Illuminating microflora: shedding light on the potential of blue light to modulate the cutaneous microbiome.

Cutaneous diseases (such as atopic dermatitis, acne, psoriasis, alopecia and chronic wounds) rank as the fourth most prevalent human disease, affecting nearly one-third of the world's population. Skin diseases contribute to significant non-fatal disability globally, impacting individuals, partners, and society at large. Recent evidence suggests that specific microbes colonising our skin and its appendages are often overrepresented in disease. Therefore, manipulating interactions of the microbiome in a non-invasive and safe way presents an attractive approach for management of skin and hair follicle conditions. Due to its proven anti-microbial and anti-inflammatory effects, blue light (380 - 495nm) has received considerable attention as a possible 'magic bullet' for management of skin dysbiosis. As humans, we have evolved under the influence of sun exposure, which comprise a significant portion of blue light. A growing body of evidence indicates that our resident skin microbiome possesses the ability to detect and respond to blue light through expression of chromophores. This can modulate physiological responses, ranging from cytotoxicity to proliferation. In this review we first present evidence of the diverse blue light-sensitive chromophores expressed by members of the skin microbiome. Subsequently, we discuss how blue light may impact the dialog between the host and its skin microbiome in prevalent skin and hair follicle conditions. Finally, we examine the constraints of this non-invasive treatment strategy and outline prospective avenues for further research. Collectively, these findings present a comprehensive body of evidence regarding the potential utility of blue light as a restorative tool for managing prevalent skin conditions. Furthermore, they underscore the critical unmet need for a whole systems approach to comprehend the ramifications of blue light on both host and microbial behaviour.

Potential Clinical Applications of the Postbiotic Butyrate in Human Skin Diseases.

Human skin is the largest organ and the most external interface between the environment and the body. Vast communities of viruses, bacteria, archaea, fungi, and mites, collectively named the skin microbiome (SM), cover the skin surface and connected structures. Skin-resident microorganisms contribute to the establishment of cutaneous homeostasis and can modulate host inflammatory responses. Imbalances in the SM structure and function (dysbiosis) are associated with several skin conditions. Therefore, novel target for the skincare field could be represented by strategies, which restore or preserve the SM natural/individual balance. Several of the beneficial effects exerted by the SM are aroused by the microbial metabolite butyrate. Since butyrate exerts a pivotal role in preserving skin health, it could be used as a postbiotic strategy for preventing or treating skin diseases. Herein, we describe and share perspectives of the potential clinical applications of therapeutic strategies using the postbiotic butyrate against human skin diseases.

Isolation and Characterization of a Novel Autographiviridae Phage and Its Combined Effect with Tigecycline in Controlling Multidrug-Resistant Acinetobacter baumannii-Associated Skin and Soft Tissue Infections.

Multidrug-resistant Acinetobacter baumannii (MDR A. baumannii) is one of the ESKAPE pathogens that restricts available treatment options. MDR A. baumannii is responsible for a dramatic increase in case numbers of a wide variety of infections, including skin and soft tissue infections (SSTIs), resulting in pyoderma, surgical debridement, and necrotizing fasciitis. To investigate an alternative medical treatment for SSTIs, a broad range lytic Acinetobacter phage, vB _AbP_ABWU2101 (phage vABWU2101), for lysing MDR A. baumannii in associated SSTIs was isolated and the biological aspects of this phage were investigated. Morphological characterization and genomic analysis revealed that phage vABWU2101 was a new species in the Friunavirus, Beijerinckvirinae, family Autographiviridae, and order Caudovirales. Antibiofilm activity of phage vABWU2101 demonstrated good activity against both preformed biofilms and biofilm formation. The combination of phage vABWU2101 and tigecycline showed synergistic antimicrobial activities against planktonic and biofilm cells. Scanning electron microscopy confirmed that the antibacterial efficacy of the combination of phage vABWU2101 and tigecycline was more effective than the phage or antibiotic alone. Hence, our findings could potentially be used to develop a therapeutic option for the treatment of SSTIs caused by MDR A. baumannii.

Comparison of non-invasive Staphylococcus aureus sampling methods on lesional skin in patients with atopic dermatitis.

