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Analysis of bacteria, inflammation, and exudation in epidermal suction blister wounds reveals dynamic changes during wound healing

Lundgren, Sigrid LU ; Petruk, Ganna LU orcid ; Wallblom, Karl LU orcid ; Cardoso, José FP LU ; Strömdahl, Ann-Charlotte LU ; Forsberg, Fredrik LU ; Luo, Congyu LU ; Nilson, Bo LU orcid ; Hartman, Erik and Fisher, Jane LU , et al. (2023) In medRxiv
Abstract
The skin microbiome undergoes dynamic changes during different phases of wound healing, however the role of bacteria in the wound healing process remains poorly described. In this study, we aimed to determine how wound bacteria develop over time in epidermal wounds, and how they interact with inflammatory processes during wound healing. To this end, we analyzed wound fluid and swab samples collected from epidermal suction blister wounds in healthy volunteers. We found that bacterial numbers, measured in swabs and dressing fluid, increased rapidly after wounding and stabilized by day 8. The composition of bacterial species identified by MALDI-TOF mass spectrometry differed between wounds, but generally consisted primarily of commensal... (More)
The skin microbiome undergoes dynamic changes during different phases of wound healing, however the role of bacteria in the wound healing process remains poorly described. In this study, we aimed to determine how wound bacteria develop over time in epidermal wounds, and how they interact with inflammatory processes during wound healing. To this end, we analyzed wound fluid and swab samples collected from epidermal suction blister wounds in healthy volunteers. We found that bacterial numbers, measured in swabs and dressing fluid, increased rapidly after wounding and stabilized by day 8. The composition of bacterial species identified by MALDI-TOF mass spectrometry differed between wounds, but generally consisted primarily of commensal bacteria and remained largely stable over time. Inflammation and neutrophil activity, measured by quantification of cytokines and neutrophil proteins in dressing fluid, peaked on day 5. Exudation, measured by quantification of protein content in dressings, also peaked at this time and strongly correlated with cytokine and neutrophil protein levels. Inflammation, neutrophil activity, and exudation were not correlated with bacterial counts at any time, indicating that in normally healing wounds, these processes are primarily driven by the host and are independent of colonizing bacteria. Our analysis provides a comprehensive understanding of epidermal wound healing dynamics in the host and the role of the microbiome in healthy wound healing.Competing Interest StatementA.S. is a founder of in2cure AB, a parent company of Xinnate AB which was the sponsor of the clinical trial from which the biobank samples used in this study are derived. G.P. is employed part-time (20%) by Xinnate AB. The other authors have declared that no conflict of interest exists.Clinical TrialNCT05378997Funding StatementThis study was funded by grants from the Swedish Research Council (project 2017-02341, 2020-02016), Edvard Welanders Stiftelse and Finsenstiftelsen (Hudfonden), the Royal Physiographic Society, the Crafoord and Österlund Foundations, and the Swedish Government Funds for Clinical Research (ALF).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Swedish ethical review authority (etikprövningsmyndigheten) gave ethical approval for this work (application number 2022-00527-01).I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesThe data that support the findings of this study are openly available in Zenodo at http://doi.org/10.5281/zenodo.10283373, reference number 10283373.BCAbicinchoninic acidCFUcolony forming unitsELISAenzyme-linked immunosorbent assayHBPheparin-binding proteinIFNinterferonILinterleukinMALDI-TOFMatrix Assisted Laser Desorption lonization -Time Of FlightMBTMALDI BiotyperMPOmyeloperoxidaseMSmass spectrometryNEneutrophil elastasePBSphosphate-buffered salineTCPthrombin-derived C-terminal peptideTNFtumor necrosis factor (Less)
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wound healing, microbiome, inflammation, exudation
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medRxiv
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32 pages
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10.1101/2023.12.07.23299659
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English
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1acf5404-724d-446f-9e69-32c13771299c
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http://medrxiv.org/content/early/2023/12/09/2023.12.07.23299659.abstract
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@article{1acf5404-724d-446f-9e69-32c13771299c,
  abstract     = {{The skin microbiome undergoes dynamic changes during different phases of wound healing, however the role of bacteria in the wound healing process remains poorly described. In this study, we aimed to determine how wound bacteria develop over time in epidermal wounds, and how they interact with inflammatory processes during wound healing. To this end, we analyzed wound fluid and swab samples collected from epidermal suction blister wounds in healthy volunteers. We found that bacterial numbers, measured in swabs and dressing fluid, increased rapidly after wounding and stabilized by day 8. The composition of bacterial species identified by MALDI-TOF mass spectrometry differed between wounds, but generally consisted primarily of commensal bacteria and remained largely stable over time. Inflammation and neutrophil activity, measured by quantification of cytokines and neutrophil proteins in dressing fluid, peaked on day 5. Exudation, measured by quantification of protein content in dressings, also peaked at this time and strongly correlated with cytokine and neutrophil protein levels. Inflammation, neutrophil activity, and exudation were not correlated with bacterial counts at any time, indicating that in normally healing wounds, these processes are primarily driven by the host and are independent of colonizing bacteria. Our analysis provides a comprehensive understanding of epidermal wound healing dynamics in the host and the role of the microbiome in healthy wound healing.Competing Interest StatementA.S. is a founder of in2cure AB, a parent company of Xinnate AB which was the sponsor of the clinical trial from which the biobank samples used in this study are derived. G.P. is employed part-time (20%) by Xinnate AB. The other authors have declared that no conflict of interest exists.Clinical TrialNCT05378997Funding StatementThis study was funded by grants from the Swedish Research Council (project 2017-02341, 2020-02016), Edvard Welanders Stiftelse and Finsenstiftelsen (Hudfonden), the Royal Physiographic Society, the Crafoord and Österlund Foundations, and the Swedish Government Funds for Clinical Research (ALF).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Swedish ethical review authority (etikprövningsmyndigheten) gave ethical approval for this work (application number 2022-00527-01).I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesThe data that support the findings of this study are openly available in Zenodo at http://doi.org/10.5281/zenodo.10283373, reference number 10283373.BCAbicinchoninic acidCFUcolony forming unitsELISAenzyme-linked immunosorbent assayHBPheparin-binding proteinIFNinterferonILinterleukinMALDI-TOFMatrix Assisted Laser Desorption lonization -Time Of FlightMBTMALDI BiotyperMPOmyeloperoxidaseMSmass spectrometryNEneutrophil elastasePBSphosphate-buffered salineTCPthrombin-derived C-terminal peptideTNFtumor necrosis factor}},
  author       = {{Lundgren, Sigrid and Petruk, Ganna and Wallblom, Karl and Cardoso, José FP and Strömdahl, Ann-Charlotte and Forsberg, Fredrik and Luo, Congyu and Nilson, Bo and Hartman, Erik and Fisher, Jane and Puthia, Manoj and Saleh, Karim and Schmidtchen, Artur}},
  keywords     = {{wound healing; microbiome; inflammation; exudation}},
  language     = {{eng}},
  month        = {{12}},
  series       = {{medRxiv}},
  title        = {{Analysis of bacteria, inflammation, and exudation in epidermal suction blister wounds reveals dynamic changes during wound healing}},
  url          = {{http://dx.doi.org/10.1101/2023.12.07.23299659}},
  doi          = {{10.1101/2023.12.07.23299659}},
  year         = {{2023}},
}