Biochem J. 2025 May 14:BCJ20240621. doi: 10.1042/BCJ20240621. Online ahead of print.
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.
PMID:40471586 | DOI:10.1042/BCJ20240621
