Summary

Atopic dermatitis is a multifactorial cutaneous chronic inflammatory disease. A crucial role in its pathogenesis is played by interaction between genomes of the host and skin microbiota, which is the basis of the holobiome theory. Genetic and environmental factors influence the microbial composition of skin. Alterations in filaggrin compromise the integrity of the skin barrier, alter skin’s hydration status and pH, and allow for increased colonization by S. aureus. Th2-mediated inflammation reduces antimicrobial peptides, lipid synthesis and epidermal differentiation, further worsening the condition. Impaired skin flora differentiation guide to excessive proliferation of S. aureus, whose toxins degrade skin proteins and form a protective layer around itself. On the other hand, common commensal bacteria produce immunoregulatory substances and inhibit the proliferation of S. aureus. Other factors, such as lipid composition and microbial communication signals, modulate the interaction between skin and microbes. Understanding atopic dermatitis in the context of the holobiome could facilitate the development of targeted therapies aimed at restoring microbial balance and skin barrier function,

References

  1. Galli E, Fortina AB, Ricci G, et al. Narrative review on the management of moderate-severe atopic dermatitis in pediatric age of the Italian Society of Pediatric Allergology and Immunology (SIAIP), of the Italian Society of Pediatric Dermatology (SIDerP) and of the Italian Society of Pediatrics (SIP). Ital J Pediatr 2022;48:95. https://doi.org/10.1186/s13052-022-01278-7.
  2. Almoughrabie S, Gallo RL Interdependence of Sebaceous Lipids and the Microbiome in Atopic Dermatitis J Invest Dermatol 2022;142:2845-2847. https://doi.org/10.1016/j.jid.2022.07.004.
  3. Moitinho-Silva L, Boraczynski N, Emmert H, et al. Host traits, lifestyle and environment are associated with human skin bacteria British Journal of Dermatology 2021;185:573-584. https://doi.org/10.1111/bjd.20072.
  4. Byrd AL, Belkaid Y, Segre JA: The human skin microbiome. Nat Rev Microbiol 2018;16:143-155. https://doi.org/10.1038/nrmicro.2017.157.
  5. Luger T, Amagai M, Dreno B et al. Atopic dermatitis: Role of the skin barrier, environment, microbiome, and therapeutic agents Journal of Dermatological Science 2021;102:142-157. https://doi.org/10.1016/j.jdermsci.2021.04.007.
  6. Nakatsuji T, Chen TH, Two AM, et al. Staphylococcus aureus exploits epidermal barrier defects in atopic dermatitis to trigger cytokine expression. J Invest Dermatol 2016;136:2192-2200. https://doi.org/10.1016/j.jid.2016.05.127.
  7. Pellerin, L, Henry J, Hsu CY et al. Defects of filaggrin-like proteins in both lesional and nonlesional atopic skin. J Allergy Clin Immunol 2013;131:1094-102. https://doi.org/10.1016/j.jaci.2012.12.1566.
  8. Knox S, Boyle NM. Skin lipids in health and disease: A review. Chem Phys Lipids 2021;236:105055. https://doi.org/10.1016/j.chemphyslip.2021.105055.
  9. Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. Lancet 2020;396:345-360. https://doi.org/10.1016/S0140-6736(20)31286-1. Erratum in: Lancet 2020;396:758. https://doi.org/10.1016/S0140-6736(20)31825-0.
  10. Miajlovic H, Fallon PG, Irvine AD et al. Effect of filaggrin breakdown products on growth of and protein expression by Staphylococcus aureus. J Allergy Clin Immunol 2010;126:1184-90.e3. https://doi.org/10.1016/j.jaci.2010.09.015.
  11. Baldwin HE, Bhatia ND, Friedman A, et al. The Role of Cutaneous Microbiota Harmony in Maintaining a Functional Skin Barrier. J Drugs Dermatol 2017;16:12-18.
  12. Yang G, Seok JK, Kang HC,et al. Skin Barrier Abnormalities and Immune Dysfunction in Atopic Dermatitis. Int J Mol Sci 2020;21:2867. https://doi.org/10.3390/ijms21082867.
  13. Werfel T, Allam JP, Biedermann T, et al. Cellular and molecular immunologic mechanisms in patients with atopic dermatitis. J Allergy Clin Immunol 2016;138:336-349. https://doi.org/10.1016/j.jaci.2016.06.010.
  14. van Smeden J, Bouwstra JA. Stratum Corneum Lipids: Their Role for the Skin Barrier Function in Healthy Subjects and Atopic Dermatitis Patients. Curr Probl Dermatol 2016;49:8-26. https://doi.org/10.1159/000441540.
  15. Sun L, Liu W, Zhang LJ. The Role of Toll-Like Receptors in Skin Host Defense, Psoriasis, and Atopic Dermatitis. J Immunol Res 2019;2019:1824624. https://doi.org/10.1155/2019/1824624.
  16. Danby SG, Cork MJ. pH in Atopic Dermatitis. Curr Probl Dermatol 2018;54:95-107. https://doi.org/10.1159/000489523.
  17. Hulpusch C, Tremmel K,Hammel G et al. Skin pH-dependent Staphylococcus aureus abundance as predictor for increasing atopic dermatitis severity. Allergy 2020;75:2888-2898. https://doi.org/10.1111/all.14461.
  18. Wanke I, Steffen H, Christ C et al. Skin commensals amplify the innate immune response to pathogens by activation of distinct signaling pathways. J Invest Dermatol 2011;131:382-390. https://doi.org/10.1038/jid.2010.328.
  19. Archer NK, Jo JH, Lee SK, et al. Injury, dysbiosis, and filaggrin deficiency drive skin inflammation through keratinocyte IL-1α release. J Allergy Clin Immunol 2019;14:1426-1443.e6. https://doi.org/10.1016/j.jaci.2018.08.042.
  20. Berdyshev E, Goleva E, Bissonnette R et al Dupilumab significantly improves skin barrier function in patients with moderate-to-severe atopic dermatitis. Allergy 2022;77:3388-3397. https://doi.org/10.1111/all.15432.
  21. Leung CY, Weitz JS. Not by (Good) Microbes Alone: Towards Immunocommensal Therapies. Trends Microbiol 2019;27:294-302. https://doi.org/10.1016/j.tim.2018.12.006.
  22. Lefèvre-Utile A, Braun C, Haftek M et al. Five Functional Aspects of the Epidermal Barrier. Int J Mol Sci 2021;22:11676. https://doi.org/10.3390/ijms222111676.
