Keratinocyte-derived defensins activate neutrophil-specific receptors Mrgpra2a/b to prevent skin dysbiosis and bacterial infection.

Healthy skin maintains a diverse microbiome and a potent immune system to fight off infections. Here, we discovered that the epithelial-cell-derived antimicrobial peptides defensins activated orphan G-protein-coupled receptors (GPCRs) Mrgpra2a/b on neutrophils. This signaling axis was required for effective neutrophil-mediated skin immunity and microbiome homeostasis. We generated mutant mouse lines lacking the entire Defensin (Def) gene cluster in keratinocytes or Mrgpra2a/b. Def and Mrgpra2 mutant animals both exhibited skin dysbiosis, with reduced microbial diversity and expansion of Staphylococcus species. Defensins and Mrgpra2 were critical for combating S. aureus infections and the formation of neutrophil abscesses, a hallmark of antibacterial immunity. Activation of Mrgpra2 by defensin triggered neutrophil release of IL-1ß and CXCL2 which are vital for proper amplification and propagation of the antibacterial immune response. This study demonstrated the importance of epithelial-neutrophil signaling via the defensin-Mrgpra2 axis in maintaining healthy skin ecology and promoting antibacterial host defense.

Therapeutic textiles: A promising approach for human skin dysbiosis?

The close interaction between skin and clothing has become an attractive cornerstone for the development of therapeutic textiles able to alleviate skin disorders, namely those correlated to microbiota dysregulation. Skin microbiota imbalance is known in several skin diseases, including atopic dermatitis (AD), psoriasis, seborrheic dermatitis, rosacea, acne and hidradenitis suppurative (HS). Such microbiota dysregulation is usually correlated with inflammation, discomfort and pruritus. Although conventional treatments, that is, the administration of steroids and antibiotics, have shown some efficacy in treating and alleviating these symptoms, there are still disadvantages that need to be overcome. These include their long-term usage with side effects negatively impacting resident microbiota members, antibiotic resistance and the elevated rate of recurrence. Remarkably, therapeutic textiles as a non-pharmacological measure have emerged as a promising strategy to treat, alleviate the symptoms and control the severity of many skin diseases. This systematic review showcases for the first time the effects of therapeutic textiles on patients with skin dysbiosis, focusing on efficacy, safety, adverse effects and antimicrobial, antioxidant and anti-inflammatory properties. The main inclusion criteria were clinical trials performed in patients with skin dysbiosis who received treatment involving the use of therapeutic textiles. Although there are promising outcomes regarding clinical parameters, safety and adverse effects, there is still a lack of information about the impact of therapeutic textiles on the skin microbiota of such patients. Intensive investigation and corroboration with clinical trials are needed to strengthen, define and drive the real benefit and the ideal biomedical application of therapeutic textiles.

Efficacy of Chlorhexidine Impregnated Wipes for the Local Dysbiosis in Atopic Dogs: A Multicentric Prospective Study.

(1) Background: Dysbiosis is frequently observed in Canine Atopic Dermatitis (CAD). Antimicrobial treatment may be necessary to treat flare ups and the use of topical treatments is beneficial to prevent the development of bacterial resistance. Wipes are an easy way to apply antiseptic agents on the skin. The aim of this study was to evaluate the benefits of 3% chlorhexidine impregnated wipes (Pyoskin® wipes, MP Labo, France) on local areas of dysbiosis in dogs with CAD. (2) Methods: A total of 20 dogs suffering from CAD presented with localised areas of dysbiosis were included in this study. Affected areas were cleansed with the daily application of chlorhexidine wipes once a day for 14 days. Follow-up visits were scheduled after one and two weeks. Clinical signs (lesions and pruritus), dysbiosis scored by cytological counts (cocci and Malassezia) and investigator and owner global appreciation were evaluated. (3) Results: A statistically significant decrease in clinical scores and cytological counts were observed as soon as D7 and until D14. Both owner and investigator appreciation were considered high (4) Conclusions: The use of chlorhexidine impregnated wipes is a useful and easy way to manage localised dysbiosis in atopic dogs and allows limiting of systemic medication to prevent bacterial resistance.

A Wall Fragment of Cutibacterium acnes Preserves Junctional Integrity Altered by Staphylococcus aureus in an Ex Vivo Porcine Skin Model.

(1) Background alteration of the skin microbiota, dysbiosis, causes skin barrier impairment resulting in disease development. Staphylococcus aureus, the main pathogen associated with dysbiosis, secretes several virulence factors, including α-toxin that damages tight junctions and compromises the integrity of the skin barrier. The use of members of the resident microbiota to restore the skin barrier, bacteriotherapy, represents a safe treatment for skin conditions among innovative options. The aim of this study is the evaluation of a wall fragment derived from a patented strain of Cutibacterium acnes DSM28251 (c40) alone and conjugated to a mucopolysaccharide carrier (HAc40) in counteracting S. aureus pathogenic action on two tight junction proteins (Claudin-1 and ZO-1) in an ex vivo porcine skin infection model. Methods: skin biopsies were infected with live S. aureus strains ATCC29213 and DSM20491. Tissue was pre-incubated or co-incubated with c40 and HAc40. (3) Results: c40 and HAc40 prevent and counteract Claudin-1 and Zo-1 damage (4) Conclusions: c40 and the functional ingredient HAc40 represent a potential non-pharmacological treatment of skin diseases associated with cutaneous dysbiosis of S. aureus. These findings offer numerous avenues for new research.

Skin Microbiota: Setting up a Protocol to Evaluate a Correlation between the Microbial Flora and Skin Parameters.

The concept of skin microbiota is not really clear and more accurate approaches are necessary to explain how microbial flora can influence skin biophysical parameters in healthy individuals and in pathology patients with non-infectious skin disease. The aim of this work is to provide a suitable, fast and reproducible protocol to correlate skin parameters with the composition of skin microbiota. For this purpose, the work was split into two main phases. The first phase was focused on the selection of volunteers by the administration of a specific questionnaire. The skin microbiota was then collected from the forehead of selected volunteers as a test area and from the shoulder as control area. On the same skin area, the biophysical parameters, such as trans-epidermal water loss (TEWL), sebum level (SL), porphyrin intensity, keratin content and stratum corneum water content were taken. All parameters were taken at t0 and after 15 days without changes in the volunteers' lifestyle. A strong correlation was found between forehead and shoulder area for porphyrin intensity, pH and TEWL parameters, and between Cutibacterium acnes and some biophysical parameters both in the forehead and the shoulder area. The procedural setup in this work represents the starting point for evaluating problematic skins and the efficacy of cosmetic products or treatment against skin dysbiosis.

Psoriasis: Interplay between dysbiosis and host immune system.

With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of both gut and skin microbiota in the pathogenesis of psoriasis. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts, have been identified as possible triggers for recurrent episodes of psoriasis. Mechanistically, gut dysbiosis leads to "leaky gut syndrome" via disruption of epithelial bilayer, thereby, resulting in translocation of bacteria and other endotoxins to systemic circulation, which in turn, results in inflammatory response. Similarly, skin dysbiosis disrupts the cutaneous homeostasis, leading to invasion of bacteria and other pathogens to deeper layers of skin or even systemic circulation further enhanced by injury caused by pruritus-induced scratching, and elicit innate and adaptive inflammation. The present review explores the correlation of both skin and gut microbiota dysbiosis with psoriasis. Also, the studies highlighting the potential of bacteriotherapeutic approaches including probiotics, prebiotics, metabiotics, and fecal microbiota transplantation for the management of psoriasis have been discussed.