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Review
. 2022 Jun 2;11(6):642.
doi: 10.3390/pathogens11060642.

Manipulating Microbiota to Treat Atopic Dermatitis: Functions and Therapies

Md Jahangir Alam  1 , Liang Xie  1   2 , Yu-Anne Yap  3 , Francine Z Marques  2   4 , Remy Robert  3
Affiliations
Review

Manipulating Microbiota to Treat Atopic Dermatitis: Functions and Therapies

Md Jahangir Alam et al. Pathogens. .

Abstract

Atopic dermatitis (AD) is a globally prevalent skin inflammation with a particular impact on children. Current therapies for AD are challenged by the limited armamentarium and the high heterogeneity of the disease. A novel promising therapeutic target for AD is the microbiota. Numerous studies have highlighted the involvement of the skin and gut microbiota in the pathogenesis of AD. The resident microbiota at these two epithelial tissues can modulate skin barrier functions and host immune responses, thus regulating AD progression. For example, the pathogenic roles of Staphylococcus aureus in the skin are well-established, making this bacterium an attractive target for AD treatment. Targeting the gut microbiota is another therapeutic strategy for AD. Multiple oral supplements with prebiotics, probiotics, postbiotics, and synbiotics have demonstrated promising efficacy in both AD prevention and treatment. In this review, we summarize the association of microbiota dysbiosis in both the skin and gut with AD, and the current knowledge of the functions of commensal microbiota in AD pathogenesis. Furthermore, we discuss the existing therapies in manipulating both the skin and gut commensal microbiota to prevent or treat AD. We also propose potential novel therapies based on the cutting-edge progress in this area.

Keywords: G-protein-coupled receptors; aryl hydrocarbon receptors; atopic dermatitis; fecal microbiota transplantation; gut microbiota; histone deacetylases; metabolites; short-chain fatty acids; skin microbiota; toll-like receptors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mechanisms of how skin microbiota regulates AD pathogenesis. Excessive S. aureus colonization on the skin leads to the formation of biofilms and the secretion of virulence factors. These virulence factors facilitate mast cell degranulation, enhance inflammatory cytokine productions and the release of histamine, and increase IgE levels. In addition, S. aureus directly stimulates keratinocytes (KC) and Langerhans cells (LC) to release proinflammatory cytokines, including TH2 cytokines, TSLP, IL-8, and IL-1β, thus inducing TH2 differentiation and inflammation. Together, excessive cutaneous S. aureus colonization promotes AD pathogenesis. Conversely, commensal Coagulase-negative staphylococci (CoNS) inhibit the colonization of S. aureus by producing lantibiotics, PSMγ, and PSMδ. They also inhibit S. aureus biofilm formation by producing the serine protease glutamyl endopeptidase (Esp). Tryptophan metabolites derived from skin microbiota can activate AHR, thus inhibiting TSLP production by KCs and improving the epidermal barrier of the skin. AHR, aryl hydrocarbon receptor; AHRE, AHR element; AMPs, antimicrobial peptides; CoNS, Coagulase-negative staphylococci; IAId, indole-3-aldehyde; IL, interleukin; ILC3, lymphoid cells type 3; KC, keratinocyte; LC, Langerhans cell; PSM, phenol-soluble modulin, TSLP, thymic stromal lymphopoietin; SE, Staphylococcal enterotoxin; TSST-1, toxic shock syndrome toxin-1. Created with BioRender.com (accessed on 4 May 2022).
Figure 2
Figure 2
Mechanisms of how gut microbiota regulate AD pathogenesis. Short-chain fatty acids (SCFAs) produced by the gut microbiota are able to activate SCFA-sensing G-protein coupled receptors (GPCRs) and/or inhibit histone deacetylases (HDACs), thus activating downstream signalling cascades that suppress inflammatory responses and restoring TH1/TH2 balance. Microbial metabolite, D-tryptophan can also restore TH1/TH2 balance. Bifidobacteria, a genus of bacteria to which many probiotics belong, are an important source of these metabolites. Microbial tryptophan metabolites can activate the aryl hydrocarbon receptor (AHR), which inhibits inflammatory responses and improve the epidermal barrier of skin. Pathogen-associated molecular patterns produced by the gut microbiota can activate toll-like receptors (TLRs) thus restoring TH1/TH2 balance. All these mechanisms benefit AD. IAld, indole-3-aldehyde; IAA, indole-3-acetic acid; IPA, indole-3-propionic acid; TA, tryptamine; ARNT, aryl hydrocarbon receptor nuclear translocator. Created with BioRender.com (accessed on 4 May 2022).
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