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Gut-Brain Axis Deregulation and Its Possible Contribution to Neurodegenerative Disorders

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Abstract

The gut-brain axis is an essential communication pathway between the central nervous system (CNS) and the gastrointestinal tract. The human microbiota is composed of a diverse and abundant microbial community that compasses more than 100 trillion microorganisms that participate in relevant physiological functions such as host nutrient metabolism, structural integrity, maintenance of the gut mucosal barrier, and immunomodulation. Recent evidence in animal models has been instrumental in demonstrating the possible role of the microbiota in neurodevelopment, neuroinflammation, and behavior. Furthermore, clinical studies suggested that adverse changes in the microbiota can be considered a susceptibility factor for neurological disorders (NDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). In this review, we will discuss evidence describing the role of gut microbes in health and disease as a relevant risk factor in the pathogenesis of neurodegenerative disorders, including AD, PD, HD, and ALS.

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Abbreviations

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

BBB:

Brain-blood barrier

BDNF:

Brain-derived neurotrophic factor

CNS:

Central nervous system CNS

ENS:

Enteric nervous system

GABA:

γ-Aminobutyric acid

GI:

Gastrointestinal

GDNF:

Glial cell line-derived neurotrophic factor

GDNF:

Glial-derived neurotrophic factor

GPR41:

G-protein-coupled receptor 41

GPR43:

G-protein-coupled receptor 43

HD:

Huntington’s disease

HTT:

Huntingtin

LPS:

Lipopolysaccharides

MCP-1:

Monocyte chemoattractant protein-1

mHTT:

Mutant huntingtin

NDs::

Neurodegenerative diseases

NGF:

Nerve growth factor

PAMPs:

Pathogen-associated molecular pattern

PD:

Parkinson’s disease

SCFAs:

Short-chain fatty acids

SOD1:

Superoxide dismutase

SPF:

Specific pathogen-free

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Funding

This work was supported by ANID, FONDECYT # 1200178 (RAQ). MAO, LN, and CI were supported by Ph.D. Fellowship from Universidad Autónoma de Chile.

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Author notes

  1. Francisca Villavicencio-Tejo and Margrethe A. Olesen both contributed equally.

Authors and Affiliations

  1. Laboratory of Neurodegenerative Diseases, Facultad de Ciencias de La Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, El Llano Subercaseaux 2801, 5to Piso, San Miguel 8910060, Santiago, Chile

    Francisca Villavicencio-Tejo, Margrethe A. Olesen & Rodrigo A. Quintanilla

  2. Laboratorio de Patógenos Gastrointestinales, Facultad de Ciencias de La Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago, Chile

    Cristian Iribarren & Katherine García

  3. Laboratorio de Microbiología Molecular y Compuestos Bioactivos, Facultad de Ciencias de La Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago, Chile

    Laura Navarro, Nancy Calisto & Gino Corsini

Authors
  1. Francisca Villavicencio-Tejo
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  2. Margrethe A. Olesen
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  3. Laura Navarro
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  4. Nancy Calisto
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  5. Cristian Iribarren
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  6. Katherine García
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  7. Gino Corsini
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  8. Rodrigo A. Quintanilla
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Contributions

FVT and MAO wrote and edited the manuscript; MAO produced manuscript figures; LN, NC, and CI write the manuscript; KG and GC edited the final draft of the manuscript; RAQ conceived and edited the final draft of the manuscript. Figures were made using Biorender.

Corresponding author

Correspondence to Rodrigo A. Quintanilla.

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Villavicencio-Tejo, F., Olesen, M.A., Navarro, L. et al. Gut-Brain Axis Deregulation and Its Possible Contribution to Neurodegenerative Disorders. Neurotox Res 42, 4 (2024). https://doi.org/10.1007/s12640-023-00681-0

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  • DOI: https://doi.org/10.1007/s12640-023-00681-0

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