Prebiotic Activity of Pinto Beans and Metabolic Outcomes in Estrogen Deficiency

斑豆的益生元活性和雌激素缺乏症的代谢结果

• 批准号: 10439276
• 负责人: Edralin A. Lucas
• 金额: $ 36.95万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10439276
• 关键词: Affect; Antihypertensive Agents; Antioxidants; Apoptotic; Beta-glucuronidase; Biomedical Research; Blood Circulation; Cardiovascular Diseases; Chronic; Chronic Disease; Clinical Research; Dietary Fiber; Enzymes; Estrogen Metabolism; Estrogens; Estrone; Fiber; Follicular Atresia; Food; Functional disorder; Future; Glucose; Glycemic Index; Goals; Health Benefit; Health Status; Heart Diseases; Human; Inflammation; Intake; Intestines; Life; Lipids; Liver; Mediating; Menopause; Metabolic; Mouse Strains; Mus; Natural Products; Outcome; Phaseolus vulgaris; Phenols; Physiological; Phytochemical; Play; Population; Postmenopause; Prevention; Production; Property; Reporting; Resistance; Risk; Risk Factors; Role; Starch; Students; Testing; Tissues; Urine; Vitamins; Volatile Fatty Acids; Woman; Work; bean; cardiometabolism; cardiovascular disorder prevention; cardiovascular disorder risk; dysbiosis; energy density; food consumption; fructooligosaccharide; graduate student; gut bacteria; gut dysbiosis; gut health; gut microbes; gut microbiota; heart disease risk; human female; improved; insulin sensitivity; microbial; microbiome; mouse model; pathogenic bacteria; polyphenol; prebiotics; prevent; response; training opportunity; undergraduate student; western diet

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.

项目概要/摘要： 雌激素缺乏会增加许多慢性疾病的风险，包括心血管疾病（CVD）。 最近的证据表明，雌激素引起的肠道微生物生态失调和肠道完整性功能障碍 缺乏提供了新的机制靶点，以对抗与 绝经肠道通过微生物的作用在雌激素的代谢中也起着重要的作用。 衍生的雌激素去结合酶（即，β-葡萄糖醛酸酶），其改变了 雌激素使其更具生物利用度。β-葡萄糖醛酸糖苷酶还可以使酚类化合物去缀合， 延长其循环并增强其生物活性。众所周知，膳食纤维，如抗性纤维， 淀粉（RS）和低聚果糖具有益生元活性，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，多酚也能够充当 益生元通过改变微生物组以有利于有益肠道微生物的定植。研究审查 天然产物中纤维和多酚组合的益生元活性及其机制 在雌激素缺乏的情况下，作用有限。平托豆（PB）富含这些生物活性物质 具有益生元活性的化合物，并且可以在雌激素缺乏时赋予健康益处。我们最近的发现 表明PB预防肠道生态失调，改善肠道完整性标志物，减少炎症， 改善了喂食西式饮食的小鼠的胰岛素敏感性。在这个应用程序中，我们建议在此基础上 通过研究PB在小鼠模型中调节心脏代谢结果的机制， 雌激素缺乏症我们假设PB，由于其许多生物活性化合物，特别是其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（SCFA），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检验：目的1）确定肠道微生物 PB和RS在雌激素缺乏症中诱导的组成和代谢结果;以及目的2）调查 肠源性β-葡萄糖醛酸酶在雌激素缺乏引起的代谢反应中的作用。拟议 这项研究将为学生提供一个极好的培训机会，我们的研究结果将促进我们的 了解益生元如PB如何介导其对雌激素缺乏症代谢结果的影响。 我们的发现将为未来的临床研究奠定基础，这符合我们的长期目标， 制定经济、安全、有效的心血管疾病预防策略。