  23. Ito Y, Amagai M. Controlling skin microbiome as a new bacteriotherapy for inflammatory skin diseases. Inflamm Regen 2022;42:26. https://doi.org/10.1186/s41232-022-00212-y.
  24. Swaney MH , Kalan LR. Living in Your Skin: Microbes, Molecules, and Mechanisms. Infect Immun 2021;89:e00695-20. https://doi.org/10.1128/IAI.00695-20.
  25. Koh LF, Ong RY. Common JE Skin microbiome of atopic dermatitis. Allergol Int 2022;71:31-39. https://doi.org/10.1016/j.alit.2021.11.001.
  26. Chia M, Naim ANM, Tay ASL, et al. Shared signatures and divergence in skin microbiomes of children with atopic dermatitis and their caregivers. J Allergy Clin Immunol 2022;150:894-908. https://doi.org/10.1016/j.jaci.2022.01.031.
  27. Edslev SM, Agner T, Andersen PS. Skin microbiome in atopic dermatitis. Acta Derm Venereol 2020;100:adv00164. https://doi.org/10.2340/00015555-3514.
  28. Halling AS, Fritz BG, Gerner T, et al Reduced Skin Microbiome Diversity in Infancy Is Associated with Increased Risk of Atopic Dermatitis in High-Risk Children. J Invest Dermatol 2023;143:2030-2038.e6. https://doi.org/10.1016/j.jid.2023.03.1682.
  29. Zheng Y, Hunt RL, Villaruz AE, et al: Commensal Staphylococcus epidermidis contributes to skin barrier homeostasis by generating protective ceramides. Cell Host Microbe 2022;30:301-313.e9. https://doi.org/10.1016/j.chom.2022.01.004.
  30. Landemaine L, Da Costa G, Fissier E, et al Staphylococcus epidermidis isolates from atopic or healthy skin have opposite effect on skin cells: potential implication of the AHR pathway modulation Frontiers in Immunology 2023;14:1098160. https://doi.org/10.3389/fimmu.2023.1098160.
  31. Hirakawa S, Saito R, Ohara H, et al. Dual oxidase 1 induced by Th2 cytokines promotes STAT6 phosphorylation via oxidative inactivation of protein tyrosine phosphatase 1B in human epidermal keratinocytes. J Immunol 2011;186:4762-4770. https://doi.org/10.4049/jimmunol.1000791.
  32. Colonna M. AHR: Making the keratinocytes thick skinned. Immunity 2014;40:863-864. https://doi.org/10.1016/j.immuni.2014.06.001.
  33. Alwan W, Di Meglio P. Guardians of the barrier: Microbiota engage AHR in keratinocytes to mantain skin homeostasis. Cell Host Microbe 2021;29:1213-1216. https://doi.org/10.1016/j.chom.2021.07.007.
  34. Galli E, Cinicola BL, Maiello N, et al. Tapinarof as a new topical treatment in atopic dermatitis. Italian Journal of Pediatric Allergy and Immunology 2025;39(2):4-10. https://doi.org/10.53151/2531-3916/2025-1074.
  35. Kennedy EA, Connolly J, Hourihane JOB, et al. 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 2017;139:166-172. https://doi.org/10.1016/j.jaci.2016.07.029.
  36. Nakatsuji T, Hata TR, Tong Y, et al. Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase 1 randomized clinical trial. Nat Med 2021;27:700-709. https://doi.org/10.1038/s41591-021-01256-2.
  37. van der Krieken DA,Rikken G,Ederveen THA, et al. Gram-positive anaerobic cocci guard skin homeostasis by regulating host-defense mechanisms. iScience 2023;26:106483. https://doi.org/10.1016/j.isci.2023.106483.
  38. Bourebaba Y,Marycz K,Mularczyk M, et al Postbiotics as potential new therapeutic agents for metabolic disorders management. Biomed Pharmacother 2022;153:113138. https://doi.org/10.1016/j.biopha.2022.113138.
  39. Jenul C, Horswill AR. Regulation of Staphylococcus aureus virulence. Microbiol Spectr 2019;7:10.1128/microbiolspec.gpp3-0031-2018. https://doi.org/10.1128/microbiolspec.GPP3-0031-2018.
  40. Schilcher K, Horswill AR. Staphylococcal biofilm development: structure, regulation, and treatment strategies. Microbiol Mol Biol Rev 2020;84:e00026-19. https://doi.org/10.1128/MMBR.00026-19.
  41. Zhou Y, Xu X, Liu Y et al Heterogeneous regulation of Staphylococcus aureus by different Staphylococcus epidermidis agr types in atopic dermatitis. J Invest Dermatol 2023;143:2484-2493.e11. https://doi.org/10.1016/j.jid.2023.05.014.
  42. Otto M. Staphylococcus epidermidis--the ‘accidental’ pathogen. Nat Rev Microbiol 2009;7:555-567. https://doi.org/10.1038/nrmicro2182.
  43. Paller AS, Kong HH, Seed P, et al. The microbiome in patients with atopic dermatitis. J Allergy Clin Immunol 2019;143:26-35. https://doi.org/10.1016/j.jaci.2018.11.015. Erratum in: J Allergy Clin Immunol 2019;143:1660. https://doi.org/10.1016/j.jaci.2019.01.022.
  44. Simpson EL,Villarreal M,Jepson B et al Atopic dermatitis subjects colonized with Staphylococcus aureus have a distinct phenotype and endotype. J Invest Dermatol 2018;138:2224-2233. https://doi.org/10.1016/j.jid.2018.03.1517.
  45. Kim J, Kim BE, Ahn K, et al. Interactions between atopic dermatitis and staphylococcus aureus infection: clinical implica-tions. Allergy Asthma Immunol Res 2019;11:593-603. https://doi.org/10.4168/aair.2019.11.5.593.
  46. Chung EJ, Luo CH, Thio CL, et al. Immunomodulatory role of Staphylococcus aureus in atopic dermatitis. Pathogens 2022;11:422. https://doi.org/10.3390/pathogens11040422.
  47. Li S, Villarreal M, Stewart S, et al. Altered composition of epidermal lipids correlates with Staphylococcus aureus colonization status in atopic dermatitis. Br J Dermatol 2017;177:e125-e127. https://doi.org/10.1111/bjd.15409.
  48. Zhang LJ, Guerrero-Juarez CF, Hata T, et al. Innate immunity. Dermal adipocytes protect against invasive Staphylococcus aureus skin infection. Science 2015;347:67-71. https://doi.org/10.1126/science.1260972.
  49. Schulz A, Jiang L, de Vor L et al Neutrophil recruitment to noninvasive MRSA at the stratum corneum of human skin mediates transient colonization. Cell Rep 2019;29:1074-81.e5. https://doi.org/10.1016/j.celrep.2019.09.055.

