Host-Microbe Interaction on the Skin and Its Role in the Pathogenesis and Treatment of Atopic Dermatitis

Atopic dermatitis (AD) is a condition with a complex and unclear aetiology. Possible causes of AD encompass alterations in the structure and function of the epidermal barrier, disturbances in the skin microbiome, immune factors, allergens, bacterial and fungal infections as well as environmental and genetic factors. In patients with AD, acute skin lesions are colonized by a greater number of bacteria and fungi than chronic lesions, clinically unchanged atopic skin and the skin of healthy people. Mechanisms promoting skin colonization by pathogens include complex interplay among several factors. Apart from disturbances of the skin microbiome, increased adhesion in atopic skin, defects of innate immune response resulting in the lack of or restriction of growth of microorganisms also contribute to susceptibility to the skin colonization of and infections, especially with Staphylococcus aureus. This review of the literature attempts to identify factors that are involved in the pathogenesis of AD-related bacterial and fungal skin colonization. Studies on the microbiome, commensal microorganisms and the role of skin microorganisms in maintaining healthy skin bring additional insight into the treatment and prevention of AD. In the light of presented mechanisms, reduction in colonization may become both causative and symptomatic treatment in AD.

Download Full-text

The Role of Immune Defects and Colonization ofStaphylococcus aureusin the Pathogenesis of Atopic Dermatitis

Analytical Cellular Pathology ◽

10.1155/2018/1956403 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Danuta Nowicka ◽

Ewelina Grywalska

Keyword(s):

Atopic Dermatitis ◽

Symptomatic Treatment ◽

Skin Lesions ◽

Specific Ige ◽

Complex Interactions ◽

Atopic Skin ◽

Skin Colonization ◽

Severity Of The Disease ◽

Immune Defects

Atopic dermatitis (AD) is a condition with a complex and not fully understood etiology. In patients with AD, acute skin lesions are colonized by a greater number ofStaphylococcus aureus(S. aureus) bacteria than chronic lesions, clinically unchanged atopic skin, or the skin of healthy people. Mechanisms promoting skin colonization byS. aureusinclude complex interactions among several factors. Apart from increased adhesion ofS. aureusin atopic skin, defects of the innate immune response resulting in the lack of restriction of the growth of microorganisms also contribute to susceptibility to colonization by and infection withS. aureus. A deficiency in the endogenous antimicrobial peptides may be partly responsible for the susceptibility to colonization by and skin infection withS. aureusin patients with AD. Majority of isolatedS. aureusstains are able to produce exotoxins, which act as superantigens. Moreover, anti-S. aureus-specific IgE was identified and measured in patients with AD, revealing that its level corresponds to the severity of the disease. This review of the literature attempts to identify factors that are involved in the pathogenesis of AD-relatedS. aureusskin colonization. In the light of presented mechanisms, a reduction of colonization may become both causative and symptomatic treatment in AD.

Download Full-text

CURRENT CONCEPTS OF ATOPIC DERMATITIS IN CHILDREN: PROBLEMS AND PROSPECTS

Российский педиатрический журнал ◽

10.18821/1560-9561-2017-20-2-99-107 ◽

2019 ◽

Vol 20 (2) ◽

pp. 99-107

Author(s):

Galina I. Smirnova

Keyword(s):

Atopic Dermatitis ◽

Immune Responses ◽

Proinflammatory Cytokines ◽

Genetic Predisposition ◽

Allergic Inflammation ◽

Skin Lesions ◽

Current Understanding ◽

Epidermal Barrier ◽

Barrier Integrity ◽

Atopic Skin

There are presented modern data describing the current understanding of the pathogenesis of atopic dermatitis (AD): a genetic predisposition to atopy, disruptions of epidermal barrier integrity and a cascade of immune responses, contributing allergic inflammation in the skin. There are both described several mechanisms of acute and chronic phases of AD, the main directions of pathogenetically substantiated treatment of AD in children and indicated the prospects of new preparations specific blockers of proinflammatory cytokines involved in the development of AD - crisaborole, apremilast, dupilumab, lebrikizumab, tralokinumab, tezepelumab. There is especially presented in details external therapy of atopic skin lesions in children with the use of means of modern dermatological cosmetics.

