Associations of Gut Microbiome Predictors of Body Fat Amount and Distribution

肠道微生物组与体脂肪量和分布的预测因子之间的关联

基本信息

批准号：
8374230
负责人：
JOHANNA W LAMPE
金额：
$ 75.13万
依托单位：
UNIVERSITY OF HAWAII AT MANOA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8374230
关键词：
Accounting Adipose tissue Affect African American Area Bacteria Behavior Binding Biochemical Biological Biological Markers Birth Blood Body Weight Body fat C-reactive protein Cardiovascular Diseases Chronic Cohort Studies Collaborations Colorectal Colorectal Cancer Data Deposition Development Diagnosis Diet Dimensions Disease Employee Strikes Endotoxins Environmental Risk Factor Epidemic Estrogens Ethnic Origin Ethnic group Fasting Fatty acid glycerol esters Feces Gall Bladder Diseases Genes Genetic Genomics Glucose Grant Hawaii Hawaiian population Hormonal Hormones Hour Human Immune system Inflammation Instruction Insulin Japanese American Latino Leptin Life Style Link Los Angeles Malignant Neoplasms Measures Mediating Metabolism Modification Monocyte Chemoattractant Protein-1 Natural Immunity Nested Case-Control Study Non-Insulin-Dependent Diabetes Mellitus Obesity Obesity associated cancer Obesity associated disease Participant Pathway interactions Pattern Permeability Phenotype Plasma Population Prevalence Preventive Intervention Protein Binding Race Regulation Sampling Sex Hormone-Binding Globulin Signaling Molecule TGFB1 gene Testing Time Toll-like receptors Tumor Necrosis Factor-alpha Variant adipokines adiponectin cancer risk cohort cytokine disorder risk fatty acid metabolism follow-up genetic variant gut microbiota innovation insulin sensitivity lifestyle factors lipid metabolism lipopolysaccharide-binding protein metabolomics microbial microbial community microbiome microorganism interaction pandemic disease predictive modeling rRNA Genes racial and ethnic sex steroid hormone uptake

项目摘要

Body fat accumulation and distribution varies across ethnic groups and may influence the prevalence of obesity-related cancers in different ethnicities. This proposal examines the association between adipose accumulation and distribution, the gut microbiome, and phenotypes associated with obesity related cancer risk in the Multi-Ethnic Cohort (MEC). As such, the gut microbiome represents a potentially modifiable obesity-associated factor that may affect cancer risk. The gut microbiome influences human metabolism via regulation of energy uptake from diet, interaction with signaling molecules involved in host fatty acid metabolism, and sub-chronic inflammation~a hallmark of obesity-related diseases. Sub-chronic inflammation may be indirectly mediated through microbially generated dietary metabolites and, directly mediated through activation ofthe innate immune system. For example, gut bacterial endotoxins bind with lipopolysaccharide binding protein (LBP) to Toll-like receptors (TLR) that activate NF 1 levels of cytokines. Variants in human genes related to fatty acid metabolism and innate immunity may alter the interaction of the host with the gut microbiome and alter inflammation associated with obesity-related cancer risk. This innovative project will use the MEC cohort to investigate the composition of the gut microbiome, using high throughput sequencing approaches, as an effect modifier of the relationship between diet, fat distribution, and cancer risk. We will: 1) identify gut microbial profiles associated with body fat amount and distribution in the 5 ethnic groups among the 2,000 MEC subjects re-contacted for this study and analyze 4,229 stool samples collected for the microbiome GWA study in project 2; 2) test the associations of these microbial profiles with diet and other lifestyle factors, and with intermediate cancer phenotypes (i.e., cytokines, adipokines, steroid hormones, insulin, IGF hormones, and LBP); 3) examine the association between circulating LBP and colorectal cancer, using a case-control study nested within the MEC and measuring LBP in plasma drawn before diagnosis from 1379 colorectal cases and 1379 controls; and 4) participate in analyses integrating the gut microbiome results with those generated in the other projects in order to clarify inter-relationships among variables across data dimensions and construct best predictive models of body fat amount and distribution, and of cancer risk.

人体脂肪的积累和分布在各种群体之间各不相同，可能会影响不同种族中与肥胖相关的癌症的普遍性。该提案研究了脂肪累积与分布，肠道微生物组和与肥胖相关的癌症风险（MEC）相关的癌症风险之间的关联。因此，肠道微生物组代表了可能影响癌症风险的潜在可改变的肥胖相关因素。肠道微生物组通过调节饮食的能量吸收，与宿主脂肪酸代谢涉及的信号分子的相互作用以及亚chr-chronic炎症的相互作用来影响人类代谢。亚基炎症可以通过微生物产生的饮食代谢产物间接介导，并通过激活先天免疫系统直接介导。例如，肠道细菌内毒素与脂多糖结合蛋白（LBP）与激活NF 1水平细胞因子的收费样受体（TLR）结合。与脂肪酸代谢和先天免疫有关的人类基因的变异可能会改变宿主与肠道微生物组的相互作用，并改变与肥胖相关癌症风险相关的炎症。这个创新的项目将使用MEC队列来研究肠道微生物组的组成，并使用高吞吐量测序方法，作为饮食，脂肪分布和癌症风险之间关系的效果修饰符。我们将：1）确定与本研究重新接触的2,000名MEC受试者中5个族裔中与体内脂肪量和分布相关的肠道微生物谱，并分析了项目2中的微生物组GWA研究的4,229个粪便样品； 2）测试这些微生物特征与饮食和其他生活方式因素的关联，以及中间癌症表型（即细胞因子，脂肪因子，类固醇激素，胰岛素，IGF激素和LBP）； 3）使用嵌套在MEC中的病例对照研究，检查循环LBP与结直肠癌之间的关联，并在1379例结直肠病例和1379个对照中诊断出在诊断之前在血浆中测量LBP； 4）参与分析，将肠道微生物组与其他项目中产生的结果整合在一起，以阐明跨数据维度的变量之间的相互关系并构建体内脂肪量和分布的最佳预测模型以及癌症风险。