Abstract
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J Neurol. 2025 May 21;272(6):413. doi: 10.1007/s00415-025-13138-5.
The gut-brain axis in early Parkinson’s disease: from prodrome to prevention.
Oliver PJ(1)(2), Civitelli L(3), Hu MT(4)(5)(6).
Author information: (1)Clinical Medical School, University of Oxford, Oxford, UK. (2)Green Templeton College, University of Oxford, Oxford, UK. (3)Nuffield Department of Clinical Neurosciences, Oxford Parkinsons’ Disease Center, University of Oxford, Oxford, UK. (4)Oxford Parkinson’s Disease Centre, University of Oxford, Oxford, UK. michele.hu@ndcn.ox.ac.uk. (5)Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. michele.hu@ndcn.ox.ac.uk. (6)Department of Neurology, West Wing, Level 3, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK. michele.hu@ndcn.ox.ac.uk.
Parkinson’s disease is the second most common neurodegenerative disorder and fastest growing neurological condition worldwide, yet its etiology and progression remain poorly understood. This disorder is characterized pathologically by the prion-like spread of misfolded neuronal alpha-synuclein proteins in specific brain regions leading to Lewy body formation, neurodegeneration, and progressive neurological impairment. It is unclear what triggers Parkinson’s and where α-synuclein protein aggregation begins, although proposed induction sites include the olfactory bulb and dorsal motor nucleus of the vagus nerve. Within the last 20 years, there has been increasing evidence that Parkinson’s could be triggered by early microbiome changes and α-synuclein accumulation in the gastrointestinal system. Gut microbiota dysbiosis that alters gastrointestinal motility, permeability, and inflammation could enable prion-like spread of α-synuclein from the gut-to-brain via the enteric nervous system. Individuals with isolated rapid eye movement sleep behavior disorder have a high likelihood of developing Parkinson’s and might represent a prodromal ‘gut-first’ subtype of the