Interplay of constipation, intestinal barrier dysfunction and fungal exposome in aetiopathogenesis of Parkinson's disease: hypothesis with supportive data.

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 the 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 (AAT), zonulin and serum intestinal fatty acid-binding protein (I-FABP). Barrier dysfunction was associated with constipation and slower radiographic colonic transit. Functional constipation was 28% more frequent with a doubling of AAT concentration. More colonic-transit test markers were retained in the transverse colon, the higher the AAT and zonulin concentrations, anatomically spotlighting abnormality for the entire colon. In contrast, the concentration of the small intestinal barrier marker I-FABP was associated with looser stool consistency, which is consistent with secondary microbial overgrowth. By showing a 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, and whose reproduction and virulence is favoured by alkalinity, tallies.