Sunnybrook Research Institute, Toronto, ON, Canada.
Department of Surgery, University of Toronto, Toronto, Canada.
PLoS One. 2023 Aug 31;18(8):e0290738. doi: 10.1371/journal.pone.0290738. eCollection 2023.
Fractures remain a huge burden and their management adversely affects individuals' function and productivity during the lengthy healing period. Gut microbiota exerts a systemic influence on diverse aspects of host physiology, including bone. The primary objective of this study was to evaluate if oral probiotic treatment before or after a fracture in a mouse model could increase cytokines and biomarkers essential for bone healing with subsequent improvement in the biomechanical properties of the healed callus.
Femoral osteotomy and intramedullary pinning were performed on C57BL/6 mice. Group 1 received either control PBS or probiotic via oral gavage for 5 weeks before fracture (pre-fracture). Group 2 received equivalent treatments for 4 weeks only after fracture (post-fracture). Fracture calluses were harvested on day 3 and 7 for RT-qPCR to quantify osteogenic-related inflammatory cytokines and bone biomarkers. Fractured femurs were evaluated day 28 post-osteotomy via microstructural analysis (μCT) and biomechanical testing (torsion).
Mice treated with probiotics pre-fracture (group 1) showed significantly increased gene expression on day 3 of cytokines TGF-β, IL-6 and IL-17F and a corresponding increase in gene expression on day 7 for Col1 and Runx2. Significant improvement was also seen in bone volume fraction, bone mineral density, tissue mineral density, maximum yield torque, stiffness and strain energy. Mice treated with probiotics post-fracture (group 2), demonstrated no changes in cytokine or bone marker gene expression with no significant changes on microstructural analysis. However, significant increases were seen in twist angle at failure and strain energy, with a corresponding reduction in torsional stiffness.
Our results suggest that oral probiotic administration, before or after a fracture, may sufficiently alter the gut flora microenvironment leading to improved bone healing biomechanical properties. The use of probiotics may provide a cost-effective and low-risk adjunctive therapy to improve fracture healing.
骨折仍然是一个巨大的负担，其在漫长的愈合期内对个体的功能和生产力产生负面影响。肠道微生物群对宿主生理的多个方面产生系统影响，包括骨骼。本研究的主要目的是评估在小鼠模型中骨折前或后进行口服益生菌治疗是否可以增加对骨骼愈合至关重要的细胞因子和生物标志物，从而改善愈合骨痂的生物力学特性。
对 C57BL/6 小鼠进行股骨切开术和髓内钉固定。第 1 组在骨折前（骨折前）通过口服灌胃接受对照 PBS 或益生菌 5 周。第 2 组仅在骨折后（骨折后）接受等效治疗 4 周。在第 3 天和第 7 天收获骨折痂进行 RT-qPCR，以定量骨形成相关炎症细胞因子和骨生物标志物。在切开术后第 28 天通过微观结构分析（μCT）和生物力学测试（扭转）评估骨折股骨。
骨折前接受益生菌治疗的小鼠（第 1 组）在第 3 天的细胞因子 TGF-β、IL-6 和 IL-17F 的基因表达显着增加，第 7 天的 Col1 和 Runx2 的基因表达也相应增加。骨体积分数、骨矿物质密度、组织矿物质密度、最大屈服扭矩、刚度和应变能也有显著改善。骨折后接受益生菌治疗的小鼠（第 2 组），细胞因子或骨标志物基因表达没有变化，微观结构分析也没有明显变化。然而，在失效时的扭角和应变能显着增加，扭转刚度相应降低。
我们的结果表明，骨折前或后口服益生菌给药可能足以改变肠道菌群微环境，从而改善骨骼愈合的生物力学特性。益生菌的使用可能为改善骨折愈合提供一种具有成本效益且低风险的辅助治疗方法。
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