Skin Microbiome In Atopic Dermatitis Research Articles

The extracellular serine protease from Staphylococcus epidermidis elicits a type 2-biased immune response in atopic dermatitis patients.

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease with skin barrier defects and a misdirected type 2 immune response against harmless antigens. The skin microbiome in AD is characterized by a reduction in microbial diversity with a dominance of staphylococci, including Staphylococcus epidermidis (S. epidermidis). To assess whether S. epidermidis antigens play a role in AD, we screened for candidate allergens and studied the T cell and humoral immune response against the extracellular serine protease (Esp). To identify candidate allergens, we analyzed the binding of human serum IgG4, as a surrogate of IgE, to S. epidermidis extracellular proteins using 2-dimensional immunoblotting and mass spectrometry. We then measured serum IgE and IgG1 binding to recombinant Esp by ELISA in healthy and AD individuals. We also stimulated T cells from AD patients and control subjects with Esp and measured the secreted cytokines. Finally, we analyzed the proteolytic activity of Esp against IL-33 and determined the cleavage sites by mass spectrometry. We identified Esp as the dominant candidate allergen of S. epidermidis. Esp-specific IgE was present in human serum; AD patients had higher concentrations than controls. T cells reacting to Esp were detectable in both AD patients and healthy controls. The T cell response in healthy adults was characterized by IL-17, IL-22, IFN-γ, and IL-10, whereas the AD patients' T cells lacked IL-17 production and released only low amounts of IL-22, IFN-γ, and IL-10. In contrast, Th2 cytokine release was higher in T cells from AD patients than from healthy controls. Mature Esp cleaved and activated the alarmin IL-33. The extracellular serine protease Esp of S. epidermidis can activate IL-33. As an antigen, Esp elicits a type 2-biased antibody and T cell response in AD patients. This suggests that S. epidermidis can aggravate AD through the allergenic properties of Esp.

Neutralizing Interleukin-13 with Tralokinumab Reduces Abundance of S. aureus in Adolescents with Atopic Dermatitis

Patients with atopic dermatitis (AD) are frequently colonized with high levels of S. aureus. Dysregulation of the skin microbiome in AD is influenced by epidermal barrier disruption and type 2 inflammation. Tralokinumab is a high-affinity, monoclonal antibody that targets IL-13, a key driver of type 2 inflammation. We assessed S. aureus abundance in lesional and non-lesional skin and evaluated the effects of tralokinumab on S. aureus abundance in adolescents with moderate-to-severe AD (ECZTRA 6, NCT03526861). 301 adolescents (aged 12-17 years) were randomized to receive tralokinumab 150mg or 300mg SQ every 2 weeks, or placebo. Skin swabs collected from lesional and non-lesional skin at baseline and Week 16 were assessed for S. aureus abundance by femA qPCR. Differences in percentage of S. aureus+ (SA+; defined as >1.07 gene copies/cm2) patients among the groups were assessed using a logistic regression model adjusting for baseline SA status and rescue use (any TCI, TCS, or systemic treatment). From baseline to Week 16, the percentage of patients with SA+ lesional skin was reduced from 83.5% to 41.0% with tralokinumab 150 mg and from 84.3% to 41.9% with tralokinumab 300 mg compared to 85.2% to 78.3% with placebo (difference vs placebo 150mg/300mg: -41.0/-39.6; P<0.001). The percentage of patients with SA+ non-lesional skin was reduced from 78.7% to 34.6% with tralokinumab 150 mg and from 72.2% to 42.4% with tralokinumab 300 mg compared to 74.4% to 68.8% with placebo (difference vs placebo 150mg/300mg: -37.0/-26.1; P≤0.001) from baseline to Week 16. These data support the targeting of IL-13 in improving AD-associated dysbiosis in adolescents.

LB1740 Role of host epigenetics with skin microbiome in atopic dermatitis

LB1740 Role of host epigenetics with skin microbiome in atopic dermatitis

Skin microbiome in atopic dermatitis: New insights from clinical trials.

