM behaviour disorder also showed increased inflammatory markers, though less consistently. Elevated serum levels of these markers suggest that gut inflammation and permeability may be early indicators of the development of Parkinson’s disease and REM behaviour disorder.

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   1. Rettura F, et al. Gut permeability and its role in Parkinson's disease: preliminary results from a pilot study. Sa1697, DDW 2024, 18–21 May, Washington DC, USA.

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Posted on 11 July 202411 July 2024