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

基本信息

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
项目类别：
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

项目摘要

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.

肠道中的微生物影响我们的新陈代谢，情绪和行为，但了解这些影响是如何显而易见的。来自1000的100万亿个细胞具有数百万基因的物种构成人类微生物组。就像一个基因=一个功能范式在很大程度上已经从遗传学领域蒸发了相互作用的途径如何导致表型，微生物学领域已在很大程度上开始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的网络相互作用以产生系统级输出。发展生态领域的核心概念之一是“基石物种”。在食物网（物种之间相互作用的网络图）中，Keystone物种相互作用比普通物种多的物种多得多，这些物种回荡消除生态系统对生态系统的影响，以使生态系统的稳定性由于损失而导致的间接影响，通常会失败，许多其他物种被消除物种。处理微生物组疾病的最棘手问题之一是微生物组他们自己的变化是强大的。虽然抗生素可以杀死绝大多数微生物，但当植物群恢复时，它们通常代表患者开始的相同植物群。唯一的患者中微生物生态系统的广泛成功改变是通过使用粪便移植物，将患者的整个肠道菌群用捐赠者的粪便取代灌肠。我的目的是将Keystone物种概念用作扰动肠道菌群的策略没有完全消除它们。通过映射微生物食品网，我的目的是确定候选基石物种。通过开发针对靶向的噬菌体疗法 Keystone候选人，我旨在重组微生物食品网以改变代谢输出，因此影响影响宿主代谢，情绪和行为的核心代谢产物。我将从两个角度进行项目：（i）我将建立一个模型，降低复杂性肠道果蝇中的微生物组，这是研究行为产量的理想选择（ii），我将检查完整通过与Gnotobiotic的合作，人性化小鼠肠道中的复杂性肠道微生物组小鼠设施以测试从更人性化的飞行系统中建立的基本原理相关的观点。