Cited by 278Gut microbiota and healthAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

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The gut microbiome in Alzheimer’s disease: what we know and what remains to be explored

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Chandra, Sidhanth, Sisodia, Sangram S., Vassar, Robert J.·2023·Molecular Neurodegeneration

DOI 10.1186/s13024-023-00595-7PMC PMC9889249

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Abstract

Alzheimer’s disease (AD), the most common cause of dementia, results in a sustained decline in cognition. There are currently few effective disease modifying therapies for AD, but insights into the mechanisms that mediate the onset and progression of disease may lead to new, effective therapeutic strategies. Amyloid beta oligomers and plaques, tau aggregates, and neuroinflammation play a critical role in neurodegeneration and impact clinical AD progression. The upstream modulators of these pathological features have not been fully clarified, but recent evidence indicates that the gut microbiome (GMB) may have an influence on these features and therefore may influence AD progression in human patients. In this review, we summarize studies that have identified alterations in the GMB that correlate with pathophysiology in AD patients and AD mouse models. Additionally, we discuss findings with GMB manipulations in AD models and potential GMB-targeted therapeutics for AD. Lastly, we discuss diet, sleep, and exercise as potential modifiers of the relationship between the GMB and AD and conclude with future directions and recommendations for further studies of this topic.

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Fig. 1 Theory of GMB involvement in AD. Environmental factors, such as diet, sleep, and exercise and the development of AD due to genetics contribute to an inflammatory environment in the gut microbiota, which leads to changes in composition and diversity over time. Changes in the gut microbiota influence gut microbiome-derived metabolites and peripheral immunity by altering peripheral immune cell gene expression and cytokine release. Changes in peripheral immunity, possibly gut-derived metabolites directly, and vagus nerve trafficked gut-derived hormones can then alter phenotype of the blood brain barrier and central nervous system cell types (microglia, astrocytes, neurons), which can then modulate amyloidosis, tauopathy, and neurodegeneration and contribute to disease pathogenesisCC BY · PubMed Central

Fig. 2 Microbiome-related therapeutic strategies for AD. Preliminary evidence from mouse and human studies suggests that probiotics/prebiotics, fecal matter transplant from healthy donors into AD patients, microbiome modifying drugs, and direct targeting of gut microbiome controlled neuroinflammatory pathways may potentially be disease modifying therapeutic strategies and may reduce amyloid, tau, and neurodegenerationCC BY · PubMed Central

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Background
The gut microbiome regulates astrocyte reaction to Aβ amyloidosis through microglial dependent and independent mechanisms
Chandra, S., Di Meco, A., Dodiya, H. B., Popovic, J., Cuddy, L. K., Weigle, I. Q., Zhang, X., Sadleir, K., Sisodia, S. S., & Vassar, R. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00635-2 · Cited by 58
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Authors: Chandra, S., Sisodia, S. S., & Vassar, R. J.
Affiliations: Northwestern University (US)
University of Chicago (US)
Corresponding author: Vassar, Robert J.
ORCID: Chandra, Sidhanth
Sisodia, Sangram S.
Vassar, Robert J.
Venue: Molecular Neurodegeneration
Publisher: Springer Science and Business Media LLC
Published: 2023-02-01
Volume: 18
Issue: 1
Pages: 9-9
ISSN: 1750-1326 (ISSN-L)
DOI: 10.1186/s13024-023-00595-7
PMC: PMC9889249
OpenAlex: W4318680477
Cited by: 278
References: 228
Citations by year: 2026: 56 · 2025: 100 · 2024: 84 · 2023: 38
FWCI: 7.37
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: Molecular Neurodegeneration (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Knowledge@UChicago (University of Chicago) (submittedVersion, cc-by-nc-nd)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
University of Chicago (cc-by)
Funders: Good ventures foundation
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 › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: Alzheimer's disease, gut microbiota, amyloid-beta, tau aggregates, neuroinflammation, neurodegeneration, gut-brain axis, microbiota-based therapy, diet, sleep, physical activity, mouse models of Alzheimer's disease
MeSH terms: Gastrointestinal Microbiome, Alzheimer Disease, Animals, Cognition, Disease Models, Animal, Humans, Amyloid beta-Peptides, Mice

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The gut microbiome in Alzheimer’s disease: what we know and what remains to be explored

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