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Bidirectional Interactions: Microbiome and Immune System Function in Cutaneous Graft-Versus-Host Disease.

Benjamin L Savitz, Kylie Duckworth1, Hanna L Slutsky2

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The skin microbiome influences chronic graft-versus-host disease (cGVHD) after stem cell transplants. Microbial imbalances worsen skin barrier dysfunction and inflammation, suggesting microbiome-targeted therapies for cGVHD.

Keywords:
allogeneic hematopoietic stem cell transplantation (HSCT)dysbiosisgraft-versus-host disease (GVHD)inflammatory skin diseaseskin microbiome

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Area of Science:

  • Immunology
  • Microbiology
  • Dermatology

Background:

  • Chronic graft-versus-host disease (cGVHD) of the skin is a complex immune response post-allogeneic hematopoietic stem cell transplantation (HSCT).
  • Emerging research implicates skin microbiome dysbiosis in cGVHD pathogenesis and progression.
  • Traditional views focus on alloimmune activation and fibrosis, but the microbiome's role is increasingly recognized.

Purpose of the Study:

  • To review the evolving understanding of the skin microbiome-immune interface in cutaneous cGVHD.
  • To explore how microbial shifts impact skin barrier function and immune activation.
  • To discuss potential microbiome-targeted therapies and diagnostic applications for cGVHD.

Main Methods:

  • Literature review focusing on the microbiome-immune interactions in cGVHD.
  • Analysis of microbial shifts, such as loss of S. epidermidis and overgrowth of S. aureus.
  • Examination of the impact of dysbiosis on barrier function, immune cell activity, and inflammation.

Main Results:

  • Microbial dysbiosis, including specific bacterial shifts, impairs skin barrier function and promotes inflammation.
  • Disruption of commensal signals reduces antimicrobial peptides and regulatory T cell activity.
  • A cycle of barrier dysfunction and microbial imbalance exacerbates cGVHD.

Conclusions:

  • The skin microbiome plays a critical role in cGVHD pathogenesis.
  • Microbiome-targeted therapies, like donor skin allografting, show promise for restoring balance and reducing inflammation.
  • Skin microbiome profiling may serve as a diagnostic biomarker for cGVHD activity and treatment response.