Evidence for cutaneous dysbiosis in dystrophic epidermolysis bullosa.


Journal

Clinical and experimental dermatology
ISSN: 1365-2230
Titre abrégé: Clin Exp Dermatol
Pays: England
ID NLM: 7606847

Informations de publication

Date de publication:
Oct 2021
Historique:
revised: 10 01 2021
received: 10 10 2020
accepted: 01 02 2021
pubmed: 9 3 2021
medline: 8 1 2022
entrez: 8 3 2021
Statut: ppublish

Résumé

The human microbiome project addresses the relationship between bacterial flora and the human host, in both healthy and diseased conditions. The skin is an ecosystem with multiple niches, each featuring unique physiological conditions and thus hosting different bacterial populations. The skin microbiome has been implicated in the pathogenesis of many dermatoses. Given the role of dysbiosis in the pathogenesis of inflammation, which is prominent in dystrophic epidermolysis bullosa (DEB), we undertook a study on the skin microbiome. To characterize the skin microbiome in a series of patients with DEB. This was a case-control study of eight patients with DEB and nine control cases enrolled between June 2017 and November 2018. The skin of patients with DEB was sampled at three different sites: untreated wound, perilesional skin and normal-appearing (uninvolved) skin. Normal skin on the forearm was sampled from age-matched healthy controls (HCs). We used a dedicated DNA extraction protocol to isolate microbial DNA, which was then analysed using next-generation microbial 16S rRNA sequencing. Data were analysed using a series of advanced bioinformatics tools. The wounds, perilesional and uninvolved skin of patients with DEB demonstrated reduced bacterial diversity compared with HCs, with the flora in DEB wounds being the least diverse. We found an increased prevalence of staphylococci species in the lesional and perilesional skin of patients with DEB, compared with their uninvolved, intact skin. Similarly, the uninvolved skin of patients with DEB displayed increased staphylococcal content and significantly different microbiome diversities (other than staphylococci) compared with HC skin. These findings suggest the existence of a unique DEB-associated skin microbiome signature, which could be targeted by specific pathogen-directed therapies. Moreover, altering the skin microbiome with increasing colonization of bacteria associated with nonchronic wounds may potentially facilitate wound healing in patients with DEB.

Sections du résumé

BACKGROUND BACKGROUND
The human microbiome project addresses the relationship between bacterial flora and the human host, in both healthy and diseased conditions. The skin is an ecosystem with multiple niches, each featuring unique physiological conditions and thus hosting different bacterial populations. The skin microbiome has been implicated in the pathogenesis of many dermatoses. Given the role of dysbiosis in the pathogenesis of inflammation, which is prominent in dystrophic epidermolysis bullosa (DEB), we undertook a study on the skin microbiome.
AIM OBJECTIVE
To characterize the skin microbiome in a series of patients with DEB.
METHODS METHODS
This was a case-control study of eight patients with DEB and nine control cases enrolled between June 2017 and November 2018. The skin of patients with DEB was sampled at three different sites: untreated wound, perilesional skin and normal-appearing (uninvolved) skin. Normal skin on the forearm was sampled from age-matched healthy controls (HCs). We used a dedicated DNA extraction protocol to isolate microbial DNA, which was then analysed using next-generation microbial 16S rRNA sequencing. Data were analysed using a series of advanced bioinformatics tools.
RESULTS RESULTS
The wounds, perilesional and uninvolved skin of patients with DEB demonstrated reduced bacterial diversity compared with HCs, with the flora in DEB wounds being the least diverse. We found an increased prevalence of staphylococci species in the lesional and perilesional skin of patients with DEB, compared with their uninvolved, intact skin. Similarly, the uninvolved skin of patients with DEB displayed increased staphylococcal content and significantly different microbiome diversities (other than staphylococci) compared with HC skin.
CONCLUSIONS CONCLUSIONS
These findings suggest the existence of a unique DEB-associated skin microbiome signature, which could be targeted by specific pathogen-directed therapies. Moreover, altering the skin microbiome with increasing colonization of bacteria associated with nonchronic wounds may potentially facilitate wound healing in patients with DEB.

Identifiants

pubmed: 33682945
doi: 10.1111/ced.14592
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1223-1229

Subventions

Organisme : EB Research Partnership foundation

Informations de copyright

© 2021 British Association of Dermatologists.

