Interrelationships between host physiology and the gut microbial community: disc

描述(申请人提供)：宿主和其肠道微生物区系之间的复杂关系是由一系列不同的相互作用形成的，其中许多尚未确定。虽然肠道微生物区系为宿主提供了许多好处，但它也与疾病有关；肠道微生物群的失调与炎症性肠病有关，饮食驱动的微生物多样性的变化可以产生 对宿主的病理性影响。此外，肠道微生物群与代谢综合征的发生有关。该项目的目标是利用北极地松鼠(Urocyteus Parryii)的极端表型来发现宿主生理和肠道微生物群落之间的相互关系，并识别可能影响或受宿主生理条件和饮食影响的肠道微生物群成员。研究设计利用圈养出生的北极地松鼠来监测生理方面(生长、肥胖、肠道发育)。将使用微生物16S rRNA基因焦解测序和TRFLPs分析产生的数据来评估肠道微生物组多样性的动态；将使用流式细胞术对群落进行计数，短链脂肪酸分析将揭示微生物组的功能变化。寄主生理学将在整个夏季活动季节进行比较，并与微生物群的测量变化相关联。这些特定的目标验证了这样的假设，即肠道微生物群落是随着宿主生理的发育变化而调节的，肠道微生物多样性、丰度和活性的变化将影响宿主生理。具体目标1将把幼年北极地松鼠从断奶到断奶后12周肠道微生物群落的发育与宿主的生理变化联系起来，特别关注冬眠前的育肥阶段。通过在冬眠前的不同发育时间点引入抗生素来调节肠道微生物群，具体目标2将描述肠道微生物群对宿主生理的影响。将进行饮食操作，以理清肥胖和宿主饮食对微生物多样性的影响，以便特定目标3将独立量化饮食对宿主生理和肠道微生物的影响。 活动季节成年松鼠的多样性、活跃度和丰富度。北极地松鼠在其年度周期中自然经历了一个短暂的极端脂肪沉积季节，这为研究肠道微生物区系与肥胖之间的相互关系提供了一个极好的平台；因此，我们的研究将有助于理解肠道微生物群落与人类肥胖发生之间的复杂相互作用。 公共卫生相关性：肠道微生物群落在发育过程中发挥着重要作用，如肠道结构和功能，以及炎症性肠病和肥胖症等病理变化。我们的实验旨在描述北极地松鼠的肠道微生物区系，这种动物自然地突破哺乳动物生理学的已知极限，目的是了解肠道微生物区系和宿主生理学之间的关系。特别是，北极地松鼠每年都会经历一段离散的深度育肥时期，为冬眠做准备，这为研究肠道微生物区系和肥胖之间的相互关系提供了一个很好的平台；因此，我们的研究将有助于理解肠道微生物群落和人类疾病之间的复杂相互作用。

DESCRIPTION (provided by applicant): The complex relationship between the host and its gut microbiota is shaped by a diverse array of reciprocal interactions, many of which are as of yet uncharacterized. While the gut microflora provides numerous benefits to the host, it has also been implicated in disease; dysbiosis of the gut microbiome is associated with inflammatory bowel disease and diet driven-shifts in microbial diversity can give rise to communities that exert a pathological effect on the host. Moreover, the gut microbiome is implicated in the development of metabolic syndrome. The goal of this project is to exploit the extreme phenotype of the arctic ground squirrel (Urocytellus parryii) to discover interrelationships between host physiology and the gut microbial community and to identify members of the gut microbiota which may influence, or be influenced by, host physiological condition and diet. The research design utilizes captive born arctic ground squirrels monitored for aspects of physiology (growth, adiposity, gut development). Dynamics of diversity of the gut microbiome will be assessed using data generated by pyrosequencing of microbial 16S rRNA genes and TRFLPs analysis; flow cytometry will be used to enumerate the community and short-chain fatty acid analysis will reveal functional changes in the microbiome. Host physiology will be compared across the summer active season and correlated to measured changes in the microbiome. The specific aims test the hypothesis that the gut microbial community is modulated in response to developmental changes in host physiology, and alteration of gut microbial diversity, abundance and activity will impact host physiology. Specific aim 1 will correlate physiological changes of th host with the development of the gut microbial community in juvenile arctic ground squirrels from weaning to 12-weeks post-weaning, with particular attention paid to the pre-hibernation fattening phase. By modulating the gut microbiome through the introduction of antibiotics at various time-points in development preceding hibernation, specific aim 2 will describe the influence of the gut microbiota on host physiology. Diet manipulations will be conducted to disentangle the influence of adiposity and diet of the host on microbial diversity such that specific aim 3 will independently quantify the effects of diet on host physiology and gut microbial diversity, activity and abundance in adult squirrels during the active season. The arctic ground squirrel naturally undergoes a brief season of extreme fat deposition during its annual cycle that provide an excellent platform upon which to investigate interrelationships between gut microbiota and obesity; therefore, our studies will contribute to the understanding of the complex interactions between the gut microbial community and development of obesity in humans . PUBLIC HEALTH RELEVANCE: The gut microbial community plays an important role in development, such as gut structure and function, and pathologies such as inflammatory bowel disease and obesity. Our experiments are designed to characterize the gut microbiota of the arctic ground squirrel, an animal that naturally pushes the known limits of mammalian physiology, with the goal of understanding the relationship between the gut microflora and host physiology. In particular, the arctic ground squirrel annually undergoes a discrete period of profound fattening in preparation for hibernation that provides an excellent platform upon which to investigate interrelationships between gut microbiota and obesity; therefore, our studies will contribute to the understanding of the complex interactions between the gut microbial community and human disease.