Objective: To evaluate whether patients with PD exhibit 1) a bloom in sulfate-reducing bacteria based on the detection of hydrogen-sulfide (H₂S) during lactulose breath testing and 2) an association between H₂S and clinical outcomes.

Background: Gastrointestinal dysfunction occurs early in the course of PD, with evidence that it can develop up to 20 years prior to diagnosis. A perturbed gut microbiome (dysbiosis) characterized by a bloom in sulfate-reducing bacteria may be particularly important to PD disease pathogenesis or progression.^1,2 We hypothesize that patients with PD exhibit elevated H₂S following lactulose ingestion, suggestive of a bloom in sulfate-reducing bacteria.

Method: 16 PD and 17 matched HC underwent motor assessments, comprehensive neuropsychological evaluation, and a lactulose breath test that included H₂, CH₄, and H₂S measurements. Chi-squared tests evaluated whether patients with PD exhibited higher rates of small intestinal bacterial overgrowth (SIBO) or H₂S positivity relative to HC. Bootstrap analyses evaluated whether patients with PD exhibited increased gastrointestinal symptoms and H₂, CH₄ and H₂S levels relative to HC accounting for age and sex. Finally, Spearman correlation analyses evaluated associations between H₂, CH₄ and H₂S levels and clinical outcomes (age of onset, motor and cognitive symptoms).

Results: Patients with PD reported significantly more gastrointestinal symptoms relative to HC, including: more severe frequency and levels of current constipation (p<0.001), lifetime frequency of stools (p=0.048), and severity of stool strain (p=0.006). Both groups had elevated rates of SIBO (SIBO Positive: 70.59% PD; 70.59% HC). 62.5% of the patients with PD were H₂S positive, whereas only 29.41% of the HC were H₂S positive, though this did not significantly differ based on chi-squared tests (p = 0.12). However, mean and max H₂S were inversely associated with both age of first PD symptom (mean: rho=-0.36, p=0.03) and visuospatial functioning (mean: rho=-0.39, p=0.03).

Conclusion: Our results highlight elevated gastrointestinal symptoms in PD relative to HC, despite similar, high rates of SIBO across both groups. A bloom in sulfate-reducing bacteria may contribute to earlier disease onset and worse visuospatial functioning. Future work in larger cohorts is necessary to further understand if a bloom in sulfate-reducing is present early in the disease course and if it progresses with clinical symptoms.

References: 1. Murros KE, Huynh VA, Takala TM, Saris PEJ. Desulfovibrio bacteria are associated with Parkinson’s disease. Front Cell Infect Microbiol. 2021;11:652617.
2. Ryman S, Vakhtin AA, Richardson SP, Lin HC. Microbiome–gut–brain dysfunction in prodromal and symptomatic Lewy body diseases. J Neurol. 2023;270(2):746-758.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/gastrointestinal-dysbiosis-and-clinical-outcomes-in-parkinsons-disease/