Objective: To characterize the clinical and microbial features of sporadic PD (sPD) and GBA1-associated PD (GBA1-PD), with a particular focus on Escherichia coli abundance, stratified by the presence of premotor REM sleep behavior disorder (RBD).
Background: Parkinson’s disease (PD) has been hypothesized to include two subtypes: “brain-first” and “body-first.” Patients carrying pathogenic variants in GBA1, the most common genetic risk factor for PD, predominantly resemble the body-first profile. The gut-brain axis and intestinal microbiome may be central to understanding these phenotypic differences.
Method: Fecal samples from patients with sPD (n=132) and GBA1-PD (n=26; 11 N370S and 15 L444P carriers) were analyzed using bacteriological culture, qPCR, and 16S rRNA sequencing. Phenotypic features and non-motor symptoms, assessed with the MNS PD scale, were compared across groups according to RBD status.
Results: The GBA1-PD group exhibited a significantly more severe non-motor profile than the sPD group (MNS PD score: 43.33±10.13 vs. 32.01±11.06, p<0.05). Patients with GBA1-PD showed a higher prevalence of depression and RBD (14/26; 53.8%) than the sPD cohort (39/132; 29.5%) (p<0.05). Notably, L444P carriers had the highest RBD prevalence (78.6%). Quantitative microbiological analysis revealed significantly higher E. coli levels in the GBA1-PD group than in the sPD group. Furthermore, L444P carriers showed the highest bacterial load (9.0±1.3), whereas N370S carriers showed lower levels (6.2±1.4) (p<0.05). E. coli abundance followed a distinct hierarchical pattern corresponding to body-first severity: L444P-RBD+ > N370S-RBD+ > sPD-RBD+.
Conclusion: The distinct clinical and microbial profiles observed in GBA1-PD support the body-first subtype hypothesis and provide a framework for explaining gut microbiome heterogeneity in PD. Specifically, the L444P variant was associated with a severe body-first phenotype characterized by high E. coli burden and prominent RBD, highlighting unique pathogenic mechanisms within the gut-brain axis.
To cite this abstract in AMA style:
I. Miliukhina, E. Kryukova, S. Pchelina. Non-Motor Phenotypes and Intestinal Microbiome Alterations in GBA1-Associated Parkinson’s Disease: Evidence for a Body-First Subtype [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/non-motor-phenotypes-and-intestinal-microbiome-alterations-in-gba1-associated-parkinsons-disease-evidence-for-a-body-first-subtype/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/non-motor-phenotypes-and-intestinal-microbiome-alterations-in-gba1-associated-parkinsons-disease-evidence-for-a-body-first-subtype/