Shifts in the Skin Microbiota after UVB Treatment in Adult Atopic Dermatitis.

BACKGROUND: The pathophysiology in atopic dermatitis (AD) is not fully understood, but immune dysfunction, skin barrier defects, and alterations of the skin microbiota are thought to play important roles. AD skin is frequently colonized with Staphylococcus aureus (S. aureus) and microbial diversity on lesional skin (LS) is reduced compared to on healthy skin. Treatment with narrow-band ultraviolet B (nb-UVB) leads to clinical improvement of the eczema and reduced abundance of S. aureus. However, in-depth knowledge of the temporal dynamics of the skin microbiota in AD in response to nb-UVB treatment is lacking and could provide important clues to decipher whether the microbial changes are primary drivers of the disease, or secondary to the inflammatory process. OBJECTIVES: To map the temporal shifts in the microbiota of the skin, nose, and throat in adult AD patients after nb-UVB treatment. METHODS: Skin swabs were taken from lesional AD skin (n = 16) before and after 3 treatments of nb-UVB, and after 6-8 weeks of full-body treatment. We also obtained samples from non-lesional skin (NLS) and from the nose and throat. All samples were characterized by 16S rRNA gene sequencing. RESULTS: We observed shifts towards higher diversity in the microbiota of lesional AD skin after 6-8 weeks of treatment, while the microbiota of NLS and of the nose/throat remained unchanged. After only 3 treatments with nb-UVB, there were no significant changes in the microbiota. CONCLUSION: Nb-UVB induces changes in the skin microbiota towards higher diversity, but the microbiota of the nose and throat are not altered.

Gardenia Jasminoides Ameliorates Antibiotic-Associated Aggravation of DNCB-Induced Atopic Dermatitis by Restoring the Intestinal Microbiome Profile.

The intestinal microbiome is considered one of the key regulators of health. Accordingly, the severity of atopic dermatitis (AD) is mediated by the skin and intestinal microbiome environment. In this study, while evaluating the aggravation in AD symptoms by the antibiotics cocktail (ABX)-induced depletion of the intestinal microbiome, we sought to verify the effect of Gardenia jasminoides (GJ), a medicinal herb used for inflammatory diseases, on AD regarding its role on the intestinal microbiome. To verify the aggravation in AD symptoms induced by the depletion of the intestinal microbiome, we established a novel mouse model by administrating an ABX to create a microbiome-free environment in the intestine, and then applied 2,4-dinitrochlorobenzene (DNCB) to induce an AD-like skin inflammatory response. While ABX treatment aggravated AD-like symptoms, the 2-week administration of GJ improved these pathological changes. DNCB application upregulated immune cell count and serum cytokine expression, which were alleviated by GJ. Moreover, pathological alterations by antibiotics and DNCB, including histological damage of the intestine and the intestinal expression of IL-17, were recovered in GJ-treated mice. The beneficial effect of GJ was due to the restoration of the intestinal microbiome composition. Overall, we suggest GJ as a potential therapeutic agent for AD due to its regulation of the intestinal microbiome.

Hippophae rhamnoides mediate gene expression profiles against keratinocytes infection of Staphylococcus aureus.

Staphylococcus aureus causes a wide range of skin diseases such as bacterial keratitis, follicles, psoriasis, cellulitis and atopic dermatitis. This study aims to investigate the S. aureus mediated molecular modulation, and the effect of HR in reversing the deleterious impact of S. aureus in keratinocytes. Human keratinocyte (HaCaT) cells were cultured in DMEM, supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin. Subcultures were divided into three flasks: control with no S. aureus and extract (C), S. aureus infected (SA) and S. aureus infected cells and extract (SE). RNA was isolated and microarray analysis was performed. The data was annotated using GO functional analysis and DAVID functional annotation. For each comparison group, significant probes were filtered out at significant cut off by fold change (P < 0.05 and/or > twofold change). For SA vs control, SE vs control, and SE vs SA, 204, 9369, 9900 probes were filtered respectively. In SA vs control, TNF signaling, NOD-like receptor and chemokine receptor signaling pathways were upregulated with key genes such as CCL2, CCL20 and BIRC3. The SE vs SA, showed significant expression variations of a number of important genes. Molecular pathways associated with ILs, TNFs, TGFs, IFNs, FGFs, MAPKs, MMPs, caspases and Wnts were either up regulated or downregulated. This effect was reversed by the extract, possibly through downregulating various proinflammatory cytokines and apoptotic pathways. Our study reveals that S. aureus inserts a negative impact on the regulation of various key genes which is apparently reversed by the HR extract.

