Probiotics: Can it modulate fracture healing?

PLoS One. 2023 Aug 31;18(8):e0290738. doi: 10.1371/journal.pone.0290738. eCollection 2023.

Abstract

Objective: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Density
  • Cytokines
  • Femoral Fractures* / therapy
  • Fracture Healing*
  • Mice
  • Mice, Inbred C57BL

Substances

  • Cytokines

Grants and funding

This study was made possible through generous support from the Canadian Orthopaedic Research Legacy (CORL) grant and the Sunnybrook Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.