Unhealthy gut, unhealthy brain: The role of the intestinal microbiota in neurodegenerative diseases
Abstract
The number of bacterial cells living within the human body is approximately equal to, or greater than, the total number of human cells. This dynamic population of microorganisms, termed the human microbiota, resides mainly within the gastrointestinal tract. It is widely accepted that highly diverse and stable microbiota promote overall human health. Colonization of the gut with maladaptive and pathogenic microbiota, a state also known as dysbiosis, is associated with a variety of peripheral diseases ranging from type 2 diabetes mellitus to cardiovascular and inflammatory bowel disease. More recently, microbial dysbiosis has been associated with a number of brain pathologies, including autism spectrum disorder, Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), suggesting a direct or indirect communication between intestinal bacteria and the central nervous system (CNS). In this review, we illustrate two pathways implicated in the crosstalk between gut microbiota and CNS involving 1) the vagus nerve and 2) transmission of signaling molecules through the circulatory system and across the blood-brain barrier (BBB). We summarize the available evidence of the specific changes in the intestinal microbiota, as well as microorganism-induced modifications to intestinal and BBB permeability, which have been linked to several neurodegenerative disorders including ALS, AD, and PD. Even though each of these diseases arises from unique pathogenetic mechanisms, all are characterized, at least in part, by chronic neuroinflammation. We provide an interpretation for the substantial evidence that healthy intestinal microbiota have the ability to positively regulate the neuroimmune responses in the CNS. Even though the evidence is mainly associative, it has been suggested that bacterial dysbiosis could contribute to an adverse neuroinflammatory state leading to increased risk of neurodegenerative diseases. Thus, developing strategies for regulating and maintaining healthy intestinal microbiota could be a valid approach for lowering individual risk and prevalence of neurodegenerative diseases.
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There is a strong connection between intestinal microbiota and nervous diseases.
“Till now, a strong connection between intestinal microbiota and nervous diseases is evidenced, and the drug GV-971 has been conditionally approved by China’s State Drug Administration for AD treatment.”
From Therapeutic effect of GLP-1 engineered strain on mice model of Alzheimer’s disease and Parkinson’s disease (2020) · cites this paper as Spielman et al. 2018
Intestinal flora of NDD patients is characterized by excessive growth of pathogenic bacteria, which increases the release of LPS, and activates microglia to cause neuroinflammation.
“The intestinal flora of NDD patients is characterized by excessive growth of pathogenic bacteria, which increases the release of LPS, and activates microglia to cause neuroinflammation (Spielman et al. 2018).”
From Therapeutic effect of GLP-1 engineered strain on mice model of Alzheimer’s disease and Parkinson’s disease (2020) · cites this paper as Spielman et al. 2018
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The Gut Microbiota-Brain Axis: A New Frontier on Neuropsychiatric Disorders
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- Authors
- Spielman, L. J., Gibson, D. L., & Klegeris, A.
- Affiliations
- University of British Columbia, Okanagan Campus (CA)
- Corresponding author
- Spielman, Lindsay Joy
- Venue
- Neurochemistry International
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 120
- Pages
- 149-163
- ISSN
- 0197-0186 (ISSN-L)
- OpenAlex
- W2887737208
- Cited by
- 266
- References
- 243
- Citations by year
- 2026: 14 · 2025: 28 · 2024: 29 · 2023: 32 · 2022: 52 · 2021: 48 · 2020: 32 · 2019: 29 · 2018: 2
- FWCI
- 2.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurochemistry International (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Crohn's and Colitis Canada
- Natural Science and Engineering Research Council of Canada (NSERC)
- Jack Brown and Family Alzheimer's Disease Research Foundation
- NSERC
- University of British Columbia Okanagan Campus.
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- gut microbiota, neurodegenerative diseases, dysbiosis, gut-brain axis, vagus nerve, blood-brain barrier permeability, neuroinflammation, neuroimmune regulation, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, autism spectrum disorder, intestinal permeability
- MeSH terms
- Gastrointestinal Microbiome, Animals, Brain, Humans, Inflammation, Neurodegenerative Diseases, Gastrointestinal Tract, Microbiota
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