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.
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