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： 据估计，全世界50岁以上的女性和男性中分别有1/3和1/5患有骨质疏松症。 骨折。仅在美国，每年对医疗体系的影响就达到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较差，这些成本是预期的 升级。因此，继续寻找预防和治疗的替代战略。 骨质疏松。最近针对肠骨轴的报道重新引起了人们对肌动蛋白的作用的兴趣 营养干预。令人信服的证据表明，益生菌会增加短链脂肪 酸(SCFA)，进而促进T调节(Treg)细胞的分化，介导 具有骨保护作用。传统益生元(即纤维)的骨骼保护益处是 归因于SCFA诱导的肠道钙摄取增加；然而，洞察力获得了更多 最近，益生菌的研究提出了益生菌是否针对肠道共生的问题 微生物区系和通过类似的免疫调节机制改变骨骼的动态平衡。最近的采用 益生元更全面的定义揭示了天然产品，如酸奶 樱桃富含果寡糖、花青素和酚酸，每一种都是 具有显著的益生菌活性。我们实验室的初步数据将表明，补充饮食 酸樱桃促进骨积累，防止骨丢失，增加单链脂肪酸(如丁酸盐)，以及 下调肠道相关淋巴组织的炎症过程。这个项目的目标是 确定酸樱桃的益生菌活性在多大程度上通过 丁酸诱导的Treg细胞的改变。我们假设酸樱桃的好处是 对骨骼的补充至少部分是通过增强Treg分化来调节的，这种分化是由 肠道微生物区系的变化以及随之而来的丁酸盐产量的增加。以下是 已经开发出目标来检验这一假设：目标1)确定饮食补充剂 酸樱桃改变了骨骼的动态平衡，这些影响在多大程度上是通过 Treg细胞的改变；以及目标2)研究来自肠道微生物区系的丁酸盐的作用 在这种骨骼反应上。拟议的研究将促进我们对生物活性如何 酸樱桃中的成分除了提供一种 为本科生研究人员提供了绝佳的培训机会。此外，这些发现可能 为未来以肠道为靶点的益生元临床研究奠定基础，该研究在 符合我们的长期目标，即发展替代治疗策略，以预防和 治疗骨质疏松症。