Oral Propolis Nanoemulsions Modulate Gut Microbiota to Balance Bone Remodeling for Enhanced Osteoporosis Therapy,ACS Nano

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Oral Propolis Nanoemulsions Modulate Gut Microbiota to Balance Bone Remodeling for Enhanced Osteoporosis Therapy
ACS Nano ( IF 15.8 ) Pub Date : 2024-09-13 , DOI: 10.1021/acsnano.4c07332
Yufei Zheng _{1,

2} , Zhaowei Zhang _{1,

2} , Zezhou Fu _{1,

2} , Aimi Fan ₃ , Nan Song ₄ , Qingqing Wang _{1,

2} , Shunwu Fan _{1,

2} , Jianbin Xu ₅ , Jiajia Xiang ₆ , Xin Liu _{1,

2}

Affiliation

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 Streptococcus 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.

中文翻译：

口服蜂胶纳米乳剂调节肠道微生物群，平衡骨重塑，增强骨质疏松症治疗

将骨代谢与肠道微生物群 (GM) 失调联系起来的骨肠轴的发现彻底改变了我们对治疗退行性骨骼疾病的理解。针对 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（PNE），用于基于转基因的骨质疏松症治疗。口服 PNE 通过调节 GM 结构和代谢物以及恢复肠道屏障功能，在卵巢切除 (OVX) 小鼠模型中表现出卓越的抗骨质疏松功效。多组学分析表明，链球菌丰度的减少和转基因代谢物l-精氨酸的增加是骨质疏松症治疗的关键因素。这些变化抑制破骨细胞活性并增强成骨细胞功能，导致平衡的骨重塑，从而通过肠-骨轴产生显着的抗骨质疏松作用。我们的研究结果加深了对 GM 与骨重塑之间复杂关系的认识，提出了一种有前途的策略，可以维持 GM 结构和代谢物的稳态，用于骨质疏松症的治疗。

更新日期：2024-09-13

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