Cited by 56Dermatology and Skin DiseasesContact Dermatitis and AllergiesAsthma and respiratory diseases

Tralokinumab treatment improves the skin microbiota by increasing the microbial diversity in adults with moderate-to-severe atopic dermatitis: Analysis of microbial diversity in ECZTRA 1, a randomized controlled trial

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Beck, Lisa A., Bieber, Thomas, Weidinger, Stephan, Tauber, Marie, Saeki, Hidehisa, Irvine, Alan D., Eichenfield, Lawrence F., Werfel, Thomas +4 more·2023·Journal of the American Academy of Dermatology

Abstract

BACKGROUND: Atopic dermatitis (AD) is characterized by microbial dysbiosis, immune dysregulation, and an impaired skin barrier. Microbial dysbiosis in AD involves a reduction in diversity primarily driven by an increased abundance of Staphylococcus aureus. Tralokinumab, an approved treatment for adults with moderate-to-severe AD, improves the skin barrier and immune abnormalities by specifically targeting the interleukin 13 cytokine, but its impact on the skin microbiome is unknown. OBJECTIVE: To investigate how tralokinumab affects the skin microbiome by examining the lesional skin of adults with moderate-to-severe AD from the phase 3 ECZTRA 1 trial (NCT03131648). METHODS: Microbiome profiling, S aureus abundance, and biomarker data were assessed in a subset of ECZTRA 1 participants (S aureus abundance at baseline and week 16; microbiome profiling at baseline, and week 8/16; and serum sampling before dose and week 4/8/16/28/52). RESULTS: Tralokinumab treatment led to increased microbial diversity, reduced S aureus abundance, and increased abundance of the commensal coagulase-negative Staphylococci. LIMITATIONS: Limitations include a lack of S aureus abundance data at week 8, sampling site variation between participants, and possible influence from concomitant systemic antiinfectives. CONCLUSION: Our findings indicate specific targeting of the interleukin 13 cytokine with tralokinumab can directly and/or indirectly improve microbial dysbiosis seen in AD skin.

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  • Recent therapies, such as dupilumab and tralokinumab, favor skin microbiota rebalancing in patients with AD.

    “Recent therapies, such as dupilumab and tralokinumab, favor skin microbiota rebalancing in patients with AD.94, 105”

    From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [105]

