Cited by 266Gut microbiota and healthNeuroinflammation and Neurodegeneration MechanismsGastrointestinal motility and disorders

Unhealthy gut, unhealthy brain: The role of the intestinal microbiota in neurodegenerative diseases

Spielman, Lindsay Joy, Gibson, Deanna Lynn, Klegeris, Andis·2018·Neurochemistry International

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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Crossref · 10.1016/j.neuint.2018.08.005

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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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