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Atopisches Ekzem und Mikrobiom

Atopic eczema and microbiome

Der Hautarzt volume 70, pages 407–415 (2019)Cite this article

Zusammenfassung

Hintergrund

Neurodermitis ist eine chronisch-entzündliche Hauterkrankung, die durch Hautbarrierestörung, Entzündung und Dysbiose gekennzeichnet ist. Darüber hinaus ist das atopische Ekzem mit anderen Krankheiten des atopischen Formenkreises wie Allergie, Rhinokonjunktivitis und Asthma assoziiert. Das Mikrobiom der Haut besteht aus Bakterien, Viren und Pilzen. Bei Patienten mit Neurodermitis ist häufig ein Ungleichgewicht des Mikrobioms (Dysbiose) feststellbar.

Fragestellung

Noch ist nicht vollständig geklärt, welchen Einfluss die Dysbiose und das kutane Mikrobiom auf die Entstehung und den Verlauf des atopischen Ekzems haben. Mittels moderner Sequenzierungsmethoden soll nun die Rolle des Hautmikrobioms bei der Pathogenese der Neurodermitis entschlüsselt werden.

Material und Methoden

Vorgestellt und diskutiert werden Ergebnisse aktueller Grundlagenarbeiten.

Ergebnisse

Das Hautmikrobiom unterscheidet sich nach Körperregion, Alter und Geschlecht und steht in ständigem Austausch mit der Hautbarriere und dem kutanen Immunsystem. Bei der Neurodermitis entsteht eine Dysbiose mit einer erhöhten Keimlast von Staphylococcus aureus und einer Verringerung von kommensalen Hautbakterien. Das veränderte Mikrobiom bei Neurodermitis kann somit auch die Hautbarriere und Entzündungsreaktionen beeinflussen.

Schlussfolgerungen

Das Verständnis des Hautmikrobioms hat sich in den letzten Jahren verbessert. Zweifellos wird davon auch das Verständnis der Pathogenese der Neurodermitis profitieren. Zugleich können diese Erkenntnisse in Zukunft die Grundlage für neue Therapie- und Präventionsstrategien bilden.

Abstract

Background

Atopic eczema is a chronic inflammatory skin disease characterized by skin barrier disruption, inflammation and dysbiosis. Furthermore, atopic eczema is associated with other diseases of the atopic group, such as allergies, rhinoconjunctivitis and asthma. The skin microbiome consists of bacteria, viruses and fungi. Patients suffering from atopic eczema often show an imbalance (dysbiosis) of the microbiome.

Objective

It is not yet completely clarified what influence dysbiosis and the cutaneous microbiome have on the development and severity of atopic eczema. Modern sequencing methods will be used to investigate the role of the skin microbiome in the pathogenesis of atopic eczema in the future.

Material and methods

This article presents and discusses the results of current basic research.

Results

The human skin microbiome differs according to body region, age and gender. It interacts with the skin barrier and the cutaneous immune system. Patients suffering from atopic eczema develop dysbiosis consisting of an increased load of Staphylococcus aureus and a reduction of commensal skin bacteria. The altered skin microbiome in patients suffering from atopic eczema may also affect skin barrier function and inflammatory reactions.

Conclusion

Knowledge of the skin microbiome has improved in recent years. This will certainly improve the understanding of the pathogenesis causing atopic eczema. These findings may also form the foundation of new treatment and prevention strategies for atopic eczema in the future.

