Intestinal biomarkers, microbiota composition, and genetic predisposition to inflammatory bowel disease as predictors of Parkinson's disease manifestation

May 8, 2025Journal of Parkinson's disease

Gut markers, bacteria, and genetic risk for inflammatory bowel disease linked to Parkinson’s disease symptoms

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Abstract

Constipation severity in Parkinson's disease patients is linked to worse cognitive function and daily living activities.

Worse mentation and limited daily living activities were associated with constipation severity in Parkinson's disease patients.
Higher disease activity scores correlated with increased constipation severity.
Elevated levels of fecal calprotectin were found in patients with constipation and were associated with longer disease duration.
Cluster analysis indicated that patients with more severe non-motor symptoms had lower levels of short-chain fatty acids, lower bacterial diversity, and higher genetic predisposition scores for inflammatory bowel disease.

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BackgroundParkinson's disease (PD) is often accompanied by gastrointestinal symptoms. While elevated inflammatory biomarkers have been reported in PD patients compared to controls, the role of intestinal dysmotility and inflammation in disease manifestation is not fully understood.ObjectiveThis study sought to determine if fecal biomarkers and genetic predisposition to intestinal inflammation could help identify PD subtypes for future targeted therapies.MethodsThe association of disease activity, assessed through United Parkinson's disease Rating Scale (UPDRS) and Non-Motor Symptoms Questionnaire (NMSQ), with constipation severity, fecal calprotectin and six short-chain fatty acid (SCFA) levels, polygenic risk scores (PRS) for inflammatory bowel disease (IBD) and PD, and microbiota diversity were investigated in 95 participants with established PD using regression analyses. Unsupervised k-means clustering was applied to stratify PD patients based on inflammatory biomarkers.ResultsHaving constipation was linked to worse mentation (UPDRSI, adj. = 0.03) and more limited daily living activities (UPDRSII, adj. = 0.03), with symptom severity linearly associated with higher disease activity (UPDRSI, adj. = 0.002; NMSQ-total, adj. = 0.02). Fecal calprotectin was elevated in those with constipation ( = 0.02) and associated with longer disease duration irrespective of the age (adj. = 0.02). Cluster analysis demonstrated that PD patients with a higher non-motor symptom UPDRSII score were more likely to have more severe constipation, lower fecal SCFA levels, lower bacterial diversity, and higher PRS-CD and PRS-IBD.ConclusionsGut dysmotility, along with pro-inflammatory intestinal profiles, and greater genetic predisposition to IBD were observed in PD patients with worse non-motor symptoms. Monitoring intestinal biomarkers may help identify PD patients for targeted interventions. p p p p p p

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Intestinal biomarkers, microbiota composition, and genetic predisposition to inflammatory bowel disease as predictors of Parkinson's disease manifestation

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