Soy Isoflavone Metabolite Equol - it's Formation and Fate

说明(申请人提供)：雌马酚是一种异黄酮类的非类固醇雌激素，是摄入的大豆异黄酮类最重要的代谢物。它是由肠道细菌产生的，在4个月大的婴儿的尿液和血液中没有发现。由于未知的原因，食用大豆食品的成年人中只有三分之一会产生等价物。最近关于预防骨质疏松症、心血管健康和更年期的研究表明，与那些不能制造马儿的人相比，豆类食物对‘马儿产生者’的有益影响明显更大，现在人们意识到，这两个不同的人群需要在饮食干预研究中加以界定。虽然Equol以两种对映体形式存在，但我们已经证明，人类只产生S-Equol，它与雌激素受体ER-β有很高的亲和力，与ER-α的结合可以忽略不计。另一方面，R-QUOL具有强大的抗雄激素特性，可以拮抗双氢睾酮的作用，使其具有药理学价值。首次测定了S和R-马酚的药代动力学。我们的目的是证明S-马酚存在于人的血浆和尿液中，不是因为这两种对映体吸收的差异，而是因为它的细菌对映体特异性形成。由于作为马匹生产者有优势，了解支配马匹生产的因素是很重要的。我们将确定Equol在早期生命中首次出现的时间，以及是早期婴儿营养类型的差异，还是断奶后饮食结构的不同导致了Equol的产生。母乳喂养导致肠道细菌定植的差异，与奶瓶喂养相比，pH值更低，这有望促进马匹的形成。初步的体外和人体数据表明，某些有利于结肠发酵的益生素大量营养素的摄入量较高，有利于马醇的形成。这将通过比较健康成年人的等量生产与其膳食中大量营养素的摄入量，使用根据食物频率问卷和3天饮食记录确定的纤维摄入量来分层分组来确定。我们将确定成人马儿生产的长期稳定性及其对抗生素使用的反应。鉴于马儿酚的临床相关性，更好地了解影响其生产的因素将有助于未来操纵马儿醇生产的战略，并提高大豆食品的整体临床有效性。

DESCRIPTION (provided by applicant): Equol, a non-steroidal estrogen of the isoflavone class, is the most important metabolite of ingested soy isoflavones. It is made by intestinal bacteria and not found in the urine and blood of infants before 4-months of age. For unknown reasons only one-third of adults consuming soy foods make equol. Recent studies of osteoporosis prevention, cardiovascular health, and menopause have shown that beneficial effects from soy foods are significantly greater in people who are 'equol-producers' compared with those unable to make equol, and it is now realized that these two distinct populations need defining in dietary intervention studies. While equol exists in two enantiomeric forms, we have shown that humans make exclusively S-equol, and it has a high affinity for estrogen receptor ER-beta and shows negligible binding to ER-alpha. R-equol on the other-hand has potent antiandrogen properties, antagonizing the actions of dihydrotestosterone, making it of pharmacological interest. For the first time, the pharmacokinetics of S- and R-equol will be determined. Our aim is to prove that S-equol occurs in human plasma and urine not because of differences in the absorption of the two enantiomers, but moreover due to its bacterial enantiomeric-specific formation. Since there are advantages to being an equol-producer it is important to understand the factors governing equol production. We will determine when equol first appears in early life and whether it is differences in the type of early infant nutrition, or the composition of the post-weaning diet that predispose to the production of equol. Breastfeeding leads to differences in intestinal bacterial colonization and a lower pH compared with bottle-feeding, and this is expected to facilitate equol formation. Preliminary in vitro and human data suggest higher intakes of certain prebiotic macronutrients conducive to colonic fermentation favor equol formation. This will be determined by comparing equol-production in healthy adults relative to their dietary intakes of macronutrients using fiber intake determined from food frequency questionnaire and 3-day diet records to stratify groups. We will determine the long-term stability of equol-production in adults and its response to antibiotic use. Given the clinical relevance of equol, a greater understanding of factors governing its production will facilitate future strategies to manipulate equol production and enhance the overall clinical effectiveness of soy foods.