Download Full-text

CURRENT CONCEPTS OF ATOPIC DERMATITIS IN CHILDREN: PROBLEMS AND PROSPECTS

Rossiiskii Allergologicheskii ZHurnal ◽

10.36691/rja292 ◽

2017 ◽

Vol 14 (4-5) ◽

pp. 30-39

Author(s):

G I Smirnova

Keyword(s):

Atopic Dermatitis ◽

Immune Responses ◽

Proinflammatory Cytokines ◽

Genetic Predisposition ◽

Allergic Inflammation ◽

Skin Lesions ◽

Current Understanding ◽

Intestinal Microbiome ◽

Barrier Integrity ◽

Atopic Skin

Modern data describing the current understanding of the pathogenesis of atopic dermatitis (AD): a genetic predisposition to atopy, disturbances of the intestinal microbiome, disruptions of epidermal barrier integrity and a cascade of immune responses, contributing allergic inflammation in the skin are presented. There are both described several mechanisms of acute and chronic phases of AD, the main directions of pathogenetically substantiated treatment of AD in children and indicated the prospects of new preparations specific blockers of proinflammatory cytokines involved in the development of AD - crisaborole, dupilumab, apremilast et al. External therapy of atopic skin lesions in AD children with modern dermatological cosmetics is presented.

Download Full-text

The Role of Staphylococcus aureus in Secondary Infections in Patients with Atopic Dermatitis (AD)

Polish Journal of Microbiology ◽

10.5604/17331331.1215600 ◽

2016 ◽

Vol 65 (3) ◽

pp. 253-259 ◽

Cited By ~ 2

Author(s):

Jacek Międzobrodzki

Keyword(s):

Staphylococcus Aureus ◽

Atopic Dermatitis ◽

Skin Barrier ◽

Skin Lesions ◽

Skin Condition ◽

Staphylococcal Infection ◽

Secondary Infections ◽

Allergic Skin ◽

Atopic Skin ◽

Favorable Conditions

Staphylococcus aureus colonizes the mucous membrane of the nasal vestibule of a significant number of healthy people. These microorganisms are opportunistic pathogens, that in favorable conditions, may cause infections of various course, location or manifestation. Secondary infections emerge in cases when other risk factors contribute to such a change. One of the diseases during which S. aureus changes its saprophytic character to a pathogenic one is atopic dermatitis (AD), an allergic skin condition of a chronic and recurrent nature. Patients with AD are highly predisposed to secondary staphylococcal infections due to active S. aureus colonization of the stratum corneum, damage of the skin barrier or a defective immune response. Microorganisms present in skin lesions destroy the tissue by secreting enzymes and toxins, and additionally stimulate secondary allergic reactions. The toxins secreted by strains of S. aureus also act as superantigens and penetrate the skin barrier contributing to a chronic inflammation of the atopic skin lesions. The S. aureus species also releases proinflammatory proteins, including enzymes that cause tissue damage. When initiating treatment it is particularly important to properly assess that the onset of the secondary bacterial infection is caused by S. aureus and thus justifying the inclusion of antibiotic therapy. Depending on the severity and extent of the staphylococcal infection, topical antibiotics are used, usually mupirocin or fusidic acid, or general antibiotic treatment is introduced. Another therapeutic strategy without antibiotics has given a positive effect in patients.

Download Full-text

Effect of Lactobacillus strains on thymus and chemokine expression in keratinocytes and development of atopic dermatitis-like symptoms

Beneficial Microbes ◽

10.3920/bm2017.0162 ◽

2018 ◽

Vol 9 (4) ◽

pp. 643-652 ◽

Cited By ~ 1

Author(s):

T. Kawahara ◽

N. Hanzawa ◽

M. Sugiyama

Keyword(s):

Atopic Dermatitis ◽

Lactobacillus Reuteri ◽

Human Keratinocytes ◽

Skin Lesions ◽

Suppressive Effect ◽

Water Soluble ◽

Beneficial Effects ◽

Tnf Α ◽

Atopic Skin ◽

Water Soluble Extract

Lactobacillus strains, a major group of lactic acid bacteria, are representative food microorganisms that have many potential beneficial effects via their interactions with immune and intestinal epithelial cells. However, little is known about the effect of Lactobacillus strains on atopic dermatitis via keratinocytes, which comprise the physical barrier of the skin. In this study, we report that Lactobacillus strains have a significant suppressive effect on tumour necrosis factor (TNF)-α-induced expression and production of thymus and activation-regulated chemokine (TARC), a T helper 2 cell chemokine responsible for atopic dermatitis, in human keratinocytes. An RNA interference study showed that the effect of Lactobacillus reuteri strain Japan Collection of Microorganisms (JCM) 1112, the most suppressive strain, depended on the presence of Toll-like receptor 2 and the induction of A20 (also known as TNF-α-induced protein 3) and cylindromatosis in HaCaT cells. Topical application of a water-soluble extract of homogenised JCM 1112 cells significantly suppressed the development of house dust mite-induced atopic skin lesions and TARC expression at the lesion sites in NC/Nga mice. Our study provides new insights into the use of Lactobacillus strains as suppressive agents against keratinocyte-involved atopic inflammation of the skin.

