Response to mechanical loading in rat Achilles tendon healing is influenced by the microbiome

Franciele Dietrich-Zagonel,Malin Hammerman,Pernilla Eliasson,Per Aspenberg,Hazel R. C. Screen

doi:10.1371/journal.pone.0229908

Franciele Dietrich-Zagonel, Malin Hammerman + Show 3 more

Open Access

https://doi.org/10.1371/journal.pone.0229908

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Journal: PloS one	Publication Date: Mar 10, 2020
Citations: 5	License type: CC BY 4.0

Affiliation: Linköping University

Abstract

We have previously shown that changes in the microbiome influence how the healing tendon responds to different treatments. The aim of this study was to investigate if changes in the microbiome influence the response to mechanical loading during tendon healing. 90 Sprague-Dawley rats were used. Specific Opportunist and Pathogen Free (SOPF) rats were co-housed with Specific Pathogen Free (SPF) rats, carrying Staphylococcus aureus and other opportunistic microbes. After 6 weeks of co-housing, the SOPF rats were contaminated which was confirmed by Staphylococcus aureus growth. Clean SOPF rats were used as controls. The rats were randomized to full loading or partial unloading by Botox injections in their calf muscles followed by complete Achilles tendon transection. Eight days later, the healing tendons were tested mechanically. The results were analysed by a 2-way ANOVA with interaction between loading and contamination on peak force as the primary outcome and there was an interaction for both peak force (p = 0.049) and stiffness (p = 0.033). Furthermore, partial unloading had a profound effect on most outcome variables. In conclusion, the response to mechanical loading during tendon healing is influenced by changes in the microbiome. Studies aiming for clinical relevance should therefore consider the microbiome of laboratory animals.

Highlights

Tendon healing is dependent on the immune system [1] which has a profound effect on the strength of the tendon callus [2, 3]
The Specific Pathogen Free (SPF) rats were only used for co-housing as they came from a different breeder facility
6 weeks of co-housing lead to higher levels of Staphylococcus aureus and Escherichia coli in the gut microbiota of the contaminated Specific Opportunist and Pathogen Free (SOPF) rats compared to the clean SOPF rats, where the levels of these bacteria were below the detectable limits

Summary

Introduction

Tendon healing is dependent on the immune system [1] which has a profound effect on the strength of the tendon callus [2, 3]. The immune system, and T cells, changes in response to alterations in the microbial environment in the gut and skin [4, 5]. To the extent that T cells play a role in tendon healing, microbial changes in the gut can indirectly influence this healing. Recent data show that changes in the gut microbiota can alter the levels of CD4 + and CD3+ T cells within the tendon callus [1]. Changes in the microbiome can influence the response to different immunomodulatory treatments, such as local PRP injections or systemic corticosteroid treatment, during tendon healing [1, 3]. To the best of our knowledge, these two studies are the first to confirm a connection between the microbiome and tendon healing outcomes

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