Références

Fine J-D, Bruckner-Tuderman L, Eady RAJ et al. Inherited epidermolysis bullosa: updated recommendations on diagnosis and classification. J Am Acad Dermatol 2014; 70: 1103-26.
Canesso MCC, Vieira AT, Castro TB et al. Skin wound healing is accelerated and scarless in the absence of commensal microbiota. J Immunol 2014; 193: 5171-80.
Hoste E, Arwert EN, Lal R et al. Innate sensing of microbial products promotes wound-induced skin cancer. Nat Commun 2015; 6: 5932.
Byrd AL, Belkaid Y, Segre JA. The human skin microbiome. Nat Rev Microbiol 2018; 16: 143-55.
Kong HH. Details matter: designing skin microbiome studies. J Invest Dermatol 2016; 136: 900-2.
Hugenholtz P, Goebel BM, Pace NR. Impact of culture-independent studies on the emerging phylogenetic view of bacterial diversity. J Bacteriol 1998; 180: 4765-74.
Langan EA, Griffiths CEM, Solbach W et al. The role of the microbiome in psoriasis: moving from disease description to treatment selection? Br J Dermatol 2018; 178: 1020-7.
Miodovnik M, Künstner A, Langan EA et al. A distinct cutaneous microbiota profile in autoimmune bullous disease patients. Exp Dermatol 2017; 26: 1221-7.
Brandling-Bennett HA, Morel KD. Common wound colonizers in patients with epidermolysis bullosa. Pediatr Dermatol 2010; 27: 25-8.
Garcia-Perez AN, de Jong A, Junker S et al. From the wound to the bench: exoproteome interplay between wound-colonizing Staphylococcus aureus strains and co-existing bacteria. Virulence 2018; 9: 363-78.
Singer H, Levin L, Garzon M. Wound culture isolated antibiograms and caregiver-reported skin care practices in children with epidermolysis bullosa. Pediatr Dermatol 2018; 35: 92-6.
Fuentes I, Guttmann-Gruber C, Tay ASL et al. Reduced microbial diversity is a feature of recessive dystrophic epidermolysis bullosa-involved skin and wounds. J Invest Dermatol 2018; 138: 2492-5.
Segata N, Izard J, Waldron L et al. Metagenomic biomarker discovery and explanation. Genome Biol 2011; 12: R60.
van der Kooi-Pol MM, Duipmans JC, Jonkman MF, van Dijl JM. Host-pathogen interactions in epidermolysis bullosa patients colonized with Staphylococcus aureus. Int J Med Microbiol 2014; 304: 195-203.
Nystrom A, Bornert O, Kuhl T et al. Impaired lymphoid extracellular matrix impedes antibacterial immunity in epidermolysis bullosa. Proc Natl Acad Sci U S A 2018; 115: E705-14.
Ellebrecht CT, Srinivas G, Bieber K et al. Skin microbiota-associated inflammation precedes autoantibody induced tissue damage in experimental epidermolysis bullosa acquisita. J Autoimmun 2016; 68: 14-22.
Johnson T, Gómez B, McIntyre M et al. The cutaneous microbiome and wounds: new molecular targets to promote wound healing. Int J Mol Sci 2018; 19: 2699.
Wolcott RD, Hanson JD, Rees EJ et al. Analysis of the chronic wound microbiota of 2,963 patients by 16S rDNA pyrosequencing. Wound Repair Regen 2016; 24: 163-74.
Kim JH, Ruegger PR, Lebig EG et al. High levels of oxidative stress create a microenvironment that significantly decreases the diversity of the microbiota in diabetic chronic wounds and promotes biofilm formation. Front Cell Infect Microbiol 2020; 10: 259.
Naik S, Bouladoux N, Linehan JL et al. Commensal-dendritic-cell interaction specifies a unique protective skin immune signature. Nature 2015; 520: 104-8.
Cogen AL, Nizet V, Gallo RL. Skin microbiota: a source of disease or defence? Br J Dermatol 2008; 158: 442-55.
Otto M. Staphylococcus epidermidis - the 'accidental' pathogen. Nat Rev Microbiol 2009; 7: 555-67.
Nelson A, Hultenby K, Hell E et al. Staphylococcus epidermidis isolated from newborn infants express pilus-like structures and are inhibited by the cathelicidin-derived antimicrobial peptide LL37. Pediatr Res 2009; 66: 174-8.
Saporito P, Vang Mouritzen M, Lobner-Olesen A, Jenssen H. LL-37 fragments have antimicrobial activity against Staphylococcus epidermidis biofilms and wound healing potential in HaCaT cell line. J Pept Sci 2018; 24: e3080.
Tamai K, Yamazaki T, Chino T et al. PDGFRalpha-positive cells in bone marrow are mobilized by high mobility group box 1 (HMGB1) to regenerate injured epithelia. Proc Natl Acad Sci U S A 2011; 108: 6609-14.

Auteurs

J Bar (J)

Division of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

O Sarig (O)

Division of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

M Lotan-Pompan (M)

Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel.
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

B Dassa (B)

Bioinformatics Unit, Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel.

M Miodovnik (M)

Division of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

A Weinberger (A)

Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel.
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

E Sprecher (E)

Division of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

E Segal (E)

Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel.
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

L Samuelov (L)

Division of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

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