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

 描述(申请人提供)：动物如何处理饮食中摄入的毒素？一种可能的方法是通过微生物区系，即与动物相关的微生物的集合。越来越多的证据表明，微生物区系在动物生物学的许多方面都起着至关重要的作用。虽然微生物群帮助动物耐受饮食毒素的机制可能很简单--微生物对这些毒素的分解 在肠道--很少有研究明确地将微生物区系的特定成员与宿主健康联系起来，然后确定这些微生物使其宿主受益的机制。回答这些基本问题对于从根本上理解动物-饮食-微生物区系的相互作用是必要的。这一应用程序利用果蝇黑腹果蝇的实验可控性来研究微生物区系如何影响宿主健康，以应对摄入的毒素，特别是饮食乙醇。D.Blackogaster已成为研究非致病宿主-微生物相互作用的模型。对此特别重要的是通过实验清除果蝇的微生物区系，然后重新引入定义的微生物群落的能力。乙醇是腐烂水果的主要成分，是野生黑腹果蝇的主要食物，过度消费对果蝇健康的许多方面都有负面影响。作为对乙醇的反应，果蝇表现出与人类相似的发育和认知障碍，因此，所发现的一般原理可能与人类的健康和行为有关。初步研究发现，当摄取添加乙醇的食物时，在正常微生物群中定居的果蝇比清除微生物的果蝇更健康。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有责任。然后，它将调查这种效应背后的潜在机制。首先，将测量每种微生物在宿主内的定植水平，以确定没有带来好处的微生物是否根本无法有效地定植宿主。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了宿主肠道中的乙醇浓度，从而表明微生物介导的宿主受益的直接机制。申请者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进行互动，申请人将获得在该奖学金结束时获得原则调查员职位所需的技能。最后，拟议的研究与他的赞助商的研究有足够的区别，这将允许申请人使用t作为在他自己的实验室进行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.