Zheng Yufei, Zhang Zhaowei, Fu Zezhou, Fan Aimi, Song Nan, Wang Qingqing, Fan Shunwu, Xu Jianbin, Xiang Jiajia, Liu Xin
Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, China.
Key Laboratory of Mechanism Research and Precision Repair of Orthopaedic Trauma and Aging Diseases of Zhejiang Province, Hangzhou, Zhejiang 310016, China.
ACS Nano. 2024 Sep 13. doi: 10.1021/acsnano.4c07332.
The discovery of the bone-gut axis linking bone metabolism to gut microbiota (GM) dysbiosis has revolutionized our understanding of managing degenerative skeletal diseases. Targeting GM regulation has emerged as a promising approach to osteoporosis treatment. Herein, we develop propolis nanoemulsions (PNEs) with enhanced gastrointestinal stability and oral bioavailability for GM-based osteoporosis therapy. Orally administered PNEs exhibit superior antiosteoporosis efficacy in an ovariectomized (OVX) mouse model by modulating the GM structure and metabolites and restoring the intestinal barrier function. Multiomics analysis reveals that a reduction in abundance and an increase in the GM metabolite l-arginine are key factors in osteoporosis management. These changes suppress osteoclast activity and enhance osteoblast function, leading to balanced bone remodeling and, thus, significant antiosteoporotic effects via the gut-bone axis. Our results deepen insights into the intricate relationship between GM and bone remodeling, suggesting a promising strategy that maintains the homeostasis of the GM structure and metabolite for osteoporosis treatment.
骨-肠轴的发现将骨代谢与肠道微生物群（GM）失调联系起来，彻底改变了我们对退行性骨骼疾病管理的理解。靶向GM调节已成为治疗骨质疏松症的一种有前景的方法。在此，我们开发了具有增强胃肠道稳定性和口服生物利用度的蜂胶纳米乳剂（PNEs），用于基于GM的骨质疏松症治疗。口服PNEs通过调节GM结构和代谢产物以及恢复肠道屏障功能，在去卵巢（OVX）小鼠模型中表现出卓越的抗骨质疏松疗效。多组学分析表明，GM丰度的降低和GM代谢产物L-精氨酸的增加是骨质疏松症管理的关键因素。这些变化抑制破骨细胞活性并增强成骨细胞功能，通过肠-骨轴导致骨重塑平衡，从而产生显著的抗骨质疏松作用。我们的结果加深了对GM与骨重塑之间复杂关系的理解，提出了一种维持GM结构和代谢产物稳态以治疗骨质疏松症的有前景策略。
