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Previous cross-sectional studies have shown that skin microbiomes in adults are distinct from those in children. However, the human skin microbiome in individuals as they sexually mature has not been studied as extensively. We performed a prospective, longitudinal study to investigate the puberty-associated shifts in skin microbiota. A total of 12 healthy children were evaluated every 6-18 months for up to 6 years. Using 16S ribosomal RNA (V1-V3) and internal transcribed spacer 1 amplicon sequencing analyzed with Divisive Amplicon Denoising Algorithm 2, we characterized the bacterial and fungal communities of five different skin and nares sites. We identified significant alterations in the composition of skin microbial communities, transitioning toward a more adult microbiome, during puberty. The microbial shifts were associated with Tanner stages (classification method for the degree of sexual maturation) and showed noticeable sex-specific differences. Over time, female children demonstrated a predominance of Cutibacterium with decreasing diversity. Among fungi, Malassezia predominated at most skin sites in more sexually mature subjects, which was more pronounced in female children. The higher relative abundances of these lipophilic taxa-C. acnes and M. restricta-were strongly associated with serum sex hormone concentrations with known influence on sebaceous gland activity. Taken together, our results support the relationship between sexual maturation, skin physiology, and the skin microbiome., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Building upon the knowledge garnered from investigations utilizing traditional culturing methods, advances in sequencing technologies have catalyzed a revolution in studying human-associated microbes: bacteria, fungi and viruses. Skin microbiome research in healthy individuals and patients with dermatologic disorders has provided insights into the complexity and biogeography of human skin microbes. The continual developments in sequencing and analyses will provide increasingly sophisticated tools to interrogate human-associated microbes, ultimately to improve our understanding of health and disease., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Growing interest in microbial contributions to human health and disease has increasingly led investigators to examine the microbiome in both healthy skin and cutaneous disorders, including acne, psoriasis, and atopic dermatitis. The need for common language, effective study design, and validated methods is critical for high-quality standardized research. Features, unique to skin, pose particular challenges when conducting microbiome research. This review discusses microbiome research standards and highlights important factors to consider, including clinical study design, skin sampling, sample processing, DNA sequencing, control inclusion, and data analysis., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Understanding the skin mycobiome (fungal communities) is important because both commensal and pathogenic fungi can drive cutaneous disease depending on host status and body sites, including the scalp, feet, and groin. Interestingly, age may also affect skin fungal infections as certain dermatophytoses (i.e., tinea capitis) are more frequent in children than adults. We previously described the skin mycobiomes in healthy adults, showing lipophilic fungi Malassezia predominate in most skin sites. Because children have less sebaceous skin before puberty, we compared the fungal communities of primary clinical samples from healthy children and adults, based on sequencing of a fungal phylogenetic marker. Although Malassezia predominated on the trunk, head, and arm skin of adults (age 18-39), children (age < 14) had more diverse fungal communities, for example, Eurotiomycetes, which includes common dermatophytes. Species-level classification showed that Malassezia globosa predominated in children. Collectively, our findings indicate that prepubertal skin is colonized by diverse fungi, whereas adult skin is predominantly obligatory lipophilic Malassezia, suggesting that fungal communities on skin profoundly shift during puberty. Mycobiome shifts during puberty are likely due to alterations in sebaceous gland activation and sebum composition. This study provides a foundational framework for studies investigating interactions between fungi, skin, and pediatric dermatophytosis., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

For two centuries, Koch's postulates have set the gold standard for establishing the microbiological etiology of infection and disease. Genomic sequencing now brings finer resolution to both bacterial strain variation and the host genetic state that may predispose to disease. In this issue of the JID, Fitz-Gibbons and colleagues present strain-based resolution of Propionibacterium acnes and its association with the common teenage malady acne vulgaris. Here I examine how Koch's postulates were envisioned and incorporate this finer resolution of both host and microbial states.

Trillions of bacteria, fungi, viruses, archaea, and small arthropods colonize the skin surface, collectively comprising the skin microbiome. Generations of researchers have classified these microbes as transient versus resident, beneficial versus pathogenic, and collaborators versus adversaries. Culturing and direct sequencing of microbial inhabitants identified distinct populations present at skin surface sites. Herein, we explore the history of this field, describe findings from the current molecular sequencing era, and consider the future of investigating how microbes and antimicrobial therapy contribute to human health.

Suppressor of tumorigenicity 14 (St14) encodes matriptase, a serine protease, which regulates processing of profilaggrin to filaggin in vivo. Here, we report that transgenic mice with 1% of wild-type St14 levels (St14(hypo/-)) display aberrant processing of profilaggrin and model human ichthyotic skin phenotypes. Scaling of the skin appears at 1 week of age with underlying epidermal acanthosis and orthohyperkeratosis as well as a CD4+ T-cell dermal infiltrate. Upregulation of antimicrobial peptides occurs when challenged by exposure to the postnatal environment. Direct genomic sequencing of bacterial 16S rRNA genes to query microbial diversity identifies a significant shift in both phylogeny and community structure between St14(hypo/-) mice and control littermates. St14(hypo/-) mice have a selective shift in resident skin microbiota with a decrease of the dominant genus of skin bacteria, Pseudomonas and an accompanying increase of Corynebacterium and Streptococcus. St14(hypo/-) mice provide early evidence that the cutaneous microbiome can be specifically altered by genetic state, which may play an important role in modulating skin disease.

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disorder that affects approximately 15% of children in the United States. A complex disorder, AD is characterized by both skin barrier impairment and immunologic abnormalities, including decreased innate immune function and a polarized adaptive immune response. Mouse models have demonstrated the complex interdependence of immune cell-keratinocyte interactions and teased apart gene-environment relationships in a controlled setting. In this issue, Nagelkerken et al. present a mouse model with transgenic expression of apolipoprotein C1 that disrupts the skin lipid barrier and manifests many hallmark features of AD.

Ichthyosis vulgaris (IV), characterized by mild scaling on limbs and lower abdomen, has an incidence of 1 in 250. Smith, McLean, and colleagues demonstrate that common mutations in filaggrin underlie IV. Filaggrin aggregates keratin intermediate filaments and is cross-linked into the cornified envelope to form the epidermal barrier. These findings reinforce the importance of the epidermal barrier in pathogenesis of skin diseases.

To achieve conditional gene expression in the differentiated layers of the epidermis, we generated transgenic mice with the tetracycline-regulated transactivator proteins, tTA (tetracycline transactivator) and rtTA (reverse tetracycline transactivator), expressed from the human involucrin promoter. Interaction with tetracycline turns off or turns on the tTA and rtTA molecules, respectively, allowing for regulation of downstream target genes during development and postnatally. These transactivator lines were crossed with reporter mice driving LacZ expression from a tetracycline response element to analyze the specificity and levels of target gene expression. Quantitative beta-galactosidase experiments demonstrate a 30-fold induction, specific to epithelial tissues. Immunohistochemistry results illustrate that the beta-galactosidase staining follows that of endogenous involucrin expression. Induction initiates at embryonic day 14.5 with expression over the entire epidermal surface by E16.5. Together with other driver lines, expressing tetracycline transactivators in the mitotically active layers of the epidermis, these mice will allow investigators to specifically modulate expression of target genes to specific stages of epidermal differentiation.