Atopic Dermatitis and the Role of the Skin Microbiome in Choosing Prevention, Treatment, and Maintenance Options.

BACKGROUND: Atopic dermatitis (AD) is a common skin condition characterized by disturbed barrier function, skin inflammation, and cutaneous dysbiosis. Clinically, it manifests as chronic-recurrent xerosis, pruritus, and erythematous lesions. Its pathophysiology is complex, making the selection of appropriate treatment options a task. AIM: To share insights gained from a literature review and discussions with experts in dermatology on key factors related to the prevention, treatment, and management of AD in relation to the skin microbiome. METHODS: Results from an expert panel were summarized and discussed to provide updated recommendations for the treatment and maintenance of AD. RESULTS: Evidence supports a strategy for managing inflammatory skin diseases with a selenium-rich post-biotic thermal water and biomass containing moisturizer. The moisturizer helps to restore homeostasis of the skin, re-populate a diverse microbiome, encourage the growth of commensal bacteria, and improve barrier function and symptoms of AD. CONCLUSIONS: Normalization of skin microbiome diversity using a topical moisturizer containing post-biotic aqua and biomass may offer a valuable option for the treatment and maintenance of inflammatory skin diseases. Clinicians should discuss the benefits of this treatment in the context of a full AD management program that covers prevention, active treatment, and maintenance. J Drugs Dermatol. 2020;19(10):935-940. doi:10.36849/JDD.2020.5393.

Galectin-9 Induced by Dietary Prebiotics Regulates Immunomodulation to Reduce Atopic Dermatitis Symptoms in 1-Chloro-2,4-Dinitrobenzene (DNCB)-Treated NC/Nga Mice.

Atopic dermatitis (AD) is a skin disorder that causes chronic itch. We investigated the inhibitory effects of a mixture of prebiotic short-chain galacto-oligosaccharides and long-chain fructooligosaccharides (scGOS/lcFOS), inulin, or ß-glucan on AD development in 1-chloro-2,4- dinitrobenzene (DNCB)-treated NC/Nga mice. Mice were randomly assigned to six groups: untreated mice, AD control, positive control (DNCB-treated NC/Nga mice fed a dietary supplement of Zyrtec), and DNCB-treated NC/Nga mice fed a dietary supplement of prebiotics such as scGOS/lcFOS (T1), inulin (T2), or ß-glucan (T3). The prebiotic treatment groups (T1, T2, and T3) showed suppression of AD symptoms, Th2 cell differentiation, and AD-like skin lesions induced by DNCB. In addition, prebiotic treatment also reduced the number of microorganisms such as Firmicutes, which is associated with AD symptoms, and increased the levels of Bacteroidetes and Ruminococcaceae, which are associated with alleviation of AD symptoms. Our findings demonstrate the inhibitory effects of prebiotics on AD development by improving the Th1/Th2 cytokine balance and beneficial symbiotic microorganisms in in vitro and in vivo models.

Reduced Fecal Calprotectin and Inflammation in a Murine Model of Atopic Dermatitis Following Probiotic Treatment.

Atopic dermatitis (AD) is one of the most common skin diseases with inflammation, chronic relapses, and intense pruritus. Its pathogenesis includes genetic susceptibility, an abnormal epidermal lipid barrier, and an increased production of IgE due to immune dysregulation. Recently, AD has been reported to be associated with intestinal inflammation and dysbiosis in human and murine models. Various probiotics are being used to control intestinal dysbiosis and inflammatory reactions. However, it is difficult to predict or determine the therapeutic effects of the probiotics, since it is rare for clinicians to use the probiotics alone to treat AD. It is also difficult to check whether the intestinal inflammation in patients with AD has improved since probiotic treatment. The aim of the present study was to determine whether mice with induced atopic dermatitis had any changes in fecal calprotectin, an indicator of intestinal inflammation, after probiotic administration. Our results showed that the fecal calprotectin levels in mice with induced dermatitis decreased significantly after the administration of probiotics. In addition, epidermal skin lesions were attenuated and inflammatory-related cytokines were downregulated after the administration of probiotics in mice with induced dermatitis. These results suggest that changes in fecal calprotectin levels could be used to assess the effectiveness of a probiotic strain as an adjuvant treatment for AD.

