Prebiotic Activity of Tart Cherry and the Immunoregulation of Bone Homeostasis

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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.