Objective: To explore the feasibility of a tiered fecal biomarker testing approach to identify potential gut–brain axis phenotypes in patients with young-onset parkinsonism in a clinical setting with limited diagnostic resources.

Background: Gastrointestinal dysfunction is among the earliest non-motor manifestations of Parkinson’s disease (PD) and is increasingly linked to disturbances in the gut–brain axis, involving intestinal inflammation, alterations in gut microbiota, and changes in microbial metabolites such as SCFAs. Microbiome-derived metabolites may contribute to the biological heterogeneity of PD. However, most available evidence originates from regions with advanced diagnostic infrastructure. In many clinical centers with limited resources, advanced microbiome analysis is not routinely available, underscoring the need for practical, scalable approaches to explore the gut–brain axis in PD.

Method: An exploratory analysis was conducted in two patients with young-onset Parkinsonism, one with early-onset and one with juvenile-onset disease, who had contrasting gastrointestinal phenotypes. Evaluation was performed using a tiered fecal biomarker strategy consisting of routine fecal microscopy, fecal inflammatory biomarkers, and analysis of microbial metabolites, including SCFAs. Stool samples were also preserved for microbiome profiling using 16S rRNA sequencing.

Results: Biomarker assessment suggested intestinal inflammation in both cases, despite differing gastrointestinal manifestations, with divergent metabolic patterns of microbial metabolite analysis, suggesting the presence of distinct gut–brain axis phenotypes. The biological profiles did not consistently correspond to the clinical presentation of gastrointestinal symptoms, indicating that overt gastrointestinal manifestations may not reliably reflect underlying intestinal biological processes in PD.

Conclusion: A tiered fecal biomarker approach appears feasible for implementation in clinical settings with limited resources and may help reveal heterogeneity in gut–brain axis phenotypes in Parkinson’s disease. This pragmatic framework may facilitate the integration of microbiome-oriented investigations in underrepresented populations and contribute to a more globally representative understanding of PD pathophysiology.

References: 1. Houser MC, Tansey MG. The gut–brain axis: Is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis? NPJ Parkinsons Dis. 2017;3:3. doi:10.1038/s41531-016-0002-0
2. Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, et al. Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord. 2015;30(3):350–358. doi:10.1002/mds.26069
3. Unger MM, Spiegel J, Dillmann KU, Grundmann D, Philippeit H, Bürmann J, et al. Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. Parkinsonism Relat Disord. 2016;32:66–72. doi:10.1016/j.parkreldis.2016.08.019

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-tiered-fecal-biomarker-approach-to-identify-gut-brain-axis-phenotypes-in-young-onset-parkinsonism-in-a-clinical-setting-with-limited-resources/