The clinical impact of cross-reactions between allergens on allergic skin diseases.

PURPOSE OF REVIEW: The route of allergen sensing via the skin appears to influence the immune system towards mounting a type 2 response, especially in genetically predisposed individuals. Allergens recognized this way may derive from microbial, animal, food, or other plant sources and trigger atopic dermatitis. Allergens can be grouped into families depending on their structure and function, harboring significant structural and sequence similarities. Cross-reactivity between allergens is believed to arise as a consequence, and to underlie the development of further atopic diseases. RECENT FINDINGS: Especially for the plant allergens of the families of PR10-related proteins and profilins, immune cross-reactions have been described. Actual studies support that food and pollen allergens can aggravate skin lesions in patients suffering from atopic dermatitis. Further on, allergens derived from air-borne or skin-borne fungi belong to common allergen families and bear cross-reactivity potential. Cross-reactivity to human homologous proteins, so-called autoallergens, is discussed to contribute to the chronification of atopic dermatitis. SUMMARY: Due to high evolutionary conservation, allergic reactions can be triggered by highly homologous members of allergen families on the humoral as well as on the cellular level.

Prevention of Atopic Dermatitis.

Despite advances in atopic dermatitis (AD) treatments, research into AD prevention has been slow. Systematic reviews of prevention strategies promoting exclusive and prolonged breastfeeding, or interventions that reduce ingested or airborne allergens during pregnancy and after birth have generally not shown convincing benefit. Maternal/infant supplements such as Vitamin D have also not shown any benefit with the possible exception of omega-3 fatty acids. Systematic reviews suggest that probiotics could reduce AD incidence by around 20%, although the studies are quite variable and might benefit from individual patient data meta-analysis. Skin barrier enhancement from birth to prevent AD and food allergy has received recent interest, and results from national trials are awaited. It is possible that trying to influence major immunological changes that characterise AD at birth through infant-directed interventions may be too late, and more attention might be directed at fetal programming in utero.

Staphylococcus aureus in Atopic Dermatitis: Past, Present, and Future.

: The role of Staphylococcus aureus (SA) in the pathogenesis and management in atopic dermatitis is rapidly evolving. The modern understanding of SA in atopic dermatitis now includes an expanded array of virulence factors, the interplay of clonal and temporal shifts in SA populations, and host factors such as filaggrin and natural moisturizing factor. New, emerging therapies that focus on long-term, targeted elimination of SA colonization are currently under investigation (Br J Dermatol 2017;17(1)63-71). Herein, we discuss and review the latest staphylococcal and microbiome-modifying therapies including topical antibiotics, topical natural oil fatty acids, anti-SA vaccines, microbial transplantation, vitamin D supplementation, dupilumab and proposed future investigative directions.

Topical ozone therapy restores microbiome diversity in atopic dermatitis.

BACKGROUND: Staphylococcus aureus (S. aureus) accounts for 90% of the microbiome in atopic dermatitis (AD) lesions and plays a role in disease flare-ups and worsens disease outcome. Ozone treatment can improve AD conditions by its bactericidal effect on S. aureus. OBJECTIVE: To study the effects of topical ozone therapy on microbiome diversity in AD lesions and explore potential probiotic pathogens correlated with AD progression. METHODS: Patients with moderate to severe bilateral skin lesions in AD were recruited. Randomized split sides were performed. One side was treated with ozone hydrotherapy followed by ozonated oil; while the contralateral side with tap water and basal oil. Patients' SCORAD scores and modified EASI were recorded before and after treatments. The microbiological compositions in targeting sites were determined using 16S rDNA sequencing. RESULTS: After three-day ozone therapy, patients showed a significant decrease in SCORAD scores and inflammatory cell infiltration in AD lesions. The micro-ecological diversity was higher in the non-lesional as compared with lesional areas (p < 0.05), which was also negatively correlated with the severity of AD (r = -0.499, p < 0.05). The proportion of S. aureus in AD lesions was positively correlated with the severity of AD (r = 0.564, p = 0.010), which was decreased after ozone treatment (p = 0.07). Ozone therapy showed an increase in microbiological diversity with a significant increase in the proportion of Acinetobacter (p < 0.05). CONCLUSION: Topical ozone therapy is highly effective for treatment for AD. It can change the proportional ratio of Staphylococcus and Acinetobacter, thereby restoring the microbiological diversity in AD lesions.

