Objective: We aimed to investigate whether the composition and function of gut microbiome obtained from shotgun metagenomic sequencing are different between Parkinson’s disease (PD) patients with premotor rapid eye movement sleep behavior disorders (RBD) and those without.

Background: The pathologic hallmark of PD is the presence of alpha-synuclein inclusions. Some evidence suggests that alpha-synuclein inclusions may originate in the enteric nervous system and spread to the brain via autonomic nerves. RBD is a parasomnia characterized by loss of muscle atonia during REM sleep, which is present in 30-50% of PD patients. Alpha-synuclein pathology in the pons is closely linked to RBD, which may be propagated from alpha-synuclein pathology in the enteric nerves of PD patients with RBD.

Method: We investigated 36 patients with PD, who were diagnosed with PD within 2 years, and 25 of their spouses as healthy controls. Among 36 patients with PD, 25 (69.4%) had RBD (PD ^RBD+) prior to the diagnosis of PD and 11 (30.5%) patients did not have RBD (PD ^RBD-). We compared taxonomic and functional profiling using shotgun metagenomic sequencing between the two groups.

Results: PD ^RBD+ group showed a different microbial composition compared to healthy controls in Bray-Curtis dissimilarity-based PCoA analysis (PERMANOVA, P=0.003), while PD ^RBD- group did not show a statistically significant difference from normal subjects. (PERMANOVA, P=0.25). The abundance of E. coli at the species level was significantly higher in the PD ^RBD+ group compared with PD ^RBD- group (MaAsLin2, q=0.002). Functional profiling showed that curli-producing genes including CsgAB operon transcriptional regulator [K04333], CsgE [K04337], and CsgG [K06214] were higher in the PD ^RBD+ group compared with PD ^RBD- group. Especially K04333 was absent in PD ^RBD- group. In PD ^RBD+, the K04333, K04337, and K06214 genes originated mainly from E.coli. In PD ^RBD- group and healthy controls, the genes originated from other bacteria such as Citrobacter and Enterobacter.

Conclusion: PD ^RBD+ patients, but not PD ^RBD-, showed increased microbial genes involved in the production of E.coli-derived curli protein, which could promote alpha-synuclein aggregation.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/distinct-characteristics-of-gut-microbiome-in-patients-with-parkinsons-disease-according-to-the-presence-of-premotor-rem-sleep-behavior-disorders/