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

描述(申请人提供)：木脂素是一种植物雌激素，由于结构和功能与内源性雌激素相似，在乳腺癌病因学中作为饮食因素已被广泛研究。在解释饮食暴露和随后的疾病风险之间的联系时，代谢的个体差异是至关重要的，这可能在一定程度上解释了饮食和乳腺癌研究中的不一致。事实上，越来越多的证据支持这样的假设，即饮食成分的影响，例如木脂素，对于在参与饮食成分代谢和/或非饮食代谢目标的基因中具有特定变异的个体，可能具有不同的表达。此外，为了变得具有生理活性，植物木脂素需要哺乳动物肠道细菌的转化。这些细菌数量众多，种类繁多，对饮食成分的新陈代谢至关重要；因此，肠道细菌组成正成为检查的目标，成为饮食暴露的重要贡献者和调节者。最后，种族也可能是一个重要的影响因素，因为种族的概念包含了遗传多样性、微生物多样性和包括饮食在内的生活方式因素。本研究的目标是确定 肠道微生物群落组成以及类固醇激素和异物代谢基因的变化如何影响哺乳动物木脂素和类固醇激素在基线和接触富含木脂素的食物(亚麻籽)后的新陈代谢，以及这些联系在非裔美国人和高加索女性中有何不同。事实上，人类是具有不同遗传背景的超级有机体，其遗传背景被不同的、代谢活跃的细菌群落所增强，其组成可以通过特定的饮食暴露而改变。我们的中心假设是，对饮食成分的代谢反应是一个人的基因构成和他的肠道细菌群落的特定组成的综合作用的结果。阐明肠道微生物群、宿主遗传学和饮食之间的相互作用将对改进针对性饮食干预措施的发展产生积极影响，以降低癌症风险。

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.