Download Full-text

Staphylococcus aureus and the Cutaneous Microbiota Biofilms in the Pathogenesis of Atopic Dermatitis

Microorganisms ◽

10.3390/microorganisms7090301 ◽

2019 ◽

Vol 7 (9) ◽

pp. 301 ◽

Cited By ~ 4

Author(s):

Enea Gino Di Domenico ◽

Ilaria Cavallo ◽

Bruno Capitanio ◽

Fiorentina Ascenzioni ◽

Fulvia Pimpinelli ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Atopic Dermatitis ◽

Immune Modulation ◽

Skin Lesions ◽

Dominant Mode ◽

Skin Microbiome ◽

Skin Microbiota ◽

Immune Disorder ◽

Close Relationship ◽

Local Immune Modulation

Biofilm is the dominant mode of growth of the skin microbiota, which promotes adhesion and persistence in the cutaneous microenvironment, thus contributing to the epidermal barrier function and local immune modulation. In turn, the local immune microenvironment plays a part in shaping the skin microbiota composition. Atopic dermatitis (AD) is an immune disorder characterized by a marked dysbiosis, with a sharp decline of microbial diversity. During AD flares biofilm-growing Staphylococcus aureus emerges as the major colonizer in the skin lesions, in strict association with disease severity. The chronic production of inflammatory cytokines in the skin of AD individuals concurs at supporting S. aureus biofilm overgrowth at the expense of other microbial commensals, subverting the composition of the healthy skin microbiome. The close relationship between the host and microbial biofilm resident in the skin has profound implications on human health, making skin microbiota an attractive target for the therapeutic management of different skin disorders.

Download Full-text

Malassezia species dysbiosis in natural and allergen-induced atopic dermatitis in dogs

Medical Mycology ◽

10.1093/mmy/myz118 ◽

2019 ◽

Vol 58 (6) ◽

pp. 756-765 ◽

Cited By ~ 1

Author(s):

Courtney Meason-Smith ◽

Thierry Olivry ◽

Sara D Lawhon ◽

Aline Rodrigues Hoffmann

Keyword(s):

Atopic Dermatitis ◽

Its Region ◽

Skin Lesions ◽

Cost Of Care ◽

Skin Lipid ◽

Malassezia Species ◽

Allergic Skin ◽

Culture Independent ◽

Atopic Skin ◽

Species Specific

Abstract Malassezia dermatitis and otitis are recurrent features of canine atopic dermatitis, increasing the cost of care, and contributing to a reduced quality of life for the pet. The exact pathogenesis of secondary yeast infections in allergic dogs remains unclear, but some have proposed an overgrowth of M. pachydermatis to be one of the flare factors. The distribution of Malassezia populations on healthy and allergic canine skin has not been previously investigated using culture-independent methods. Skin swabs were collected from healthy, naturally affected allergic, and experimentally sensitized atopic dogs. From the extracted DNA, fungal next-generations sequencing (NGS) targeting the ITS region with phylogenetic analysis of sequences for species level classification, and Malassezia species-specific quantitative real-time polymerase chain reaction (qPCR) were performed. M. globosa was significantly more abundant on healthy canine skin by both methods (NGS P < .0001, qPCR P < .0001). M. restricta was significantly more abundant on healthy skin by NGS (P = .0023), and M. pachydermatis was significantly more abundant on naturally-affected allergic skin by NGS (P < .0001) and on allergen-induced atopic skin lesions by qPCR (P = .0015). Shifts in Malassezia populations were not observed in correlation with the development of allergen-induced skin lesions. Differences in the lipid dependency of predominant Malassezia commensals between groups suggests a role of the skin lipid content in driving community composition and raises questions of whether targeting skin lipids with therapeutics could promote healthy Malassezia populations on canine skin.

Download Full-text

The Propensity to Form Biofilm in vitro by Staphylococcus aureus Strains Isolated from the Anterior Nares of Patients with Atopic Dermatitis: Clinical Associations

Dermatology ◽

10.1159/000511182 ◽

2020 ◽

pp. 1-7

Author(s):

Leszek Blicharz ◽

Maryla Michalak ◽

Ksenia Szymanek-Majchrzak ◽

Grażyna Młynarczyk ◽

Krzysztof Skowroński ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Atopic Dermatitis ◽

