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

描述（由申请人提供）：木脂素是一种植物雌激素，由于其结构和功能与内源性雌激素相似，作为乳腺癌病因的饮食因素已被广泛研究。在解释饮食暴露与随后的疾病风险之间的关系时，代谢的个体差异是至关重要的，并且可能部分解释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一种假设，即一种膳食成分（如木脂素）的作用可能在个体中表达不同，这些个体具有参与膳食成分和/或非膳食代谢目标代谢的特定基因变异。此外，为了具有生理活性，植物木脂素需要通过哺乳动物肠道细菌进行转化。这些细菌数量众多，种类繁多，对膳食成分的代谢至关重要；因此，肠道细菌组成作为饮食暴露的重要贡献者和调节剂正在成为检查的目标。最后，种族也可能是一个重要的影响调节因素，因为种族的概念包括遗传多样性、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

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.