Atopic dermatitis (AD) is a chronic skin inflammatory disorder, with extensive burden among both children and adults.1 Recent advances in mechanistic understanding of underlying inflammatory pathways associated with AD phenotypes have resulted in improved options for topical and systemic treatment,2 with efficacy of monotherapies (e.g. abrocitinib, baricitinib, dupilumab, lebrikizumab, nemolizumab, tralokinumab, upadacitinib) ranging from 56.7% to 83.6%.3 Progression of AD is influenced by a combination of genetic, environmental and microbial covariates, and several studies have demonstrated the potential role of skin resident microbial flora (especially the bacterium Staphylococcus aureus) in AD,4 which may also impact response to therapy. Pertinent to this topic, Rauer et al.5 present their results from microbiome analysis of skin samples collected from patients with AD in the current issue of The Journal of the European Academy of Dermatology and Venereology. The authors analyzed baseline demographic and microbiome data from 60 moderate-to-severe AD patients from a previously reported cohort in New York, USA, to investigate correlation between disease severity and composition of the skin microbiome. Skin microbiome was sampled by swabbing lesional and adjacent non-lesional skin, and characterized by sequencing hypervariable regions V1–V3 of the 16S rRNA gene. Severity of AD was determined using SCORAD (SCORing Atopic Dermatitis), the validated clinical tool used to assess the extent and severity of eczema. Rauer et al. used objective SCORAD (oSCORAD, which considers only extent and intensity of AD) to determine correlation of AD severity with microbiome. These authors reported the skin microbiome of AD patients was dominated by S. aureus, which was detected in 79% of samples and was the most abundant species in 49% of lesional and 28% of non-lesional samples. Interestingly, diversity of skin microbiome correlated with oSCORAD, with lower diversity in lesional skin compared to non-lesional skin. High AD severity was associated with low evenness (a key determinant of microbiome composition), independent of skin sampling location. These results indicate dysbiosis in the microbiome population in lesional skin. Moreover, these authors identified S. aureus as a major contributor to association of microbiome diversity with AD severity and AD-affected skin sites. Among clinical variables, ethnicity was found to be an important covariate in the association between AD severity and skin microbiome. However, given the small sample size for sub-group analysis in the study, the contribution of ethnicity to skin microbiome and AD severity warrants further investigation. While elevated levels of S. aureus in the skin microbiome of AD patients have previously been reported,4 the study by Rauer et al.5 underscores the clinical relevance of this association as the samples were collected from patients at baseline of a well-designed clinical trial. Further analysis of skin microbiome during the progression of disease is likely to shed important insight into the interplay between changes in microbial composition and response to therapy. Given these interesting findings, a reasonable next step could be inclusion of skin microbiome sampling into clinical trials as exploratory endpoints in future clinical trials of AD. This would allow assessment if the identified microbial changes are linked with patient outcomes or medication response in a controlled setting. Ultimately this may then allow patient stratification based on microbial composition. Expanding those findings beyond the microbiome, such as targeting skin fungal mycobiome or virome may also reveal new insights into the contribution of microbial populations in AD. An important clinical implication of these results is that abundance of S. aureus may be used as a surrogate for skin microbial dysbiosis, especially since this organism may be more easily measured in a clinical setting using quantitative PCR rather than complete or complex microbiome analysis. Sequencing results can subsequently be obtained to analyze the microbiome, and used as a validation tool. The current study by Rauer et al.5 highlights key relationships between the skin microbiome and severity of AD, and will greatly inform ongoing efforts to develop new personalized therapeutic options for this disease. The authors have no conflicts of interest to declare. Data sharing is not applicable to this article as no new data were created or analyzed in this study.

The Intestinal and Skin Microbiome in Patients with Atopic Dermatitis and Their Influence on the Course of the Disease: A Literature Review

Bacteria inhabiting the digestive tract are responsible for our health. The microbiome is essential for the development of the immune system and homeostasis of the body. Maintaining homeostasis is very important, but also extremely complicated. The gut microbiome is related to the skin microbiome. It can therefore be assumed that changes in the microbes inhabiting the skin are greatly influenced by the bacteria living in the intestines. Changes in the composition and function of microbes (dysbiosis in the skin and intestines) have recently been linked to changes in the immune response and the development of skin diseases, including atopic dermatitis (AD). This review was compiled by collaborating Dermatologists specializing in atopic dermatitis and psoriasis. A comprehensive review of the current literature was performed using PubMed and limited to relevant case reports and original papers on the skin microbiome in atopic dermatitis. The inclusion criterion was that the paper was published in a peer-reviewed journal in the last 10 years (2012-2022). No limitations on the language of the publication or the type of study were made. It has been shown that any rapid changes in the composition of the microflora may be associated with the appearance of clinical signs and symptoms of the disease. Various studies have proven that the microbiome of many systems (including the intestines) may have a significant impact on the development of the inflammatory process within the skin in the course of AD. It has been shown that an early interaction between the microbiome and immune system may result in a noticeable delay in the onset of atopic diseases. It seems to be of high importance for physicians to understand the role of the microbiome in AD, not only from the pathophysiological standpoint but also in terms of the complex treatment that is required. Perhaps young children diagnosed with AD present specific characteristics of the intestinal microflora. This might be related to the early introduction of antibiotics and dietary manipulations in breastfeeding mothers in the early childhood of AD patients. It is most likely related to the abuse of antibiotics from the first days of life.