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Abbreviations

AE:

Atopisches Ekzem, auch: atopische Dermatitis oder Neurodermitis

AMP:

Antimikrobielle Peptide

APZ:

Antigenpräsentierende Zellen

HPV:

Humanes Papillomavirus

Ig:

Immunglobulin(e)

IL:

Interleukin(e)

NMF:

Natürliche Feuchtigkeitsfaktoren

16S rDNA:

16S ribosomale DNA

S. aureus :

Staphylococcus aureus

S. epidermidis :

Staphylococcus epidermidis

S. hominis :

Staphylococcus hominis

TJ:

„Tight junctions“

TLR:

Toll-like-Rezeptor

Literatur

  1. Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD (2018) Atopic dermatitis. Nat Rev Dis Primers 4(1):1

    Article  Google Scholar 

  2. Mallol J, Crane J, von Mutius E, Odhiambo J, Keil U, Stewart A et al (2013) The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three: a global synthesis. Allergol Immunopathol (madr) 41(2):73–85

    CAS  Article  Google Scholar 

  3. von Mutius E, Braun-Fahrlander C, Schierl R, Riedler J, Ehlermann S, Maisch S et al (2000) Exposure to endotoxin or other bacterial components might protect against the development of atopy. Clin Exp Allergy 30(9):1230–1234

    Article  Google Scholar 

  4. Drucker AM, Wang AR, Li WQ, Sevetson E, Block JK, Qureshi AA (2017) The burden of atopic dermatitis: summary of a report for the national eczema association. J Invest Dermatol 137(1):26–30

    CAS  Article  Google Scholar 

  5. Ferreira MA, Vonk JM, Baurecht H, Marenholz I, Tian C, Hoffman JD et al (2017) Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology. Nat Genet 49(12):1752–1757

    CAS  Article  Google Scholar 

  6. Bieber T, D’Erme AM, Akdis CA, Traidl-Hoffmann C, Lauener R, Schappi G et al (2017) Clinical phenotypes and endophenotypes of atopic dermatitis: where are we, and where should we go? J Allergy Clin Immunol 139(4S):58–64

    Article  Google Scholar 

  7. Czarnowicki T, He H, Krueger JG, Guttman-Yassky E (2019) Atopic dermatitis endotypes and implications for targeted therapeutics. J Allergy Clin Immunol 143(1):1–11

    Article  Google Scholar 

  8. Simpson EL, Bruin-Weller M, Flohr C, Ardern-Jones MR, Barbarot S, Deleuran M et al (2017) When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council. J Am Acad Dermatol 77(4):623–633

    Article  Google Scholar 

  9. Brunner PM, Pavel AB, Khattri S, Leonard A, Malik K, Rose S et al (2019) Baseline IL-22 expression in patients with atopic dermatitis stratifies tissue responses to fezakinumab. J Allergy Clin Immunol 143(1):142–154

    CAS  Article  Google Scholar 

  10. Guttman-Yassky E, Bissonnette R, Ungar B, Suarez-Farinas M, Ardeleanu M, Esaki H et al (2019) Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis. J Allergy Clin Immunol 143(1):155–172

    CAS  Article  Google Scholar 

  11. Eyerich S, Eyerich K, Traidl-Hoffmann C, Biedermann T (2018) Cutaneous barriers and skin immunity: differentiating a connected network. Trends Immunol 39(4):315–327

    CAS  Article  Google Scholar 

  12. Rippke F, Schreiner V, Schwanitz HJ (2002) The acidic milieu of the horny layer: new findings on the physiology and pathophysiology of skin pH. Am J Clin Dermatol 3(4):261–272

    Article  Google Scholar 

  13. Czarnowicki T, Krueger JG, Guttman-Yassky E (2017) Novel concepts of prevention and treatment of atopic dermatitis through barrier and immune manipulations with implications for the atopic march. J Allergy Clin Immunol 139(6):1723–1734

    CAS  Article  Google Scholar 

  14. Wanke I, Steffen H, Christ C, Krismer B, Gotz F, Peschel A et al (2011) Skin commensals amplify the innate immune response to pathogens by activation of distinct signaling pathways. J Invest Dermatol 131(2):382–390

    CAS  Article  Google Scholar 

  15. Eyerich K, Pennino D, Scarponi C, Foerster S, Nasorri F, Behrendt H et al (2009) IL-17 in atopic eczema: linking allergen-specific adaptive and microbial-triggered innate immune response. J Allergy Clin Immunol 123(1):59–66

