Emerging Links between Microbiome Composition and Skin Immunology in Diaper Dermatitis: A Narrative Review

Diaper dermatitis is a common type of irritant contact dermatitis occurring in infants and toddlers. Its occurrence is triggered by an unfavorable environment under the diaper, damage to skin integrity by fecal enzyme degradation, overhydration and disruption of the lipid bilayer structure facilitating the entry of irritants and microorganisms. In diaper dermatitis development, the central proinflammatory cytokines are IL-1α, IL-8 and TNF-α. The initial release of IL-1α and TNF-α starts a further cascade of pro-inflammatory chemo- and cytokines, resulting in inflammation and erythema of the skin. A recently recognized factor in diaper dermatitis is the composition of the skin microbiome; common pathogenic strains Candida albicans and Staphylococcus aureus are associated with skin irritation. The resulting impaired microbiome composition produces a local inflammatory response and may thus worsen the initial dermatitis clinical presentation and subsequent healing. Introduction of probiotics is an attractive treatment for microbiome modulation, which has shown success in other skin conditions in adults and children. Probiotics are thought to work as a protective shield against irritants, maintain low skin pH, secrete beneficial metabolites, and block pathogen invasion. There is preliminary evidence that certain probiotics given orally or topically could be used as a gentle intervention in diaper dermatitis.

Propionibacterium (Cutibacterium) granulosum Extracellular DNase BmdE Targeting Propionibacterium (Cutibacterium) acnes Biofilm Matrix, a Novel Inter-Species Competition Mechanism

Acne vulgaris is the most common dermatological disorder worldwide affecting more than 80% of adolescents and young adults with a global prevalence of 231 million cases in 2019. The involvement of the skin microbiome disbalance in the pathophysiology of acne is recognized, especially regarding the relative abundance and diversity of Propionibacterium acnes a well-known dominant human skin commensal. Biofilms, where bacteria are embedded into a protective polymeric extracellular matrix, are the most prevalent life style for microorganisms. P. acnes and its biofilm-forming ability is believed to be a contributing factor in the development of acne vulgaris, the persistence of the opportunistic pathogen and antibiotic therapy failures. Degradation of the extracellular matrix is one of the strategies used by bacteria to disperse the biofilm of competitors. In this study, we report the identification of an endogenous extracellular nuclease, BmdE, secreted by Propionibacterium granulosum able to degrade P. acnes biofilm both in vivo and in vitro. This, to our knowledge, may represent a novel competitive mechanism between two closely related species in the skin. Antibiotics targeting P. acnes have been the mainstay in acne treatment. Extensive and long-term use of antibiotics has led to the selection and spread of resistant bacteria. The extracellular DNase BmdE may represent a new bio-therapeutical strategy to combat P. acnes biofilm in acne vulgaris.

Host-Microbe Interaction on the Skin and Its Role in the Pathogenesis and Treatment of Atopic Dermatitis

Atopic dermatitis (AD) is a condition with a complex and unclear aetiology. Possible causes of AD encompass alterations in the structure and function of the epidermal barrier, disturbances in the skin microbiome, immune factors, allergens, bacterial and fungal infections as well as environmental and genetic factors. In patients with AD, acute skin lesions are colonized by a greater number of bacteria and fungi than chronic lesions, clinically unchanged atopic skin and the skin of healthy people. Mechanisms promoting skin colonization by pathogens include complex interplay among several factors. Apart from disturbances of the skin microbiome, increased adhesion in atopic skin, defects of innate immune response resulting in the lack of or restriction of growth of microorganisms also contribute to susceptibility to the skin colonization of and infections, especially with Staphylococcus aureus. This review of the literature attempts to identify factors that are involved in the pathogenesis of AD-related bacterial and fungal skin colonization. Studies on the microbiome, commensal microorganisms and the role of skin microorganisms in maintaining healthy skin bring additional insight into the treatment and prevention of AD. In the light of presented mechanisms, reduction in colonization may become both causative and symptomatic treatment in AD.

Effectiveness of antifungal treatments during chytridiomycosis epizootics in populations of an endangered frog

