Elucidating the Host Metabolic Response to Consumption of Kombucha-associated Microorganisms

项目摘要 康普茶是一种受欢迎的发酵茶，含有益生菌。这种饮料在2005年 自世纪之交以来，美国就开始使用这种药物，据说它对健康有许多好处。其中一些 健康声明已经粗略地检查过了，但是，没有一个经过严格的测试， 康普茶的微生物组分与宿主之间的相互作用仍然未被探索。我将阐明 宿主对康普茶相关微生物的消耗的代谢反应（K.微生物），从而告知 它在补充保健方法中的用途。单个益生菌对人类健康的影响是 当人类消耗复杂的饮食时，很难去卷积，有数万亿的肠道微生物（包括许多 未鉴定的物种），并且测量宿主-微生物相互作用在人类受试者中是不可行的。因此，我们认为， 动物模型系统对于研究食用益生菌的影响是必不可少的， 康普茶，对宿主的生理过程。秀丽隐杆线虫是一个很好的模式系统 怎么K。微生物调节控制脂质稳态的宿主途径，因为它们的微生物组是 通过提供的食物来源很容易操作，它们是研究代谢的完善系统 以及体内的衰老过程。我已经建立了一个标准化的方法来维持C。节食的优雅的人 由K组成。与发酵培养物中发现的群落一致的微生物 （通过16 S rRNA测序确认）。在初步调查中，我观察到C。 elegans elegans exclusively消费K.微生物，与对照饮食相比（E.大肠杆菌，标准的实验室食物 来源），具有改变的核心脂质代谢基因表达（例如，β-氧化、脂肪酸去饱和）， 降低脂肪水平，延长平均寿命。关键是，K. 微生物对宿主生理的改变是完全未知的。因此，我计划用分子和基因 方法在C.系统地确定了控制宿主对线虫的反应的分子机制， K.微生物消耗并阐明康普茶中必要且足够的成分，以赋予 观察到的代谢和寿命表型。拟议中的实验将提供前所未有的洞察力 K.微生物的消耗重新配置宿主的新陈代谢。

PROJECT SUMMARY Kombucha is a popular fermented tea that contains probiotics. This beverage has seen a surge in popularity in the United States since the turn of the century and is purported to have many health benefits. Some of these health claims have been cursorily examined, however, none have been rigorously tested and the mechanistic interactions between the microbial components of Kombucha and the host remains unexplored. I will elucidate the host metabolic response to consumption of Kombucha-associated microbes (K. microbes), thereby informing its use in complementary health approaches. The impact of individual probiotic microbes on human health is difficult to deconvolute as humans consume a complex diet, have trillions of gut microbes (including many unidentified species), and measuring host-microbe interactions is not feasible in human subjects. Therefore, animal model systems are essential to investigate the effects of consuming probiotics, including those in Kombucha, on host physiological processes. Caenorhabditis elegans is an excellent model system to explore how K. microbes modulate the host pathways that govern lipid homeostasis, because their microbiomes are easily manipulated through the food source provided and they are a well-established system to study metabolism and the aging process in vivo. I have established a standardized method to maintain C. elegans on a diet exclusively consisting of K. microbes that is consistent with the community found in the fermenting culture (confirmed through 16S rRNA sequencing). In preliminary investigations, I observed that populations of C. elegans exclusively consuming K. microbes, as compared to a control diet (E. coli, the standard laboratory food source), have altered expression of core lipid metabolism genes (e.g., beta-oxidation, fatty acid desaturation), decreased fat levels, and an increased median lifespan. Critically, the molecular mechanisms by which K. microbes alter host physiology is completely unknown. Therefore, I plan to use molecular and genetic approaches in C. elegans to systematically identify the molecular mechanisms that govern the host response to K. microbe consumption and elucidate the components of Kombucha that are necessary and sufficient to confer the observed metabolic and lifespan phenotypes. The proposed experiments will provide unprecedented insight into the mechanism by which K. microbe consumption reconfigures host metabolism.