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Gastrointestinal dysfunction in Parkinson’s disease: molecular pathology and implications of gut microbiome, probiotics, and fecal microbiota transplantation

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Abstract

Gastrointestinal symptoms and gut dysbiosis may occur before the onset of motor symptoms in Parkinson's disease (PD). Prediagnostic and prodromal features, such as constipation and α-synuclein pathology, can be detected several years before the clinical diagnosis of PD and have the potential to develop as early PD biomarkers. Environmental toxins and gut dysbiosis may trigger oxidative stress and mucosal inflammation, and initiate α-synuclein accumulation in the enteric nervous system, early in PD. Chronic gut inflammation can lead to a leaky gut and systemic inflammation, neuro inflammation, and neuro degeneration via gut–vagus–brain signaling or through blood–brain barrier permeability. Concepts regarding the gut–brain signaling in PD pathogenesis are changing rapidly and more investigation is required. The gut microbiota interacts with the human body by modulating the enteric and central nervous systems, and immune activity. Understanding the immune responses between gut microbiota and human body might help in elucidating the PD pathogenesis. As changes in gut microbiota composition might be associated with different clinical phenotypes of PD, gut microbiota-modulating interventions, such as probiotics and fecal microbiota transplantation (FMT), have the potential to restore the gut dysbiosis, reduce inflammation, and possibly modulate the clinical PD phenotype.

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Acknowledgement

The authors thank B. Mounika and Dr Natasha Das, Delhi for their support in drafting the article and revising it with inputs from the authors.

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Authors and Affiliations

  1. Department of Neurosciences, King’s College London, Institute of Psychiatry, Psychology and Neuroscience, London, UK

    Vinod Metta, Valentina Leta & K. Ray Chaudhuri

  2. Parkinson’s Foundation Centre of Excellence, King’s College Hospital, London, London, UK

    Vinod Metta, Valentina Leta & K. Ray Chaudhuri

  3. Nizams Institute of Medical Sciences, Hyderabad, India

    Kandadai Rukmini Mrudula & Rupam Borgohain

  4. Vikram Hospitals Bengaluru, Bangalore, India

    L. K. Prashanth

  5. Medanta Institute of Neurosciences, New Delhi, India

    Vinay Goyal

  6. Department of Gastroenterology, King’s College London, Institute Parkinson’s Foundation Centre of Excellence, King’s College Hospital, London, London, UK

    Guy Chung-Faye

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Metta, V., Leta, V., Mrudula, K.R. et al. Gastrointestinal dysfunction in Parkinson’s disease: molecular pathology and implications of gut microbiome, probiotics, and fecal microbiota transplantation. J Neurol 269, 1154–1163 (2022). https://doi.org/10.1007/s00415-021-10567-w

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