There is evidence that Staphylococcus aureus colonisation is linked to severity of atopic dermatitis. As no gold standard for S. aureus sampling on atopic dermatitis skin lesions exists, this study compared three commonly used methods. In addition, effectiveness of standard skin disinfection to remove S. aureus colonisation from these inflamed skin lesions was investigated. In 30 atopic dermatitis patients, three different S. aureus sampling methods, i.e. detergent scrubbing, moist swabbing and tape stripping, were performed on naïve and disinfected skin lesions. Two different S. aureus selective media, mannitol salt agar and chromID agar, were used for bacterial growing. Quantifying the S. aureus load varied significantly between the different sampling methods on naïve skin lesions ranging from mean 51 to 1.5 × 104 CFU/cm2 (p < 0.001). The qualitative detection on naïve skin was highest with the two detergent-based techniques (86% each), while for tape stripping, this value was 67% (all on chromID agar). In comparison, mannitol salt agar was less sensitive (p < 0.001). The disinfection of the skin lesions led to a significant reduction of the S. aureus load (p < 0.05) but no complete eradication in the case of previously positive swab. The obtained data highlight the importance of the selected sampling method and consecutive S. aureus selection agar plates to implement further clinical studies for the effectiveness of topical anti-staphylococcal antibiotics. Other disinfection regimes should be considered in atopic dermatitis patients when complete de-colonisation of certain skin areas is required, e.g. for surgical procedures.

A Journey on the Skin Microbiome: Pitfalls and Opportunities.

The human skin microbiota is essential for maintaining homeostasis and ensuring barrier functions. Over the years, the characterization of its composition and taxonomic diversity has reached outstanding goals, with more than 10 million bacterial genes collected and cataloged. Nevertheless, the study of the skin microbiota presents specific challenges that need to be addressed in study design. Benchmarking procedures and reproducible and robust analysis workflows for increasing comparability among studies are required. For various reasons and because of specific technical problems, these issues have been investigated in gut microbiota studies, but they have been largely overlooked for skin microbiota. After a short description of the skin microbiota, the review tackles methodological aspects and their pitfalls, covering NGS approaches and high throughput culture-based techniques. Recent insights into the "core" and "transient" types of skin microbiota and how the manipulation of these communities can prevent or combat skin diseases are also covered. Finally, this review includes an overview of the main dermatological diseases, the changes in the microbiota composition associated with them, and the recommended skin sampling procedures. The last section focuses on topical and oral probiotics to improve and maintain skin health, considering their possible applications for skin diseases.

Prevalence and histopathological characterization of Masai Giraffe (Giraffa camelopardalis tippelskirchi) skin disease in Tarangire-Manyara ecosystem, Northern Tanzania.

BACKGROUND: Masai Giraffes have declined dramatically in recent decades due to loss of habitat and illegal hunting. Hence, it is critically important that the epidemiology and etiology of so-called giraffe skin disease (GSD) is understood well. AIM: To assess the prevalence and histopathological characteristics of GSD in the Tarangire-Manyara Ecosystem (TME), northern Tanzania. METHODS: The study used road transects to gather field information on GSD. Eighty-four giraffes were sighted by systematic random sampling in the six study sites. Examination of giraffes involved body distribution of lesions, severity of the lesions and whether they were associated with age and sex of the affected giraffes. Five giraffes with GSD were immobilized for tissue collection and histopathological analysis. RESULTS: Prevalence among adults was 79%. Affected animals typically had 1-5 lesions which were mostly moderate and were predominantly observed on the forelegs. GSD positivity rate was higher among females versus males, whereas males had a higher rate of severe lesions and generally had more lesions than females. Calves showed no lesions. All tissue sections from five affected giraffes showed the presence of large quantities of fungal elements (hyphae and spores) that involved hair shafts and sub-cutaneous tissue after staining with Grocott Methenamine Silver as special fungal staining technique. CONCLUSIONS: Our findings suggest the involvement of fungal infection in GSD pathogenesis. CLINICAL RELEVANCE: We recommend further characterization of the lesions using modern molecular techniques and culture to identify primary and secondary or opportunistic etiologies, and the order in which the pathogens occur in the lesions.

Protocol for the systematic review of the epidemiology of superficial Streptococcal A infections (skin and throat) in Australia.

