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.

项目概要/摘要： 在世界范围内，估计有1/3的女性和1/5的男性在50岁以上的经验， 骨折仅在美国，每年对医疗保健系统的影响就达190亿美元，但随着我们的 人口老龄化和对现有药物选择的依从性差，这些成本是预期的 升级因此，继续寻找替代策略来预防和治疗 骨质疏松最近针对肠-骨轴的报道重新引起了人们对 营养干预。令人信服的证据表明，益生菌会增加短链脂肪 酸（SCFAs），这反过来又促进T调节（TREG）细胞的分化， 骨保护作用。传统益生元的骨骼保护益处（即，纤维）已 归因于SCFA诱导的肠道钙摄取增加;然而， 最近，益生菌的研究提出了益生元是否靶向肠道微生物的问题， 通过类似的免疫调节机制改变骨稳态。最近通过 对益生元更全面的定义表明，天然产品，如果馅饼， 樱桃是低聚果糖、花青素和酚酸的极好来源， 具有显著的益生元活性我们实验室的初步数据显示， 酸樱桃促进骨生成，防止骨丢失，增加SCFA（例如，丁酸盐），和 下调肠道相关淋巴组织中的炎症过程。该项目的目标是 确定酸樱桃的益生元活性在多大程度上介导了它对骨骼的影响， 丁酸盐诱导的Treg细胞的改变。我们假设酸樱桃的好处 补充剂对骨的作用至少部分是由增强的TREG分化介导的， 肠道微生物群的改变以及随之而来的丁酸盐产量的增加。以下 目的是为了验证这一假设：目的1）确定膳食补充剂如何 酸樱桃改变了骨内稳态，这些作用在多大程度上是由 目的2）研究来源于肠道微生物群的丁酸盐的作用 骨骼的反应。拟议的研究将促进我们对生物活性物质如何 酸樱桃中的成分除了提供一种 为本科研究人员提供了极好的培训机会。此外，这些发现可能 为未来旨在用益生元靶向肠道的临床研究奠定基础， 符合我们开发预防和治疗替代治疗策略的长期目标 骨质疏松症的治疗。