CAREER: Microbial contributions to host phenotypic flexibility

职业：微生物对宿主表型灵活性的贡献

• 批准号: 1942587
• 负责人: Kevin Kohl
• 金额: $ 134.89万
• 依托单位: University of Pittsburgh
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1942587&HistoricalAwards=false
• 关键词: CAREER; Microbial; contributions; host; phenotypic

Understanding how animals physiologically respond to changes in their environment is a large challenge in biology. Scientists have discovered that animals host diverse communities of microbes (microbiomes) that help their hosts in many ways, such as digesting fiber or training the immune system. This project focuses on how animals respond to changes in diet and the role of the animals' microbiomes in these responses. For example, animals can change many aspects of their digestive system (intestinal length, activities of digestive enzymes, etc.) in response to changes in nutritional composition. However, not all species respond the same way: herbivorous, omnivorous, and insectivorous rodents respond differently to varying levels of dietary protein and fiber. To ascertain if these differences are due to the animals’ physiology or their gut microbiome, microbiomes of rodent hosts with different feeding strategies will be inoculated into germ-free mice and then these animals will be given contrasting diets. This research will determine whether the different microbiomes allow hosts to respond differently to changes in diet. Understanding these dynamics could be important for species conservation, agricultural practices, etc. Additionally, this grant will fund an undergraduate research experience where students design independent research projects on microbial isolates. This program will allow for students to generate hypotheses, design experiments, and analyze their own results. Phenotypic flexibility, or the ability of organisms to modulate phenotype in response to environmental changes, allows animals to maintain performance in face of environmental variation. The hologenomic theory of evolution states that natural selection acts on the collection of host and microbial genomes as a unit. One poorly understood aspect of the hologenomic theory of evolution is how much of phenotypic flexibility is facilitated by the host versus by host-associated microbes. Diet is one environmental variable that yields phenotypic flexibility in animal physiology. For example, animals fed high fiber diets generally lengthen their small intestines and enlarge portions of their hindgut. However, not all animal species respond the same to changes in diet composition. Is the source of this variation in responsiveness driven by the animal genome or by host-associated microbes? This question will be tested by inoculating germ-free mice with microbial communities from different wild rodents. Inoculated mice will then be fed diets varying in protein and fiber content to test whether distinct microbial communities yield differences in phenotypic flexibility. Moreover, students in a Course-based Undergraduate Research Experience (CURE) will culture specific microbial species with varying functional capabilities. Students will then design independent research projects to test original hypotheses. Furthermore, these isolates will be powerful for follow-up studies to identify particular microbial taxa that drive aspects of host phenotypic flexibility.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.

了解动物对环境变化的生理反应是生物学的一大挑战。科学家们发现，动物体内存在着多种多样的微生物群落，这些微生物群落在许多方面帮助宿主，例如消化纤维或训练免疫系统。该项目的重点是动物如何应对饮食变化以及动物微生物组在这些反应中的作用。例如，动物可以改变其消化系统的许多方面（肠道长度，消化酶的活性等）。以应对营养成分的变化。然而，并非所有物种的反应都是一样的：草食性、杂食性和食虫性啮齿动物对不同水平的膳食蛋白质和纤维的反应不同。为了确定这些差异是否是由于动物的生理学或肠道微生物组造成的，将具有不同喂养策略的啮齿动物宿主的微生物组接种到无菌小鼠中，然后将这些动物给予对比饮食。这项研究将确定不同的微生物组是否允许宿主对饮食变化做出不同的反应。了解这些动态可能是重要的物种保护，农业实践等，此外，这笔赠款将资助本科生的研究经验，学生设计独立的研究项目对微生物分离。该计划将允许学生生成假设，设计实验，并分析自己的结果。表型灵活性，或生物体响应环境变化而调节表型的能力，使动物能够在面对环境变化时保持性能。进化的全基因组理论指出，自然选择作用于宿主和微生物基因组作为一个单位的集合。进化的全基因组理论的一个知之甚少的方面是，宿主与宿主相关的微生物在多大程度上促进了表型的灵活性。饮食是一个环境变量，在动物生理学中产生表型的灵活性。例如，喂食高纤维饮食的动物通常会延长其小肠并扩大后肠部分。然而，并非所有动物物种对饮食组成的变化都有相同的反应。这种反应性变异的来源是由动物基因组还是由宿主相关微生物驱动的？这个问题将通过无菌小鼠与来自不同野生啮齿动物的微生物群落进行测试。然后将给接种的小鼠喂食蛋白质和纤维含量不同的饮食，以测试不同的微生物群落是否产生表型灵活性的差异。此外，学生在基于课程的本科研究经验（CURE）将培养具有不同功能能力的特定微生物物种。然后，学生将设计独立的研究项目来测试原始假设。此外，这些分离株将是强大的后续研究，以确定特定的微生物类群，驱动主机表型flexible.This奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

项目成果

Functional convergence in gastric lysozymes of foregut-fermenting rodents, ruminants, and primates is not attributed to convergent molecular evolution

• DOI: 10.1016/j.cbpb.2024.110949
• 发表时间: 2024-02-10
• 期刊: COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY
• 影响因子: 2.2
• 作者: Barts，Nick;Bhatt，Roshni H.;Kohl，Kevin D.
• 通讯作者: Kohl，Kevin D.

Gut Microbial Ecology of Five Species of Sympatric Desert Rodents in Relation to Herbivorous and Insectivorous Feeding Strategies

五种同域沙漠啮齿动物的肠道微生物生态学与草食性和食虫性喂养策略的关系

• DOI: 10.1093/icb/icac045
• 发表时间: 2022
• 期刊: Integrative And Comparative Biology
• 影响因子: 2.6
• 作者: Kohl, Kevin D.;Dieppa-Colón, Etan;Goyco-Blas, José;Peralta-Martínez, Karen;Scafidi, Luke;Shah, Sarth;Zawacki, Emma;Barts, Nick;Ahn, Young;Hedayati, Stefanie
• 通讯作者: Hedayati, Stefanie

Diet alters rodent fecal pellet size: implications for paleoecological and demographic studies using fecal dimensions

• DOI: 10.1093/jmammal/gyab098
• 发表时间: 2021-09
• 期刊: Journal of Mammalogy
• 影响因子: 1.7
• 作者: Maya Maurer;Karen Peralta Martínez;B. Trevelline;Domenique Tripoli;M. Dearing;T. Derting;R. Mota;B. Pasch;K. Kohl

Comparative digestive morphology and physiology of five species of Peromyscus under controlled environment and diet

受控环境和饮食条件下五种白鼠属的消化形态和生理学比较

• DOI: 10.1016/j.cbpa.2022.111265
• 发表时间: 2022
• 期刊: Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology
• 作者: Yawitz, Tate A.;Barts, Nick;Kohl, Kevin D.
• 通讯作者: Kohl, Kevin D.