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Alzheimer’s disease and gut microbiota modifications: The long way between preclinical studies and clinical evidence
Abstract
Recent studies have suggested the role of an infectious component in the pathogenesis of Alzheimer's disease (AD). In light of this, research has focused on some bacteria constituting the intestinal microbial flora which can produce amyloid. Once generated, the latter hypothetically triggers a systemic inflammatory response which compromises complex brain functions, such as learning and memory. Clinical studies have shown that, in cognitively impaired elderly patients with brain amyloidosis, there is lower abundance in the gut of E. rectale and B. fragilis, two bacterial species which have an anti-inflammatory activity, versus a greater amount of pro-inflammatory genera such as Escherichia/Shigella. According to these findings, some clinical studies have demonstrated that supplementation with Lactobacilli- and Bifidobacteria- based probiotics has improved cognitive, sensory and emotional functions in subjects with AD. Moreover, certain herbal products, in particular dietetic polyphenols, have proved capable of restoring dysbiosis and, therefore, their prebiotic role could be effective in counteracting the onset of AD regardless of their activity of free radical scavenging or enhancement of the cell stress response. One of the recent greatest novelties in the field of neurodegenerative diseases is the chance to prevent or slow down AD progression with agents, such as probiotics and prebiotics, acting outside the central nervous system.
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“In the stools of patients with AD, the abundance of pro-inflammatory bacteria (Escherichia/Shigella) increases and the abundance of anti-inflammatory bacteria (Eubacterium rectale) and Bacteroides fragilis decreases (Mancuso and Santangelo 2018).”
From Therapeutic effect of GLP-1 engineered strain on mice model of Alzheimer’s disease and Parkinson’s disease (2020) · cites this paper as Mancuso and Santangelo 2018
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“Moreover, though clinical and preclinical studies agree that there is a general decrease in microbial diversity during AD (16,17), these changes comprise many bacterial species, and probiotic supplementation has not been exhaustively interrogated for all of these.”
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Zhu, J., Liu, S., Zhang, H., Zhao, W., Ding, J., Dai, R., Xu, K., He, C., Liu, J., Yang, L., et al. (2023) · Apmis · doi:10.1111/apm.13339 · Cited by 14
“Conversely, Proteobacteria were at 31% and 30% in the AD-prone and wildtype groups at 3 months of age but dropped to only approximately 9% at 6 and 9 months of age.”
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Izzeddine, N. A., Ahmad, K., Bacha, C., Jabbour, M., Najjar, M., Salhab, S., Ghadieh, H. E., Kanaan, A., Azar, S. T., Khattar, Z. A., et al. (2025) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2025.05.014 · Cited by 19
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“Thus, it is of great significance to the elaborating therapeutic mechanism of rhubarb for AD from the view of gut microbiota (Mancuso and Santangelo, 2018).”
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Creutzfeldt-Jakob Disease: Alterations of Gut Microbiota
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Network pharmacology to elucidate the role of phytotherapy in neurocognitive disorders
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Gut Microbiome as a Target for Anti-ageing Interventions
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Alzheimer disease effects of different stages on intestinal flora
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Microbiome Based Diseases Diagnostics
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TUDCA Ameliorates Cognitive Impairment in APP/PS1 Mice by Modulating the Microbiota–Gut–Brain Axis
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Regulation of development of central nervous system and related diseases by gut microflora
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A gut-brain connection: probiotics L9 and A6 offer new insights into Alzheimer’s disease prevention
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Metadata
- Authors
- Mancuso, C., & Santangelo, R.
- Affiliations
- Università Cattolica del Sacro Cuore (IT)
- Corresponding author
- Mancuso, Cesare
- Venue
- Pharmacological Research
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 129
- Pages
- 329-336
- ISSN
- 1043-6618 (ISSN-L)
- OpenAlex
- W2774851697
- Cited by
- 232
- References
- 108
- Citations by year
- 2026: 21 · 2025: 29 · 2024: 30 · 2023: 25 · 2022: 29 · 2021: 27 · 2020: 28 · 2019: 23 · 2018: 20
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacological Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Catholic University
- 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
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- Alzheimer's disease, gut microbiota, gut-brain axis, amyloid, Bacteroides fragilis, lactobacilli, Bifidobacterium, probiotics, prebiotics, polyphenols, dysbiosis, neuroinflammation, cognitive impairment, neurodegeneration
- MeSH terms
- Gastrointestinal Microbiome, Aging, Alzheimer Disease, Animals, Humans
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