西农刘志刚:甘露寡糖通过肠-脑轴改善AD小鼠的认知及行为
创作:szx 审核:szx 04月18日
  • 8周的甘露寡糖干预可显著改善AD小鼠的认知功能及空间记忆,并缓解焦虑及强迫行为;
  • 甘露寡糖可减少大脑皮层、海马及杏仁核中的Aβ累积,平衡大脑的氧化还原状态,并抑制神经炎症应答;
  • 甘露寡糖可降低皮质酮及促肾上腺皮质激素释放激素,并上调去甲肾上腺素的表达,以缓解下丘脑-垂体-肾上腺轴的失调;
  • 甘露寡糖可减少肠道屏障破坏,恢复肠道菌群组成,增加乳杆菌属并减少螺杆菌属,促进丁酸盐产生;
  • 补充短链脂肪酸也有类似作用。
主编推荐语
szx
西北农林科技大学的刘志刚团队在Brain Behavior and Immunity上发表的一项最新研究,发现在5xFAD AD小鼠模型中,甘露寡糖可通过恢复肠道菌群组成及短链脂肪酸产生,并维持肠道屏障功能,以减少大脑中的Aβ累积,抑制神经炎症,平衡氧化还原状态,调节下丘脑-垂体-肾上腺轴,从而改善小鼠的认知、记忆及行为。
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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

甘露寡糖通过调节肠-脑轴缓解5xFAD阿尔兹海默症小鼠模型的认知及行为障碍

10.1016/j.bbi.2021.04.005

04-09, Article

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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 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 probiotic, can be translated into a novel microbiota-targeted approach for managing metabolic and neurodegenerative diseases.

First Authors:
Qing Liu,Yujia Xi

Correspondence Authors:
Zhigang Liu

All Authors:
Qing Liu,Yujia Xi,Qianxu Wang,Jinhui Liu,Peiran Li,Xue Meng,Kai Liu,Weixuan Chen,Xuebo Liu,Zhigang Liu

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