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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Nutritional Immunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1493560

Modulation of the Gut-Bone Axis: Lacticaseibacillus paracasei LC86 Improves Bone Health via Anti-inflammatory Metabolic Pathways in Zebrafish Models of Osteoporosis and Cartilage Damage

Provisionally accepted
  • 1 Nanjing Agricultural University, Nanjing, Jiangsu Province, China
  • 2 University of Leeds, Leeds, England, United Kingdom
  • 3 Wecare Probiotics Co., Ltd, Suzhou, Liaoning Province, China
  • 4 Hubei University of Medicine, Shiyan, Hubei, China
  • 5 Shanghai Business School, Shanghai, Shanghai Municipality, China

The final, formatted version of the article will be published soon.

    Aim: Osteoporosis and cartilage injury are major health concerns with limited treatment options. This study investigates the therapeutic effects of Lacticaseibacillus paracasei LC86 (LC86) on osteoporosis and cartilage damage in a zebrafish (Danio rerio) model, focusing on its modulation of the gut-bone axis and its potential mechanisms for enhancing bone health.Methods: A Dexamethasone-induced zebrafish model was used to mimic osteoporosis and cartilage injury. Zebrafish were divided into control, model, and LC86 treatment groups (3×10 7 CFU/mL). Bone and cartilage health were assessed using Alizarin red staining and fluorescence microscopy. Bone marker expression (sp7, runx2a, bmp2a, bmp4, and col2a1a) was quantified via qPCR. Metabolic alterations were analyzed using untargeted metabolomics, and changes in gut microbiota were examined through 16S rRNA gene sequencing.Results: LC86 treatment significantly improved bone and cartilage health, as evidenced by increased fluorescence intensity in the skull, hard bone, and cartilage (p < 0.01, p < 0.05). qPCR results showed upregulation of key bone-related genes (sp7, runx2a, bmp2a, bmp4, and col2a1a), 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.Conclusions: 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.

    Keywords: Osteoporosis, Cartilage injury, Lacticaseibacillus paracasei, gut-bone axis, Zebrafish model

    Received: 09 Sep 2024; Accepted: 26 Mar 2025.

    Copyright: © 2025 Dong, Zhou, Gai, Cai, Han and Zou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Mei Han, Shanghai Business School, Shanghai, Shanghai Municipality, China
    Kang Zou, Nanjing Agricultural University, Nanjing, 210095, Jiangsu Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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