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

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.

Extracellular Vesicles from Akkermansia muciniphila Elicit Antitumor Immunity Against Prostate Cancer via Modulation of CD8+ T Cells and Macrophages

“…22,41,42 Moreover, our recent work revealed that Akk-EVs recapitulate the effects of Akk on promoting bone metabolism balance and protecting against osteoporosis. 23 In this study, we found that these EVs could elicit a protective effect via reducing the tumor burden in PCa mice.…”

“…The medium was then concentrated with Amicon Ultra-15 Centrifugal Filter (100 kDa; Millipore), and the EV pellet was obtained by serial gradient centrifugation with OptiPrep™ solution (60% w/v iodixanol; Sigma-Aldrich) at 100,000 × g for 18 h at 4 °C. 23 Collected EVs were resuspended in PBS and filtered through a 0.22 μm filter to avoid any contamination. After total protein concentration quantification, EVs were stored at −80 °C for further study.…”

Effect of Extracellular Vesicles Derived From Lactobacillus plantarum Q7 on Gut Microbiota and Ulcerative Colitis in Mice

“…Proteobacteria was reported to be the main phylum of pathogenic bacteria, which promoted the production of excessive pro-inflammatory cytokines and related to IBD pathogenesis (24,42). Akkermansia was a confirmed probiotic with anti-inflammatory effect by improving neutrophil infiltration and alleviating intestinal inflammation (44)(45)(46). Bifidobacteria could exert an anti-inflammatory effect through induction of intestinal IL-10 and protect from Th1driven inflammation (42).…”

Extracellular vesicles derived from the periodontal pathogen Filifactor alocis induce systemic bone loss through Toll‐like receptor 2

“…SCFAs, the main metabolites in the colon generated from bacterial fermentation of dietary fibres, increased bone mineral density by inhibiting osteoclast differentiation and bone resorption (Lucas et al., 2018 ). A recent study showed that EVs derived from gut microbiota enriched in Akkermansia muciniphila from healthy children showed suppressive effects on osteoclastogenesis and protective effects against osteoporosis in ovariectomized mice (Liu et al., 2021 ). A. muciniphila is a promising probiotic that also suppresses P. gingivalis ‐induced osteoclast activation and bone resorption (Huck et al., 2020 ).…”