Critical Role of the Gut Microbiota in Prunes' Prevention of Glucocorticoid Induced Osteoporosis

This study investigates the potential for dietary prune supplementation to prevent glucocorticoid-induced osteoporosis (GIO) in female mice and to define relationships between bone outcomes and gut microbiota composition. Prolonged glucocorticoid (GC) treatment is a known cause of significant trabecular bone loss and is associated with gut microbiota dysbiosis in mouse models. Given evidence that prunes, a dried fruit with prebiotic properties, can improve bone outcomes in sex-steroid deficiency models and markedly alter gut microbial composition in rodents and humans, the authors tested whether dietary prune (DP) supplementation could mitigate GC-driven bone loss and how DP affects the intestinal microbial community in an established GIO model. In the experiment, skeletally mature 16-week-old female C57BL/6J mice were implanted with either placebo or prednisolone pellets (5 mg) and maintained for eight weeks on an AIN-93M control diet or diets modified to include 5%, 15%, or 25% (w/w) dried California prune powder. As expected, GC-treated mice developed significant trabecular bone loss in the distal femur. Importantly, supplementation with as little as 5% DP effectively prevented trabecular bone loss in GC-treated animals.

Further, DP demonstrated dose-dependent effects: mice receiving GC plus 15% or 25% DP exhibited increased trabecular bone volume fraction compared to GC alone. Remarkably, even in placebo (non-GC-treated) groups, a 25% DP diet produced approximately a threefold increase in distal femur trabecular bone volume fraction, an unusually large anabolic bone response for a natural, gut-targeted intervention in healthy mice. Alongside these robust bone effects, both GC treatment and 25% DP supplementation induced substantial shifts in gut microbiota composition, with several specific taxonomic changes strongly associated with bone health metrics. The study employed μCT analyses of distal femur trabecular bone to assess bone volume fraction, bone mineral density, bone mineral content, and microarchitectural parameters such as trabecular thickness, number, and spacing, with n = 10 per group. Food intake was monitored weekly and showed no overall pattern of group differences, indicating that bone outcomes were not attributable to gross differences in consumption.

The combined findings provide the first direct demonstration that dietary prune supplementation can effectively prevent the negative trabecular bone effects of prolonged glucocorticoid therapy in this mouse model, while concurrently associating with pronounced shifts in the gut microbiota. These results support the concept that the microbiota is a mechanistic mediator of GIO and a viable target for dietary strategies to protect bone health during extended GC exposure. The study opens avenues for further mechanistic work to identify microbial taxa or metabolites that mediate prune's bone-protective effects and suggests potential translational exploration of prune-based dietary interventions for patients requiring long-term glucocorticoid therapy.