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

基本信息

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
项目类别：
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

项目摘要

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，50 岁以上的女性中约有三分之一和男性中约有五分之一患有骨质疏松症断裂。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较差，这些成本是预期的升级。因此，人们继续寻找预防和治疗的替代策略骨质疏松症。最近针对肠骨轴的报告重新引起了人们对肠骨轴作用的兴趣营养干预。令人信服的证据表明，益生菌可增加短链脂肪酸（SCFA），进而促进调节 T 细胞（TREG）的分化，从而介导骨保护作用。经典益生元（即纤维）的骨骼保护益处已被证实归因于 SCFA 诱导的肠道钙吸收增加；然而，见解获得了更多最近对益生菌的研究提出了益生元是否针对肠道共生菌的问题微生物群并通过类似的免疫调节机制改变骨稳态。最近采用的对益生元的更全面的定义表明，天然产品，例如酸樱桃提供低聚果糖、花青素和酚酸的极好来源，每种具有显着的益生元活性。我们实验室的初步数据表明，补充饮食与酸樱桃一起促进骨质增生，防止骨质流失，增加 SCFA（例如丁酸盐），以及下调肠道相关淋巴组织的炎症过程。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其对骨骼的影响丁酸盐诱导的 TREG 细胞改变。我们假设酸樱桃的好处骨补充至少部分是通过增强的 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。下列已制定目标来检验这一假设：目标 1) 确定膳食补充剂如何与酸樱桃一起改变骨骼稳态以及这些影响的介导程度 TREG 细胞的改变；目标 2) 研究肠道微生物群中丁酸盐的作用关于这个骨骼反应。拟议的研究将增进我们对生物活性如何的理解酸樱桃中的成分除了提供为本科生研究人员提供了绝佳的培训机会。此外，这些发现可以为未来旨在利用益生元靶向肠道的临床研究奠定基础，符合我们开发替代治疗策略来预防和治疗的长期目标治疗骨质疏松症。