PDF(Pubmed)
Abstract：
BACKGROUND: Caloric restriction (CR) might be effective for alleviating/preventing Alzheimer\'s disease (AD), but the biological mechanisms remain unclear. In the current study, we explored whether CR caused an alteration of gut microbiome and resulted in the attenuation of cognitive impairment of AD animal model.
METHODS: Thirty-week-old male APP/PS1 transgenic mice were used as AD models (AD mouse). CR was achieved by 30% reduction of daily free feeding (ad libitum, AL) amount. The mice were fed with CR protocol or AL protocol for six consecutive weeks.
RESULTS: We found that with CR treatment, AD mice showed improved ability of learning and spatial memory, and lower levels of Aβ40, Aβ42, IL-1β, TNF-α, and ROS in the brain. By sequencing 16S rDNA, we found that CR treatment resulted in significant diversity in composition and abundance of gut flora. At the phylum level, Deferribacteres (0.04%), Patescibacteria (0.14%), Tenericutes (0.03%), and Verrucomicrobia (0.5%) were significantly decreased in CR-treated AD mice; at the genus level, Dubosiella (10.04%), Faecalibaculum (0.04%), and Coriobacteriaceae UCG-002 (0.01%) were significantly increased in CR-treated AD mice by comparing with AL diet.
CONCLUSIONS: Our results demonstrate that the attenuation of AD following CR treatment in APP/PS1 mice may result from alterations in the gut microbiome. Thus, gut flora could be a new target for AD prevention and therapy.
METHODS: Thirty-week-old male APP/PS1 transgenic mice were used as AD models (AD mouse). CR was achieved by 30% reduction of daily free feeding (ad libitum, AL) amount. The mice were fed with CR protocol or AL protocol for six consecutive weeks.
RESULTS: We found that with CR treatment, AD mice showed improved ability of learning and spatial memory, and lower levels of Aβ40, Aβ42, IL-1β, TNF-α, and ROS in the brain. By sequencing 16S rDNA, we found that CR treatment resulted in significant diversity in composition and abundance of gut flora. At the phylum level, Deferribacteres (0.04%), Patescibacteria (0.14%), Tenericutes (0.03%), and Verrucomicrobia (0.5%) were significantly decreased in CR-treated AD mice; at the genus level, Dubosiella (10.04%), Faecalibaculum (0.04%), and Coriobacteriaceae UCG-002 (0.01%) were significantly increased in CR-treated AD mice by comparing with AL diet.
CONCLUSIONS: Our results demonstrate that the attenuation of AD following CR treatment in APP/PS1 mice may result from alterations in the gut microbiome. Thus, gut flora could be a new target for AD prevention and therapy.
摘要：
背景：热量限制（CR）可能有效缓解/预防阿尔茨海默病（AD），但生物学机制尚不清楚。在目前的研究中,我们探讨了CR是否会引起肠道微生物组的改变并减轻AD动物模型的认知障碍。
方法：采用30周龄雄性APP/PS1转基因小鼠作为AD模型（AD小鼠）。通过减少30%的每日自由喂养来实现CR(随意，AL）金额。用CR方案或AL方案连续6周喂养小鼠。
结果：我们发现CR治疗，AD小鼠表现出改善的学习和空间记忆能力，和较低水平的Aβ40，Aβ42，IL-1β，TNF-α,和大脑中的ROS。通过对16SrDNA进行测序，我们发现CR治疗导致肠道菌群组成和丰度的显著多样性。在门一级，去铁杆菌（0.04%），杆菌(0.14%),Tenericutes（0.03％），和Verrucomicrobia（0.5％）在CR治疗的AD小鼠中明显减少；在属水平上，Dubosiella（10.04%），粪杆菌（0.04%），与AL饮食相比，在CR处理的AD小鼠中，CoriobacteriaceaeUCG-002（0.01％）显着增加。
结论：我们的结果表明，在APP/PS1小鼠中，CR治疗后AD的减弱可能是由于肠道微生物组的改变所致。因此，肠道菌群可能成为AD预防和治疗的新靶点。
方法：采用30周龄雄性APP/PS1转基因小鼠作为AD模型（AD小鼠）。通过减少30%的每日自由喂养来实现CR(随意，AL）金额。用CR方案或AL方案连续6周喂养小鼠。
结果：我们发现CR治疗，AD小鼠表现出改善的学习和空间记忆能力，和较低水平的Aβ40，Aβ42，IL-1β，TNF-α,和大脑中的ROS。通过对16SrDNA进行测序，我们发现CR治疗导致肠道菌群组成和丰度的显著多样性。在门一级，去铁杆菌（0.04%），杆菌(0.14%),Tenericutes（0.03％），和Verrucomicrobia（0.5％）在CR治疗的AD小鼠中明显减少；在属水平上，Dubosiella（10.04%），粪杆菌（0.04%），与AL饮食相比，在CR处理的AD小鼠中，CoriobacteriaceaeUCG-002（0.01％）显着增加。
结论：我们的结果表明，在APP/PS1小鼠中，CR治疗后AD的减弱可能是由于肠道微生物组的改变所致。因此，肠道菌群可能成为AD预防和治疗的新靶点。