Skin Lesions ◽

Microtiter Plate ◽

Skin Microbiome ◽

Microtiter Plate Assay ◽

Mean Values ◽

Lesional Skin ◽

Inflammatory Dermatosis

Background: Atopic dermatitis is a chronic inflammatory dermatosis with complex pathogenesis. The skin microbiome in atopic dermatitis is dominated by Staphylococcus aureus which shows the ability to produce biofilm. Objectives: The aim of this work was to assess the influence of S. aureus biofilm on the course of atopic dermatitis. Methods: Disease severity was evaluated based on the SCORAD index in 56 adult patients with atopic dermatitis. Microtiter plate assay of the propensity to form biofilm was performed on S. aureus strains isolated from the anterior nares, lesional skin, and nonlesional skin. Microbiological results were correlated to the clinical parameters and total IgE concentration. Results: Biofilm-producing strains of S. aureus were identified in 76.3% (29/38) and 79.1% (34/43) of samples from the anterior nares and lesional skin, respectively (p > 0.05), and in 48.5% (16/33) of samples from nonlesional skin (p < 0.03). Patients colonized by biofilm-producing strains of S. aureus within the anterior nares showed statistically higher mean values of total and objective SCORAD and its components (extent, dryness), and of the largest extent of skin lesions during the flares in the last year when compared to patients colonized by non-biofilm-producing strains. Carriage of biofilm-producing S. aureus on lesional skin was associated with higher mean values of the extent of skin lesions during stable periods of the disease. Conclusions: The results of this study may suggest a relationship between the production of biofilm by S. aureus strains colonizing the anterior nares and the course of atopic dermatitis. Biofilm seems crucial for dispersal and persistent colonization of large areas of the skin by this pathogen. Destruction of S. aureus biofilm could positively affect the course of atopic dermatitis.

Download Full-text

Cheek Microbial Communities Vary in Young Children with Atopic Dermatitis in China

Dermatology ◽

10.1159/000502469 ◽

2019 ◽

Vol 236 (2) ◽

pp. 160-169

Author(s):

Liya Song ◽

Qian Wang ◽

Yumei Zheng ◽

Laiji Ma ◽

Yuanyuan Chen ◽

...

Keyword(s):

Atopic Dermatitis ◽

Biofilm Formation ◽

Klebsiella Oxytoca ◽

Skin Lesions ◽

Skin Condition ◽

Skin Microbiome ◽

Hacat Cells ◽

Bacterial Fermentation ◽

Complex Interactions

Background: Atopic dermatitis (AD) is a chronic, recurrent skin condition with recently increased incidence in younger children. AD development has been correlated with the skin microbiome, and Staphylococcus aureus enrichment causes significant increases in skin lesions. Objective: Our objectives were to compare the microbial diversity of the cheek skin of children with or without AD aged 0–1 years in China, and to determine whether 4 types of skin-isolated bacteria could inhibit S. aureus in vitro. Methods: The skin microbial samples of cheek skin of children were sequenced by 16S rRNA V1-V2 region. Four skin isolated bacterial fermentation supernatants were tested for effects on S. aureus growth, membrane formation, and induction of cytokine secretion from HaCaT cells. Results: Bacterial diversity decreased significantly in skin with severe AD compared to healthy skin (p < 0.01). Seven phyla had content >1%, 4 of which differed in AD (p < 0.05). 38 genera had content >1%, 15 differed (p < 0.05). Differences in 8 species were observed (p < 0.05). In vitro antibacterial and cellular experiments showed that S. aureus growth, biofilm formation, and induction of interleukin (IL)-1α and IL-6 secretion from HaCaT cells were significantly inhibited by Klebsiella oxytoca, Kocuria rhizophila, and Staphylococcus epidermidis culture supernatants (p < 0.05). Conclusion: Skin microbiome changes in children varied with age and with AD. There were complex interactions between skin isolated bacteria and S. aureus which could inhibit S. aureus growth and biofilm formation in vitro, suggesting that these microorganisms could be used in AD treatment.

Download Full-text

Suppression of DNCB-Induced Atopic Skin Lesions in Mice by Wikstroemia indica Extract

Nutrients ◽

10.3390/nu12010173 ◽

2020 ◽

Vol 12 (1) ◽

pp. 173 ◽

Cited By ~ 3

Author(s):

So-Yeon Lee ◽

No-June Park ◽

Jonghwan Jegal ◽

Beom-Geun Jo ◽

Sangho Choi ◽

...

Keyword(s):

Atopic Dermatitis ◽

Chinese Medicine ◽

Inflammatory Diseases ◽

Ethanolic Extract ◽

Skin Lesions ◽

Transepidermal Water Loss ◽

Hairless Mice ◽

Cutaneous Inflammation ◽

Atopic Skin ◽

Dermal Administration

Wikstroemia indica (L.) C.A. Mey. is used in traditional Chinese medicine to treat inflammatory diseases such as arthritis and bronchitis. In this study, we aimed to investigate the effects of an ethanolic extract of W. indica on cutaneous inflammation in mice with 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD). Dermal administration of W. indica ethanolic extract to DNCB-sensitized hairless mice with dermatitis, for two weeks, reduced erythema, scaling, and edema. Skin hydration was improved and transepidermal water loss was reduced at a W. indica concentration of 1%. Furthermore, W. indica also significantly reduced serum IgE and IL-4 concentrations in our mouse model. These results suggest that W. indica has potential as a topical treatment for AD and as an adjunctive agent to control AD.

Download Full-text