The Role of the Skin Mycobiome in Atopic Dermatitis: Implication of Yeast and Fungus Overgrowth in Disease Exacerbation

Dermatitis®Vol. 35, No. S1 LettersFree AccessThe Role of the Skin Mycobiome in Atopic Dermatitis: Implication of Yeast and Fungus Overgrowth in Disease ExacerbationAjay S. Dulai, Mildred Min, and Raja K. SivamaniAjay S. Dulaihttps://orcid.org/0009-0000-2045-1819Integrative Skin Science and Research, Sacramento, CA, USA.Search for more papers by this author, Mildred MinIntegrative Skin Science and Research, Sacramento, CA, USA.College of Medicine, California Northstate University, Elk Grove, CA, USA.Search for more papers by this author, and Raja K. SivamaniE-mail Address: [email protected]Integrative Skin Science and Research, Sacramento, CA, USA.College of Medicine, California Northstate University, Elk Grove, CA, USA.Pacific Skin Institute, Sacramento, CA, USA.Department of Dermatology, University of California-Davis, Sacramento, CA, USA.R.K.S. serves as a scientific advisor for LearnHealth, Codex Labs, and Arbonne and as a consultant to Burt's Bees, Novozymes, Nutrafol, Novartis, Bristol Myers Squibb, Abbvie, Leo, Biogena, UCB, Incyte, Pfizer, Sanofi, Novartis, Sun, and Regeneron Pharmaceuticals.Search for more papers by this authorPublished Online:1 Feb 2024https://doi.org/10.1089/derm.2023.0248AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookXLinked InRedditEmail Atopic dermatitis (AD) is a common chronic inflammatory disease, affecting up to 20% of children and between 7% and 14% of adults in Europe and the United States.1 The pathogenesis of AD is multifactorial but involves skin barrier function, the immune system, environmental factors, and the influence of the local microbiome.Emerging evidence shows that the skin microbiome is involved in the pathogenesis of AD. Notably, increased colonization of Staphylococcus aureus has been associated with disease severity and exacerbation.2 Since this discovery, most studies have utilized 16S sequencing, limiting the analysis to bacteria. However, there is also evidence that dysbiosis of the fungal component of the skin microbiome, known as the mycobiome, can be observed in AD lesions.We have completed a succinct review of publications that investigate the role of the skin mycobiome in AD.One study characterized the differences between the mycobiome of 8 AD patients and healthy controls utilizing ITS2-based sequencing.3 Although the control group had high levels of the genus Malassezia, this was reduced in AD patients, and replaced by Alternaria, Aureobasidium, Aspergillus, and Cladosporium.3 Furthermore, 5 species belonging to Malassezia were determined to be distinctively in abundance in AD: Malessezia slooffiae, Malessezia dermatis, Malessezia japonica, Malessezia yamatoensis, and Malessezia obtusa.3Another study categorized both the mycobiome and microbiome changes in AD patients using ITS1 sequencing for the fungal organisms and 16S sequencing for bacterial organisms.4 Notably, a 137-fold increase in Alternaria was recorded on affected AD skin when compared with unaffected skin (P = 0.18). This increase was the highest in patients who had a history of childhood-onset flexural dermatitis. Furthermore, there was a decrease in Alternaria by 15-fold in control subjects (no P value reported).4Alternaria was found to act synergistically with Staphylococcus to promote production of inflammatory cytokines and structural proteins, such as increased tumor necrosis factor-alpha and thymic stromal lymphopoietin expression.4Although evidence suggests the skin microbiome can induce immune responses in AD patients, there is limited evidence on how treatments can modulate these mechanisms. One clinical study recorded changes in the skin mycobiome in AD patients after emollient treatment.5 Fungal organisms were identified using ITS1 sequencing. Shannon diversity index was significantly increased in nonlesional skin (P ≤ 0.04).5 Furthermore, researchers noted an association between bacteria and pathogenic fungi (Aspergillus spp. and Candida spp.) in the pretreatment sample but not after application of emollients, suggesting that emollient application disrupted a negative interaction between the bacteria and pathogenic fungi in lesional skin. A summary of these findings is included in Table 1.Table 1. Changes in the Skin Mycobiome in Atopic DermatitisAuthor (year)Sample Size, nMethod of SequencingIncreasedDecreasedOther ChangesHan et al. (2018)316ITS2 sequencingAlternaria, Aureobasidium, Aspergillus, and CladosporiumMalessezia slooffiae, Malessezia dermatis, Malessezia japonica, Malessezia yamatoensis, and Malessezia obtusaMalassezia—Hammond et al. (2022)46ITS1 sequencingAlternaria—Alternaria and Staphylococcus found to synergistically increase proinflammatory cytokinesChandra et al. (2018)510ITS1 sequencingShannon diversity index in nonlesional skin after emollient applicationNonsignificant decrease in Shannon Diversity Index of fungal organisms in lesional skin after emollient applicationEmollient application reduced associations between pathogenic fungi (Aspergillus spp. and Candida spp.)The role of the yeast and fungi in the skin mycobiome has largely been overlooked in discussion of the skin microbiome of AD. The inclusion of skin mycobiome analysis in clinical trials for AD is critical for understanding how fungi and yeasts, in addition to bacteria, contribute to disease exacerbation. Additional research must be conducted to understand the therapeutic potential of targeted treatments of the mycobiome, and how these affect the microbiome and general health of the patient.This will enable the development of new treatments that utilize both the myco- and microbiome to improve patient outcomes. The studies reviewed here utilized internal transcribed spacer (ITS) (either ITS1 or ITS2)-based sequencing approaches and future studies should expand to shotgun metagenomic sequencing for inclusion of both identification and functional analysis of the mycobiome in the context of the local bacterial populations as well. Overall, future discussions of the skin microbiome in AD should include analysis and discussion of bacteria, yeast, and fungi.References1. Bylund S, Kobyletzki LB, Svalstedt M, et al. Prevalence and incidence of atopic dermatitis: a systematic review. Acta Derm Venereol 2020;100(12):adv00160. Crossref, Medline, Google Scholar2. Edslev SM, Agner T, Andersen PS. Skin microbiome in atopic dermatitis. Acta Derm Venereol 2020;100(12):adv00164. Crossref, Medline, Google Scholar3. Han SH, Cheon HI, Hur MS, et al. Analysis of the skin mycobiome in adult patients with atopic dermatitis. Exp Dermatol 2018;27(4):366–373. Crossref, Medline, Google Scholar4. Hammond M, Gamal A, Mukherjee PK, et al. Cutaneous dysbiosis may amplify barrier dysfunction in patients with atopic dermatitis. Front Microbiol 2022;13:944365. Crossref, Medline, Google Scholar5. Chandra J, Retuerto M, Seite S, et al. Effect of an emollient on the mycobiome of atopic dermatitis patients. J Drugs Dermatol 2018;17(10):1039–1048. Medline, Google ScholarFiguresReferencesRelatedDetails Volume 35Issue S1Feb 2024 Information© 2024 American Contact Dermatitis Society. All Rights Reserved.To cite this article:Ajay S. Dulai, Mildred Min, and Raja K. Sivamani.The Role of the Skin Mycobiome in Atopic Dermatitis: Implication of Yeast and Fungus Overgrowth in Disease Exacerbation.Dermatitis®.Feb 2024.S111-S112.http://doi.org/10.1089/derm.2023.0248Published in Volume: 35 Issue S1: February 1, 2024Online Ahead of Print:November 22, 2023 TopicsAtopic dermatitis PDF download