Mannan oligosaccharide attenuates cognitive and behavioral disorders in the 5xFAD Alzheimer's disease mouse model via regulating the gut microbiota-brain axis
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive deficits and psychiatric symptoms. The gut microbiota-brain axis plays a pivotal role during AD development, which could target nutritional intervention. The prebiotic mannan oligosaccharide (MOS) has been reported to reshape the gut microbiome and enhanced the formation of the neuroprotective metabolites short-chain fatty acids (SCFAs). Here, we found that an 8-week treatment of MOS (0.12%, w/v in the drinking water) significantly improved cognitive function and spatial memory, accompanied by attenuated the anxiety- and obsessive-like behaviors in the 5xFAD transgenic AD mice model. MOS substantially reduced the Aβ accumulation in the cortex, hippocampus, and amygdala of the brain. Importantly, MOS treatment significantly balanced the brain redox status and suppressed the neuroinflammatory responses. Moreover, MOS also alleviated the HPA-axis disorders by decreasing the levels of hormones corticosterone (CORT) and corticotropin-releasing hormone (CRH) and upregulated the norepinephrine (NE) expressions. Notably, the gut barrier integrity damage and the LPS leak were prevented by the MOS treatment. MOS re-constructed the gut microbiota composition, including increasing the relative abundance of Lactobacillus and reducing the relative abundance of Helicobacter. MOS enhanced the butyrate formation and related microbes levels. The correlation analysis indicated that the reshaped gut microbiome and enhanced butyrate formation are highly associated with behavioral alteration and brain oxidative status. SCFAs supplementation experiment also attenuated the behavioral disorders and Aβ accumulation in the AD mice brain, accompanied by balanced HPA-axis and redox status. In conclusion, the present study indicated that MOS significantly attenuates the cognitive and mental deficits in the 5xFAD mice, which could be partly explained by the reshaped microbiome and enhanced SCFAs formation in the gut. MOS, as a prebiotics, can be translated into a novel microbiota-targeted approach for managing metabolic and neurodegenerative diseases.
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Probiotic and prebiotic interventions aimed at elevating SCFA levels have neuroprotective effects in AD mouse models by inhibiting glial activation and Aβ deposition.
“Moreover, probiotic and prebiotic interventions aimed at elevating SCFA levels have demonstrated neuroprotective effects in AD mouse models by inhibiting glial activation and Aβ deposition.301–306”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [304]
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- Authors
- Liu, Q., Xi, Y., Wang, Q., Liu, J., Li, P., Meng, X., Liu, K., Chen, W., Liu, X., & Liu, Z.
- Affiliations
- Northwest A&F University (CN)
- Cornell University (US)
- Corresponding author
- Liu, Qing
- Liu, Jinhui
- Liu, Kai
- Liu, Xuebo
- Liu, Zhigang
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2021-07
- Volume
- 95
- Pages
- 330-343
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W3156209056
- Cited by
- 241
- References
- 84
- Citations by year
- 2026: 40 · 2025: 66 · 2024: 60 · 2023: 43 · 2022: 26 · 2021: 6
- FWCI
- 21.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alexander von Humboldt-Stiftung
- China Postdoctoral Science Foundation
- National Natural Science Foundation of China
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- mannan oligosaccharides, Alzheimer's disease, 5xFAD mice, gut-brain axis, prebiotics, short-chain fatty acids, butyrate, amyloid-beta deposition, neuroinflammation, oxidative stress, hypothalamic-pituitary-adrenal axis, anxiety-like behavior, intestinal barrier integrity, LPS, Lactobacillus, Helicobacter, cognitive impairment, spatial memory
- MeSH terms
- Gastrointestinal Microbiome, Alzheimer Disease, Animals, Brain, Cognition, Mannans, Mice, Transgenic, Oligosaccharides, Neurodegenerative Diseases, Mice
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