A randomized, double-blind, placebo-controlled, clinical trial of a probiotic/prebiotic supplement for the dietary management of age-related bone loss.

摘要/项目总结 目前推荐的随着年龄增长维持骨量的策略仅限于消耗 富含维生素和矿物质的饮食，并进行负重活动。如果没有更具体有效的 随着年龄的增长，老年人会患上骨质疏松症，骨折的风险增加 需要处方药，副作用和限制性成本。因此，存在对安全的未满足的需求。 和有效的饮食干预的代谢过程中潜在的骨质流失。我们的长期目标是 开发安全有效的益生元/益生菌组合补充剂，用于 骨质减少和骨质疏松症的代谢过程。本项目的目的是测试 益生菌/益生元组合（"合生元"）在骨骼上的临床试验， 对合生元作用的机械见解。我们的中心假设是，一种新的植物源性药物 食品合生元（"SBD 111"）将改善双能X射线吸收测定法（DXA）得出的腰椎骨 骨密度（BMD）、定量计算机断层扫描（QCT）得出的骨强度-也称为生物力学 计算机断层扫描分析，或BCT和体积BMD（vBMD），骨转换标志物， 炎症和肠道微生物组功能在老年女性（> 60岁）与安慰剂相比。以强为导 初步数据将通过进行一项为期18个月的随机、双盲、安慰剂- 在220名老年妇女中进行的对照临床试验。我们的具体目标是：目标1a和1b 每日摄入SBD111个月对腰椎DXA-BMD主要结局和次要结局的影响 （BCT衍生的椎体压缩骨强度、vBMD和骨转换标志物）。目标2a 和2b确定每日摄入SBD111 18个月对炎症和肠道标志物的影响 微生物在女性中的作用我们将采用全宏基因组和元转录组鸟枪测序 剖析肠道微生物组功能的变化[定义为糖基水解酶，甲基萘醌7，简称甲基萘醌7， 链脂肪酸（SCFA）和微生物多样性]，可以介导SBD111对骨转换的影响， 炎症我们还将考虑摄入总膳食纤维，益生元纤维和益生菌食品， 改变SBD111对骨骼、炎症和肠道微生物组的影响。 如果成功，这项拟议的试验将导致开发潜在的安全，廉价的健康促进策略 用于骨质减少和骨质疏松症的代谢过程的饮食管理。 1

ABSTRACT / PROJECT SUMMARY Currently recommended strategies for primary maintenance of bone mass with age are limited to consuming a diet rich in vitamins and minerals and performing weight bearing activity. Without more specific and effective ways to maintain bone mass with age, older adults will develop osteoporosis and elevated fracture risk necessitating prescription drugs, with side effects and restrictive costs. Hence, there is an unmet need for safe and effective dietary interventions for the metabolic processes underlying bone loss. Our long term goal is to develop safe and effective prebiotic/probiotic combination supplements for the dietary management of the metabolic processes underlying osteopenia and osteoporosis. The objective of this project is to test the efficacy of an probiotic/prebiotic combination (“synbiotic”) on the skeleton in a clinical trial that is designed to provide mechanistic insights into the action of the synbiotic. Our central hypothesis is that a novel plant-derived medical food synbiotic (“SBD111”) will improve dual energy x-ray absorptiometry (DXA) derived lumbar spine bone mineral density (BMD), quantitative computed tomography (QCT) derived bone strength — aka Biomechanical Computed Tomography analysis, or BCT— and volumetric BMD (vBMD), markers of bone turnover, inflammation, and gut microbiome function in older women (>60 years) compared to placebo. Guided by strong preliminary data this hypothesis will be tested by performing an 18-month randomized, double-blinded, placebo- controlled clinical trial in 220 older women. Our specific aims are: Aim 1a and 1b To determine the effect of 18 months of daily intake of SBD111 on the primary outcome of lumbar spine DXA-BMD and secondary outcomes (BCT-derived vertebral compressive bone strength, vBMD, and markers of bone turnover) in women. Aim 2a and 2b To determine the effect of 18 months of daily intake of SBD111 on markers of inflammation and gut microbiome function in women. We will employ whole metagenome and meta-transcriptome shotgun sequencing to dissect changes in gut microbiome function [defined as changes in glycosyl hydrolase, menaquinone 7, short chain fatty acid (SCFA), and microbial diversity], which can mediate the effect of SBD111 on bone turnover and inflammation. We will also consider intake of total dietary fiber, prebiotic fiber, and probiotic foods that could modify the effect of SBD111 on bone, inflammation, and gut microbiome. If successful, this proposed trial will lead to developing potentially safe, inexpensive health promoting strategies for the dietary management of the metabolic processes underlying osteopenia and osteoporosis. 1