    CAS  Article  Google Scholar 

  16. Clark RA (2010) Skin-resident T cells: the ups and downs of on site immunity. J Invest Dermatol 130(2):362–370

    CAS  Article  Google Scholar 

  17. Nakatsuji T, Chen TH, Narala S, Chun KA, Two AM, Yun T et al (2017) Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci Transl Med 9(378). https://doi.org/10.1126/scitranslmed.aah4680

    Article  PubMed  PubMed Central  Google Scholar 

  18. Harder J, Dressel S, Wittersheim M, Cordes J, Meyer-Hoffert U, Mrowietz U et al (2010) Enhanced expression and secretion of antimicrobial peptides in atopic dermatitis and after superficial skin injury. J Invest Dermatol 130(5):1355–1364

    CAS  Article  Google Scholar 

  19. Werfel T, Allam JP, Biedermann T, Eyerich K, Gilles S, Guttman-Yassky E et al (2016) Cellular and molecular immunologic mechanisms in patients with atopic dermatitis. J Allergy Clin Immunol 138(2):336–349

    CAS  Article  Google Scholar 

  20. Traidl S, Kienlin P, Begemann G, Jing L, Koelle DM, Werfel T et al (2018) Patients with atopic dermatitis and history of eczema herpeticum elicit herpes simplex virus-specific type 2 immune responses. J Allergy Clin Immunol 141(3):1144–1147

    Article  Google Scholar 

  21. Human Microbiome Project C (2012) A framework for human microbiome research. Nature 486(7402):215–221

    Article  Google Scholar 

  22. Grice EA, Segre JA (2011) The skin microbiome. Nat Rev Microbiol 9(4):244–253

    CAS  Article  Google Scholar 

  23. Kong HH, Andersson B, Clavel T, Common JE, Jackson SA, Olson ND et al (2017) Performing skin microbiome research: a method to the madness. J Invest Dermatol 137(3):561–568

    CAS  Article  Google Scholar 

  24. Altunbulakli C, Reiger M, Neumann AU, Garzorz-Stark N, Fleming M, Huelpuesch C et al (2018) Relations between epidermal barrier dysregulation and staphylococci-dominated microbiome dysbiosis in atopic dermatitis. J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2018.07.005

    Article  PubMed  Google Scholar 

  25. Zipperer A, Konnerth MC, Laux C, Berscheid A, Janek D, Weidenmaier C et al (2016) Human commensals producing a novel antibiotic impair pathogen colonization. Nature 535(7613):511–516

    CAS  Article  Google Scholar 

  26. Byrd AL, Belkaid Y, Segre JA (2018) The human skin microbiome. Nat Rev Microbiol 16(3):143–155

    CAS  Article  Google Scholar 

  27. Kennedy EA, Connolly J, Hourihane JO, Fallon PG, McLean WHI, Murray D et al (2017) Skin microbiome before development of atopic dermatitis: early colonization with commensal staphylococci at 2 months is associated with a lower risk of atopic dermatitis at 1 year. J Allergy Clin Immunol 139(1):166–172

    Article  Google Scholar 

  28. Meylan P, Lang C, Mermoud S, Johannsen A, Norrenberg S, Hohl D et al (2017) Skin colonization by staphylococcus aureus precedes the clinical diagnosis of atopic dermatitis in infancy. J Invest Dermatol 137(12):2497–2504

    CAS  Article  Google Scholar 

  29. Thorsteinsdottir S, Thyssen JP, Stokholm J, Vissing NH, Waage J, Bisgaard H (2016) Domestic dog exposure at birth reduces the incidence of atopic dermatitis. Allergy 71(12):1736–1744

    CAS  Article  Google Scholar 

  30. Ahmadizar F, Vijverberg SJH, Arets HGM, de Boer A, Lang JE, Garssen J et al (2018) Early-life antibiotic exposure increases the risk of developing allergic symptoms later in life: a meta-analysis. Allergy 73(5):971–986

