4.8 Article

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

Journal

ADVANCED SCIENCE
Volume 8, Issue 9, Pages -

Publisher

WILEY
DOI: 10.1002/advs.202004831

Keywords

Akkermansia muciniphila; bone homeostasis; extracellular vesicles; gut microbiota

Funding

  1. National Natural Science Foundation of China [81670807, 81871822, 81522012, 82072504, 81702237, 81701383, 81801395, 81974127, 81600699]
  2. Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2019-RC-HL-024]
  3. Science and Technology Plan Project of Hunan Province [2017XK2039, 2018RS3029]
  4. Innovation Driven Project of Central South University [2019CX014, 2018CX029]
  5. Hunan Province Natural Science Foundation of China [2020JJ5883, 2020JJ5900, 2020JJ4914]
  6. Hunan Provincial Innovation Foundation for Postgraduate [CX2018B045]
  7. Special Funding for the Construction of Innovative Provinces in Hunan [2019SK2301, 2020SK3002]
  8. Fundamental Research Funds for the Central Universities of Central South University [2017zzts211, 2019zzts804, 2018zzts895]
  9. Free Exploration Program of Central South University [502221901]
  10. China Postdoctoral Science Foundation [2020T130142ZX, 2019T120717, 2018M632998]

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Recent studies have shown that gut microbiota from children can prevent decreases in bone mass and strength in osteoporotic mice induced by ovariectomy. The secretion of extracellular vesicles plays a crucial role in the bone-protective effects induced by gut microbiota and the bacterium Akkermansia muciniphila.
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.

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