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.

项目总结/文摘: