Extracellular Vesicles from Child Gut Microbiota Enter into Bone to Preserve Bone Mass and Strength

• Main Authors: Jiang‐Hua Liu, Chun‐Yuan Chen, Zheng‐Zhao Liu, Zhong‐Wei Luo, Shan‐Shan Rao, Ling Jin, Teng‐Fei Wan, Tao Yue, Yi‐Juan Tan, Hao Yin, Fei Yang, Fei‐Yu Huang, Jian Guo, Yi‐Yi Wang, Kun Xia, Jia Cao, Zhen‐Xing Wang, Chun‐Gu Hong, Ming‐Jie Luo, Xiong‐Ke Hu, Yi‐Wei Liu, Wei Du, Juan Luo, Yin Hu, Yan Zhang, Jie Huang, Hong‐Ming Li, Ben Wu, Hao‐Ming Liu, Tuan‐Hui Chen, Yu‐Xuan Qian, You‐You Li, Shi‐Kai Feng, Yang Chen, Lu‐Yue Qi, Ran Xu, Si‐Yuan Tang, Hui Xie
• Format: Article
• Language: English
• Published: Wiley 2021-05-01
• Series: Advanced Science
• Subjects: Akkermansia muciniphila; bone homeostasis; extracellular vesicles; gut microbiota
• Online Access: https://doi.org/10.1002/advs.202004831

Abstract Recently, the gut microbiota (GM) has been shown to be a regulator of bone homeostasis and the mechanisms by which GM modulates bone mass are still being investigated. Here, it is found that colonization with GM from children (CGM) but not from the elderly (EGM) prevents decreases in bone mass and bone strength in conventionally raised, ovariectomy (OVX)‐induced osteoporotic mice. 16S rRNA gene sequencing reveals that CGM reverses the OVX‐induced reduction of Akkermansia muciniphila (Akk). Direct replenishment of Akk is sufficient to correct the OVX‐induced imbalanced bone metabolism and protect against osteoporosis. Mechanistic studies show that the secretion of extracellular vesicles (EVs) is required for the CGM‐ and Akk‐induced bone protective effects and these nanovesicles can enter and accumulate into bone tissues to attenuate the OVX‐induced osteoporotic phenotypes by augmenting osteogenic activity and inhibiting osteoclast formation. The study identifies that gut bacterium Akk mediates the CGM‐induced anti‐osteoporotic effects and presents a novel mechanism underlying the exchange of signals between GM and host bone.