Immunoepigenetic-gut microbiome axis in the social networks of health disparate youth

健康不同青年社交网络中的免疫表观遗传-肠道微生物组轴

• 批准号: 10022453
• 负责人: Alika Keolaokalani Maunakea
• 金额: $ 38.58万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-26 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10022453
• 关键词: Address; Affect; Behavior; Behavioral; Biological; Biological Availability; Biological Markers; Body Weight; Cells; Censuses; Chronic; Chronic Disease; Clinical; Communities; DNA Methylation; Data; Diabetes Mellitus; Diagnosis; Diagnostic; Diet; Disease; Environment; Epigenetic Process; Ethnic group; Etiology; Exposure to; Gene Expression; Genes; Genetic Transcription; Geographic Information Systems; Goals; Hawaii; Health; Health Status; Health behavior; High Prevalence; Immune; Immune system; Immunologics; Individual; Inflammation; Inflammation Mediators; Inflammatory; Japanese American; Joints; Lead; Life; Life Style; Link; Longitudinal Studies; Measures; Minority; Native Hawaiian; Native-Born; Neighborhoods; Nested Case-Control Study; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Pacific Island Americans; Play; Population; Prevention strategy; Program Development; Research; Research Design; Risk; Risk Factors; Risk stratification; Role; Science; Shapes; Social Environment; Social Network; Socioeconomic Status; Structure; Testing; Time; Youth; base; blood glucose regulation; cardiometabolic risk; cardiometabolism; cohort; community partnership; diabetes risk; disorder risk; dysbiosis; early onset; epigenomics; ethnic difference; experience; gene environment interaction; genome-wide; glycemic control; gut microbiome; gut microbiota; health disparity; improved; insight; lifestyle intervention; microbiome composition; monocyte; multidisciplinary; novel; obesogenic; programs; racial and ethnic; response; sample collection; sex; social

PROJECT SUMMARY/ABSTRACT The primary goal of this study is to empower youth in health disparate communities to ameliorate risk for cardiometabolic diseases by evaluating immunoepigenetic-gut microbiome interactions among social networks. Native Hawaiians and Pacific Islanders (NHPIs) experience a disproportionately higher prevalence and earlier onset of Type-2 diabetes mellitus (DM) than other U.S. racial/ethnic groups. These health disparities may result from social network influences on shaping an individual's health behaviors/lifestyle and exposure to an obesogenic environment, as well as from gene-environment interactions underlying DM progression. The detrimental effects of social environments may include an increase in systemic inflammation, a hallmark of cardiometabolic diseases where monocytes of the immune system play a major role. Indeed, we observed an association between neighborhood social environments and inflammation in health disparate populations. Epigenetic mechanisms including DNA methylation regulate transcription of pro-inflammatory genes of monocytes, a key mediator of inflammation, and respond to changes in the gut microbiome associated with lifestyle. Dysbiosis of gut microbiota may be an underlying attribute of inflammatory-related conditions such as DM, which also affects bioavailability of substrates essential for epigenetic processes. Our preliminary data reveal significant genome-wide changes to DNA methylation and gene expression states of pro-inflammatory genes that associated with monocyte inflammatory activity and glycemic control in NHPIs with DM undergoing a lifestyle intervention. Additionally, we observed significant changes to the gut microbiome composition of NHPI youth that associated with reduced risk for DM, which clustered in their social networks. Our data suggest that social environments influence the gut microbiome and the epigenomic landscape of monocytes, which may prime their inflammatory state and contribute to inflammation that consequently lead to disrupted glucose homeostasis. We seek to explore this “immunoepigenetic-gut microbiome axis” among the social networks of NHPIs at risk for DM. Our unique multidisciplinary team will test the hypotheses that the neighborhood social environment conditions the monocyte epigenomic landscape associated with inflammation, which (1) increases DM risk, (2) propagates among social networks, and (3) is ameliorated by a community-based life development program that impacts the immunoepigenetic-gut microbiome axis. In a two- part study, we will identify an immunoepigenetic signature of DM risk associated with neighborhood level factors using the Multiethnic Cohort (MEC) in a nested case-control study design, and link this with changes to the gut microbiome and subclinical measures of DM in the social networks of NHPI youth over time in a community-based longitudinal study. Responsive to PAR-16-355, this study seeks to advance the science of epigenomics focused on health disparities and expand approaches for understanding epigenetic mechanisms by which social factors lead to biological changes that affect health disparities among NHPIs.

项目总结/摘要 这项研究的主要目标是使健康状况不同的社区的青年能够减轻 通过评估社交网络之间的免疫表观遗传-肠道微生物组相互作用， 夏威夷原住民和太平洋岛民（NHPIs）的患病率不成比例地高， 2型糖尿病（DM）的发病率高于其他美国种族/族裔群体。这些健康差异可能 由于社会网络对塑造个人健康行为/生活方式的影响， 肥胖的环境，以及从基因-环境相互作用的基础DM进展。的 社会环境的有害影响可能包括全身性炎症的增加，这是 免疫系统的单核细胞起主要作用的心脏代谢疾病。我曾观察到， 邻里社会环境与健康不同人群炎症之间的关联。 包括DNA甲基化在内的表观遗传学机制调节了促炎基因的转录， 单核细胞是炎症的关键介质，并对与炎症相关的肠道微生物组的变化做出反应。 生活方式肠道微生物群的生态失调可能是炎症相关病症的潜在属性， DM，这也影响表观遗传过程所必需的底物的生物利用度。我们的初步数据 揭示了DNA甲基化和促炎性细胞因子基因表达状态的显著全基因组变化， 与糖尿病合并NHPIs的单核细胞炎症活性和血糖控制相关的基因 生活方式干预此外，我们观察到肠道微生物组组成发生了显着变化 NHPI青年与DM风险降低相关，聚集在他们的社交网络中。我们的数据 表明社会环境影响肠道微生物组和单核细胞的表观基因组景观， 这可能引发他们的炎症状态，并导致炎症，从而导致破坏 葡萄糖稳态我们试图在社会群体中探索这种“免疫表观遗传-肠道微生物组轴”， 有糖尿病风险的NHPI网络。我们独特的多学科团队将测试假设， 邻里社会环境条件下的单核细胞表观基因组景观与 炎症，（1）增加DM风险，（2）在社交网络中传播，（3）通过 以社区为基础的生命发展计划，影响免疫表观遗传肠道微生物组轴。在两个- 部分研究中，我们将确定一个免疫表观遗传签名的糖尿病风险与邻里水平 在巢式病例对照研究设计中使用多种族队列（MEC）的因素，并将其与以下变化联系起来 NHPI青少年社交网络中的肠道微生物组和DM亚临床指标随时间的变化， 社区纵向研究。响应PAR-16-355，本研究旨在推进 表观基因组学侧重于健康差异，并扩大理解表观遗传机制的方法 社会因素导致生物变化，影响国家卫生机构之间的健康差距。