Microbiome: Role in Inflammatory Skin Diseases

Abstract

As the body’s largest organ, the skin harbors a highly diverse microbiota, playing a crucial role in resisting foreign pathogens, nurturing the immune system, and metabolizing natural products. The dysregulation of human skin microbiota is implicated in immune dysregulation and inflammatory responses. This review delineates the microbial alterations and immune dysregulation features in common Inflammatory Skin Diseases (ISDs) such as psoriasis, rosacea, atopic dermatitis(AD), seborrheic dermatitis(SD), diaper dermatitis(DD), and Malassezia folliculitis(MF).The skin microbiota, a complex and evolving community, undergoes changes in composition and function that can compromise the skin microbial barrier. These alterations induce water loss and abnormal lipid metabolism, contributing to the onset of ISDs. Additionally, microorganisms release toxins, like Staphylococcus aureus secreted α toxins and proteases, which may dissolve the stratum corneum, impairing skin barrier function and allowing entry into the bloodstream. Microbes entering the bloodstream activate molecular signals, leading to immune disorders and subsequent skin inflammatory responses. For instance, Malassezia stimulates dendritic cells(DCs) to release IL-12 and IL-23, differentiating into a Th17 cell population and producing proinflammatory mediators such as IL-17, IL-22, TNF-α, and IFN-α.This review offers new insights into the role of the human skin microbiota in ISDs, paving the way for future skin microbiome-specific targeted therapies.

Keywords:

• skin microbiota
• inflammatory skin diseases
• atopic dermatitis
• seborrheic dermatitis
• rosacea
• acne
• psoriasis
• diaper dermatitis
• Malassezia folliculitis

Abbreviations

AD, atopic dermatitis; aryl-hydrocarbon receptor; AMP, antimicrobial peptides; AMPS, antimicrobial peptide; APCs, antigen-presenting cells; C. albicans, Candida albicans; CAP18, cathelicidin antimicrobial peptide 18; CGRP, calcitonin gene-related peptide; CLFA, clumping factors A; CLFB, clumping factors B; CLR, C-type lectin receptor; CONS, coagulase-negative staphylococci; cPLA2, cytosolic PLA2; CRISPR/Cas, CRISPR-associated proteins system; CXCL8, C-X-C motif ligand 8; DC, dendritic cell; DCs, dendritic cells; DD, Diaper Dermatitis; DF, dandruff; ESAT-6, early secretory antigenic 6; FDP, filaggrin degradation products; FFA, free fatty acid; FNBP, fibronectin binding protein; HBD, humanβ- defensin; HBD-2, humanβ-defensin 2; HBD-3, humanβ-defensin 3; HLA, human leukocyte antigen; HSP70, heat shock protein 70; IFN-γ, interferon-gamma; IL, interleukin; IL-23, interleukin-23; iNOS, inducible nitric oxide synthase; irak4, interleukin-1 receptor-associated kinase 4; ISDA, iron-regulated surface determinant protein A; ISDs, inflammatory skin diseases; KC, keratinocytes; LPC, Lys phosphatidylcholines; LTA, Lipoteichoic acid; MF, Malassezia folliculitis; M. globose, Malassezia. globosa; M. furfur, Malassezia. furfur; M. restricta, Malassezia. restricta; M. sympodialis, Malassezia. sympodialis; MMP-9, matrix metallo proteinase-9; MPAKs, mitogen-activated protein kinase; MyD88, myeloid differentiation primary response 88; NFAT, activated T cells; NF-κB, nuclear factor κ B; NOD, nucleotide-binding oligomerization domain; OMN, Omiganan; P. acnes, Propionibacterium acnes; PLA2, phospholipase A2; PSM-γ, phenol solubility regulating protein-γ; PSM-δ, phenol solubility regulating protein-δ; Roxp, radical oxygenase; RT2, ribotype 2; RT4, ribotype 4; RT5, ribotype 5; SAgs, Staphylococcus aureus superantigens; S. aureus, Staphylococcus aureus; SCFAs, short-chain fatty acids; SD, Seborrheic dermatitis; SE, Staphylococcal enterotoxins; SEA, Staphylococcal enterotoxin A; SEB, Staphylococcal enterotoxin B; SEC, Staphylococcal enterotoxin C; SPL, sphingolipids; S. Alvi, Snodgrassella alvi; S. Epidermidis, Staphylococcus epidermidis; TARC, thymus and activation of cytokines; TRAF6, TNFR-associated factor 6; TEWL, transepidermal water loss; TGF-β, transforming growth factor-beta; TLR, Toll-like receptor; TNF, tumor necrosis factor; TSLP, thymic stromal lymphopoietin; TSST, toxic shock syndrome toxin. (See Table 4).

Table 4 Abbreviations

Data Sharing Statement

The analyzed data in this study are available from the corresponding author upon reasonable request.

Acknowledgments

We are grateful to the authors and patients of all the articles.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

All authors declare no conflicts of interest in this work.

Additional information

Funding

This work was supported by the Chengdu University of Traditional Chinese Medicine “Xinglin Scholars” Discipline Talent Research Improvement Program, Project Number: QJJJ2021001; Chengdu University of Traditional Chinese Medicine “Foundation Thickening” Action Plan (2023-42); Chengdu University of Traditional Chinese Medicine Hospital’s “Hundred Person Plan” (21-L03 and 22-B09). “Young Qihuang” Scholars of the State Administration of Traditional Chinese Medicine (2022-256)