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Authors

Gianluca Mirra - Pediatric Allergology Unit, Department of Pediatric Medicine, S. Pietro Hospital Fatebenefratelli, Roma, Italy

Bianca Gragnoli - Department of Clinical and Experimental Medicine, Section of Paediatrics, University of Pisa, Pisa, Italy

Francesca Cipriani - Department of Clinical and Experimental Medicine, Section of Paediatrics, University of Pisa, Pisa, Italy

Pasquale Comberiati - Department of Clinical and Experimental Medicine, Section of Paediatrics, University of Pisa, 56126 Pisa

Giampaolo Ricci - Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Italy

Elena Galli - Pediatric Allergology Unit, Department of Pediatric Medicine, S. Pietro Hospital Fatebenefratelli, Roma, Italy

Nunzia Maiello - Department of Woman, Child and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy

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Copyright (c) 2026 Italian Journal of Pediatric Allergy and Immunology

How to Cite
Mirra, G., Gragnoli, B., Cipriani, F., Comberiati, P. ., Ricci, G., Galli, E. ., & Maiello, N. (2026). Atopic Dermatitis and Holobiome: a review on molecular mechanisms and Host-Microbiota Interactions. Italian Journal of Pediatric Allergy and Immunology, 67(2). https://doi.org/10.53151/2531-3916/2026-2456
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