Altered Maturation of the Skin Microbiome in Infants with Atopic Dermatitis.

The aim of this study was to investigate the early-life development of the skin microbiome in atopic dermatitis. Nineteen infants with atopic dermatitis and 19 healthy infants were evaluated 3 times, at 3 months intervals, within the first 30 months of life. Tape-strips were collected from volar forearms, cheeks, and eczema lesions, and the skin microbiome was assessed by 16S rRNA sequencing. Both the community structure and richness of the skin microbiome of infants with atopic dermatitis differed significantly from that of healthy infants, with greater richness in healthy infants. For infants with atopic dermatitis, the community composition was not dominated by Staphylococci. For healthy infants, community composition and richness correlated significantly with age, while such a pattern was not revealed in infants with atopic dermatitis. This suggests a slower maturation of the skin microbiome in atopic dermatitis, which precedes the staphylococcal predominance observed in older children and adults.

The role of the skin microbiome in atopic dermatitis - correlations and consequences.

The physical barrier function of the skin is significantly supported by the (epi-)dermal immune system and the skin's own microbiome. Atopic dermatitis is characterized by an imbalance of all these three factors. The skin microbiome establishes itself immediately after birth and plays an important role in the development and maintenance of immune homeostasis. The clinical picture of atopic dermatitis shows, among other things, changes in the skin microbiome. Particularly during an acute phase, a strongly reduced bacterial diversity as well as the dominance of a single pathogen, Staphylococcus aureus, is observed. Staphylococcus aureus exacerbates the inflammatory process; furthermore, the bacteria produce proteases and toxins that further weaken the already severely compromised barrier function of the skin of patients with atopic dermatitis. However, knowledge of dermal dysbiosis also yields new treatment options for the therapy of the disease. In particular, the application of active bacteria represents a direct influence on the skin microbiome. Results of initial clinical studies on various approaches demonstrate promising results; this article provides an overview of work in this area.

Disorders of the skin microbiome in atopic dermatitis and psoriasis

The notion of skin microbiome encompasses a heterogeneous group of microorganisms that belong to various taxonomic units, such as bacteria, archaea, viruses, and fungi. The impact of these microbial community constituents upon the epidermal barrier condition, and upon the immune system functioning, is being intensely scrutinized. There is a particular interest in studying the role that the microorganisms of genus Staphylococcus spp. play in the course of physiological and pathological processes occurring in the skin. This review examines in detail the interaction of the microorganisms of genus Staphylococcus spp. with the microbial community constituents, as well as with the skin immune system in normal condition and in the condition associated with inflammatory dermatoses. There are also the data given on S. aureus pathogenicity factors, the data on the impact of this microorganism upon the course of atopic dermatitis, and upon the course of psoriasis. The review examines the role that coagulase-negative staphylococci, S. epidermidis in particular, play in maintaining the microbiome homeostasis. The review as well examines the impact of the skin microbiome upon the development and activity of the skin immune system, and upon maintaining the integrity of the epidermal barrier.

The microbiome of the human skin and its variability in psoriasis and atopic dermatitis.

The human organism is inhabited by very diverse microorganisms, which constitute the so-called human microbiome and are necessary for the proper functioning of the macroorganism. The correct microbiome ensures homeostasis of the body. A disturbance in its homeostasis leads to dysbiosis. Such deviations may also be related to the development of inflammatory skin diseases, including atopic dermatitis and psoriasis. This review aims to analyse the most current published data on the microbiome of the human skin and examine its role in cutaneous skin diseases, such as atopic dermatitis and psoriasis. This review was compiled by collaborating dermatologists specializing in atopic dermatitis and psoriasis. A comprehensive review of current literature was done using PubMed and limited to relevant case reports and original papers on the skin microbiome in atopic dermatitis and/or psoriasis. It has not been yet established whether changes in the microbiome are the cause or consequence of disease (atopic dermatitis/psoriasis). However, it was found that in the cases where pathological microflora predominated, an intensification of lesion severity is observed, while with clinical improvement, commensal microflora is restored. Modification of the composition of the microflora may lead to changes in the activation of the immune system and eventually to the development of inflammatory diseases. Adverse effects on the microbiome may include antibiotics, poor diet, stress and adverse environmental conditions. However, more research is needed to identify exact details and mechanisms.

