Blackcurrants Modify Gut Microbiota and Reduce Osteoporosis Risk in Postmenopausal Females

Postmenopausal osteoporosis (PMO) is a debilitating and progressive metabolic bone disorder caused by estrogen deficiency after menopause, leading to an imbalance in bone remodeling. Owing to its high morbidity and serious complications, substantial efforts have been devoted to its prevention and treatment. Emerging evidence indicates that the gut microbiome plays a pivotal role in bone health through immune and endocrine pathways, influencing bone turnover via cytokine signaling, metabolite production, and calcium balance.

Our previous 6-month trial suggested that blackcurrant (BC) may exert bone-protective effects through integrated effects on bone remodeling, gut microbiota, and metabolite signaling. Therefore, the overall goal of this study is to investigate the effects of BC supplementation on changes in gut microbiota and bone density in postmenopausal females and to elucidate the interrelationship of BC and gut microbiota with regard to bone loss mitigation. This will be accomplished using a multidisciplinary, comprehensive multi-omics approach to examine interactions among BC, gut microbiota, bacterial metabolites, and the immune and endocrine systems in relation to bone metabolism.

Investigators will conduct a randomized, placebo-controlled trial of BC supplementation for 12 months in postmenopausal females aged 45-70 years. The primary endpoint will be changes in whole-body, lumbar spine, total hip, and femoral neck bone mineral density. The secondary endpoint will be changes in biomarkers of bone remodeling. To further delineate underlying mechanisms, changes in the community structure of the gut microbiome, inflammatory-immune markers, and endocrine markers will be assessed. Additional analyses will include proteomics to identify protein biomarkers, metabolomics to identify key metabolites associated with BC supplementation and bone-related outcomes, and genotyping to evaluate genetic polymorphisms in bone-related genes.

The specific objectives of this study are to investigate the effects of BC extract on: 1) bone density and bone remodeling biomarkers; and 2) changes in gut microbiota abundance and composition, inflammatory-immune and endocrine biomarkers, protein biomarkers (proteomics), key metabolites (metabolomics), and their relationships with changes in bone density, including evaluation of genetic polymorphisms in bone-related genes (genomics).

This study will provide further insight into whether and how BC consumption may reduce the risk of postmenopausal bone and will improve understanding of the role of the gut microbiome in postmenopausal bone loss. Findings may provide novel insight into how anthocyanin-rich berries reduce PMO risk via the gut-bone axis and may support the development of future dietary recommendations and strategies for adult females approaching or experiencing menopause.

Inclusion criteria

• postmenopausal (defined as no more than 10 years since final menstrual cycle) females aged 45-70 years
• not on hormone replacement therapy for at least one year before initiation of the study
• maintaining normal exercise level (< 7 hours/week) and willing to avoid exercise for 24 hours prior to blood and stool sampling
• willing to ingest a dietary blackcurrant supplement or placebo (up to 1,176 mg/day, three 392mg capsules)
• willing to avoid other dietary supplements for the duration of the study
• willing to avoid intake of foods extremely rich in anthocyanins and fermented dairy products containing viable Bifidobacteria or Lactobacilli
• willing to have three blood draws, three stool collections, and three bone scans

Exclusion criteria

• history of cardiovascular disease, osteoporosis, metabolic bone disease, cancer, diabetes mellitus, arthritis, or other chronic inflammatory diseases
• current smokers
• taking prescription medications known to alter bone and calcium metabolism
• taking anabolic agents such as parathyroid hormone or growth hormone, or steroid within 3 months before the start of the study
• taking medications that alter bleeding (such as antiplatelets or anticoagulants) or those with a bleeding disorder
• alcohol consumption exceeding 2 drinks/day (approximately 14g of ethanol per drink) or a total of 12/week
• those with planned surgery during the study period or within 2 weeks of ending the intervention
• those with sensitivities or allergies to any of the ingredients for the placebo (rice powder)
• planning a procedure that includes iodine, barium or nuclear medicine isotopes within the study period
• UConn students and/or employees who any key personnel teach or who report to any key personnel
• study key personnel, partners of key personnel, or dependents/relatives of any key personnel