Excellence in Research: Influence of Neuropeptide Regulation and the Gut Microbiota on Foraging and Food Choice
Excellence in Research: Influence of Neuropeptide Regulation and the Gut Microbiota on Foraging and Food Choice
批准号:
1901546
负责人:
Kimberlei Richardson
金额:
$90.0万
依托单位:
依托单位国家:
美国
项目类别:
Standard Grant
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-09-01 至 2024-08-31
中文摘要
肠道中的微生物相互作用,并可能影响改变宿主行为的神经化学系统的功能。肠道微生物区系可以与大脑沟通,通过影响觅食活动/行为和食物选择来确保食物摄入量和能量消耗得到充分维持。肠道、其微生物群落和大脑之间的关系可能是双向的,大脑中一个可能有助于这种交流的神经肽系统是食欲素系统。食欲素系统与许多过程有关,如活动和摄食。这个项目的目标是调查肠道微生物区系在觅食和食物选择后如何影响宿主的健康,食欲素系统的拮抗,以及肠道微生物区系的干扰(通过长期接触益生菌或抗生素)。该项目将使用啮齿动物行为模型来识别对特定饮食具有高或低偏好的雄性和雌性,然后使用食欲素系统的药理学操作来分析从粪便和结肠样本分析的微生物群落结构和多样性的变化。此外,还将使用益生菌和抗生素给药来检查这些方案如何控制摄食行为,影响食欲素神经元的活性,以及微生物的结构和多样性。这些数据将加强社会对大脑如何与微生物群落沟通,以及这种相互作用如何影响生存所需的基本觅食行为,以及维持维持能量平衡所涉及的基本动态平衡过程的理解。描绘胃肠道系统、微生物群落和大脑之间的关系对于我们理解微生物区系-肠道-脑轴的双向交流以及驱动觅食行为和食物选择的信号通路至关重要。该项目的目标是调查肠道微生物区系影响觅食和食物选择的能力,并确定神经肽调节(通过食欲素)是否在微生物适应性中发挥作用。食欲素是一种神经肽,通过增加食物摄入量来调节能量平衡,并有助于增加能量消耗。食物选择测试和竞争性觅食测试将用于评估不同能量密集型饮食和性别对摄食行为、宿主健康、食欲素神经元活动和微生物组动态的影响。还将确定通过益生菌和抗生素小组进行的微生物组改变是否会影响行为、生理和/或神经化学活动。据推测,肠道微生物区系通过影响觅食和食物选择参与肠道-大脑信号传递,食欲素系统有助于驱动这些行为的机制。除了为普通大众提供关于饮食选择及其在多个范围内的影响的有价值的数据外,这项工作还将为HBCU的学生提供研究和教育机会,并帮助研究人员所在的大学制定更强有力的教育项目。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。
英文摘要
Microorganisms located in the gut interact and may influence the function of neurochemical systems that alter behavior in their hosts. The gut microbiota may communicate with the brain to ensure that food intake and energy expenditure are adequately maintained by influencing foraging activity/behavior and food choices. It is possible that the relationship between the gut, its microbial community and the brain is bidirectional, and one possible neuropeptide system in the brain that may contribute to this communication is the orexin system. The orexin system has been associated with many processes, such as activity and feeding. The goal of this project is to investigate how gut microbiota influence host fitness after foraging and food choice, orexin system antagonism, and disturbances of the gut microbiota (via long-term exposure to probiotics or antibiotics). This project will use a rodent behavioral model to identify males and females with high or low-preference for a particular diet and then use pharmacological manipulations of the orexin system to analyze shifts in structure and diversity of microbial communities as analyzed from fecal and colon samples. In addition, probiotic and antibiotic administrations will be employed to examine how these regimens control feeding behavior, affect orexin neuronal activity, and microbial structure and diversity. These data will enhance society's understanding of how the brain communicates with microbial communities and how this interaction can impact fundamental food seeking behaviors that are required for survival and maintain fundamental homeostatic processes involved in maintenance of energy balance. Delineating the relationship between the gastrointestinal system, its microbial community, and the brain is critical to our understanding of the bidirectional communication of the microbiota-gut-brain axis and signaling pathways that drive foraging behavior and food choice. The goal of this project is to investigate the ability of gut microbiota to influence foraging and food choice and determine whether neuropeptide regulation (via orexins) plays a role in microbial fitness. Orexins are neuropeptides that regulate energy balance, by increasing food intake and contribute to increased energy expenditure. Food choice testing and competitive foraging tests will be used to assess the impact of varying energy-dense diets and sex on feeding behavior, host fitness, orexin neuronal activity, and microbiome dynamics. It will also be determined whether microbiome alterations via a panel of probiotics and antibiotics impacts behavioral, physiological, and/or neurochemical activity. It is hypothesized that gut microbiota participate in gut-brain signaling by influencing foraging and food choice and that the orexin system contributes to the mechanisms that drive these behaviors. In addition to providing valuable data for the general populace about dietary choices and their impacts across multiple scales this work will provide research and educational opportunities for students at an HBCU and help in developing stronger educational programs at the investigator's home university.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.
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