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

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.

Stratum corneum lipidomics analysis reveals altered ceramide profile in atopic dermatitis patients across body sites with correlated changes in skin microbiome.

Atopic dermatitis (AD) is driven by the interplay between a dysfunctional epidermal barrier and a skewed cutaneous immune dysregulation. As part of the complex skin barrier dysfunction, abnormalities in lipid organization and microbiome composition have been described. We set out to systematically investigate the composition of the stratum corneum lipidome, skin microbiome and skin physiology parameters at three different body sites in patients with AD and healthy volunteers. We analysed tape strips from different body areas obtained from 10 adults with AD and 10 healthy volunteers matched for FLG mutation status for 361 skin lipid species using the Metabolon mass spectrometry platform. 16S rRNA data were available from all probands. Our study showed that the lipid composition differs significantly between body sites and between AD patients and healthy individuals. Ceramide species NS was significantly higher in AD patients compared to healthy volunteers and was also higher in AD patients with a FLG mutation compared to AD patients without a FLG mutation. The correlation analysis of skin lipid alterations with the microbiome showed that Staphylococcus colonization in AD is positively correlated with ceramide subspecies AS, ADS, NS and NDS. This is the first study to reveal site-specific lipid alterations and correlations with the skin microbiome in AD.

Staphylococcus epidermidis protease EcpA can be a deleterious component of the skin microbiome in atopic dermatitis

Staphylococcus aureus and Staphylococcus epidermidis are the most abundant bacteria found on the skin of patients with atopic dermatitis (AD). S aureus is known to exacerbate AD, whereas S epidermidis has been considered a beneficial commensal organism. In this study, we hypothesized that S epidermidis could promote skin damage in AD by the production of a protease that damages the epidermal barrier. The protease activity of S epidermidis isolates was compared with that of other staphylococcal species. The capacity of S epidermidis to degrade the barrier and induce inflammation was examined by using human keratinocyte tissue culture and mouse models. Skin swabs from atopic and healthy adult subjects were analyzed for the presence of S epidermidis genomic DNA and mRNA. S epidermidis strains were observed to produce strong cysteine protease activity when grown at high density. The enzyme responsible for this activity was identified as EcpA, a cysteine protease under quorum sensing control. EcpA was shown to degrade desmoglein-1 and LL-37 invitro, disrupt the physical barrier, and induce skin inflammation in mice. The abundance of S epidermidis and expression of ecpA mRNA were increased on the skin of some patients with AD, and this correlated with disease severity. Another commensal skin bacterial species, Staphylococcus hominis, can inhibit EcpA production by S epidermidis. S epidermidis has commonly been regarded as a beneficial skin microbe, whereas S aureus has been considered deleterious. This study suggests that the overabundance of S epidermidis found on some atopic patients can act similarly to S aureus and damage the skin by expression of a cysteine protease.

327 Staphylococcus epidermidis protease EcpA is a deleterious component of the skin microbiome in atopic dermatitis

327 Staphylococcus epidermidis protease EcpA is a deleterious component of the skin microbiome in atopic dermatitis

Skin Microbiome in Atopic Dermatitis.

Atopic dermatitis is a common inflammatory skin disease with a complex pathogenesis that includes imbalanced immune system signalling, impaired skin barrier and enhanced Staphylococcus aureus skin colonization. The skin bacterial communities are characterized by increasing abundance of S. aureus, leading to reduced diversity compared with the bacterial communities on healthy skin, and increasing disease severity. In contrast, fungal communities are richer and more diverse on the skin of patients with atopic dermatitis, although distribution of the most common species is similar in patients and controls. Filaggrin deficiency in atopic dermatitis skin might be related to the enhanced skin colonization by S. aureus. In addition, S. aureus expressing variant virulence factors have been shown to elicit atopic dermatitis-like phenotypes in mice, indicating that specific S. aureus strains can induce flare-ups. This review aims to provide an overview of the recent literature on the skin microbiome in atopic dermatitis.

The Skin Microbiome in Atopic Dermatitis—a Potential Treatment Target?

