Cited by 347Gut microbiota and healthAlzheimer's disease research and treatmentsGastrointestinal motility and disorders

The impact of the microbiota-gut-brain axis on Alzheimer’s disease pathophysiology

Doifode, Tejaswini, Giridharan, Vijayasree V., Generoso, Jaqueline S., Bhatti, Gursimrat, Collodel, Allan, Schulz, Paul E., Forlenza, Orestes V., Barichello, Tatiana·2021·Pharmacological Research

Abstract

The gut microbiota is a complex ecosystem that comprises of more than 100 trillion symbiotic microbial cells. The microbiota, the gut, and the brain form an association, 'the microbiota-gut-brain axis,' and synchronize the gut with the central nervous system and modify the behavior and brain immune homeostasis. The bidirectional communication between gut and brain occurs via the immune system, the vagus nerve, the enteric nervous system, and microbial metabolites, including short-chain fatty acids (SCFAs), proteins, and tryptophan metabolites. Recent studies have implicated the gut microbiota in many neurodegenerative diseases, including Alzheimer's disease (AD). In this review, we present an overview of gut microbiota, including Firmicutes, Bacteroidetes, SCFA, tryptophan, bacterial composition, besides age-related changes in gut microbiota composition, the microbiota-gut-brain axis pathways, the role of gut metabolites in amyloid-beta clearance, and gut microbiota modulation from experimental and clinical AD models. Understanding the role of the microbiota may provide new targets for treatment to delay the onset, progression, or reverse AD, and may help in reducing the prevalence of AD.

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Crossref · 10.1016/j.phrs.2020.105314

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  • The microbiota-gut-brain axis hypothesis suggests a bidirectional communication system between the gut and the brain, involving metabolic, endocrine, neural, and immune pathways.

    “The microbiota–gut–brain axis hypothesis suggests a bidirectional communication system between the gut and the brain, involving metabolic, endocrine, neural, and immune pathways.”
  • Dysbiosis can lead to a compromised intestinal epithelial barrier, allowing harmful substances and microorganisms to enter the bloodstream and trigger systemic inflammation, which may affect microglia and exacerbate neuroinflammation.

    “Dysbiosis, or disruption of the microbiota’s composition and functionality, can occur due to factors such as dietary changes, antibiotic use, psychosocial stress, or immune irregularities, leading to a compromised intestinal epithelial barrier.”

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Authors
Doifode, T., Giridharan, V. V., Generoso, J. S., Bhatti, G., Collodel, A., Schulz, P. E., Forlenza, O. V., & Barichello, T.
Affiliations
  • The University of Texas Health Science Center at Houston (US)
  • Universidade do Extremo Sul Catarinense (BR)
  • Universidade de São Paulo (BR)
Corresponding author
Barichello, Tatiana
Venue
Pharmacological Research
Publisher
Elsevier BV
Published
2021-02
Volume
164
Pages
105314
ISSN
1043-6618 (ISSN-L)
OpenAlex
W3107364628
Cited by
347
References
213
Citations by year
2026: 50 · 2025: 78 · 2024: 78 · 2023: 70 · 2022: 48 · 2021: 23
FWCI
3.35
Type
journal article
Language
en
Open access
closed
Locations
  • Pharmacological Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • the Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), USA
  • Graduate Program in Health Sciences, University of Southern Santa Catarina
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • Fundação de Amparo à Pesquisa e Inovação de Santa Catarina
  • Alzheimer’s Association
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
microbiota-gut-brain axis, Alzheimer's disease, gut microbiota, short-chain fatty acids, tryptophan metabolites, amyloid-beta clearance, vagus nerve, enteric nervous system, neuroinflammation, Firmicutes, Bacteroidetes, gut microbiota modulation, neurodegenerative diseases
MeSH terms
Gastrointestinal Microbiome, Alzheimer Disease, Animals, Brain, Humans

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