Gut Permeability and Neuroinflammation Linked in Parkinson’s Disease

Jun 17, 2024

Photo Credit: Dr Microbe

A relationship between gut permeability and neuroinflammation has been found in patients with Parkinson’s disease, and what this could mean for the condition.

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 procaspase-1 and caspase-1 on western blot analysis and an increase in CD68+ macrophages. Patients with rapid eye movement (REM) behavior disorder, which often precedes the onset of Parkinson’s disease, also showed increased inflammatory markers.

A prospective study of 28 patients with Parkinson’s disease and 18 patients with REM behavior disorder, all of whom reported gastrointestinal symptoms without serious organic diseases and did not receive any therapies affecting gastrointestinal motility.¹ Additionally, the study included 14 healthy controls for comparison. Serum ELISA assays measured levels of tumor necrosis factor (TNF), caspase-1, and lipopolysaccharide-binding protein (LBP). Colonic biopsies from 10 patients with Parkinson’s disease, four patients with REM behavior disorder, and nine healthy controls assessed tissue expression of inflammation markers via western blot and immunofluorescence.

The primary endpoints included levels of systemic inflammatory markers, gut permeability indicators, and colonic tissue inflammation markers. All groups were comparable in age and sex. Serum assays revealed significantly elevated LBP levels in Parkinson’s disease (35.0±0.3; P=0.002) and REM behavior disorder (32.2±1.1; P=0.01) patients compared with healthy controls (23.1±2.1). TNF (0.1±0.02 vs 0.04±0.02; P=0.03) and caspase-1 (16.9±9.4 vs 9.9±2.7; P=0.04) levels were significantly increased only in the Parkinson’s disease group compared with healthy controls. Western blot analysis showed higher procaspase-1 (157.3±17.8 vs 100.0±5.1; P=0.02) and caspase-1 (168.3±23.3 vs 83.5±12.3; 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 Parkinson’s disease and REM behavior disorder groups compared with healthy controls.

The study demonstrates increased gut inflammation in patients with Parkinson’s disease, evidenced by increased levels of procaspase-1, caspase-1, CD68+ macrophages, and apoptosis-associated speck-like protein expression in colonic tissue. Patients with REM behavior 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 these conditions.

Medical writing support was provided by Federica Angius.