Effects of 308 nm excimer light treatment on the skin microbiome of atopic dermatitis patients.

BACKGROUND: The skin microbiome has been implicated in the pathophysiology of atopic dermatitis (AD). Although 308 nm excimer light treatment is an effective phototherapy for AD, its effects on the skin microbiome currently remain unclear. Therefore, we investigated the effects of the excimer light treatment on the skin bacterial and fungal microbiome of lesional skin of AD. METHODS: Swab samples were collected from 11 healthy controls, non-lesional and lesional skin of 11 AD patients. The excimer light treatment was administered to the lesional skin. The composition of the skin microbiome, the clinical score and skin barrier function of the lesional skin were examined before and after the treatment. The composition of the skin microbiome was determined by sequencing bacterial 16S and fungal internal transcribed spacer regions. RESULTS: The excimer light treatment significantly changed the composition of the bacterial microbiome in the lesional skin of AD, as well as improved the clinical score and skin barrier function. The treatment increased the relative abundance of the phylum Cyanobacteria and decreased that of the phylum Bacteroidetes in lesional skin. At the species level, the treatment significantly decreased the relative abundance of Staphylococcus aureus (S aureus) in lesional skin. There was also a significant correlation between the reduction of S aureus and improvement of the clinical outcomes. CONCLUSION: Our findings suggest that alterations of the skin microbiome with excimer light treatment, specifically the decrease in the abundance of S aureus, are partly involved in the improvement of AD lesions.

Postbiotics and Their Potential Applications in Early Life Nutrition and Beyond.

Postbiotics are functional bioactive compounds, generated in a matrix during fermentation, which may be used to promote health. The term postbiotics can be regarded as an umbrella term for all synonyms and related terms of these microbial fermentation components. Therefore, postbiotics can include many different constituents including metabolites, short-chain fatty acids (SCFAs), microbial cell fractions, functional proteins, extracellular polysaccharides (EPS), cell lysates, teichoic acid, peptidoglycan-derived muropeptides and pili-type structures. Postbiotics is also a rather new term in the '-biotics' field. Where consensus exists for the definitions of pre- and probiotics, this is not yet the case for postbiotics. Here we propose a working definition and review currently known postbiotic compounds, their proposed mechanisms, clinical evidence and potential applications. Research to date indicates that postbiotics can have direct immunomodulatory and clinically relevant effects and evidence can be found for the use of postbiotics in healthy individuals to improve overall health and to relief symptoms in a range of diseases such as infant colic and in adults atopic dermatitis and different causes of diarrhea.

The Microbiome and Atopic Dermatitis: A Review.

The microbiome is defined as the sum of microbes, their genomes, and interactions in a given ecological niche. Atopic dermatitis is a multifactorial chronic inflammatory skin disease leading to dryness and itchiness of the skin. It is often associated with comorbidities such as allergic rhinoconjunctivitis and asthma. Today, culture-free techniques have been established to define microbes and their genomes that may be both detrimental and beneficial for their host. There are signs that microbes, both on skin and in the gut, may influence the course of atopic dermatitis. Antiseptic treatment has been used for decades, however now, with the help of traditional culture-based methods and modern metagenomics, we are beginning to understand that targeted treatment of dysbiosis may possibly become part of an integrated therapy plan in the future.

Skin bacterial transplant in atopic dermatitis: Knowns, unknowns and emerging trends.

Dysbiosis is a key pathogenic factor in the cycle of skin barrier impairment and inflammation in atopic dermatitis (AD). Skin microbial composition in AD is characterized by increased presence of Staphylococcus aureus (S. aureus) and decrease in microbial diversity and commensal bacterial species. Attenuation of S. aureus-driven inflammation aids in breaking the itch-scratch cycle via modulation of the cutaneous immune response. Skin bacterial transplant (SBT), a form of bacteriotherapy, is an intriguing treatment modality for restoration of a healthy skin microbiome in AD patients. Studies on the effects of topically-applied bacterial products, probiotics and SBT have yielded promising results in animal models and human studies of AD. This review discusses the rationale and evidence for SBT in AD and outlines future investigative directions for the clinical application of microbiome restoration in dermatology.

