Microbiome and Worsening Glycemia Among Mexican Americans in Starr County, Texas

德克萨斯州斯塔尔县墨西哥裔美国人的微生物组和血糖恶化

• 批准号: 9977172
• 负责人: ERIC L BROWN
• 金额: $ 60.98万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9977172
• 关键词: 16S ribosomal RNA sequencing; Affect; Anatomy; Architecture; Automobile Driving; Bacteria; Chronic Disease; Communities; Complex; County; DNA; Data; Development; Diabetes Mellitus; Diabetes prevention; Diet; Evaluation; Feces; Food; Funding; Genetic Variation; Genotype; Health; Human Genetics; Human Microbiome; Individual; Longitudinal Studies; Metabolic; Metabolic Diseases; Mexican Americans; Non-Insulin-Dependent Diabetes Mellitus; Nose; Physiological; Prediabetes syndrome; Prevention; Protocols documentation; Role; Sample Size; Sampling; Seasonal Variations; Site; Source; Specimen; Staphylococcus aureus; Stimulus; Testing; Texas; Time; Variant; base; diabetes education; diabetes prevention program; exome; fecal microbiome; gut microbiome; longitudinal analysis; metagenomic sequencing; microbiome; nasal microbiome; prevent; response; trend; virome; whole genome

The human microbiome varies by anatomic site, physiologic state, and time as it responds to internal and external stimuli. While accumulating data show associations with type 2 diabetes, there is a paucity of data on the progression from normal glycemia to prediabetes and diabetes. The longitudinal study proposed here will allow evaluating relationships of the microbiome with prediabetes development and progression to type 2 diabetes while separating the confounding effects of temporality. This study will evaluate 600 Mexican American individuals from Starr County, Texas at baseline and 3, 6, 12, 24, and 36 months later. Most importantly, these individuals will be composed of 300 with normal glycemia and 300 with prediabetes. Stool and nasal microbiomes will be evaluated. Evaluating 600 Mexican Americans in Starr County, Texas at 6 points in time over 3 years and from two microbiome sites will generate 7,200 samples and associated data to achieve the following: Aim 1. Determine the influence of time and seasonality on nasal and gut microbiome diversity, relative abundance, and change through 16S ribosomal RNA sequencing of stool and nasal samples from 600 Mexican American individuals without diabetes - half with prediabetes and half with normal glycemia. Aim 2. Test hypotheses that the development of prediabetes and progression to type 2 diabetes will be correlated with and impacted by the diversity and abundance of the gut and nasal microbiomes and that these microbiomes interact. Aim 3. From stool and nasal samples of incident cases of prediabetes and type 2 diabetes and from those with the greatest changes in relative abundance and diversity from one time point to the next, determine the species driving the changes through whole genome sequencing metagenomics on 680 specimens. We also propose two exploratory/opportunistic aims. One, because species level determinations in Aim 3 will provide data on the DNA virome and two, because all individuals have been previously genotyped and whole exome sequenced. The sample sizes for these opportunistic aims are modest, but the uniqueness of the data merit evaluation. Aim 4: Conduct a preliminary evaluation of the distribution, abundance, and diversity of the DNA virome from those samples being sequenced to the species level in Aim 3. Aim 5. Determine the effects of rare and common human genetic variation on the composition and dynamics of the nasal and gut microbiomes over time. The proposed longitudinal analyses are paramount to better understanding the impact of the microbiome on the development of prediabetes, progression to type 2 diabetes, and their reciprocal relationships. They will identify genera most associated with change and will identify those species that drive changes in relative abundance and/or diversity. Perhaps most significant is that the microbiome offers a readily modifiable target. However, before that, there must be an understanding of normal variation over time and its relationship to the development of prediabetes and type 2 diabetes.

人体微生物群因其对内部和外部的反应而因解剖位置、生理状态和时间的不同而不同。 刺激物。虽然积累的数据显示与2型糖尿病有关，但关于 从正常血糖到糖尿病前期和糖尿病的进展。这里提出的纵向研究将允许 评价微生物组与糖尿病前期发展和进展为2型糖尿病的关系 同时分离出时间性的混杂效应。这项研究将评估600名墨西哥裔美国人 在基线以及3、6、12、24和36个月后，来自德克萨斯州斯塔尔县的个人。最重要的是，这些 个人将由300名血糖正常的人和300名糖尿病前期患者组成。粪便和鼻腔微生物区系 将会被评估。对德克萨斯州斯塔尔县的600名墨西哥裔美国人进行了3年6分的评估 来自两个微生物群地点的数据将产生7,200个样本和相关数据，以实现以下目标：1. 确定时间和季节性对鼻和肠道微生物群多样性、相对丰度和 600名墨西哥裔美国人粪便和鼻腔16S核糖体RNA测序的变化 没有糖尿病的人--一半患有糖尿病前期，另一半血糖正常。目标2.测试假设 糖尿病前期的发展和2型糖尿病的进展将与 肠道和鼻腔微生物群落的多样性和丰富性，以及这些微生物群落的相互作用。目标3.从 糖尿病前期和2型糖尿病发病病例的粪便和鼻腔样本 相对丰度和多样性从一个时间点到下一个时间点的变化，决定了推动 全基因组测序元基因组学在680例标本中的变化。我们还提出了两个 探索性/机会主义目标。其一，因为目标3的物种水平测定将提供有关DNA的数据 病毒和两种，因为所有个体之前都已进行了基因分型和整个外显子组测序。这个 这些机会主义目标的样本量不大，但数据的独特性值得评估。目标4： 对DNA病毒体的分布、丰度和多样性进行初步评估 目标3.目标5.确定稀有和常见的影响 随着时间的推移，人类遗传变异对鼻腔和肠道微生物群落组成和动态的影响。这个 拟议的纵向分析对于更好地了解微生物组对 糖尿病前期的发展，发展为2型糖尿病，以及它们之间的相互关系。他们会找出 与变化最相关的属，并将识别推动相对丰度变化的物种 和/或多样性。也许最重要的是，微生物组提供了一个容易修改的靶标。然而， 在此之前，必须了解随时间的正常变化及其与发育的关系 糖尿病前期和2型糖尿病。