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References 34 · Cited by 56

Research works printed but not linked: 27

  1. Bieber T. Targeting T2 inflammation by dupilumab impacts on the microbiomic 'Menage a Trois' of atopic dermatitis. J Invest Dermatol. 2020;140(1):15-17. https://doi.org/10.1016/j.jid.2019. 07.680 · DOI
  2. Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. Lancet. 2020;396(10247):345-360. https://doi.org/10.1016/S0140- 6736(20)31286-1 · DOI
  3. Silverberg JI. Atopic dermatitis in adults. Med Clin North Am. 2020; 104(1):157-176. https://doi.org/10.1016/j.mcna.2019.08.009 · DOI
  4. Byrd AL, Deming C, Cassidy SKB, et al. Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis. Sci Transl Med. 2017;9(397). https:// doi.org/10.1126/scitranslmed.aal4651 · DOI
  5. Edslev SM, Agner T, Andersen PS. Skin microbiome in atopic dermatitis. Acta Derm Venereol. 2020;100(12):adv00164. https://doi.org/10.2340/00015555-3514 · DOI
  6. Shi B, Leung DYM, Taylor PA, Li H. Methicillin-resistant Staphylococcus aureus colonization is associated with decreased skin commensal bacteria in atopic dermatitis. J Invest Dermatol. 2018;138(7):1668-1671. https://doi.org/10. 1016/j.jid.2018.01.022 · DOI
  7. Simpson EL, Villarreal M, Jepson B, et al. Patients with atopic dermatitis colonized with Staphylococcus aureus have a distinct phenotype and endotype. J Invest Dermatol. 2018; 138(10):2224-2233. https://doi.org/10.1016/j.jid.2018.03.1517 · DOI
  8. Fleury OM, McAleer MA, Feuillie C, et al. Clumping factor B promotes adherence of Staphylococcus aureus to corneocytes in atopic dermatitis. Infect Immun. 2017;85(6). https://doi.org/ 10.1128/IAI.00994-16 · DOI
  9. Ogonowska P, Gilaberte Y, Bara nska-Rybak W, Nakonieczna J. Colonization with Staphylococcus aureus in atopic dermatitis patients: attempts to reveal the unknown. Front Microbiol. 2020;11:567090. https://doi.org/10.3389/fmicb.2020.567090 · DOI
  10. Ong PY, Leung DY. The infectious aspects of atopic dermatitis. Immunol Allergy Clin North Am. 2010;30(3):309-321. https://doi. org/10.1016/j.iac.2010.05.001 · DOI
  11. Tauber M, Balica S, Hsu CY, et al. Staphylococcus aureus density on lesional and nonlesional skin is strongly associated with disease severity in atopic dermatitis. J Allergy Clin Immunol. 2016;137(4):1272-1274.e3. https://doi.org/10.1016/j.jaci.2015. 07.052 · DOI
  12. Feuillie C, Vitry P, McAleer MA, et al. Adhesion of Staphylo- coccus aureus to corneocytes from atopic dermatitis patients is controlled by natural moisturizing factor levels. mBio. 2018; 9(4). https://doi.org/10.1128/mBio.01184-18 · DOI
  13. Towell AM, Feuillie C, Vitry P, et al. Staphylococcus aureus binds to the N-terminal region of corneodesmosin to adhere to the stratum corneum in atopic dermatitis. Proc Natl Acad Sci U S A. 2021;118(1). https://doi.org/10.1073/pnas.2014444118 · DOI
  14. Baurecht H, R€ uhlemann MC, Rodr ıguez E, et al. Epidermal lipid composition, barrier integrity, and eczematous inflammation are associated with skin microbiome configuration. J Allergy Clin Immunol. 2018;141(5):1668-1676.e16. https://doi.org/10. 1016/j.jaci.2018.01.019 · DOI
  15. Paller AS, Kong HH, Seed P, et al. The microbiome in patients with atopic dermatitis. J Allergy Clin Immunol. 2019;143(1):26- 35. https://doi.org/10.1016/j.jaci.2018.11.015 · DOI · Paper page
  16. Geoghegan JA, Irvine AD, Foster TJ. Staphylococcus aureus and atopic dermatitis: a complex and evolving relationship. Trends Microbiol. 2018;26(6):484-497. https://doi.org/10.1016/j.tim. 2017.11.008 · DOI
  17. Moran MC, Cahill MP, Brewer MG, et al. Staphylococcal virulence factors on the skin of atopic dermatitis patients. mSphere. 2019;4(6). https://doi.org/10.1128/mSphere.00616-19 · DOI
  18. Williams MR, Costa SK, Zaramela LS, et al. Quorum sensing between bacterial species on the skin protects against epidermal injury in atopic dermatitis. Sci Transl Med. 2019; 11(490). https://doi.org/10.1126/scitranslmed.aat8329 · DOI · Paper page
  19. Uberoi A, Bartow-McKenney C, Zheng Q, et al. Commensal microbiota regulates skin barrier function and repair via signaling through the aryl hydrocarbon receptor. Cell Host Microbe. 2021;29(8):1235-1248.e8. https://doi.org/10.1016/j. chom.2021.05.011 · DOI
  20. Nguyen AV, Soulika AM. The dynamics of the skin's immune system. Int J Mol Sci. 2019;20(8). https://doi.org/10.3390/ ijms20081811 · DOI
  21. Brunner PM, Guttman-Yassky E, Leung DY. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017;139(4S):S65- S76. https://doi.org/10.1016/j.jaci.2017.01.011 · DOI
  22. Biedermann T, Skabytska Y, Kaesler S, Volz T. Regulation of T cell immunity in atopic dermatitis by microbes: the yin and yang of cutaneous inflammation. Front Immunol. 2015;6:353. https://doi.org/10.3389/fimmu.2015.00353 · DOI
  23. Olesen CM, Ingham AC, Thomsen SF, et al. Changes in skin and nasal microbiome and staphylococcal species following treatment of atopic dermatitis with dupilumab. Microorgan- isms. 2021;9(7). https://doi.org/10.3390/microorganisms9071 487 · DOI
  24. Callewaert C, Nakatsuji T, Knight R, et al. IL-4Ralpha blockade by dupilumab decreases Staphylococcus aureus colonization and increases microbial diversity in atopic dermatitis. J Invest Dermatol. 2020;140(1):191-202.e7. https://doi.org/10.1016/j.jid. 2019.05.024 · DOI
  25. Silverberg JI, Toth D, Bieber T, et al. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multi- centre, placebo-controlled phase III ECZTRA 3 trial. Br J Dermatol. 2021;184(3):450-463. https://doi.org/10.1111/bjd. 19573 · DOI
  26. DeVore SB, Gonzalez T, Sherenian MG, Herr AB, Khurana Hershey GK. On the surface: skin microbial exposure contrib- utes to allergic disease. Ann Allergy Asthma Immunol. 2020; 125(6):628-638. https://doi.org/10.1016/j.anai.2020.08.025 · DOI
  27. Nakatsuji T, Hata TR, Tong Y, et al. Development of a human skin commensal microbe for bacteriotherapy of atopic derma- titis and use in a phase 1 randomized clinical trial. Nat Med. 2021;27(4):700-709. https://doi.org/10.1038/s41591-021- 01256-2 · DOI · Paper page

Authors
Beck, L. A., Bieber, T., Weidinger, S., Tauber, M., Saeki, H., Irvine, A. D., Eichenfield, L. F., Werfel, T., Arlert, P., Jiang, L., Røpke, M., & Paller, A. S.
Affiliations
  • University of Rochester Medicine (US)
  • University Hospital Bonn (DE)
  • University Hospital Schleswig-Holstein (DE)
  • Centre National de la Recherche Scientifique (FR)
  • Nippon Medical School (JP)
  • Trinity College Dublin (IE)
  • University of California San Diego (US)
  • Medizinische Hochschule Hannover (DE)
  • Leo Pharma (Denmark) (DK)
  • Northwestern University (US)
Corresponding author
Beck, Lisa A.
Venue
Journal of the American Academy of Dermatology
Publisher
Elsevier BV
Published
2023-04
Volume
88
Issue
4
Pages
816-823
ISSN
0190-9622 (ISSN-L)
OpenAlex
W4310675662
Cited by
56
References
34
Citations by year
2026: 12 · 2025: 15 · 2024: 18 · 2023: 11
FWCI
10.76
Type
journal article
Language
en
Open access
Locations
  • Journal of the American Academy of Dermatology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • Eli Lilly and Company
  • Pfizer
  • Sanofi
  • Regeneron Pharmaceuticals
  • Les Laboratories Pierre Fabre
  • Incyte
  • Ortho Dermatologics
  • Glenmark Pharmaceuticals
  • Galderma
  • Medac
  • LEO Pharma
Topics
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
Keywords
tralokinumab, atopic dermatitis, skin microbiome, microbial diversity, Staphylococcus aureus, coagulase-negative staphylococci, IL-13, dysbiosis, skin barrier
MeSH terms
Adult, Antibodies, Monoclonal, Dermatitis, Atopic, Humans, Skin, Staphylococcus aureus, Cytokines, Interleukin-13, Microbiota, Dysbiosis

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