Parkinson's Disease: The Emerging Role of Gut Dysbiosis, Antibiotics, Probiotics, and Fecal Microbiota Transplantation

Sudhir K Dutta, Sandeep Verma, Vardhmaan Jain, Balarama K Surapaneni, Rakesh Vinayek, Laila Phillips, Padmanabhan P Nair, Sudhir K Dutta, Sandeep Verma, Vardhmaan Jain, Balarama K Surapaneni, Rakesh Vinayek, Laila Phillips, Padmanabhan P Nair

Abstract

The role of the microbiome in health and human disease has emerged at the forefront of medicine in the 21st century. Over the last 2 decades evidence has emerged to suggest that inflammation-derived oxidative damage and cytokine induced toxicity may play a significant role in the neuronal damage associated with Parkinson's disease (PD). Presence of pro-inflammatory cytokines and T cell infiltration has been observed in the brain parenchyma of patients with PD. Furthermore, evidence for inflammatory changes has been reported in the enteric nervous system, the vagus nerve branches and glial cells. The presence of α-synuclein deposits in the post-mortem brain biopsy in patients with PD has further substantiated the role of inflammation in PD. It has been suggested that the α-synuclein misfolding might begin in the gut and spread "prion like" via the vagus nerve into lower brainstem and ultimately to the midbrain; this is known as the Braak hypothesis. It is noteworthy that the presence of gastrointestinal symptoms (constipation, dysphagia, and hypersalivation), altered gut microbiota and leaky gut have been observed in PD patients several years prior to the clinical onset of the disease. These clinical observations have been supported by in vitro studies in mice as well, demonstrating the role of genetic (α-synuclein overexpression) and environmental (gut dysbiosis) factors in the pathogenesis of PD. The restoration of the gut microbiome in patients with PD may alter the clinical progression of PD and this alteration can be accomplished by carefully designed studies using customized probiotics and fecal microbiota transplantation.

Keywords: Dysbiosis; Fecal microbiota transplantation; Microbiota; Parkinson disease; Probiotics.

Conflict of interest statement

Conflicts of interest: Sudhir K Dutta has a US patent pending and Padmanabhan P Nair is the ceo of Non-invasive Technology, LLP.

Figures

Figure
Figure
Bidirectional gut-brain axis pathophysiological cascasde in the development of Parkinson’s disease. ENS, enteric nervous system; SCFA, short-chain fatty acid; GABA, gamma-aminobutyric acid; CNS, central nervous system; PNS, peripheral nervous system.

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