Staphylococcus aureus antibiotic susceptibility patterns in pediatric atopic dermatitis.

BACKGROUND/OBJECTIVES: Staphylococcus aureus is the most prevalent bacterial pathogen in atopic dermatitis (AD) patients presenting with skin infections. Despite the known association between S aureus and AD, guidance on empiric antibiotics for skin infections in pediatric AD patients is limited. METHODS: We conducted a retrospective study over a five-year period to characterize the S aureus strains recovered from pediatric AD patients with clinically apparent bacterial skin infections treated in an academic medical center. We assessed patient demographics and dilute bleach bath usage to determine whether these factors were correlated with methicillin resistance. Culture results from our AD cohort were also compared to those from pediatric patients presenting to the Saint Louis Children's Hospital emergency department (ED) with S aureus skin abscesses from 2013 to 2015. RESULTS: Methicillin-sensitive S aureus (MSSA) was more prevalent (77.8%) than methicillin-resistant S aureus (MRSA) (22.2%). There was no correlation between MRSA and age, sex, race, or dilute bleach bath use. In comparison with pediatric patients presenting to the ED, AD patients had lower rates of MSSA susceptibility to doxycycline and MRSA susceptibility to trimethoprim-sulfamethoxazole (TMP-SMX). CONCLUSIONS: First-generation cephalosporins remain appropriate empiric therapy for most pediatric AD patients. In patients with a history of MRSA, empiric doxycycline or TMP-SMX could be considered, given their high MRSA susceptibility rates.

Skin Microbiome Compositional Changes in Atopic Dermatitis Accompany Dead Sea Climatotherapy.

Dead Sea climatotherapy (DSC) is a well-established therapeutic modality for the treatment of several diseases, including atopic dermatitis. Skin microbiome studies have shown that skin microbiome diversity is anticorrelated with both atopic dermatitis severity and concurrent Staphylococcus aureus overgrowth. This study aimed to determine whether DSC induces skin microbiome changes concurrent with clinical improvements in atopic dermatitis. We sampled 35 atopic dermatitis patients and ten healthy controls on both the antecubital and popliteal fossa. High-resolution microbial community profiling was attained by sequencing multiple regions of the 16S rRNA gene. Dysbiosis was observed in both lesional and nonlesional sites, which was partially attenuated following treatment. Severe AD skin underwent the most significant community shifts, and Staphylococcus epidermidis, Streptococcus mitis and Micrococcus luteus relative abundance were significantly affected by Dead Sea climatotherapy. Our study highlights the temporal shifts of the AD skin microbiome induced by Dead Sea climatotherapy and offers potential explanations for the success of climatotherapy on a variety of skin diseases, including AD.

Microbiosis in pathogenesis and intervention of atopic dermatitis.

Atopic dermatitis (AD) is a chronic, non-contagious, inflammatory skin disorder characterized by relapsing eczematous lesions. Its pathogenesis remains incompletely understood. The current evidence has emerged to show that skin and gut microbiome play critical roles in the pathogenesis and progression of AD. Skin mircrobiome mainly refers to skin commensal organisms that promote normal immune system functions and prevent the colonization of pathogens; while gut microbiome can modulate immunologic, metabolic and neuroendocrine functions. With the current knowledge of microbiome effects on the onset of the disease, there are evolving multifarious interventions targeting microbiome for the treatment of AD. In this report, we have reviewed the critical roles of microbiosis in the pathogenesis of AD, summarized potential mechanisms mediated by microbiosis and aimed to enlighten a theoretical basis for its therapeutic applications in the treatment of AD.

Changes in Lesional and Non-lesional Skin Microbiome During Treatment of Atopic Dermatitis.

The aim of this study was to evaluate changes in the skin surface microbiome in patients with atopic dermatitis during treatment. The effect of narrowband ultraviolet B phototherapy was also studied to determine the influence of exposure to ultraviolet. A total of 18 patients with atopic dermatitis were included in the study. Patients were divided into 2 groups based on treatment: 1 group treated with narrowband ultraviolet B phototherapy and topical corticosteroid, and the other group treated with topical corticosteroid only. Skin swabs and high-throughput sequencing of 16S ribosomal RNA bacterial genes were performed at 3 time-points. The microbial diversity of lesional skin increased greatly after treatment. The proportion of Staphylococcus aureus showed a significant positive correlation with eczema severity. In conclusion, a drastic increase in microbial diversity and decrease in S. aureus proportion were observed with eczema treatment. Narrowband ultraviolet B treatment did not exert additive effects on eczema improvement; however, it appeared to reduce the recurrence of eczema.

