Restoration of the human skin microbiome following immune recovery after hematopoietic stem cell transplantation

You Che¹, Jungmin Han¹, Catriona P Harkins¹, Peng Hou¹, Sean Conlan², Clay Deming², Adel Amirkhani¹, Molly A Bingham³, Cassandra J Holmes¹, Hanna Englander¹, Zeyang Shen²; NISC Comparative Sequencing Program⁴; Leslie Castelo-Soccio¹, Dimana Dimitrova⁵, Jennifer A Kanakry⁵, Jenna R E Bergerson⁶, Luigi D Notarangelo⁶, Stefania Pittaluga⁷, Chen Zhao³, Stefania Dell'Orso⁸, Sung-Yun Pai⁹, Dennis D Hickstein⁹, Steven M Holland⁶, Isaac Brownell¹, Keisuke Nagao¹, Corina E Gonzalez⁹, Nirali N Shah¹⁰, Alexandra F Freeman⁶, Helen C Su¹¹, Julia A Segre², Heidi H Kong¹²

Affiliations

¹ Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA.
² Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
³ Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
⁴ NIH Intramural Sequencing Center, National Human Genome Research Institute, NIH, Rockville, MD 20892, USA.
⁵ Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
⁶ Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
⁷ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
⁸ Genomic Technology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA.
⁹ Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
¹⁰ Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
¹¹ Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
¹² Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA. Electronic address: konghe@mail.nih.gov.

PMID: 40730159
PMCID: PMC12313297 (available on 2026-07-28)
DOI: 10.1016/j.chom.2025.07.002

Restoration of the human skin microbiome following immune recovery after hematopoietic stem cell transplantation

You Che et al. Cell Host Microbe. 2025.

. 2025 Aug 13;33(8):1412-1427.e5.

doi: 10.1016/j.chom.2025.07.002. Epub 2025 Jul 28.

Authors

Affiliations

¹ Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA.
² Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
³ Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
⁴ NIH Intramural Sequencing Center, National Human Genome Research Institute, NIH, Rockville, MD 20892, USA.
⁵ Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
⁶ Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
⁷ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
⁸ Genomic Technology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA.
⁹ Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
¹⁰ Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
¹¹ Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
¹² Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD 20892, USA. Electronic address: konghe@mail.nih.gov.

PMID: 40730159
PMCID: PMC12313297 (available on 2026-07-28)
DOI: 10.1016/j.chom.2025.07.002

Abstract

The human skin microbiome is intricately intertwined with host immunity. While studies have elucidated microbial influences on immunity, understanding how immune alterations modulate this equilibrium remains limited. We investigated the dual impact of immune deficiency and hematopoietic stem cell transplantation (HSCT) on the skin microbiome in 24 patients with dedicator of cytokinesis 8 (DOCK8) deficiency, a rare inborn error of immunity. Analyzing 590 metagenomic and 534 16S rDNA sequencing samples across eight skin sites, we observed disrupted microbiota pre-HSCT (median eukaryotic viruses 67.6% vs. 0.04% in controls), with extremely diverse human papillomaviruses (HPVs) and polyomaviruses-including oncogenic viruses. Specific bacterial species markedly changed, including decreased Staphylococcus aureus post-HSCT. DNA eukaryotic viruses dramatically decreased (79.7% ± 28.3% to 4.9% ± 8.6%; p < 0.01) 12 months post-HSCT. Recovered microbial communities remained relatively stable through 1-year follow-up with clearance of oncogenic HPV and no convergence with transplant donors. These results highlight the immune system's critical role in restoring microbial balance and skin health.

Keywords: DOCK8; eczema; hematopoietic stem cell transplantation; metagenome; microbiome; papillomavirus; polyomavirus; skin microbiome; viruses; warts.

Published by Elsevier Inc.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

References

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Restoration of the human skin microbiome following immune recovery after hematopoietic stem cell transplantation

Affiliations

Restoration of the human skin microbiome following immune recovery after hematopoietic stem cell transplantation

Authors

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources