Objective: Gut dysbiosis is implicated in Parkinson disease (PD) pathogenesis, but less is known about the interaction of PD associated gene variants and gut microbiota. One such gene is GBA, which can cause gut and immune dysfunction. We hypothesize that GBA+ PD individuals are more susceptible to gut dysbiosis than GBA-.

Background: Pathogenic GBA variants are found in 5-15% of PD individuals. While GBA variants increase PD risk, penetrance is incomplete. Potential gene-environment interactions may modify PD risk. GBA mutations disrupt gut physiology, suggesting carriers of pathogenic variants may be sensitive to gut dysbiosis. Gut and systemic inflammation from dysbiosis is an environmental factor implicated in PD development. Therefore, dysbiosis and GBA variants may act additively on PD development.

Method:

 Gene-tested PD individuals were recruited. Cohorts were assigned based on present or absent pathogenic GBA variants. Recruitment is ongoing; N=20 per group is the goal. Subjects have one study visit with questionnaires (MDS-UPDRS parts 1-4, GIDS-PD, SCOPA-AUT, Bristol stool scale, PDQ-39, PD sleep scale, fatigue severity scale, and HADS), MDS-UPDRS part 3, and sample collection (blood, nasal swab, saliva). Stool samples were collected at home. Preliminary demographics were balanced, except the GBA– group was older (by about 4 years, p=0.285). Gut leak serum assays (LBP and zonulin) and fecal calprotectin (intestinal inflammation) were done on an interim cohort (GBA+ n=14, GBA– n=11). Student’s T-test was used to compare GBA+ and GBA– questionnaire and serum measures. Two-way ANOVA (GBA status and age) was used for fecal calprotectin, which increases with age. GBA– patients were older on average. We plan to repeat these analyses and do Principal Component Analysis on bacterial species in stool, nasal swabs, and saliva.

Results: Currently, we have twenty-five of forty planned subjects. Preliminary results show no difference in symptom questionnaires, MDS-UPDRS part 3, or gut leak markers (zonulin and LBP). However, there is a higher fecal calprotectin trend in GBA+ patients, suggesting more gut inflammation.

Conclusion: Our preliminary data showed no difference between GBA+ vs GBA– PD for motor/non-motor symptoms or gut leak. Elevated calprotectin in GBA+ PD individuals may suggest greater gut inflammation in GBA+ PD. Results of microbiota interrogation will be presented in the meeting.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/examining-the-gut-microbiome-in-parkinson-patients-with-gba-mutations/