Glucocorticoid-induced loss of beneficial gut bacterial extracellular vesicles is associated with the pathogenesis of osteonecrosis

Abstract

Osteonecrosis of the femoral head (ONFH) commonly occurs after glucocorticoid (GC) therapy. The gut microbiota (GM) participates in regulating host health, and its composition can be altered by GC. Here, this study demonstrates that cohousing with healthy mice or colonization with GM from normal mice attenuates GC-induced ONFH. 16 S rRNA gene sequencing shows that cohousing with healthy mice rescues the GC-induced reduction of gut Lactobacillus animalis . Oral supplementation of L. animalis mitigates GC-induced ONFH by increasing angiogenesis, augmenting osteogenesis, and reducing cell apoptosis. Extracellular vesicles from L. animalis ( L. animalis -EVs) contain abundant functional proteins and can enter the femoral head to exert proangiogenic, pro-osteogenic, and antiapoptotic effects, while its abundance is reduced after exposure to GC. Our study suggests that the GM is involved in protecting the femoral head by transferring bacterial EVs, and that loss of L. animalis and its EVs is associated with the development of GC-induced ONFH.

Extracellular Vesicles of Probiotics: Shedding Light on the Biological Activity and Future Applications

“…Among the 60 of them, 15 and 45 concerned Gram-negative and Gram-positive bacteria, respectively. All articles assessed the size of the produced EVs, of which 49 determined it using only one technique (21 with electron microscopy [ 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ], 19 with NTA [ 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ], and 9 with DLS [ 42 , 45 , 49 , 50 , 91 , 92 ,…”

“…Only 9 papers analyzed the electrical charge of EVs, of which 7 used DLS [ 31 , 36 , 37 , 38 , 39 , 42 , 45 ] and 2 used NTA [ 84 , 85 ]. The quantity of EVs produced was examined in 18 articles, of which 14 used NTA [ 31 , 33 , 38 , 39 , 72 , 73 , 74 , 76 , 77 , 79 , 83 , 87 , 88 , 89 ], 2 used TRSP [ 49 , 50 ], 1 used flow cytometry [ 45 ], and 1 used spectrophotometry [ 51 ]. Detailed information on the numerical data of the above-presented results can be found in Table S1 .…”

“…Whereas the function of adhesins and peptidoglycan rearrangement proteins in EVs has been described above and is similar in Gram-positive bacteria, proteins responsible for metabolism deserve special attention. Based on the data collected in Table 1 , it can be noticed that this group includes proteins related to the biosynthesis or breakdown of various classes of nutrients, and they are produced by many representatives of probiotics, such as Lactiplantibacillus [ 32 , 54 ], Lacticaseibacillus [ 36 ], Limosilactobacillus [ 34 , 38 ], Ligilactobacillus [ 76 ], Lactobacillus [ 33 , 74 ], Bifidobacterium [ 64 ], Propionibacterium [ 78 , 79 ], Lactococcus [ 62 ], and Pediococcus [ 42 ]. In addition to this, numerous proteins determining an uptake of glycerol [ 54 ], vitamins [ 54 ], amino acids and peptides [ 54 , 76 ], phosphates [ 74 , 76 ], inorganic acid ions [ 76 ], and iron [ 64 ] were detected.…”

The Current and Future Perspectives of Postbiotics

“…Chen et al recently demonstrated the osteoprotective effects of specific enterobacteria and their extracellular vesicles in a study (EVs) [ 66 ]. Glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) mice caged with healthy mice alleviated ONFH symptoms and restored the GC-induced reduction of intestinal bacteria L. animalis and extracellular vesicles from L. animalis ( L. animalis -EVs).…”

The bridge of the gut–joint axis: Gut microbial metabolites in rheumatoid arthritis

“…Glucocorticoid-induced loss of beneficial gut bacterial extracellular vesicles is associated with the pathogenesis of osteonecrosis. Beneficial gut bacterial extracellular vesicles can enter the femoral head, increase angiogenesis and bone formation, reduce apoptosis, and alleviate bone destruction symptoms ( 19 ). Jones et al.…”