Microbially-mediated ethanol resistance in Drosophila: host benefits and potential mechanisms

 描述（由申请人提供）：动物如何处理饮食中摄入的毒素？一个潜在的方法是通过微生物群-也就是与动物相关的微生物的集合。越来越多的证据表明，微生物群在动物生物学的许多方面起着至关重要的作用。虽然微生物群可能帮助动物耐受饮食毒素的机制可能很简单-微生物分解这些毒素 在肠道-很少，如果有的话，做研究明确联系的具体成员的微生物群宿主的健康，然后确定机制，这些微生物受益于他们的主机。回答这些基本问题对于从根本上理解动物-饮食-微生物群的相互作用是必要的。本申请利用果蝇的实验易处理性来研究微生物群如何响应于摄入的毒素（特别是膳食乙醇）而影响宿主健康。D.黑腹菌已成为研究非致病性宿主与微生物相互作用的模型。对此特别重要的是能够通过实验清除果蝇的微生物群，然后重新引入定义的微生物群落。乙醇是腐烂水果的主要成分，而腐烂水果是野生杜松子的主要食物。黑腹果蝇和过度食用对果蝇健康的许多方面产生负面影响。在对乙醇的反应中，苍蝇表现出与人类相似的发育和认知障碍，因此，发现的一般原则可能与人类健康和行为有关。初步工作发现，当摄入补充乙醇的饮食时，具有正常微生物群的苍蝇比没有微生物的苍蝇更健康。通过将苍蝇与单个微生物菌株联系起来，这项研究将确定哪些微生物对这种益处负责。然后，它将研究这种效应的潜在机制。首先，将测量宿主内每种微生物的定殖水平，以确定不赋予益处的微生物是否仅仅不能有效地定殖宿主。接下来，将测量苍蝇肠道中的乙醇浓度，以确定有益细菌是否降低宿主肠道中的乙醇浓度，从而表明微生物介导的宿主益处的直接机制。申请人将精通完成该项目所需的所有实验技术。此外，通过与他的赞助商和加州大学伯克利分校社区的其他成员的互动，申请人将获得所需的技能，以确保在这个奖学金的结论作为一个主要研究员的位置。最后，拟议的研究与其赞助商的研究有足够的区别，这将允许申请人在自己的实验室中使用t作为独立研究计划的基础。

 DESCRIPTION (provided by applicant): How does an animal deal with toxins ingested in the diet? One potential way is through the microbiota - that is, the assemblage of microbes that are associated with an animal. Evidence is accumulating that the microbiota plays an essential role in many aspects of animal biology. While the mechanism by which the microbiota may help an animal tolerate dietary toxins is potentially straightforward - microbial breakdown of those toxins in the intestinal tract - rarely, if ever, do studies explicitly link specific members of the microiota to host health and then identify the mechanisms by which those microbes benefit their host. Answering these basic questions is necessary for a fundamental understanding of the animal-diet-microbiota interaction. This application leverages the experimental tractability of the fruit ly Drosophila melanogaster to investigate how the microbiota affects host health in response to an ingested toxin, specifically dietary ethanol. D. melanogaster has emerged as a model for investigating non-pathogenic host-microbe interactions. Particularly important to this is the ability to experimentally clear Drosophila of its microbiota and then re-introduce defined microbial communities. Ethanol is a major component of rotting fruit, the primary diet of wild D. melanogaster and overconsumption negatively affects numerous aspects of fly health. In response to ethanol, flies show similar developmental and cognitive impairment as humans, thus, general principles discovered may be relevant to human health and behavior. Preliminary work has found that, when ingesting ethanol-supplemented diets, flies colonized with their normal microbiota are healthier than flies cleared of their microbes. By associating flies with individual microbial strains, this study will identify which microbes are responsible for this benefit. It will then investigate the potential mechanisms that underlie this effect. First, the colonization level of each microbe within the host will be measured to determine if microbes that do not impart a benefit are simply unable to effectively colonize the host. Next, the ethanol concentration in fly intestines will be measured to determine if beneficial bacteria are reducing ethanol concentrations in the host gut, thus suggesting a direct mechanism for microbially-mediated host benefit. The applicant will become proficient in all experimental techniques needed to complete this project. Additionally, through interactions with his Sponsors and other members of the UC Berkeley community, the applicant will gain the skills required to secure a position as a Principle Investigator at the conclusion of this fellowship. Finally, the proposed research is sufficiently distinct from that of his Sponsors, which will allow the applicant to use t as the basis for an independent research program in his own laboratory.