Prebiotic Activity of Tart Cherry and the Immunoregulation of Bone Homeostasis

酸樱桃的益生元活性和骨稳态的免疫调节

• 批准号: 10046896
• 负责人: STEPHEN L CLARKE
• 金额: $ 44.09万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10046896
• 关键词: Adoption; Age; Age-Related Bone Loss; Animal Model; Animals; Anthocyanins; Bacillus; Bone Resorption; Butyrates; C57BL/6 Mouse; Calcium; Cell Differentiation process; Cells; Cherry - dietary; Clinical Research; Data; Diet; Dietary Intervention; Dietary Supplementation; Disease; FDA approved; Fermentation; Fiber; Foundations; Fracture; Fright; Fruit; Future; Goals; Gut associated lymphoid tissue; Healthcare Systems; Homeostasis; IL2RA gene; Immunologics; Inflammatory; Interferons; Interleukin-10; Intestines; Lactobacillus casei rhamnosus; Mediating; Musculoskeletal Diseases; Natural Products; Oligosaccharides; Osteogenesis; Osteoporosis; Patients; Peripheral; Pharmaceutical Preparations; Pharmacology; Prevention strategy; Probiotics; Process; Production; Public Health; Regimen; Reporting; Research Design; Research Personnel; Role; Site; Source; Supplementation; T-Lymphocyte; Testing; Therapeutic; Tumor Necrosis Factor Suppression; Up-Regulation; Volatile Fatty Acids; WNT Signaling Pathway; Woman; age related; aging population; bone; bone loss; chronic pain; commensal microbes; cost; design; disability; experience; fructooligosaccharide; gut microbiota; immunoregulation; insight; interest; men; microbiota; novel; novel strategies; novel therapeutics; osteoblast differentiation; osteoclastogenesis; osteoporosis with pathological fracture; phenolic acid; prebiotics; prevent; protective effect; response; side effect; skeletal; therapeutic target; training opportunity; treatment strategy; undergraduate student; uptake

Project Summary/Abstract: Worldwide, an estimated 1 in 3 women and 1 in 5 men over the age of 50 y experience an osteoporotic fracture. In the U.S. alone, the impact on the healthcare system is $19 billion annually, but with our aging population and poor compliance with existing pharmacological options these costs are expected to escalate. Consequently, the search has continued for alternative strategies to prevent and treat osteoporosis. Recent reports targeting the gut-bone axis have provided renewed interest in the role of nutritional interventions. Compelling evidence has shown that probiotics increase short chain fatty acids (SCFAs), which in turn promote the differentiation of T regulatory (TREG) cells that mediate osteoprotective effects. The bone-protective benefits of classic prebiotics (i.e., fibers) have been attributed to a SCFA-induced increase in intestinal calcium uptake; however, insights gained more recently from studies of probiotics raise the question of whether prebiotics target gut commensal microbiota and alter bone homeostasis by similar immunoregulatory mechanisms. The recent adoption of a more comprehensive definition of prebiotics has revealed that natural products such as tart cherries provide an excellent source of fructo-oligosaccharide, anthocyanin and phenolic acid, each with notable prebiotic activity. Preliminary data from our lab will show that supplementing the diet with tart cherry promotes bone accrual, protects against bone loss, increases SCFAs (e.g., butyrate), and downregulates inflammatory processes in gut-associated lymphoid tissues. The goal of this project is to determine the extent to which the prebiotic activity of tart cherry mediates it effects on bone via butyrate-induced alterations in TREG cells. We hypothesize that the benefits of tart cherry supplementation on bone are mediated, at least in part, by enhanced TREG differentiation resulting from alterations in the gut microbiota and the consequent increase in butyrate production. The following aims have been developed to test this hypothesis: Aim 1) To determine how dietary supplementation with tart cherry alters bone homeostasis and the extent to which these effects are mediated by alterations in TREG cells; and Aim 2) To investigate the role of butyrate derived from the gut microbiota on this skeletal response. The proposed studies will advance our understanding of how the bioactive components in tart cherry mediate their effects on the gut-bone axis in addition to providing an excellent training opportunity for undergraduate researchers. Furthermore, these findings could establish the foundation for future clinical studies designed to target the gut with prebiotics, which is in line with our long-term goal of developing alternative therapeutic strategies for the prevention and treatment of osteoporosis.

项目摘要/摘要： 在全球范围内，估计有3个女性中有1人和50岁以上的5分之一的男性经历了骨质疏松症 断裂。仅在美国，对医疗保健系统的影响每年为190亿美元，但我们 人口老龄化和对现有药理选择的依从性不佳，预计这些费用是 升级。因此，搜索一直在寻求预防和治疗的替代策略 骨质疏松症。针对肠道轴的最新报告对 营养干预措施。令人信服的证据表明，益生菌会增加短链脂肪 酸（SCFA）又促进了介导的T调节（Treg）细胞的分化 骨保护作用。经典益生元（即纤维）的骨保护益处已经 归因于SCFA引起的肠钙吸收的增加；但是，见解获得了更多 最近，益生菌研究提出了益生元是否靶向肠道的问题 微生物群和通过类似的免疫调节机制改变骨稳态。最近的采用 对益生元的更全面的定义表明，天然产品（例如蛋ut） 樱桃提供了果酱 - 寡糖，花青素和酚酸的极好来源 具有明显的益生元活性。我们实验室的初步数据将表明补充饮食 用酸樱桃促进骨骼应计，防止骨质流失，增加SCFA（例如丁酸酯），并且 下调肠道相关淋巴组织中的炎症过程。这个项目的目标是 确定蛋cherry樱桃的益生元活性在多大程度上通过 丁酸酯诱导的Treg细胞改变。我们假设酸樱桃的好处 至少部分通过增强的Treg分化而导致的骨骼补充。 肠道菌群的改变以及随之而来的丁酸盐产生增加。下列 已经开发了以检验此假设的目的：目标1）确定饮食补充的方式 酸樱桃会改变骨稳态以及这些作用的介导的程度 Treg细胞的改变；目标2）研究源自肠道菌群的丁酸酯的作用 在这种骨骼反应上。拟议的研究将提高我们对生物活性的理解 酸樱桃中的组件还介导其对肠骨轴的影响，此外还提供了 本科研究人员的绝佳培训机会。此外，这些发现可能 为未来的临床研究建立基础 与我们为预防制定替代性治疗策略的长期目标与 治疗骨质疏松症。