The gut microbiota composition affects dietary polyphenols-mediated cognitive resilience in mice by modulating the bioavailability of phenolic acids
The gut microbiota composition affects dietary polyphenols-mediated cognitive resilience in mice by modulating the bioavailability of phenolic acids
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DOI：
10.1038/s41598-019-39994-6
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发表时间：
2019-03-05
影响因子：
4.6
通讯作者：
Pasinetti, Giulio M.
中科院分区：
文献类型：
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作者：
Frolinger, Tal;Sims, Steven;Pasinetti, Giulio M.
饮食多酚促进睡眠剥夺（SD），压力和神经变性模型的记忆。膳食多酚的生物学特性在很大程度上取决于其酚类代谢产物衍生物的生物利用度，而这些代谢产物是由肠道微生物群调节的。我们最近证明，补充葡萄衍生的生物活性膳食多酚制剂（BDPP）可以改善sd诱导的认知障碍。本研究考察了肠道微生物群在BDPP预防SD患者记忆损伤能力中的作用。C57BL6/J小鼠接受抗生素混合物（ABX）或BDPP或两者同时治疗，在恐惧调节训练结束时被剥夺睡眠，并在第二天评估恐惧记忆。分析粪便样品中的肠道菌群组成，测定血浆中bdpp驱动的酚酸代谢物提取。我们报道BDPP对SD记忆的有益作用被abx诱导的生态失调减弱。我们确定了与bdpp衍生的酚酸的生物利用度相关的粪便微生物群的特定群落，而酚酸反过来又与记忆促进有关。这些结果表明，肠道菌群组成显著影响酚酸的生物利用度，从而驱动膳食多酚的认知恢复特性。我们的研究结果提供了一个临床前模型，用于测试肠道微生物群-多酚的因果关系，最终目标是潜在地开发用于预防/治疗认知障碍的膳食多酚。
Dietary polyphenols promote memory in models of sleep deprivation (SD), stress, and neurodegeneration. The biological properties of dietary polyphenols greatly depend upon the bioavailability of their phenolic metabolites derivatives, which are modulated by gut microbiota. We recently demonstrated that supplementation with grape-derived bioactive dietary polyphenol preparation (BDPP) improves SD-induced cognitive impairment. This study examined the role of the gut microbiota in the ability of BDPP to prevent memory impairment in response to SD. C57BL6/J mice, treated with antibiotics mix (ABX) or BDPP or both, were sleep-deprived at the end of a fear conditioning training session and fear memory was assessed the next day. Gut microbiota composition was analyzed in fecal samples and BDPP-driven phenolic acid metabolites extraction was measured in plasma. We report that the beneficial effect of BDPP on memory in SD is attenuated by ABX-induced dysbiosis. We identified specific communities of fecal microbiota that are associated with the bioavailability of BDPP-derived phenolic acids, which in turn, are associated with memory promotion. These results suggest the gut microbiota composition significantly affects the bioavailability of phenolic acids that drive the dietary polyphenols' cognitive resilience property. Our findings provide a preclinical model with which to test the causal association of gut microbiota-polyphenols, with the ultimate goal of potential developing dietary polyphenols for the prevention/treatment of cognitive impairment.