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

果蝇微生物介导的乙醇抗性：宿主益处和潜在机制

• 批准号: 8984233
• 负责人: James Chandler
• 金额: $ 5.42万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8984233
• 关键词: Adult; Affect; Alcohol consumption; Animals; Bacteria; Biology; Cells; Communities; Data; Development; Diet; Diet Research; Drosophila genus; Drosophila melanogaster; Ethanol; Event; Fellowship; Female; Fertility; Fruit; Health; Health behavior; Host resistance; Human; Impaired cognition; Individual; Ingestion; Intestines; Laboratories; Link; Longevity; Measures; Mediating; Microbe; Modeling; Mono-S; Pattern; Play; Positioning Attribute; Research; Research Personnel; Resistance; Role; Secure; Staining method; Stains; Techniques; Testing; Time; TimeLine; Tissues; Toxic effect; Toxin; Work; alcohol response; base; dietary supplements; egg; feeding; fitness; fly; gut microbiota; insight; interest; member; microbial; microbial community; mortality; prevent; programs; public health relevance; research study; response; skills; success; theories

 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.

 描述（由申请人提供）：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群——即与动物相关的微生物的组合。越来越多的证据表明微生物群在动物生物学的许多方面发挥着重要作用。虽然微生物群帮助动物耐受饮食毒素的机制可能很简单——微生物分解这些毒素 在肠道中——很少有研究明确将微生物群的特定成员与宿主健康联系起来，然后确定这些微生物有益于宿主的机制。回答这些基本问题对于从根本上了解动物-饮食-微生物群的相互作用是必要的。该应用利用果蝇的实验易处理性来研究微生物群如何响应摄入的毒素（特别是膳食乙醇）而影响宿主健康。黑腹果蝇已成为研究非致病性宿主-微生物相互作用的模型。对此尤为重要的是能够通过实验清除果蝇的微生物群，然后重新引入确定的微生物群落。乙醇是腐烂水果的主要成分，是野生黑腹果蝇的主要食物，过量食用会对苍蝇健康的许多方面产生负面影响。针对乙醇，果蝇表现出与人类相似的发育和认知障碍，因此，发现的一般原理可能与人类健康和行为相关。初步研究发现，当摄入添加乙醇的饮食时，定植有正常微生物群的果蝇比清除了微生物的果蝇更健康。通过将果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带来了这种益处。然后它将研究造成这种效应的潜在机制。首先，将测量宿主内每种微生物的定植水平，以确定不带来益处的微生物是否根本无法有效地定植于宿主。接下来，将测量果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，从而提出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，申请人将获得在该奖学金结束时获得首席研究员职位所需的技能。最后，拟议的研究与其赞助商的研究完全不同，这将允许申请人在自己的实验室中使用该研究作为独立研究计划的基础。