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

在行为模型中开发降低复杂性的肠道微生物组模型，Droso

• 批准号: 8601669
• 负责人: William Basil Ludington
• 金额: $ 38.56万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-19 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8601669
• 关键词: Address; Affect; Antibiotics; Bacteria; Bacteriophages; Behavior; Behavioral; Behavioral Assay; Biodiversity; Biological Models; Cells; Clostridium difficile; Collaborations; Complex; Compost; Diabetes Mellitus; Disease; Dose; Drosophila genus; Drosophila melanogaster; Ecology; Ecosystem; Equilibrium; Event; Feces; Food Webs; Freedom; Genes; Genetic; Germ; Gnotobiotic; Goals; Health; Health behavior; Hospitals; Human; Human Microbiome; Human body; Immune system; Individual; Infection; Inflammatory Bowel Diseases; Internet; Lead; Length of Stay; Life Cycle Stages; Link; Maps; Measures; Medical; Metabolic; Metabolism; Microbe; Microbiology; Modeling; Modern Medicine; Moods; Mus; Nature; Nervous system structure; Obesity; Onset of illness; Organism; Output; Pathway interactions; Patients; Phenotype; Physiology; Problem behavior; Research; Rest; Risk; Sewage; Source; System; Testing; Therapeutic; Time; Transplantation; Variant; animal care; base; enema administration; fly; interest; killings; microbial; microbiome; pathogen; public health relevance; resistant strain; theories; therapeutic target; tool

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.

我们肠道中的微生物影响我们的新陈代谢、情绪和行为，但是 理解这些影响是如何产生的显然是复杂的。 1000 个细胞中的 100 万亿个 具有数百万个基因的物种构成了人类微生物组。正如一个基因=一个 功能范式已在很大程度上从遗传学领域消失，以利于理解 相互作用的途径如何导致表型，微生物学领域已经基本上开始研究 认识到生态学是许多微生物组疾病状态的核心。生态学意味着一个 生物和非生物因素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（物种间相互作用的网络图）中，关键物种相互作用 比一般物种多得多的物种，并且这些物种产生了回响 当它们被消除时对生态系统的影响，从而使生态系统的稳定性 经常失败，许多其他物种因失去基石而受到间接影响而被消灭 物种。 治疗微生物组疾病最棘手的问题之一是微生物组 它们本身就很容易改变。虽然抗生素可以杀死绝大多数微生物， 当菌群恢复时，它们通常代表与患者开始时相同的菌群。唯一的 患者体内微生物生态系统的广泛成功改变是通过使用粪便 移植，即使用捐赠者的粪便替换患者的整个肠道菌群 灌肠。 我的目标是使用关键物种概念作为扰乱肠道菌群的策略 而不完全消除它们。通过绘制微生物食物网图，我的目标是确定 候选关键物种。通过开发针对噬菌体的靶向疗法 重点候选人，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。 我将从两个角度处理该项目：（i）我将建立一个模型，降低复杂性 果蝇中的微生物组，这是研究行为输出的理想选择（ii）我将全面检查- 通过与无菌菌合作研究人源化小鼠肠道中复杂的肠道微生物组 鼠标设施，以更人性化的方式测试飞行系统中建立的基本原理 相关观点。