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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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“Abundance of the pro-inflammatory genus Escherichia/Shigella was significantly increased in Amyþ compared with Amy patients.”
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Bano, N., Khan, S., Ahamad, S., Kanshana, J. S., Dar, N. J., Khan, S. J., Nazir, A., & Bhat, S. A. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102515 · Cited by 49
Microbiome-Mediated Upregulation of MicroRNA-146a in Sporadic Alzheimer’s Disease
Zhao, Y., & Lukiw, W. J. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00145 · Cited by 47
Targeting Gut Microbiota Dysbiosis: Potential Intervention Strategies for Neurological Disorders
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“In addition, some researchers reported that supplementing with polyphenols could reduce the Firmicutes-to-Bacteroidetes ratio in the gut, which is associated with reduced inflammation and may be beneficial in lowering the risk of AD [78].”
BackgroundPellegrini, C., Daniele, S., Antonioli, L., Benvenuti, L., D’Antongiovanni, V., Piccarducci, R., Pietrobono, D., Citi, V., Piragine, E., Flori, L., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103523 · Cited by 49
“, activation of NLRP3 inflammasome) and contribute to both bowel motor dysfunctions and neuroinflammation/neurodegeneration in the CNS, via immune gut–brain ascending pathways [5].”
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Gut Microbiota and Microbiota-Related Metabolites as Possible Biomarkers of Cognitive Aging
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“Emerging evidence even suggests a link between specific food- and gut microbiota-derived metabolites and cognitive aging and associated diseases, in particular dementia and its most frequent form, Alzheimer’s disease (AD) [7,8].”
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NLRP3 inflammasome in Alzheimer’s disease: molecular mechanisms and emerging therapies
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“Firmicutes is recognized as a risk factor for the development of Alzheimer ’ s disease (Mancuso and Santangelo, 2017).”
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“Understanding the role of the microbiome in the pathogenesis of different neurological disorders, the connection of microbiome alteration, increased intestinal permeability and neurological malfunction gives numerous prospects on therapy development [159,170].”
BackgroundImplications of Microorganisms in Alzheimer’s Disease
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“Several recent investigations have found a substantial correlation between gut microbiome changes and cognitive behavior [133,134].”
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“[27] As a mucin-degrading bacterium, Ruminococcus can lead to compromised intestinal permeability,[28-30] which may increase the translocation of intestinal bacterial products to the brain.”
BackgroundGut-brain axis and Alzheimer's disease: Therapeutic interventions and strategies
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“…fragilis LPS, BF-LPS), microRNA-like small non-coding RNAs (sncRNA), and an extensive variety of bacterial-derived amyloids (Hofer, 2014; Foster et al., 2016; Lukiw, 2016a,b; Zhan et al., 2016, 2018; Mancuso and Santangelo, 2017; Yang and Chiu, 2017; Zhao et al., 2017a,b,c; Zhao and Lukiw, 2018).”
BackgroundChanges to the gut microbiota in mice induced by infection with Toxoplasma gondii
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“Approximately, there will be 66 million AD patients worldwide by 2030 and up to 115 million by 2050 [5].”
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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