Journal
JOURNAL OF BONE AND MINERAL RESEARCH
Volume 36, Issue 4, Pages 768-778Publisher
WILEY
DOI: 10.1002/jbmr.4231
Keywords
NUTRITION; GENETIC ANIMAL MODELS; SEX STEROIDS; OSTEOPOROSIS; THERAPEUTICS— OTHER
Categories
Funding
- National Institutes of Health [R01-AT008754, O2S1-AT008754, R01-AR059357, T32-AR065971]
- Veterans Administration [I01 BX002104, IK6BX004596]
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This study identified a blueberry cultivar that protects female mice from musculoskeletal loss induced by ovariectomy, while increasing gut microbiome diversity. The intervention was shown to protect females from estrogen deficiency and improve antioxidant defense responses in the body.
There is an unmet need for interventions with better compliance that prevent the adverse effects of sex steroid deficiency on the musculoskeletal system. We identified a blueberry cultivar (Montgomerym [Mont]) that added to the diet protects female mice from musculoskeletal loss and body weight changes induced by ovariectomy. Mont, but not other blueberries, increased the endogenous antioxidant response by bypassing the traditional antioxidant transcription factor Nrf2 and without activating estrogen receptor canonical signaling. Remarkably, Mont did not protect the male skeleton from androgen-induced bone loss. Moreover, Mont increased the variety of bacterial communities in the gut microbiome (alpha-diversity) more in female than in male mice; shifted the phylogenetic relatedness of bacterial communities (beta-diversity) further in females than males; and increased the prevalence of the taxon Ruminococcus1 in females but not males. Therefore, this nonpharmacologic intervention (i) protects from estrogen but not androgen deficiency; (ii) preserves bone, skeletal muscle, and body composition; (iii) elicits antioxidant defense responses independently of classical antioxidant/estrogenic signaling; and (iv) increases gut microbiome diversity toward a healthier signature. These findings highlight the impact of nutrition on musculoskeletal and gut microbiome homeostasis and support the precision medicine principle of tailoring dietary interventions to patient individualities, like sex. (c) 2020 American Society for Bone and Mineral Research (ASBMR).
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