Objective: The aim of the study was to compare the fecal microbial composition of a group of PD patients with and without premotor RBD.

Background: Changes in gut microbial composition determining a pro-inflammatory environment (gut dysbiosis) are associated with PD. In particular, a reduction in bacteria producing short chain fatty acids (SCFAs), signaling molecules with anti-inflammatory and antioxidant properties, has been reported [1,2].
Recent findings [3] indicate that two distinct PD subtypes exist, a “brain-first” subtype, where α-synuclein pathology arises primarily in the brain, and a “body-first” subtype, where the pathology originates in the enteric or peripheral autonomic nervous system and then spreads to the brain through a trajectory that involves the brainstem. Therefore, body-first subtype is characterized by the premotor appearance of RBD. Gut dysbiosis could play a causative role only in the body-first subtype.

Method: Newly-diagnosed, untreated PD patients were included in the study. We subdivided our population in a group of patients who presented RBD at least 1 year before motor onset and a group with no sign of premotor RBD. The presence of RBD was assessed through a structured RBD questionnaire. Differences in fecal microbiota composition between RBD-positive and RBD-negative patients were investigated.

Results: Out of 21 patients 5 were RBD-positive and 16 RBD-negative. The analysis of fecal microbial composition, after correction for multiple potential confounders, showed a reduction of the Microbacteriaceae and Eubacteriaceae families and an increase of Sphingobacteriaceae in RBD-positive patients compared to RBD-negative patients. At a genus level, a reduction of the SCFAs-producing bacteria, such as Acetobacterium and important members within Lachnospiraceae family, such as Blautia and Balutia spp, was found in RBD-positive patients.

Conclusion: The reduction of SCFAs-producing bacteria, Blautia and related species, in RBD-positive patients, point to a dysbiotic, pro-inflammatory shift in gut microbial composition in a subgroup of patients with body-first PD subtype. This confirms the possible causative role of gut-brain axis and microbiota selectively in this phenotype.

References: [1] Vascellari S, Palmas V, Melis M et al. Gut Microbiota and Metabolome Alterations Associated with Parkinson’s Disease. mSystems. 2020 Sep 15;5(5):e00561-20. [2] Keshavarzian A, Green SJ, Engen PA et al. Colonic bacterial composition in Parkinson’s disease. Mov Disord. 2015 Sep;30(10):1351-60. [3] Horsager J, Andersen KB, Knudsen et al. Brain-first versus body-first Parkinson’s disease: a multimodal imaging case-control study. Brain. 2020 Oct 1;143(10):3077-3088.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/pd-phenotype-with-premotor-rbd-is-associated-with-a-dysbiotic-profile-of-gut-microbiota/