Staphylococcus aureus (S. aureus) frequently colonize the skin of patients with atopic dermatitis (AD). The abundance of S. aureus increases during flares, accompanied by a reduction in bacterial diversity. This flare-associated imbalance in the cutaneous microflora (dysbiosis) correlates with disease severity. However, the causality of this association has not yet been fully established, and this review aims to further explore the relation between the skin microbiome and AD along with the clinical implications hereof. Recently, it has been shown that the skin microbiome in clinically unaffected skin of AD patients differs from that of healthy individuals. In addition, mutations in the gene encoding the structural protein filaggrin (FLG) have been shown to influence the skin microbiome. Skin barrier impairments, which characterize the AD phenotype, influence the skin microbiome and increase the susceptibility to colonization with S. aureus. In turn, S. aureus can promote skin inflammation by a broad spectrum of virulence factors. Modulation of the skin microbiome by transferring beneficial skin commensals to the skin of AD patients may represent a promising strategy for the future management of AD.

The emerging role of skin microbiome in atopic dermatitis and its clinical implication

In recent years, the importance of the microbiome in maintaining healthy skin has become apparent. Both the classic microbiology cultivation techniques used since the early 1970s and the next-generation sequencing procedures refined in the past decade reveal the importance of skin microbiome in healthy and diseased skin. To strengthen and eventually restore a healthy microbiome in patients with dermatological conditions like atopic dermatitis (AD), it is important to consider the factors that influence the composition of the microbiome, such as skin pH and skin barrier integrity. Moreover, targeting the microbiome may support established treatment regimens in years to come. Initial studies have generated promising results, suggesting that AD treatments, including select emollients and topical corticosteroids, have a positive impact on the microbiome. This paper reviews different aspects of microbiome in AD and their implications in clinical practice.

SKIN MICROBIOME IN ATOPIC DERMATITIS AND FEATURES OF VARIOUS BACKGROUND SKIN CARE

In recent years, there has been an increasing incidence of atopic dermatitis in children. This paper provides a literature review on the skin microbiome in atopic dermatitis, and the pharmacological features of various background skin care products.

Microbiome in atopic dermatitis.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease affecting ~10–20% of the general population. AD is characterized by disturbances in epidermal barrier function and hyperactive immune response. Recently, changes in the skin and intestinal microbiome have been analyzed in more detail. The available data suggest a link between disturbed skin microbiome and course of the disease. Flares of the disease are associated with an expansion of Staphylococcus aureus on lesional skin and a substantial loss of biodiversity in skin microbiome. Staphylococci exoproteins and superantigens evoke inflammatory reactions in the host. Skin microbiome includes superficial stratum corneum that is affected by environmental factors such as exposure to germs and cleansing. Available evidence argues for a link between epidermal barrier impairment and disturbances in skin microbiome in AD. In contrast to skin microbiome, intestinal microbiome seems to become stabilized after infancy. There is also a significant heritable component for intestinal microbiome. The microbial taxa, relative percentages and quantities vary remarkably between the different parts of the intestinal tract. Early intestinal microbial colonization may be a critical step for prevention of further development of AD. Skin barrier-aimed topical treatments help to develop a neo-microbiome from deeper compartments. Probiotics, prebiotics and synbiotics have been investigated for the treatment of AD, but further investigations are needed. Targeted treatment options to normalize skin and intestinal microbiome in AD are under investigation.

474 Skin microbiome in atopic dermatitis (AD): Interactions between bacteria (Staphylococcus) and fungi (Alternaria)

474 Skin microbiome in atopic dermatitis (AD): Interactions between bacteria (Staphylococcus) and fungi (Alternaria)

The Skin Microbiome in Atopic Dermatitis and Its Relationship to Emollients.

Human-associated bacterial communities on the skin, skin microbiome, likely play a central role in development of immunity and protection from pathogens. In atopic patients, the skin bacterial diversity is smaller than in healthy subjects. To review treatment strategies for atopic dermatitis in Canada, taking the skin microbiome concept into account. An expert panel of 8 Canadian dermatologists explored the role of skin microbiome in clinical dermatology, specifically looking at atopic dermatitis. The panel reached consensus on the following: (1) In atopic patients, the skin microbiome of lesional atopic skin is different from nonlesional skin in adjacent areas. (2) Worsening atopic dermatitis and smaller bacterial diversity are strongly associated. (3) Application of emollients containing antioxidant and antibacterial components may increase microbiome diversity in atopic skin. The skin microbiome may be the next frontier in preventive health and may impact the approach to atopic dermatitis treatment.