OBJECTIVE: We have produced a protocol for the comprehensive systematic review of the current literature around superficial group A Streptococcal infections in Australia. METHODS: MEDLINE, Scopus, EMBASE, Web of Science, Global Health, Cochrane, CINAHL databases and the gray literature will be methodically and thoroughly searched for studies relating to the epidemiology of superficial group A Streptococcal infections between the years 1970 and 2019. Data will be extracted to present in the follow up systematic review. CONCLUSION: A rigorous and well-organised search of the current literature will be performed to determine the current and evolving epidemiology of superficial group A Streptococcal infections in Australia.

Genetic diversity and phenotypic characterization of Iodobacter limnosediminis associated with skin lesions in freshwater fish.

The relatively unknown genus Iodobacter sp. has been repeatedly isolated from skin ulcers and saprolegniosis on freshwater fish in Finland, especially farmed salmonids. Genetic characterization verified that all 23 bacterial isolates studied here belonged to the species Iodobacter limnosediminis, previously undescribed from the fish microbiota. Whole-genome pulsed-field gel electrophoresis revealed variability between the I. limnosediminis strains, suggesting that they were most likely of environmental origin. Two I. limnosediminis strains caused lesions in 27%-53% of brown trout (Salmo trutta) injected intramuscularly (p ≤ .05). The lesions represented moderate to severe tissue damage, but for most fish, the tissues had been repaired by the end of the experiment through the accumulation of fibrocytes and macrophages at the site of the lesion. I. limnosediminis was reisolated from some lesions and/or internal organs. Phenotypically and biochemically, I. limnosediminis resembles several common bacterial species found in the aquatic environment, as it grows well on several media as whitish medium-sized colonies, is Gram negative and rod-shaped. Here, we characterized I. limnosediminis strains with several methods, including MALDI-TOF. This characterization will help in further investigations into the occurrence and possible involvement of I. limnosediminis in skin lesions of freshwater fish.

Commensal microbiota regulates skin barrier function and repair via signaling through the aryl hydrocarbon receptor.

The epidermis forms a barrier that defends the body from desiccation and entry of harmful substances, while also sensing and integrating environmental signals. The tightly orchestrated cellular changes needed for the formation and maintenance of this epidermal barrier occur in the context of the skin microbiome. Using germ-free mice, we demonstrate the microbiota is necessary for proper differentiation and repair of the epidermal barrier. These effects are mediated by microbiota signaling through the aryl hydrocarbon receptor (AHR) in keratinocytes, a xenobiotic receptor also implicated in epidermal differentiation. Mice lacking keratinocyte AHR are more susceptible to barrier damage and infection, during steady-state and epicutaneous sensitization. Colonization with a defined consortium of human skin isolates restored barrier competence in an AHR-dependent manner. We reveal a fundamental mechanism whereby the microbiota regulates skin barrier formation and repair, which has far-reaching implications for the numerous skin disorders characterized by epidermal barrier dysfunction.

Novel mechanisms of microbial crosstalk with skin innate immunity.

Skin is an organ with a dynamic ecosystem that harbours pathogenic and commensal microbes, which constantly communicate amongst each other and with the host immune system. Evolutionarily, skin and its microbiota have evolved to remain in homeostasis. However, frequently this homeostatic relationship is disturbed by a variety of factors such as environmental stress, diet, genetic mutations, and the microbiome itself. Commensal microbes also play a major role in the maintenance of microbial homeostasis. In addition to their ability to limit pathogens, many skin commensals such as Staphylococcus epidermidis and Cutibacterium acnes have recently been implicated in disease pathogenesis either by directly modulating the host immune components or by supporting the expansion of other pathogenic microbes. Likewise, opportunistic skin pathogens such as Staphylococcus aureus and Staphylococcus lugdunensis are able to breach the skin and cause disease. Though much has been established about the microbiota's function in skin immunity, we are in a time where newer mechanistic insights rapidly redefine our understanding of the host/microbial interface in the skin. In this review, we provide a concise summary of recent advances in our understanding of the interplay between host defense strategies and the skin microbiota.

Antimicrobial peptides and proteins: Interaction with the skin microbiota.

