Objective: The objective of this study was to investigate the gut microbiota in a pilot cohort of Australian patients with PD, and a rodent model of aSyn over-expression. Further, this study also examined the relationship between brain aSyn levels and the gut environment in a rodent model of PD, and the subsequent influence of lipopolysaccharide (LPS) treatment on mouse PD symptoms in vivo.

Background: Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder in Australia, with motor, cognitive and gastrointestinal symptoms. Notably, gastrointestinal dysfunction can appear well before the onset of cardinal motor symptoms. Therefore, research has begun to focus on the interaction between the gut microbiota, gastrointestinal symptoms, and enteric alpha-synuclein (aSyn) aggregation in PD.

Method: Microbial abundance and diversity of humans and mice were determined using targeted sequencing of the V3 and V4 regions of 16S ribosomal RNA gene. Both C57BL-6N-Tg (Thy1-SNCA)15Mjff/J (Thy1-aSyn) and C57BL-6N mice underwent gut microbial sequencing and behavioural assessments (nasal adhesive removal, hindlimb clasp reflex and inverted grid). LPS was administered to intestinal epithelial cells (IEC-6) for 4 hours, and Thy1-aSyn mice for 12 consecutive nights. Brain aSyn and intestinal tight junction proteins were assessed using immunohistochemistry and immunocytochemistry.

Results: The relative abundance of LPS-producing Gammaproteobacteria was significantly elevated in patients with PD (573.82-fold) compared to controls. In Thy1-aSyn mice, progressively increasing brain aSyn levels were not associated with noticeable motor impairments, nor significantly altered microbiota relative abundance or diversity. Thy1-aSyn mice showed no evidence of altered intestinal permeability at 8 weeks of age, as determined by ZO-1 or e-cadherin proteins. After LPS treatment, Thy1-aSyn mice showed poorer hindlimb scores compared to baseline and untreated mice at 10 weeks.

Conclusion: This study supports a proinflammatory gut microbiome as an environmental trigger for PD pathogenesis, however suggests that other environmental or genetic factors are required to exacerbate motor impairments in Thy1-aSyn mice. Future studies should examine the effect of multiple inflammatory triggers in Thy1-aSyn mice coupled with gastrointestinal investigations.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/gut-feelings-about-parkinsons-disease-the-influence-of-the-gut-microbiota-in-a-rodent-model/