Chargo Nicholas J, Neugebauer Kerri, Guzior Douglas V, Quinn Robert A, Parameswaran Narayanan, McCabe Laura R
Department of Physiology, Michigan State University, East Lansing, MI, United States.
College of Osteopathic Medicine, Michigan State University, East Lansing, MI, United States.
Front Cell Dev Biol. 2024 Feb 5;11:1324649. doi: 10.3389/fcell.2023.1324649. eCollection 2023.
Glucocorticoid-induced osteoporosis (GIO) is a significant side effect of prolonged glucocorticoid (GC) treatment. Chronic GC treatment also leads to trabecular bone loss and gut microbiota dysbiosis in mice. The gut dysbiosis is mechanistically linked to GIO, which indicates that the microbiota can be targeted to prevent GIO. Prunes, a dried fruit and prebiotic, have emerged in the literature as an effective treatment for sex-steroid deficiency induced osteoporosis (primary osteoporosis). Prunes also significantly alter the composition of the gut microbiota in both rodent models and human studies. Therefore, we tested if dietary prune (DP) supplementation could prevent GC-induced bone loss and affect microbiota composition in an established model of GIO. Sixteen-week-old, skeletally mature, female C57BL/6J mice were treated with a subcutaneous 5 mg placebo or prednisolone pellet for 8 weeks and fed an AIN-93M control diet or a diet 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. More importantly, as little as 5% DP supplementation effectively prevented trabecular bone loss. Further, dose dependent increases in trabecular bone volume fraction were observed in GC + 15% and GC + 25% DP mice. Amazingly, in the placebo (non-GC treated) groups, 25% DP supplementation caused a ∼3-fold increase in distal femur trabecular bone volume fraction; this sizable bone response has not been previously observed in healthy mice with gut targeted natural treatments. Along with the striking effect on bone health, GC treatment and 25% DP supplementation led to drastic shifts in gut microbiota composition and several specific changes are strongly associated with bone health. Taken together, these results are the first to demonstrate that DP supplementation effectively prevents the negative effects of prolonged GC therapy on trabecular bone health and strongly associates with shifts in the composition of the gut microbiota.
糖皮质激素诱导的骨质疏松症（GIO）是长期糖皮质激素（GC）治疗的一种重要副作用。慢性GC治疗还会导致小鼠小梁骨丢失和肠道微生物群失调。肠道失调与GIO存在机制上的联系，这表明微生物群可作为预防GIO的靶点。李子干是一种干果兼益生元，在文献中已成为治疗性类固醇缺乏所致骨质疏松症（原发性骨质疏松症）的有效疗法。在啮齿动物模型和人体研究中，李子干也会显著改变肠道微生物群的组成。因此，我们在一个已建立的GIO模型中测试了补充膳食李子干（DP）是否可以预防GC诱导的骨质流失并影响微生物群组成。16周龄、骨骼成熟的雌性C57BL/6J小鼠皮下植入5mg安慰剂或泼尼松龙药丸，持续8周，并喂食AIN-93M对照饮食或经改良以包含5%、15%或25%（w/w）加利福尼亚李子干粉的饮食。正如预期的那样，接受GC治疗的小鼠在股骨远端出现了明显的小梁骨丢失。更重要的是，仅补充5%的DP就能有效预防小梁骨丢失。此外，在GC + 15% DP组和GC + 25% DP组小鼠中观察到小梁骨体积分数呈剂量依赖性增加。令人惊讶的是，在安慰剂（未接受GC治疗）组中，补充25%的DP使股骨远端小梁骨体积分数增加了约3倍；这种显著的骨骼反应在采用针对肠道的天然疗法的健康小鼠中此前尚未观察到。除了对骨骼健康产生显著影响外，GC治疗和补充25%的DP还导致肠道微生物群组成发生剧烈变化，并且一些特定变化与骨骼健康密切相关。综上所述，这些结果首次证明补充DP能有效预防长期GC治疗对小梁骨健康的负面影响，并与肠道微生物群组成的变化密切相关。
