The gut-brain axis: is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis?
Open accessAbstract
The state of the intestinal environment can have profound effects on the activity of the central nervous system through the physiological contributions of the microbiota, regulation of intestinal barrier function, and altered activity of peripheral neurons. The common language employed for much of the gut-brain communication is the modulation of immune activity. Chronic proinflammatory immune activity is increasingly being recognized as a fundamental element of neurodegenerative disorders, and in Parkinson’s disease, inflammation in the intestine appears particularly relevant in pathogenesis. We review the evidence that intestinal dysfunction is present in Parkinson’s disease and that it may reflect the earliest manifestations of Parkinson’s disease pathology, and we link these findings to dysregulated immune activity. Based on this, we present a model for Parkinson’s disease pathogenesis in which the disorder originates in the intestine and progresses with inflammation as its underlying mechanism. More in-depth investigations into the physiological mechanisms underlying peripheral pre-motor symptoms in Parkinson’s disease are expected to lead to the development of novel diagnostic and therapeutic measures that can slow or limit progression of the disease to more advanced stages involving debilitating motor and cognitive symptoms.
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Systemic gut inflammation drives pro-inflammatory cytokine production, blood-brain barrier disruption, and migration of inflammatory cells into the brain causing neuronal dysfunction and cell death.
“while systemically gut inflammation drives pro-inflammatory cytokine production, blood–brain barrier disruption, and migration of inflammatory cells into the brain causing neuronal dysfunction and cell death [32, 33].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [32]
The Introduction’s “Mechanisms of intestinal modulation of CNS activity” section links intestinal inflammation to systemic proinflammatory responses, blood–brain barrier disruption, and access of activated immune cells to the brain; it also links neuroinflammation to neuronal dysfunction and death. But it describes several steps as possibilities, while the citing sentence presents the entire chain as an established consequence of gut inflammation. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredSystemic inflammation induced by intestinal inflammation and barrier disruption is key in gut-brain communication.
“Systemic inflammation induced by intestinal inflammation and barrier disruption is key in gut–brain communication [57,58,59].”
From Neuroprotective Effects of Bifidobacterium breve CCFM1067 in MPTP-Induced Mouse Models of Parkinson’s Disease (2022) · cites this paper as [57]
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<p>Colonic inflammation affects myenteric alpha-synuclein in nonhuman primates</p>
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- Authors
- Houser, M. C., & Tansey, M. G.
- Affiliations
- Emory University (US)
- Corresponding author
- Tansey, Malú G.
- Venue
- npj Parkinson's Disease
- Published
- 2017-01-11
- Volume
- 3
- Issue
- 1
- Pages
- 3-3
- ISSN
- 2373-8057 (ISSN-L)
- PMC
- PMC5445611
- OpenAlex
- W2575605891
- Cited by
- 588
- References
- 125
- Citations by year
- 2026: 53 · 2025: 54 · 2024: 55 · 2023: 66 · 2022: 69 · 2021: 112 · 2020: 64 · 2019: 54 · 2018: 47 · 2017: 14
- FWCI
- 34.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- npj Parkinson s Disease (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Science Foundation (1444932)
- Michael J. Fox Foundation for Parkinson's Research
- Parkinson's Disease Foundation
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS092122)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- gut-brain axis, Parkinson's disease, intestinal inflammation, intestinal dysmotility, gut microbiota, intestinal barrier function, neuroinflammation, immune dysregulation, neurodegeneration, pathogenesis
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