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Communication between the gut and the brain (the ‘gut-brain axis’) is increasingly being implicated in the pathogenesis of various neurodegenerative diseases. Intestinal inflammation and alterations in the gut microbiota are proposed to contribute to initiation and progression of pathology in PD [1]. Recently, intestinal infection has been shown to trigger parkinsonian neuropathology in Pink1 KO mice [2]. In a parallel development, aberrant innate immune pathway signalling caused parkinsonism in Pink1 or Prkn KO mice challenged with exhaustive exercise or mtDNA mutations [3]. These studies highlight an important role for PINK1/Parkin in preventing aberrant immune pathway activity, and the contribution of systemic inflammation to neurodegeneration. While some evidence linking Drosophila Pink1/parkin pathology and gut homeostasis has been proposed [4],[5], we are examining which immune signalling pathways may play a key role [6].
The gut also provides a crucial barrier to the external environment and is populated with commensal bacteria (microbiota). Consequently, both diet and the microbiota have a strong influence on intestinal integrity and organismal health [7]. We are assessing the impact of different environmental factors, such as microbiota number and type, in Pink1/parkin mutant intestine integrity. These investigations will give important insight into how mitochondrial homeostasis affects gut integrity, and further inform the relationship between the gut and the brain in the context of neurodegeneration.


  1. Houser, MC & Tansey, MG (2017)
    The gut-brain axis: is intestinal inflammation a silent driver of Parkinson's disease pathogenesis?
    NPJ Parkinsons Dis 3, 3. doi:10.1038/s41531-016-0002-0
  2. Matheoud, D et al. (2019)
    Intestinal infection triggers Parkinson's disease-like symptoms in Pink1(-/-) mice.
    Nature 571, 565-569. doi:10.1038/s41586-019-1405-y
  3. Sliter, DA et al. (2018)
    Parkin and PINK1 mitigate STING-induced inflammation.
    Nature 561, 258-262. doi:10.1038/s41586-018-0448-9
  4. Fedele, G et al. (2021)
    Gut-brain axis neurodegeneration in a Drosophila model of Parkinson’s disease is linked to mitochondrial dysfunction.
    Research Square doi:10.21203/, doi:10.21203/
  5. Feltzin, V, Wan, KH, Celniker, SE & Bonini, NM (2019)
    Role and impact of the gut microbiota in a Drosophila model for parkinsonism.
    bioRxiv, 718825. doi:10.1101/718825
  6. Lee, JJ, Andreazza, S & Whitworth, AJ (2020)
    The STING pathway does not contribute to behavioural or mitochondrial phenotypes in Drosophila Pink1/parkin or mtDNA mutator models.
    Sci Rep 10, 2693. doi:10.1038/s41598-020-59647-3
  7. Clark, RI & Walker, DW (2018)
    Role of gut microbiota in aging-related health decline: insights from invertebrate models.
    Cell Mol Life Sci 75, 93-101. doi:10.1007/s00018-017-2671-1