Mannan oligosaccharide attenuates cognitive and behavioral disorders in the 5xFAD Alzheimer's disease mouse model via regulating the gut microbiota-brain axis

Apr 11, 2021Brain, behavior, and immunity

Mannan oligosaccharide may reduce thinking and behavior problems in an Alzheimer's mouse model by affecting the gut-brain connection

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Abstract

An 8-week treatment with mannan oligosaccharide (MOS) significantly improved cognitive function and reduced anxiety-like behaviors in a mouse model of Alzheimer's disease.

MOS treatment significantly decreased the accumulation of amyloid-beta (Aβ) in critical brain regions associated with Alzheimer's disease.
Cognitive improvements were accompanied by better spatial memory and reduced anxiety and obsessive-like behaviors.
MOS balanced the brain's oxidative status and reduced neuroinflammation.
The treatment decreased levels of stress-related hormones and increased norepinephrine expression.
MOS preserved gut barrier integrity and altered gut microbiota composition, favoring beneficial microbes like Lactobacillus.
Enhanced production of short-chain fatty acids (SCFAs) was linked to improvements in cognitive function and brain health.

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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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Mannan oligosaccharide attenuates cognitive and behavioral disorders in the 5xFAD Alzheimer's disease mouse model via regulating the gut microbiota-brain axis

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