Eczema-protective probiotic alters infant gut microbiome functional capacity but not composition: sub-sample analysis from a RCT.

Probiotic Lactobacillus rhamnosus HN001 given in early life has been shown to reduce infant eczema risk, but its effect on gut microbiota development has not been quantitatively and functionally examined. The aim of this study was to investigate the impact of early life probiotic exposure on the composition and functional capacity of infant gut microbiota from birth to 2 years considering the effects of age, delivery mode, antibiotics, pets and eczema. We performed shotgun metagenomic sequencing analysis of 650 infant faecal samples, collected at birth, 3, 12, and 24 months, as part of a randomised, controlled, 3-arm trial assessing the effect of L. rhamnosus HN001, Bifidobacterium animalis subsp. lactis HN019 supplementation on eczema development in 474 infants. There was a 50% reduced eczema risk in the HN001 probiotic group compared to placebo. Both mothers (from 35 weeks gestation until 6 months post-partum if breastfeeding) and infants (from birth to 2 years) received either a placebo or one of two probiotics, L. rhamnosus HN001 (6×109 cfu), or B. animalis subsp. lactis HN019 (9×109 cfu). L. rhamnosus HN001 probiotic supplementation was associated with increased overall glycerol-3 phosphate transport capacity and enrichment of L. rhamnosus. There were no other significant changes in infant gut microbiota composition or diversity. Increased capacity to transport glycerol-3-phosphate was positively correlated with relative abundance of L. rhamnosus. Children who developed eczema had gut microbiota with increased capacity for glycosaminoglycan degradation and flagellum assembly but had no significant differences in microbiota composition or diversity. Early life HN001 probiotic use is associated with both increased L. rhamnosus and increased infant gut microbiota functional capacity to transport glycerol-3 phosphate. The mechanistic relationship of such functional alteration in gut microbiota with reduced eczema risk and long-term health merits further investigation.

The atopic dermatitis-like lesion and the associated MRSA infection and barrier dysfunction can be alleviated by 2,4-dimethoxy-6-methylbenzene-1,3-diol from Antrodia camphorata.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disease with an associated barrier dysfunction and Staphylococcus aureus infection. The mainstay steroid and calcineurin inhibitor therapy shows some adverse effects. 2,4-Dimethoxy-6-methylbenzene-1,3-diol (DMD) is a benzenoid isolated from Antrodia camphorata. OBJECTIVE: We investigated the inhibitory effect of DMD on methicillin-resistant S. aureus (MRSA), the chemokine production in stimulated keratinocytes, and the AD-like lesion found in ovalbumin (OVA)-sensitized mice. METHODS: The antimicrobial effect and cutaneous barrier function were evaluated using an in vitro culture model and an in vivo mouse model of AD-like skin. RESULTS: DMD exhibited a comparative minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against MRSA with nalidixic acid, a conventional antibiotic. The MIC and MBC for DMD was 78.1 and 156.3 µg/ml, respectively. DMD also showed the ability to eliminate the clinical bacteria isolates with resistance to methicillin and vancomycin. The DNA polymerase and gyrase inhibition evoked by DMD for bacterial lethality was proposed. In the activated keratinocytes, DMD stopped the upregulation of chemokines (CCL5 and CCL17) and increased the expression of differentiation proteins (filaggrin, involucrin, and integrin ß-1). Topical application of DMD facilely penetrated into the skin, with AD-like skin displaying 2.5-fold greater permeation than healthy skin. The in vivo assessment using the mouse model with OVA sensitization and MRSA inoculation revealed a reduction of transepidermal water loss (TEWL) and bacterial burden by DMD by about 2- and 100-fold, respectively. Differentiation proteins were also restored after topical DMD delivery. CONCLUSION: Our data demonstrated an advanced concept of AD treatment by combined barrier repair and bacterial eradication with a sole agent for ameliorating the overall complications.