Flaxseed effects on hormones and lignans: role of race, genes, and gut microbiome

亚麻籽对激素和木脂素的影响：种族、基因和肠道微生物组的作用

基本信息

批准号：
8550782
负责人：
JOHANNA W LAMPE
金额：
$ 82.77万
依托单位：
ROSWELL PARK CANCER INSTITUTE CORP
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：
2012-09-25 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8550782
关键词：
Accounting Affect African American American Bacteria Cancer Etiology Caucasians Caucasoid Race Characteristics Chemoprevention Communities Complement Development Diet Dietary Component Dietary Factors Dietary Fiber Dietary Intervention Dietary Lignans Dietary Practices Edible Plants Estrogens European Excretory function Exposure to Failure Flax Food Future Genes Genetic Genetic Variation Goals Gonadal Steroid Hormones Hormones Human In Vitro Incidence Individual Individual Differences Intake Intervention Intervention Studies Lignans Malignant Neoplasms Metabolic Metabolism Outcome Pathway interactions Phylogenetic Analysis Phytoestrogens Plants Postmenopause Production Race Randomized Role Seeds Translating Variant Vegetables Woman Xenobiotics cancer chemoprevention cancer risk diet and cancer disorder risk hormone metabolism improved in vivo lifestyle factors malignant breast neoplasm microbial microbial community microbiome mortality response steroid hormone steroid hormone metabolism urinary

项目摘要

DESCRIPTION (provided by applicant): Lignans are phytoestrogens which have been studied fairly extensively as dietary factors in breast cancer etiology due to structural and functional similarities to endogenous estrogens. Individual variation in metabolism is critical to consider when interpreting associations between dietary exposures and subsequent disease risk, and may partly explain inconsistencies in studies of diet and breast cancer. In fact, accumulating evidence supports the hypothesis that the effect of a dietary component, e.g. lignans, may be expressed differentially for individuals possessing specific variation in genes involved either in the metabolism of the dietary component and/or that of the non-dietary metabolic target. Also, to become physiologically active, plant lignans require transformation by the mammalian gut bacteria. These bacteria are numerous, diverse, and essential to the metabolism of dietary components; thus, gut bacterial composition is becoming a target for examination as an important contributor to and modifier of dietary exposures. Finally, race may also be an important effect modifier, as the concept of race incorporates genetic diversity, microbial diversity, and lifestyle factors including diet. The objective in the present study is to determine how variation in gut microbial community composition and in steroid hormone and xenobiotic metabolizing genes affects the metabolism of mammalian lignans and steroid hormones at baseline and after exposure to a lignan-rich food (flaxseed), and how these associations differ for African American and Caucasian women. Humans are, in fact, superorganisms with a diverse genetic background that is augmented by diverse and metabolically active bacterial communities, the composition of which can be modified by specific dietary exposures. Our central hypothesis is that the metabolic response to a dietary component results from the combined effects of an individual's genetic makeup and the particular composition of that individual's gut bacterial communities. Elucidation of interactions between the gut microbiome, host genetics, and diet will have a positive impact on development of improved targeted dietary interventions to reduce cancer risk.

描述（由申请人提供）：木质脂蛋白是植物雌激素，由于与内源性雌激素的结构和功能相似性，在乳腺癌病因中相当广泛地研究了乳腺癌病因的饮食因素。在解释饮食暴露与随后的疾病风险之间的关联时，代谢的个体变异至关重要，并且可能部分解释了饮食和乳腺癌研究的不一致。实际上，积累的证据支持以下假设：饮食成分的影响，例如木质散发木质的人可能会差异化，这些个体在饮食成分和/或非生物代谢靶标的代谢中涉及的基因中具有特异性变化。同样，为了成为生理活跃，植物木质植物需要哺乳动物肠道细菌进行转化。这些细菌对饮食成分的代谢有很多，多样化，并且必不可少。因此，肠道细菌成分正成为对饮食暴露的重要贡献和修饰的检查的靶标。最后，种族也可能是一个重要的效果修饰符，因为种族的概念结合了遗传多样性，微生物多样性和生活方式因素，包括饮食。本研究的目的是确定肠道微生物群落组成以及类固醇激素和异种生物代谢基因的变化如何影响基线时哺乳动物lignans和类固醇激素的代谢，以及暴露于富含木质的食物之后（女性）以及这些关联如何有所不同。实际上，人类是具有多种遗传背景的超生物，被多样化和代谢活跃的细菌群落增强，其组成可以通过特定的饮食暴露来改变。我们的核心假设是，对饮食成分的代谢反应是由于个人的遗传构成的综合作用以及该人的肠道细菌群落的特殊组成。阐明肠道微生物组，宿主遗传学和饮食之间的相互作用将对改善目标饮食干预措施的发展产生积极影响，以降低癌症风险。