Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY, USA.
J Alzheimers Dis. 2018;63(2):409-421. doi: 10.3233/JAD-171151.
A growing body of experimental data suggests that microbes in the gut influence behavior and can alter brain physiology and neurochemistry. Although promising, researchers are only starting to understand the potential of the gut microbiota for use in neurological disease. Recent evidence demonstrated that gastrointestinal activities are linked to mood disorders such as anxiety, depression, and most recently, cognitive functions in age-related neurodegenerative disorders. Studies from our group and others are uncovering new evidence suggesting that the gut microbiota plays a crucial role in the metabolism and bioavailability of certain dietary compounds and synthetic drugs. Based on this evidence, this review article will discuss the implications of the gut microbiota in mechanisms of bioavailability and biotransformation with an emphasis on dietary polyphenol compounds. This will be followed by a survey of ongoing innovative research identifying the ability of individual gut bacteria to enhance the bioavailability of gut-derived, brain-penetrating, bioactive polyphenol metabolites that ultimately influence mechanisms associated with the promotion of resilience against psychological and cognitive impairment in response to stress. Lastly, current research initiatives aimed at promoting the generation of brain bioactive polyphenol metabolites by specialized gut microbes will be discussed, specifically the use of gnotobiotic mice to develop bioengineered second generation probiotics. We propose that leveraging the gut microbial ecosystem to generate brain targeted bioactive metabolites from dietary polyphenols can attenuate lifestyle risk factors and promote resilience against age-related cognitive decline.
越来越多的实验数据表明，肠道中的微生物会影响行为，并能改变大脑的生理和神经化学。尽管前景广阔，但研究人员才刚刚开始了解肠道微生物群在神经疾病中的应用潜力。最近的证据表明，胃肠道活动与情绪障碍有关，如焦虑、抑郁，以及最近与年龄相关的神经退行性疾病中的认知功能有关。我们小组和其他小组的研究正在揭示新的证据，表明肠道微生物群在某些膳食化合物和合成药物的代谢和生物利用度中起着至关重要的作用。基于这一证据，本文将讨论肠道微生物群在生物利用度和生物转化机制中的意义，重点是饮食多酚化合物。接下来将调查正在进行的创新研究，这些研究确定了单个肠道细菌增强肠道衍生、穿透大脑、具有生物活性的多酚代谢物生物利用度的能力，这些代谢物最终影响与促进对压力引起的心理和认知损伤的恢复力相关的机制。最后，将讨论目前旨在通过专门的肠道微生物来促进产生脑生物活性多酚代谢物的研究计划，特别是使用无菌小鼠来开发生物工程第二代益生菌。我们提出，利用肠道微生物生态系统从膳食多酚中产生针对大脑的生物活性代谢物，可以减轻生活方式的风险因素，并促进对与年龄相关的认知能力下降的恢复力。
