Prebiotic Activity of Pinto Beans Reduces Neuroinflammation in Estrogen Deficiency

斑豆的益生元活性可减少雌激素缺乏症的神经炎症

• 批准号: 10715516
• 负责人: Edralin A. Lucas
• 金额: $ 16.86万
• 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/10715516
• 关键词: 4-vinylcyclohexene diepoxide; Adipose tissue; Administrative Supplement; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease risk; Area; Astrocytes; Attenuated; Bacteria; Beta-glucuronidase; Biological Availability; Biomedical Research; Brain; Clinical Research; Consumption; Development; Dietary Intervention; Disease; Disease Progression; Distant; Enzymes; Equilibrium; Estrogen Metabolism; Estrogen decline; Estrogen deficiency; Estrogens; Food; Funding; Future; Goals; Health Benefit; Health Promotion; Human; Immune; Inflammation; Link; Maintenance; Memory impairment; Menopause; Metabolic; Microglia; Modeling; Mus; Natural Products; Nervous System; Neurons; Outcome; Pathology; Persons; Phaseolus vulgaris; Physiology; Phytoestrogens; Population; Postmenopause; Prevalence; Prevention; Process; Production; Property; Regulation; Reporting; Research; Resistance; Risk; Role; Sampling; Signal Transduction; Source; Starch; Supplementation; Synaptic plasticity; Testing; Tissues; Training; Tryptophan; United States; Volatile Fatty Acids; Woman; Work; bean; behavior measurement; brain health; cardiometabolism; cell type; commensal bacteria; design; disorder prevention; dysbiosis; effectiveness evaluation; enzyme activity; experience; food consumption; graduate student; gut bacteria; gut health; gut microbiota; gut-brain axis; human old age (65+); improved; men; microbial; mouse model; neural; neuroinflammation; nutrition; parent project; pathogenic bacteria; prebiotics; prevent; primary outcome; secondary outcome; training opportunity; undergraduate student; western diet

Project Summary/Abstract: The prevalence of of Alzheimer’s disease (AD) is 2–3 times higher in post-menopausal women and pathology progression and memory impairment is worse in women than men. The rapid decline in circulating estrogen in postmenopausal women has been proposed as a trigger for the development of AD in this population. Previous studies have established a relationship between circulating estrogen levels, gut health including gut microbial population, and brain function. Estrogen deficiency-associated microbial dysbiosis is associated with reduced diversity of gut bacteria (i.e., bacteria with β-glucuronidase activity) that can deconjugate estrogen-containing compounds including phytoestrogens as well as those involved in the production of short chain fatty acids (SCFAs) and tryptophan (Trp) metabolites. Recent studies have identified the influence of SCFAs as well as Trp metabolites in the stimulation and maintenance of brain function. Our parent project is designed to investigate the mechanism through which pinto bean (PB) modulates cardiometabolic outcomes in a mouse model of estrogen deficiency. In this administrative supplement application, we propose to extend that work by examining the effects of PB on the gut-brain axis and subsequent effects on the prevention of neuroinflammation associated with AD in estrogen deficiency, much like the at-risk postmenopausal population. We hypothesize that PB, due to its many bioactive compounds, particularly its Trp and resistant starch (RS) content, will modulate gut microbial composition to maintain gut integrity and increase the production of gut-derived metabolites (i.e., SCFAs and Trp metabolites) consequently improving gut health, reducing neuroinflammation and slowing down the progression of AD in estrogen deficiency. This hypothesis will be tested by: Aim 1: determining the effects of PB and RS on gut microbial composition and gut-derived metabolites and their subsequent effects on markers of neuroinflammation in estrogen deficiency; and Aim 2: investigating the role of β-glucuronidase inhibition combined with PB in the prevention of neuroinflammation in estrogen deficiency. The proposed supplemental study will expand the scope of our current R15 and will now focus to include both metabolic outcomes and prevention of AD in estrogen deficiency. Both studies will provide extensive training opportunities for graduate and undergraduate students, and cross-training between the field of nutrition and brain physiology. Our findings will help advance our understanding of how foods with prebiotic properties such as PB promote health and prevent diseases. Our findings will also help lay the groundwork for future clinical studies, in line with our long-term goal of developing economical, safe and effective strategies for disease prevention.

项目摘要/摘要： 阿尔茨海默病(AD)的患病率在绝经后妇女和病理进展中高出2-3倍 而且，女性的记忆障碍比男性更严重。绝经后循环雌激素水平的快速下降 妇女被认为是该人群中阿尔茨海默病发病的诱因。以前的研究已经建立了一个 循环雌激素水平、肠道健康(包括肠道微生物种群)和脑功能的关系。 与雌激素缺乏相关的微生物失调与肠道细菌多样性降低有关(即 β-葡萄糖醛酸苷酶活性)，可以去结合含有雌激素的化合物，包括植物雌激素以及 参与生产短链脂肪酸(SCFAs)和色氨酸(Trp)代谢物。最近的研究表明 确定了单链脂肪酸和色氨酸代谢物在刺激和维持大脑功能方面的影响。我们的 父项目旨在研究Pinto Bean(PB)调节心脏代谢的机制 雌激素缺乏小鼠模型的结果。在这项行政补充申请中，我们建议延长 这项工作是通过研究PB对肠道-脑轴的影响以及随后对预防高血压的影响来完成的。 雌激素缺乏与AD相关的神经炎症，就像绝经后的高危人群一样。我们 假设PB由于其许多生物活性化合物，特别是其色氨酸和抗性淀粉(RS)含量，将 调节肠道微生物组成以保持肠道完整性并增加肠道衍生代谢物的产生(即， SCFAs和Trp代谢物)，从而改善肠道健康，减少神经炎症，减缓 雌激素缺乏与阿尔茨海默病的进展这一假设将通过以下方式进行检验：目标1：确定PB和RS的影响 肠道微生物组成、肠源性代谢物及其对神经炎标志物的影响 目的2：研究β-葡萄糖醛酸酶抑制联合PB在雌激素缺乏中的作用。 预防雌激素缺乏症的神经炎症。拟议的补充研究将扩大我们的 目前的R15版本，现在将重点包括雌激素缺乏的代谢结果和AD的预防。两者都有 研究将为研究生和本科生提供广泛的培训机会，并在 营养学和脑生理学领域。我们的发现将有助于我们进一步了解含有益生素的食物是如何 像PB这样的特性可以促进健康，预防疾病。我们的发现也将有助于为未来的工作奠定基础 临床研究，符合我们开发经济、安全和有效的疾病策略的长期目标 预防。