Developing a reduced complexity model gut microbiome in the behavior model, Droso

我们肠道中的微生物影响我们的新陈代谢，情绪和行为，但问题是， 理解这些影响是如何产生的显然是复杂的。100万亿个细胞从1000个 由数百万个基因组成的物种构成了人类微生物组。就像一个基因=一个一样 功能范式在很大程度上已经从遗传学领域消失，有利于理解 相互作用的途径如何导致表型，微生物学领域已经在很大程度上开始 认识到生态是许多微生物组疾病状态的核心。生态学意味着 生物和非生物因素的网络相互作用，产生系统级输出。 发展生态学领域的核心概念之一是“关键物种”。 在食物网（物种之间相互作用的网络图）中，关键物种相互作用 比一般的物种要多得多， 当它们被消除时对生态系统的影响，例如生态系统的稳定性 由于失去了基石，许多其他物种因间接影响而被淘汰 物种 治疗微生物组疾病最棘手的问题之一是微生物组 他们自己对变化很敏感。虽然抗生素可以杀死绝大多数微生物， 当植物群恢复时，它们通常代表与患者开始时相同的植物群。唯一的 通过使用粪便，广泛成功地改变了患者的微生物生态系统 移植，其中患者的整个肠道植物群被供体的粪便替换， 灌肠 我的目的是使用关键物种概念作为一种策略，通过它来扰乱肠道植物群 而不是完全消除它们。通过绘制微生物食物网，我的目标是确定 候选关键物种。通过开发靶向噬菌体疗法， 关键候选人，我的目标是重组微生物食物网，以改变代谢输出， 从而影响影响宿主代谢、情绪和行为的核心代谢物。 我将从两个角度来处理这个项目：（i）我将建立一个模型，减少复杂性肠道 果蝇中的微生物组，这是研究行为输出的理想选择（ii）我将研究完整的 通过与gnotobiotic合作， 鼠标设施，以测试从一个更人性化的飞行系统建立的基本原则， 相关视角。

Microbes in our guts influence our metabolism, moods, and behaviors, but the problem of understanding how these influences arise is demonstrably complex. 100 trillion cells from 1000 species with millions of genes make up the human microbiome. Just as the one gene = one function paradigm has largely evaporated from the field of genetics in favor of understanding how pathways of interactions lead to a phenotype, the field of microbiology has largely begun to recognize that ecology is at the core of many microbiome disease states. Ecology means that a web of biotic and abiotic factors interact to produce a system-level output. One of the core concepts that has developed the field of ecology is the 'keystone species'. In a food web (network map of the interactions between species), keystone species interact with many more species than the average species does and these species have reverberating effects on an ecosystem when they are eliminated, such that the stability of the ecosystem often fails and many other species are eliminated by indirect effects due to loss of the keystone species. One of the toughest problems in treating ailments of the microbiome is that microbiomes themselves are robust to change. While antibiotics can kill off the vast majority of microbes, when the flora recover, they usually represent the same flora the patient started with. The only widely successful change of the microbial ecosystem in patients is through the use of fecal transplants, whereby the entire gut flora of a patient is replaced with a donor's stool using an enema. My aim is to use the keystone species concept as a strategy by which to perturb the gut flora without eliminating them entirely. By mapping the microbial food web, I aim to determine candidate keystone species. By developing targeted bacteriophage therapies against the keystone candidates, I aim to restructure microbial food webs to change the metabolic output, thus affecting the core metabolites that affect host metabolism, mood, and behavior. I will approach the project from two angles: (i) I will establish a model, reduced complexity gut microbiome in the fruit fly, which is ideal for studying behavioral outputs (ii) I will examine full- complexity gut microbiomes in humanized mouse guts through a collaboration with a gnotobiotic mouse facility to test fundamental principles established in the fly system from a more human- relevant perspective.