The cutaneous microbiota comprises all living skin microorganisms. There is increasing evidence that the microbiota plays a crucial role in skin homeostasis. Accordingly, a dysbiosis of the microbiota may trigger cutaneous inflammation. The need for a balanced microbiota requires specific regulatory mechanisms that control and shape the microbiota. In this review, we highlight the present knowledge suggesting that antimicrobial peptides (AMPs) may exert a substantial influence on the microbiota by controlling their growth. This is supported by own data showing the differential influence of principal skin-derived AMPs on commensal staphylococci. Vice versa, we also illuminate how the cutaneous microbiota interacts with skin-derived AMPs by modulating AMP expression and how microbiota members protect themselves from the antimicrobial activity of AMPs. Taken together, the current picture suggests that a fine-tuned and well-balanced AMP-microbiota interplay on the skin surface may be crucial for skin health.

The aryl hydrocarbon receptor at the forefront of host-microbe interactions in the skin: A perspective on current knowledge gaps and directions for future research and therapeutic applications.

The skin is home to a community of skin microbiota including bacteria, viruses and fungi, which are widely accepted to be of importance for skin homeostasis but also associated with skin diseases. Detailed knowledge on the skin microbiota composition and its changes in a number of skin diseases is available. Yet, specific interactions between microbes and the host skin cells or how they communicate with each other are less well understood. To identify, understand and eventually therapeutically exploit causal relationships of microbial dysbiosis with disease, studies are required that address the receptors and mediators involved in host-microbe interactions. In this perspective article, we provide an outlook on one of such receptors, namely the aryl hydrocarbon receptor (AHR). The AHR is well known for being a ligand-activated transcription factor regulating the proliferation, differentiation and function of many cell types present in the skin. Its targeting by anti-inflammatory therapeutics such as coal tar and Tapinarof is effective in atopic dermatitis and psoriasis. AHR signalling is activated upon binding of wide variety of small chemicals or ligands, including microbiota-derived metabolites. New evidence has emerged pointing towards a key role for epidermal AHR signalling through skin microbiota-derived metabolites. In response, AHR-driven expression of antimicrobial peptides and stratum corneum formation may alter the skin microbiota composition. This a self-perpetuating feedback loop calls for novel therapeutic intervention strategies for which we herein discuss the requirements in future mechanistic studies.

The role of the skin microbiota in the modulation of cutaneous inflammation-Lessons from the gut.

Inflammation is a vital defense mechanism used to protect the body from invading pathogens, but dysregulation can lead to chronic inflammatory disorders such as psoriasis and atopic dermatitis. Differences in microbiota composition have been observed in patients with inflammatory skin conditions compared with healthy individuals, particularly within lesions. There is also increasing evidence accumulating to support the notion that the microbiome contributes to the onset or modulates the severity of inflammatory diseases. Despite the known protective effects of orally administered lactic acid bacteria against inflammation, few studies have investigated the potential protective effects of topical application of bacteria on skin health and even fewer have looked at the potential anti-inflammatory effects of skin commensals. If lack of diversity and reduction in the abundance of specific commensal strains is observed in inflammatory skin lesions, and it is known that commensal bacteria can produce anti-inflammatory compounds, we suggest that certain members of the skin microbiota have anti-inflammatory properties that can be harnessed for use as topical therapeutics in inflammatory skin disorders.

Prevalence of superficial-cutaneous fungal infections in Shiraz, Iran: A five-year retrospective study (2015-2019).

BACKGROUND: Superficial and cutaneous fungal infections are common in tropical areas. The aim of this study was to provide a basic database of superficial and cutaneous mycoses and the most common etiological agents among patients. METHODS: Between 2015 and 2019, a total of 1807 patients suspected of superficial and cutaneous mycosis referring to the mycology laboratory of Shiraz medical school, Fars, Iran were evaluated. Specimens were taken from the patients' affected area, and clinical samples were examined by direct microscopy and culture. The epidemiological profile of the patients was collected. RESULTS: A total of 750 patients were confirmed with mycoses. Positive samples totaled 750 cases consisting of the nail (373/49.7%), skin (323/43%), head (47/6.26%), and mucosal membrane (4/0.5%). The yeasts group included 304 Candida spp. (70.3%), 123 Malassezia spp. (28.47%), and 5 Rhodotorula spp. (1.1%). The filamentous fungi were distributed as 34.8% dermatophytes and 7.5% non-dermatophyte. The clinical types of dermatophytosis were tinea unguium (110/261), tinea capitis (50/261), tinea pedis (48/261), tinea corporis (37/261), and tinea cruris (16/261). Non-dermatophyte molds included A. flavus 17, A. niger 4, Aspergillus spp. 15, Penicillium. 10, Fusarium 6, Mucor 2, Stemphylium 1, and Alternaria 1. CONCLUSION: This study provides useful data for the study trends of superficial and cutaneous fungal infections in a specific area. The mycological data confirmed higher incidence of candidiasis (mainly onychomycosis) and dermatophytosis in patients affected by fungal pathogens, which helped to better understand the epidemiological aspects of these mycoses.

