Pasinetti: Project 3; Role of Microbiome in Promotion of Cognitive and Psychological Resilience (Faith)

摘要/摘要 食用富含葡萄多酚的植物混合物的人体受试者表现出显著的 生物活性酚酸的存在和丰度与已知抗炎健康的差异 福利。我们假设肠道微生物亚群中的人与人之间的差异对加工至关重要 日粮多酚的生物利用度影响生物活性酚类代谢物的生物利用度，尤其是 酚酸对外周组织和脑组织的影响，因此，影响了 富含多酚的植物补充剂，包括保持心理和认知弹性 在应激条件下，这是我们植物性膳食补充剂研究中心应用的重点。 每个个体的肠道微生物区系中都有一组独特的大约100种不同的细菌，其中一些 这增加了生物活性酚类代谢物的生物利用度和多样性 在人类或动物模型食用富含多酚的饮食的背景下，大脑。来识别人类的内脏 调节酚酸生物利用度的微生物，我们将使用组合生理学和统计学 建模以剖析富含多酚的植物补充剂、肠道微生物区系和 酚酸生物利用度。我们将把不同人类捐献者的微生物区系移植到诺生菌小鼠体内。 给出了植物补充剂，以量化微生物区系组成中个体间差异对 酚类代谢物的生物利用度，重点是那些被证实可以调节心理和/或 认知韧性。然后，我们将针对特定的人类捐赠者微生物群进行高通量机器人分离 使用我们开发的分离、归档和检索大量细菌菌株的方法 肠道微生物。我们将使用一种组合灵知菌筛选方法来定植个体灵知菌 与从感兴趣的人类捐赠者分离的菌株组合的小鼠，并应用统计建模和 特征选择算法用于识别调节生物活性酚酸的微生物菌株 血清和大脑。这些研究将确定微生物区系的个别菌株或亚群 酚酸的产生在调节植物保鲜效果方面起着关键作用 心理和/或认知韧性在压力条件下的挑战。从这些结果中，我们将 产生一种人源性益生菌鸡尾酒，经验证可调节生物可用、生物活性的酚类物质 已确定具有重要生物功能的代谢物。

Summary/Abstract Human subjects consuming a grape based polyphenol-rich botanical mixture demonstrate significant differences in the presence and abundance of bioactive phenolic acids with known anti-inflammatory health benefits. We hypothesize that interpersonal differences in subsets of the gut microbiota critical for processing and bioavailability of dietary polyphenols affect bioavailability of bioactive phenolic metabolites, particular phenolic acids, to peripheral and brain tissues, and therefore, impact the potential health benefits of polyphenol-rich botanical supplements, including the preservation of psychological and cognitive resilience under stress conditions, which is the focus of our Botanical Dietary Supplement Research Center application. Each individual harbors a unique set of roughly 100 different bacterial species in their gut microbiota some of which increase the bioavailability and diversity of bioactive phenolic metabolites in the periphery and in the brain in the context of humans or animal models consuming a polyphenol-rich diet. To identify the human gut microbes that modulate phenolic acid bioavailability, we will use combinatorial gnotobiotics and statistical modeling to dissect the interrelationship between a polyphenol-rich botanical supplement, gut microbiota, and phenolic acid bioavailability. We will transplant the microbiota of different human donors into gnotobiotic mice given the botanical supplements to quantify the role of interindividual variation in microbiota composition on the bioavailability of phenolic metabolites, with an emphasis on those verified to modulate psychological and/or cognitive resilience. We will then target specific human donor microbiotas for high-throughput robotic isolation of individual bacterial strains using methods we developed for isolating, archiving, and retrieving large numbers of gut microbes. We will use a combinatorial gnotobiotic screening method to colonize individual gnotobiotic mice with combinations of strains isolated from the human donors of interest and apply statistical modeling and feature selection algorithms to identify microbial strains that modulate bioactive phenolic acids of interest in the serum and the brain. These studies will identify individual strains or subsets of the microbiota critical for generation of phenolic acids that play key roles in modulating the efficacy of the botanicals in preserving psychological and/or cognitive resilience under challenges by stress conditions. From these results, we will generate a human-derived probiotic cocktail validated to modulate biologically available, bioactive phenolic metabolites established to have important biological functions.