Cutaneous dysbiosis may amplify barrier dysfunction in patients with atopic dermatitis

Abstract

Atopic dermatitis (AD) is associated with cutaneous dysbiosis, barrier defects, and immune dysregulation, but the interplay between these factors needs further study. Early-onset barrier dysfunction may facilitate an innate immune response to commensal organisms and, consequently, the development of allergic sensitization. We aimed to compare the cutaneous microbiome in patients with active dermatitis with and without a history of childhood flexural dermatitis (atopic dermatitis). Next-gen Ion-Torrent deep-sequencing identified AD-associated changes in the skin bacterial microbiome (“bacteriome”) and fungal microbiome (“mycobiome”) of affected skin in swabs from areas of skin affected by dermatitis. Data were analyzed for diversity, abundance, and inter-kingdom correlations. Microbial interactions were assessed in biofilms using metabolic activity (XTT) assay and scanning electron microscopy (SEM), while host-pathogen interactions were determined in cultured primary keratinocytes exposed to biofilms. Increased richness and abundance of Staphylococcus, Lactococcus, and Alternaria were found in atopics. Staphylococcus and Alternaria formed robust mixed-species biofilms (based on XTT and SEM) that were resistant to antifungals/antimicrobials. Furthermore, their biofilm supernatant was capable of influencing keratinocytes biology (pro-inflammatory cytokines and structural proteins), suggesting an additive effect on AD-associated host response. In conclusion, microbial inter-kingdom and host-microbiome interactions may play a critical role in the modulation of atopic dermatitis to a greater extent than in non-atopic adults with allergic contact dermatitis.

Successful Treatment of Prurigo Nodularis by Dupilumab: Report of 24 Patients

“…Besides, in our study, most patients (16/24, 66.6%) are found with an elevated level of serum IgE but a normal level of the total number of blood eosinophils, and this result is similar to another research [15]. Pathological mechanisms of AD still remain unclear, but immune dysregulation, barrier defects, and cutaneous dysbiosis are demonstrated to be involved and the importance of Th2 cells has been focused [16][17][18]. Several studies have proved the overexpression of some Th2 cytokines (such as IL-4, IL-31) [19,20] in prurigo, suggesting that dupilumab may benefit patients with PN by blocking type 2 inflammation.…”

Atopic Dermatitis and Ulcerative Colitis Successfully Treated with Upadacitinib

“…Parallel to the recent treatment advancements, our understanding of the pathogenesis of AD is rapidly evolving: following the identification of Th2 skewed immunity, altered skin barrier, and abnormal keratinocyte polarization, the role of cutaneous dysbiosis has been recently recognized to contribute to inefficient barrier function and susceptibility to infection [ 7 ]. In a study by Hammond et al, the bacterial and fungal microbiomes were assessed at skin sites at which AD had manifested and compared with those of subjects with non-atopic dermatitis [ 8 ]. The results showed an increase in Staphilococcus aureus , Lactococcus , and Alternaria in samples from AD-affected skin.…”

“…Alternaria is an established pathogen linked to asthma and AD and its antigens have been hypothesized to play a role in the development of allergies; for instance, filaggrin mutation and sensitization with Alternaria were shown to enhance sensitization to food and, possibly, respiratory allergens [ 9 ]. Moreover, mixed biofilms formed by Staphilococcus and Alternaria are capable of worsening AD by negatively affecting barrier function and modulating the expression of pro-inflammatory cytokines such as thymic stromal lymphopoietin (TSLP) [ 8 ]. These results suggest that in AD subjects with skin barrier disfunction, the microbiome has a prominent role in transcutaneous sensitization.…”

Dupilumab as an innovative therapy for symptomatic management of chemotherapy‐induced pruritus: A case series

“…Mainstay management of chemotherapy‐induced pruritus includes corticosteroids, antihistamines, and neuromodulators like gabapentin. Other management options include immunomodulatory treatments such as azathioprine or methotrexate 7 . Still, chemotherapy‐induced pruritus does not have mainstream efficacious treatment, prompting the need for additional treatment options.…”