Butyrate Improves Skin/Lung Fibrosis and Intestinal Dysbiosis in Bleomycin-Induced Mouse Models.

Systemic sclerosis (SSc) is an autoimmune disorder characterized by fibrosis of the skin and internal organs. Despite several studies on SSc treatments, effective treatments for SSc are still lacking. Since evidence suggests an association between intestinal microbiota and SSc, we focused on butyrate, which has beneficial effects in autoimmune diseases as a bacterial metabolite. Here, we investigated the therapeutic potential of sodium butyrate (SB) using a bleomycin-induced fibrosis mouse model of SSc and human dermal fibroblasts (HDFs). SB attenuated bleomycin-induced dermal and lung fibrosis in mice. SB influenced fecal microbiota composition (phyla Actinobacteria and Bacteroidetes, genera Bifidobacterium and Ruminococcus_g2). SB controlled macrophage differentiation in mesenteric lymph nodes, spleen, and bronchoalveolar lavage cells of mice with bleomycin-induced skin fibrosis. Profibrotic and proinflammatory gene expression was suppressed by SB administration in skin. Furthermore, SB inhibited transforming growth factor ß1-responsive proinflammatory expression with increased acetylation of histone 3 in HDFs. Subcutaneous SB application had antifibrogenic effects on the skin. Butyrate ameliorated skin and lung fibrosis by improving anti-inflammatory activity in a mouse model of SSc. Butyrate may exhibit indirect and direct anti-fibrogenic action on fibroblasts by regulating macrophage differentiation and inhibition of histone deacetylase 3. These findings suggest butyrate as an SSc treatment.

Secondary syphilis mimicking tinea cruris in an HIV infected patient: a case report.

Syphilis is known as the great imitator with various clinical presentations which often lead to confusion and misdiagnosis. A 28-year-old male presented with non-pruritic and painless erythematous patches around the anus and scrotum. Initial differential diagnosis with tinea cruris. Fungal examination was negative. Serological tests for syphilis were positive and anti-HIV screening was reactive. A diagnosis of secondary syphilis was established and the patient was given intramuscular injection of 2.4 million unit of benzathine penicillin. The skin lesions improved significantly 1 week after treatment, confirming a diagnosis of secondary syphilis with HIV. Annular skin lesions in secondary syphilis are uncommon and often misleading. This case emphasizes the importance of considering secondary syphilis in the differential diagnosis of annular lesions.

Red Light-Triggered Intracellular Carbon Monoxide Release Enables Selective Eradication of MRSA Infection.

Carbon monoxide (CO) is an important gaseous signaling molecule. The use of CO-releasing molecules such as metal carbonyls enables the elucidation of the pleiotropic functions of CO. Although metal carbonyls show a broad-spectrum antimicrobial activity, it remains unclear whether the bactericidal property originates from the transition metals or the released CO. Here, we develop nonmetallic CO-releasing micelles via a photooxygenation mechanism of 3-hydroxyflavone derivatives, enabling CO release under red light irradiation (e.g., 650 nm). Unlike metal carbonyls that non-specifically internalize into both Gram-positive and Gram-negative bacteria, the nonmetallic micelles are selectively taken up by S. aureus instead of E. coli cells, exerting a selective bactericidal effect. Further, we demonstrate that the CO-releasing micelles can cure methicillin-resistant S. aureus (MRSA)-infected wounds, simultaneously eradicating MRSA pathogens and accelerating wound healing.