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

摘要/项目摘要 目前推荐的随年龄增长的初级骨量维持策略仅限于消耗 饮食富含维生素和矿物质，并能进行负重活动。如果没有更具体和有效的 保持骨量的方法随着年龄的增长，老年人会患上骨质疏松症和骨折风险增加 需要处方药，有副作用和限制性成本。因此，对安全的需求尚未得到满足。 对骨质流失的代谢过程进行有效的饮食干预。我们的长期目标是 开发安全有效的益生菌/益生菌组合补充剂，用于肉鸡的饮食管理 骨量减少和骨质疏松症背后的代谢过程。这个项目的目标是测试疗效。 在一项临床试验中，骨骼上的益生菌/益生菌组合(“合生元”)旨在提供 对合生体作用的机械论洞察。我们的中心假设是一种从植物中提取的新型药物 食品合生素(“SBD111”)将改善双能X射线骨密度仪(DXA)来源的腰椎骨 骨密度(BMD)、定量计算机断层扫描(QCT)得出的骨强度(又名生物力学) 计算机断层扫描分析，或BCT-和体积骨密度(VBMD)，骨转换的标志， 与安慰剂相比，老年女性(&gt；60岁)的炎症和肠道微生物群功能。以Strong为指导 初步数据将通过进行为期18个月的随机、双盲、安慰剂试验来检验这一假设。 220例老年妇女的临床对照试验。我们的具体目标是：目标1a和1b，以确定18 每日摄入SBD111几个月对腰椎DXA-BMD和二次结局的影响 (BCT得出的椎体压缩骨强度、vBMD和骨转换标志物)。目标2a 和2b确定每天摄入SBD111 18个月对炎症和肠道标志物的影响 微生物群在女性中的作用。我们将使用整个元基因组和元转录组鸟枪式测序 解剖肠道微生物组功能的变化[定义为糖基水解酶、孟喹酮7、 链脂肪酸(SCFA)和微生物多样性]，这可以介导SBD111对骨转换和 发炎。我们还将考虑摄入总膳食纤维、益生菌纤维和益生菌食物，这些食物可能 修改SBD111对骨骼、炎症和肠道微生物群的影响。 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 用于骨量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