Prebiotic Activity of Pinto Beans and Metabolic Outcomes in Estrogen Deficiency

项目摘要/摘要： 雌激素缺乏增加了许多慢性疾病的风险，包括心血管疾病(CVDS)。 最近的证据表明，雌激素会导致肠道微生物失调和肠道完整性障碍 缺乏提供了新的机制靶点来对抗与以下相关的心脏代谢紊乱 更年期。肠道也通过微生物的作用在雌激素的新陈代谢中发挥重要作用。 衍生的雌激素去结合酶(即β-葡萄糖醛酸酶)，改变肝脏肠-肝循环。 雌激素使其更具生物利用度。β-葡萄糖醛酸苷酶还可以去结合酚类化合物，从而 延长它们的循环，增强它们的生物活性。众所周知，膳食纤维等具有抵抗力 淀粉(RS)和低聚果糖具有益生活性，可用于对抗 雌激素缺乏对肠道健康和代谢结果的影响。然而，多酚也能够起到 益生素通过改变微生物组，有利于有益的肠道微生物的定居。研究检查 天然产物中纤维与多酚结合的益生菌活性及其机制 在雌激素缺乏的情况下的作用是有限的。平托豆(PB)富含这些生物活性物质 具有益生素活性的化合物，可在雌激素缺乏时有益于健康。我们最新的发现 证明PB可预防肠道菌群失调，改善肠道完整性的指标，减少炎症，以及 改善了喂食西式饮食的小鼠的胰岛素敏感性。在本应用程序中，我们建议在此基础上 通过在小鼠模型中研究PB调节心脏代谢结果的机制进行工作 雌激素缺乏症。我们推测，由于PB有许多生物活性物质，特别是它的RS 含量，将调节肠道微生物组成，改变β-葡萄糖醛酸酶活性以及 短链脂肪酸(SCFAs)，从而改善肠道健康和代谢结果 雌激素缺乏症。这一假设将通过以下方式进行验证：目标1)确定肠道微生物的变化 雌激素缺乏时PB和RS的组成和代谢结果；以及目的2)调查 肠源性β-葡萄糖醛酸苷酶在雌激素缺乏引起的代谢反应中的作用。建议数 研究将为学生提供一个极好的训练机会，我们的研究结果将促进我们的 了解PB等益生元如何在雌激素缺乏时调节其对代谢结果的影响。 我们的发现将为未来的临床研究奠定基础，这与我们的长期目标是一致的 制定经济、安全、有效的心血管疾病预防策略。

Project Summary/Abstract: Estrogen deficiency increases the risk for many chronic diseases including cardiovascular diseases (CVDs). Recent evidence demonstrating gut microbial dysbiosis and gut integrity dysfunction that occur in estrogen deficiency provides new mechanistic targets to counter the cardiometabolic disturbances associated with menopause. The gut also plays an important role in the metabolism of estrogen through the action of microbial- derived estrogen deconjugating enzyme (i.e., β-glucuronidase) which alters the enterohepatic recirculation of estrogen making it more bioavailable. β-glucuronidase can also deconjugate phenolic compounds that can prolong their circulation and enhance their bioactivity. It is well established that dietary fibers such as resistant starch (RS) and fructooligosaccharides have prebiotic activity and could be used to counter the effects of estrogen deficiency on gut health and metabolic outcomes. However, polyphenols are also capable of acting as prebiotics by shifting the microbiome to favor the colonization of beneficial gut microbes. Studies examining the prebiotic activity of combination of fiber and polyphenols found in natural products and their mechanisms of action in the context of estrogen deficiency are limited. Pinto beans (PB) are rich in in these bioactive compounds with prebiotic activity and can confer health benefits in estrogen deficiency. Our recent findings demonstrated that PB prevented gut dysbiosis, improved markers of gut integrity, reduced inflammation, and improved insulin sensitivity in mice fed a Western-style diet. In this application, we proposed to build on that work by investigating the mechanism through which PB modulates cardiometabolic outcomes in a mouse model of estrogen deficiency. We hypothesize that PB, due to its many bioactive compounds particularly its RS content, will modulate gut microbial composition and alter β-glucuronidase activity as well as the production of short chain fatty acids (SCFAs) which will consequently improve gut health and metabolic outcomes in estrogen deficiency. This hypothesis will be tested by: Aim 1) determining the alterations in gut microbial composition and metabolic outcomes induced by PB and RS in estrogen deficiency; and Aim 2) investigating the role of the gut-derived β-glucuronidase in the metabolic response due to estrogen deficiency. The proposed study will provide an excellent training opportunity for students and our findings will advance our understanding of how prebiotics such as PB mediate their effects on metabolic outcomes in estrogen deficiency. Our findings will lay the groundwork for future clinical studies, which is in line with our long-term goal of developing economical, safe and effective strategies for cardiovascular disease prevention.