{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:29:31Z","timestamp":1792718971850,"version":"4.5.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Osteoporosis and cartilage injury are major health concerns with limited treatment options. This study investigates the therapeutic effects of <jats:italic>Lacticaseibacillus paracasei<\/jats:italic> LC86 (LC86) on osteoporosis and cartilage damage in a zebrafish (<jats:italic>Danio rerio<\/jats:italic>) model, focusing on its modulation of the gut-bone axis and its potential mechanisms for enhancing bone health.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A Dexamethasone-induced zebrafish model was used to mimic osteoporosis and cartilage injury. Zebrafish were divided into control, model, and LC86 treatment groups (3\u00d710<jats:sup>7<\/jats:sup> CFU\/mL). Bone and cartilage health were assessed using Alizarin red staining and fluorescence microscopy. Bone marker expression (<jats:italic>sp7<\/jats:italic>, <jats:italic>runx2a<\/jats:italic>, <jats:italic>bmp2a<\/jats:italic>, <jats:italic>bmp4<\/jats:italic>, and <jats:italic>col2a1a<\/jats:italic>) was quantified via qPCR. Metabolic alterations were analyzed using untargeted metabolomics, and changes in gut microbiota were examined through 16S rRNA gene sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>LC86 treatment significantly improved bone and cartilage health, as evidenced by increased fluorescence intensity in the skull, hard bone, and cartilage (<jats:italic>p<\/jats:italic> &amp;lt; 0.01, <jats:italic>p<\/jats:italic> &amp;lt; 0.05). qPCR results showed upregulation of key bone-related genes (<jats:italic>sp7<\/jats:italic>, <jats:italic>runx2a<\/jats:italic>, <jats:italic>bmp2a<\/jats:italic>, <jats:italic>bmp4<\/jats:italic>, and <jats:italic>col2a1a<\/jats:italic>), indicating enhanced bone and cartilage structure. Metabolomics analysis revealed alterations in over 300 metabolites, with changes in anti-inflammatory and energy pathways. Gut microbiota analysis demonstrated an increase in beneficial bacteria and a decrease in pathogenic genera.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>LC86 significantly improved bone health, cartilage structure, and gut microbiota composition in a Dexamethasone-induced zebrafish model, supporting its potential as a therapeutic strategy for osteoporosis and cartilage injury via modulation of the gut-bone axis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1493560","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T07:42:11Z","timestamp":1744789331000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Modulation of the gut-bone axis: Lacticaseibacillus paracasei LC86 improves bone health via anti-inflammatory metabolic pathways in zebrafish models of osteoporosis and cartilage 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