Collaborative Research: Excellence in Research: Interactive Effects of Dietary Fat and Gut Microbiota on Neurobehavioral Development in Gallus gallus

合作研究：卓越研究：膳食脂肪和肠道微生物群对鸡内神经行为发育的相互作用

• 批准号: 2000324
• 负责人: Yewande Fasina
• 金额: $ 75.92万
• 依托单位: North Carolina Agricultural & Technical State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2000324&HistoricalAwards=false
• 关键词: Collaborative; Research; Excellence; Interactive; Effects

Dietary fat is not only an important source of energy in human and animal diets, but it can also result in production of metabolites that may alter specific physiological functions in living organisms, including those associated with behavior. Dietary fat can impact both the composition of the gut microbiome and the generation of metabolites by the gut microbiome. Using chickens (Gallus gallus) as a vertebrate model, this study will investigate the interactive effects of dietary fat type and quantity on the composition of metabolites produced by gut microbiota, and will identify consequent changes in brain function (neurotransmitter signaling) and bird behavior. This study will utilize cutting-edge analytical techniques including genomics, metagenomics, gene expression, and electrophysiology to examine these interactive effects, with this work being conducted by both faculty and student researchers at three collaborating institutions. This study will provide mentored research experiences to more than a dozen biological and animal science students from the historically black institutions (HBCUs) involved in this project, as well as training three PhD students. Results from this study are expected to lead to a more complete understanding of how dietary fat types and the microbiota impact animal health, with potential applications to human health and the agricultural production of chickens. By involving undergraduate students from two HBCUs in the research, the project will help motivate impactful scientific researchers of the future.There is a growing body of evidence suggesting that dietary fat type and concentration impact the physiological and behavioral conditions of animals with respect to nutrient levels, brain function, and reactivity to stress. However, the molecular mechanisms by which dietary fat and gut microbiota interact to influence the central serotonergic system are yet to be elucidated in birds. In this study, male and female chickens of varying ages will serve as model vertebrate animals to understand how changes in dietary fat type and concentration impact the activity of the central serotonergic system. Changes in gut microbiota in response to diet and age will be evaluated through 16S rRNA sequencing and shotgun metagenomics. Resulting shifts in metabolites produced from intestinal microbial fermentation processes will be determined by metabolomics, and relevant metabolites will be tracked from the gut through the blood, and to the brain. A systems-based analysis will enable the identification of metabolites that cross the blood-brain barrier to potentially modulate brain signaling and serotonin synthesis. Changes in bird behavior will be studied by using video recordings and software to perform neurobehavioral analysis. Expression levels of genes involved in production of behavior-modulating neurotransmitters will be quantified as correlates of dietary fat and gut microbiota interactions. The results may lead to improvements in the agricultural production of chickens. This multifaceted project will provide integrative STEM training experiences for undergraduate students and three PhD-level trainees. The project represents a new cross-disciplinary research area in the collaborating laboratories to investigate the gut-brain-microbiome axis, and will impact the research environment at two HBCUs.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

膳食脂肪不仅是人类和动物饮食中的重要能量来源，而且还可以导致代谢产物的产生，从而改变生物体内的特定生理功能，包括那些与行为相关的功能。膳食脂肪可以影响肠道微生物组的组成和肠道微生物组代谢产物的产生。本研究以鸡(Gallus Gallus)作为脊椎动物模型，研究饲料脂肪类型和数量对肠道微生物区系代谢产物组成的交互影响，并确定相应的脑功能(神经递质信号)和鸟类行为的变化。这项研究将利用包括基因组学、元基因组学、基因表达和电生理学在内的尖端分析技术来检查这些交互影响，这项工作由三个合作机构的教职员工和学生研究人员共同进行。这项研究将为参与该项目的十几名来自历史上的黑人机构(HBCU)的生物和动物科学专业的学生提供指导研究经验，并培训三名博士生。这项研究的结果有望更全面地了解饮食脂肪类型和微生物区系如何影响动物健康，并可能应用于人类健康和鸡的农业生产。通过让两所HBCU的本科生参与这项研究，该项目将有助于激励未来有影响力的科学研究人员。越来越多的证据表明，饮食脂肪的类型和浓度会影响动物的生理和行为条件，包括营养水平、大脑功能和对压力的反应。然而，在鸟类中，饮食脂肪和肠道微生物区系相互作用影响中枢5-羟色胺系统的分子机制尚未阐明。在这项研究中，不同年龄的公鸡和母鸡将作为脊椎动物的模型动物，以了解饮食脂肪类型和浓度的变化如何影响中枢5-羟色胺能系统的活性。肠道微生物区系随饮食和年龄的变化将通过16S rRNA测序和鸟枪式元基因组学进行评估。肠道微生物发酵过程中产生的代谢物的变化将由代谢组学确定，相关代谢物将从肠道通过血液跟踪到大脑。基于系统的分析将能够识别跨越血脑屏障的代谢物，从而潜在地调节大脑信号和5-羟色胺的合成。鸟类行为的变化将通过使用视频记录和软件进行神经行为分析来研究。参与行为调节神经递质产生的基因的表达水平将被量化为饮食脂肪和肠道微生物区系相互作用的相关性。这一结果可能会改善鸡的农业生产。这个多方面的项目将为本科生和三名博士生提供综合STEM培训经验。该项目代表了合作实验室中一个新的跨学科研究领域，以调查肠道-大脑-微生物组轴，并将影响两个HBUC的研究环境。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。