The recently-emerged amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd) has had an unprecedented impact on global amphibian populations, and highlights the urgent need to develop effective mitigation strategies. We conducted in-situ antifungal treatment experiments in wild populations of the endangered mountain yellow-legged frog during or immediately after Bd-caused mass die-off events. The objective of treatments was to reduce Bd infection intensity (“load”) and in doing so alter frog-Bd dynamics and increase the probability of frog population persistence despite ongoing Bd infection. Experiments included treatment of early life stages (tadpoles and subadults) with the antifungal drug itraconazole, treatment of adults with itraconazole, and augmentation of the skin microbiome of subadults with Janthinobacterium lividum, a commensal bacterium with antifungal properties. All itraconazole treatments caused immediate reductions in Bd load, and produced longer-term effects that differed between life stages. In experiments focused on early life stages, Bd load was reduced in the 2 months immediately following treatment and was associated with increased survival of subadults. However, Bd load and frog survival returned to pre-treatment levels in less than 1 year, and treatment had no effect on population persistence. In adults, treatment reduced Bd load and increased frog survival over the entire 3-year post-treatment period, consistent with frogs having developed an effective adaptive immune response against Bd. Despite this protracted period of reduced impacts of Bd on adults, recruitment into the adult population was limited and the population eventually declined to near-extirpation. In the microbiome augmentation experiment, exposure of subadults to a solution of J. lividum increased concentrations of this potentially protective bacterium on frogs. However, concentrations declined to baseline levels within 1 month and did not have a protective effect against Bd infection. Collectively, these results indicate that our mitigation efforts were ineffective in causing long-term changes in frog-Bd dynamics and increasing population persistence, due largely to the inability of early life stages to mount an effective immune response against Bd. This results in repeated recruitment failure and a low probability of population persistence in the face of ongoing Bd infection.

MinION™ Nanopore Sequencing of Skin Microbiome 16S and 16S-23S rRNA Gene Amplicons

Human skin microbiome dysbiosis can have clinical consequences. Characterizing taxonomic composition of bacterial communities associated with skin disorders is important for dermatological advancement in both diagnosis and novel treatments. This study aims to analyze and improve the accuracy of taxonomic classification of skin bacteria with MinION™ nanopore sequencing using a defined skin mock community and a skin microbiome sample. We compared the Oxford Nanopore Technologies recommended procedures and concluded that their protocols highly bias the relative abundance of certain skin microbiome genera, most notably a large overrepresentation of Staphylococcus and underrepresentation of Cutibacterium and Corynebacterium. We demonstrated that changes in the amplification protocols improved the accuracy of the taxonomic classification for these three main skin bacterial genera. This study shows that MinION™ nanopore could be an efficient technology for full-length 16S rRNA sequencing; however, the analytical advantage is strongly influenced by the methodologies. The suggested alternatives in the sample processing improved characterization of a complex skin microbiome community using MinION™ nanopore sequencing.

Abnormal Somatosensory Behaviors Associated With a Gain-of-Function Mutation in TRPV3 Channels

Thermosensitive transient receptor potential V3 (TRPV3) is a polymodal receptor implicated in nociceptive, thermoceptive, pruritoceptive, and inflammatory pathways. Reports focused on understanding the role of TRPV3 in thermoception or nociception are not conclusive. Previous studies also show that aberrant hyperactivity of TRPV3 channels results in spontaneous itch and dermatitis-like symptoms, but the resultant behavior is highly dependent on the background of the animal and the skin microbiome. To determine the function of hyperactive TRPV3 channels in somatosensory sensations, we tested different somatosensory behaviors using a genetic mouse model that carries a gain-of-function point mutation G573S in the Trpv3 gene (Trpv3G573S). Here we report that Trpv3G573S mutants show reduced perception of cold, acetone-induced cooling, punctate, and sharp mechanical pain. By contrast, locomotion, noxious heat, touch, and mechanical itch are unaffected in Trpv3G573S mice. We fail to observe any spontaneous itch responses and/or dermatitis in Trpv3G573S mutants under specific pathogen (Staphylococcus aureus)-free conditions. However, we find that the scratching events in response to various pruritogens are dramatically decreased in Trpv3G573S mice in comparison to wild-type littermates. Interestingly, we observe sensory hypoinnervation of the epidermis in Trpv3G573S mutants, which might contribute to the deficits in acute mechanical pain, cool, cold, and itch sensations.

Forensic Human Identification for Cutaneous Microbiome, a Brief Review

Forensic Science compounds many study areas in context of solving crimes, one of which is the forensic microbiology. Combined with genomic approaches, microbiology has shown strong performance in studies regarding the relationship between microorganisms present on human skin and environment. The Human Microbiome Project (HMP) has contributed significantly to characterization of microbial complexity and their connection to human being. The purpose of this work consists of a historical overview of scientific articles, demonstrating the growth and possibility of using skin microbiome in forensic identification. Studies about use of cutaneous microbiome in human identification, as well its forensic approaches, were looked into for writing of this review. Comparisons among cutaneous microbial communities and manipulated objects have been tested using 16S rRNA, as well as a thorough sequencing of the bacterial genome. From use of ecological measures of distance to genetic markers with nucleotide variants and predictive algorithms, research has shown promising results for advances in field of forensic identification. The development of metagenomic microbial panel markers, named hidSkinPlax for targeted sequencing has been designed and tested with great results. Research results show satisfactory potential in human identification by cutaneous microbiome and the possibility for contributive use in elucidating crimes.