Interplay of constipation, intestinal barrier dysfunction and fungal exposome in aetiopathogensis of Parkinson’s disease; hypothesis with supportive data
File(s)
Published online version
Author(s)
Type
Journal Article
Abstract
Constipation is a forerunner to Parkinson’s disease (PD) diagnosis, worsening thereafter. We explore the relationship of intestinal barrier dysfunction to constipation, and whether intestinal fungal load is an aggravating factor. Fungal load was quantified by real-time PCR, using ITS1F-ITS2 primer-set, on microbial DNA-extract from stool in 68 participants with PD, 102 without. Fungal load was 60% higher per decade after age 60 years, with no PD-status interaction with age. After age adjustment, it was associated inversely with dietary renal acid load. It was unrelated to presence of constipation or barrier dysfunction. Neither consumption of antimicrobials nor of other targeted exogenous substances was associated. Enzyme-linked-immunosorbent assays measured barrier dysfunction markers, faecal alpha-1 antitrypsin and zonulin and serum intestinal-fatty-acid-binding-protein. Barrier dysfunction was associated with constipation and slower colonic transit. Functional constipation was 28% more frequent with a doubling of alpha-1 antitrypsin concentration. More colonic-transit-test markers were retained in transverse colon, the higher alpha-1 antitrypsin and zonulin concentrations, anatomically spotlighting abnormality for entire colon. In contrast, the concentration of the small intestinal barrier marker, fatty-acid-binding-protein, was associated with looser stool consistency, that is consistent with secondary microbial overgrowth. By showing the relationship of intestinal barrier dysfunction to constipation, this study supports the hypothesis that dysfunction may be consequential. Dysfunction may be a necessary, but not sufficient, precursor to PD, in allowing inflammaging. Since ageing is the clearest risk for PD, a gut pathogen escalating in abundance from the sixth decade, integral to fungal load, whose reproduction and virulence is favoured by alkalinity, tallies.
Date Issued
2025-05-14
Date Acceptance
2025-05-14
Citation
Biochemical Journal, 2025
ISSN
0264-6021
Publisher
Portland Press
Journal / Book Title
Biochemical Journal
Copyright Statement
© 2025 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0
License URL
Identifier
10.1042/BCJ20240621/973784/bcj-2024-0621.pdf
Publication Status
Published online
Date Publish Online
2025-05-14