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The impact of the microbiota-gut-brain axis on Alzheimer’s disease pathophysiology
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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“The microbiota–gut–brain axis hypothesis suggests a bidirectional communication system between the gut and the brain, involving metabolic, endocrine, neural, and immune pathways.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [18]
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“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.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [18]
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Cited by
Sorted by citations
Więckowska-Gacek, A., Mietelska-Porowska, A., Wydrych, M., & Wojda, U. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101397 · Cited by 343
The Potential Role of Gut Microbiota in Alzheimer’s Disease: From Diagnosis to Treatment
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Understanding the Gut–Brain Axis and Its Therapeutic Implications for Neurodegenerative Disorders
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Liao, H., Li, H., Bao, H., Jiang, L., Du, J., Guo, Y., & Si, Y. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.909436 · Cited by 55
Metadata
- 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
- ORCID
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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