Hossain Mosharraf, Sultana Tamima, Moon Ji Eun, Moon Gi-Seong, Jeong Je Hoon
Department of Neurosurgery, College of Medicine, Soonchunhyang University, Bucheon Hospital, Bucheon 14584, South Korea.
Department of Biostatistics, Clinical Trial Center, Soonchunhyang University, Bucheon Hospital, Bucheon 14585, South Korea.
Sci Rep. 2025 May 27;15(1):18586. doi: 10.1038/s41598-025-02089-6.
Postmenopausal osteoporosis poses a significant clinical challenge, as conventional therapies are often ineffective or poorly tolerated owing to adverse effects or underlying health conditions, underscoring the need for alternative treatments. This study investigated the anti-osteoporotic effects of a novel probiotic mixture combining Limosilactobacillus reuteri MGE 3301 (LR) and Weissella cibaria MGE 3110 (WC), which were selected for their anti-inflammatory properties and ability to modulate bone metabolism, in an ovariectomized rat model. Thirty-five female Wistar rats were randomly assigned to five groups: Sham, Ovariectomy (OVX), OVX with LR supplementation (OVX/LR), OVX with WC (OVX/WC), and OVX with a combination of LR and WC (OVX/LR/WC), under ARRIVE guidelines and ethical approval. Each probiotic group received 1 × 10⁹ CFU/mL/day for 16 weeks starting at 5 weeks post-OVX. Micro-computed tomography and histopathological analyses revealed that the OVX/LR/WC group had superior trabecular bone preservation compared with that in the OVX control group, with significant improvements in bone mineral density (+ 54.2%), bone volume fraction (+ 24.8%), trabecular thickness (+ 13.6%), and trabecular number (+ 20%), along with decreased trabecular separation (- 8.1%; p < 0.05). RT-qPCR analysis of bone marrow demonstrated that LR/WC suppressed osteoclastogenic mediators (RANKL: -1.35-fold; TNF-α: -2.5-fold; IL-6: -1.9-fold) while elevating osteoprotective osteoprotegerin expression (+ 3.14-fold; p < 0.05). Serum analysis showed reduced CTX-I (- 38.9%) and elevated calcium (+ 30.8%) levels in OVX/LR/WC versus OVX rats (p < 0.05), indicating suppressed bone resorption and enhanced mineral homeostasis. These findings indicate that LR/WC probiotic supplementation attenuates OVX-induced bone loss by modulating bone turnover markers and inflammatory cytokines. To our knowledge, this is the first study to assess the combined effects of LR and WC in an osteoporosis animal model, highlighting its potential as an adjunctive therapeutic candidate for osteoporosis. However, few notable imitations include undefined human dosing and the unassessed long-term safety of probiotics. Future clinical trials must validate the efficacy, elucidate mechanisms (e.g., gut-bone axis interactions), and assess safety in postmenopausal women to advance therapeutic applicability.
绝经后骨质疏松症带来了重大的临床挑战，因为传统疗法往往因不良反应或潜在健康状况而无效或耐受性差，这凸显了替代治疗的必要性。本研究在去卵巢大鼠模型中，研究了一种新型益生菌混合物（结合罗伊氏乳杆菌MGE 3301（LR）和西巴韦氏菌MGE 3110（WC））的抗骨质疏松作用，这两种菌因其抗炎特性和调节骨代谢的能力而被选中。按照ARRIVE指南并经伦理批准，将35只雌性Wistar大鼠随机分为五组：假手术组、卵巢切除组（OVX）、补充LR的OVX组（OVX/LR）、补充WC的OVX组（OVX/WC）以及补充LR和WC组合的OVX组（OVX/LR/WC）。从OVX术后5周开始，每个益生菌组每天接受1×10⁹ CFU/mL，持续16周。显微计算机断层扫描和组织病理学分析显示，与OVX对照组相比，OVX/LR/WC组的小梁骨保存情况更好，骨矿物质密度（+54.2%）、骨体积分数（+24.8%）、小梁厚度（+13.6%）和小梁数量（+20%）均有显著改善，同时小梁间距减小（-8.1%；p<0.05）。骨髓的RT-qPCR分析表明，LR/WC抑制破骨细胞生成介质（RANKL：-1.35倍；TNF-α：-2.5倍；IL-6：-1.9倍），同时提高骨保护素骨保护蛋白的表达（+3.14倍；p<0.05）。血清分析显示，与OVX大鼠相比，OVX/LR/WC组的CTX-I水平降低（-38.9%），钙水平升高（+30.8%）（p<0.05），表明骨吸收受到抑制，矿物质稳态增强。这些发现表明，补充LR/WC益生菌可通过调节骨转换标志物和炎性细胞因子来减轻OVX诱导的骨质流失。据我们所知，这是第一项评估LR和WC在骨质疏松动物模型中联合作用的研究，突出了其作为骨质疏松症辅助治疗候选药物的潜力。然而，一些明显的局限性包括未确定人体给药剂量以及未评估益生菌的长期安全性。未来的临床试验必须验证其疗效，阐明作用机制（如肠-骨轴相互作用），并评估绝经后妇女的安全性，以提高治疗的适用性。