    CAS  Article  Google Scholar 

  31. Harada K, Saito M, Sugita T, Tsuboi R (2015) Malassezia species and their associated skin diseases. J Dermatol 42(3):250–257

    Article  Google Scholar 

  32. Glatz M, Bosshard PP, Hoetzenecker W, Schmid-Grendelmeier P (2015) The role of Malassezia spp. in atopic dermatitis. J Clin Med 4(6):1217–1228

    CAS  Article  Google Scholar 

  33. Hannigan GD, Zheng Q, Meisel JS, Minot SS, Bushman FD, Grice EA (2017) Evolutionary and functional implications of hypervariable loci within the skin virome. PeerJ 5:e2959

    Article  Google Scholar 

  34. El-Heis S, Crozier SR, Healy E, Robinson SM, Harvey NC, Cooper C et al (2017) Maternal stress and psychological distress preconception: association with offspring atopic eczema at age 12 months. Clin Exp Allergy 47(6):760–769

    CAS  Article  Google Scholar 

  35. Harter K, Hammel G, Krabiell L, Linkohr B, Peters A, Schwettmann L et al (2019) Different psychosocial factors are associated with seasonal and perennial allergies in adults—cross-sectional results of the KORA FF4 study. Int Arch Allergy Immunol. https://doi.org/10.1159/000499042

    Article  PubMed  Google Scholar 

  36. Orivuori L, Mustonen K, de Goffau MC, Hakala S, Paasela M, Roduit C et al (2015) High level of fecal calprotectin at age 2 months as a marker of intestinal inflammation predicts atopic dermatitis and asthma by age 6. Clin Exp Allergy 45(5):928–939

    CAS  Article  Google Scholar 

  37. Byrd AL, Deming C, Cassidy SKB, Harrison OJ, Ng WI, Conlan S et al (2017) Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis. Sci Transl Med 9(397). https://doi.org/10.1126/scitranslmed.aal4651

    Article  PubMed  PubMed Central  Google Scholar 

  38. Myles IA, Earland NJ, Anderson ED, Moore IN, Kieh MD, Williams KW et al (2018) First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis. JCI Insight 3(9). https://doi.org/10.1172/jci.insight.120608

    Article  PubMed  PubMed Central  Google Scholar 

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Author information

Affiliations

  1. Lehrstuhl und Institut für Umweltmedizin UNIKA‑T, Technische Universität München und Helmholtz Zentrum München, Neusäßer Str. 47, 86156, Augsburg, Deutschland

    C. Traidl-Hoffmann

  2. ZIEL – Institute for Food & Health, Technische Universität München, Freising, Deutschland

    C. Traidl-Hoffmann

  3. Hochschulambulanz für Umweltmedizin, Universitätsklinikum Augsburg, Augsburg, Deutschland

    C. Traidl-Hoffmann

Authors
  1. M. Reiger
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  2. V. Schwierzeck
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  3. C. Traidl-Hoffmann
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Corresponding author

Correspondence to C. Traidl-Hoffmann.

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Interessenkonflikt

C. Traidl-Hoffmann war als Beraterin und Referentin gegen Honorar tätig für Sanofi, Novartis, Töpfer, Sebapharma bzw. erhielt Forschungsgelder von Sebapharma, Danone Nutricia, Töpfer. M. Reiger und V. Schwierzeck geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Reiger, M., Schwierzeck, V. & Traidl-Hoffmann, C. Atopisches Ekzem und Mikrobiom. Hautarzt 70, 407–415 (2019). https://doi.org/10.1007/s00105-019-4424-6

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Schlüsselwörter

  • Dysbiose
  • Mikrobiota
  • Inflammation
  • Immunsystem
  • Allergien

Keywords

  • Dysbiosis
  • Microbiota
  • Inflammation
  • Immune system
  • Allergies