The skin microbiome stratifies patients with cutaneous T cell lymphoma and determines event-free survival

Study information

Reviewed Marked as Reviewed by Peace Sandy on 2024-10-16

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

39198450

DOI Digital object identifier for electronic documents.

10.1038/s41522-024-00542-4

URI

https://pubmed.ncbi.nlm.nih.gov/39198450/

Authors

Licht P, Dominelli N, Kleemann J, Pastore S, Müller ES, Haist M, Hartmann KS, Stege H, Bros M, Meissner M, Grabbe S, Heermann R, Mailänder V

Journal

NPJ biofilms and microbiomes

Year

2024

Mycosis fungoides (MF) is the most common entity of Cutaneous T cell lymphomas (CTCL) and is characterized by the presence of clonal malignant T cells in the skin. The role of the skin microbiome for MF development and progression are currently poorly understood. Using shotgun metagenomic profiling, real-time qPCR, and T cell receptor sequencing, we compared lesional and nonlesional skin of 20 MF patients with early and advanced MF. Additionally, we isolated Staphylococcus aureus and other bacteria from MF skin for functional profiling and to study the S. aureus virulence factor spa. We identified a subgroup of MF patients with substantial dysbiosis on MF lesions and concomitant outgrowth of S. aureus on plaque-staged lesions, while the other MF patients had a balanced microbiome on lesional skin. Dysbiosis and S. aureus outgrowth were accompanied by ectopic levels of cutaneous antimicrobial peptides (AMPs), including adaptation of the plaque-derived S. aureus strain. Furthermore, the plaque-derived S. aureus strain showed a reduced susceptibility towards antibiotics and an upregulation of the virulence factor spa, which may activate the NF-κB pathway. Remarkably, patients with dysbiosis on MF lesions had a restricted T cell receptor repertoire and significantly lower event-free survival. Our study highlights the potential for microbiome-modulating treatments targeting S. aureus to prevent MF progression.

Experiment 1

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Reviewed Marked as Reviewed by Peace Sandy on 2024-10-16

Curated date: 2024/10/03

Curator: Jayybb

Revision editor(s): Jayybb, Peace Sandy

Subjects

Location of subjects: Germany

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Skin epidermis Epidermis,Skin,Vertebrate epidermis,Skin epidermis,skin epidermis

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Cutaneous T-cell lymphoma CTCL,cutaneous T cell lymphoma,cutaneous T-cell lymphoma,cutaneous T-cell non-Hodgkin lymphoma,cutaneous T-cell non-Hodgkin's lymphoma,PCTCL,primary cutaneous T-cell non-Hodgkin lymphoma,primary cutaneous T-cell non-Hodgkin's lymphoma,skin T-cell non-Hodgkin's lymphoma,T-cell non-Hodgkin's lymphoma of skin,T-cell non-Hodgkin's lymphoma of the skin,Cutaneous T-cell lymphoma

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Healthy control( ΔSA-neutral subgroup)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Mycosis fungoides( ΔSA-positive)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients with significant dysbiosis on MF lesions exhibiting S. aureus expansion. Antimicrobial peptides (AMPs) were probably less prevalent when the overgrowth occurred, and S. aureus was able to adapt to these peptides to become a more virulent strain on the lesions.

Group 0 sample size Number of subjects in the control (unexposed) group: 20

Group 1 sample size Number of subjects in the case (exposed) group: 20

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 1 month

Lab analysis

Sequencing type: PCR

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: raw counts

Statistical test: ANOVA

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Richness Number of species: decreased

Signature 1

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Reviewed Marked as Reviewed by Peace Sandy on 2024-10-16

Curated date: 2024/10/03

Curator: Jayybb

Revision editor(s): Jayybb, Peace Sandy

Source: fig 2b, d-g

Description: Differential abundance analysis of microbial species for N = 65 metagenomic samples.

Abundance in Group 1: increased abundance in Mycosis fungoides( ΔSA-positive)

NCBI	Quality Control	Links
Staphylococcus aureus

Revision editor(s): Jayybb, Peace Sandy

Signature 2

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Reviewed Marked as Reviewed by Peace Sandy on 2024-10-16

Curated date: 2024/10/03

Curator: Jayybb

Revision editor(s): Jayybb, Peace Sandy

Source: fig 2b, d-g

Description: Differential abundance analysis of microbial species for N = 65 metagenomic samples.

Abundance in Group 1: decreased abundance in Mycosis fungoides( ΔSA-positive)

NCBI	Quality Control	Links
Staphylococcus epidermidis
Staphylococcus hominis
Cutibacterium acnes

Revision editor(s): Jayybb, Peace Sandy