Abstract
The microbiome-gut-brain axis has been proposed as a pathogenic path in Parkinson’s disease (PD). Dietary driven dysbiosis and reduced gut barrier function could facilitate the interaction of toxic external or internal factors with the enteric nervous system, where PD could start. Amyloid bacterial protein such as curli can act as seed to corrupt enteric α-synuclein and lead to its aggregation. Misfolded α-synuclein can propagate to and throughout the brain. Here, we aimed at understanding if fibre deprivation and amyloidogenic protein curli could, individually or together, exacerbate the phenotype in both enteric and central nervous systems of a transgenic mouse overexpressing wild-type human α-synuclein. We analysed the gut microbiome, motor behaviour, gastrointestinal and brain pathologies in these mice. Our findings show that external interventions, akin to unhealthy life habits in humans, can exacerbate PD-like pathologies in mice. We believe that our results shed light on how lifestyle affects PD progression.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- PD
- Parkinson’s disease
- αSyn
- alpha-synuclein
- pS129-αSyn
- phosphorylated S129 alpha-synuclein
- TG
- Thy1-Syn14 transgenic mice
- WT
- wild-type littermates
- FR
- fibre-rich or normal chow
- FD
- fibre-deprived diet
- EC
- wild-type E. coli expressing curli protein
- ΔEC
- curli-operon KO E. coli strain