Lene Bay

Gaining a deeper understanding of the variation in skin microbiota across habitats and layers provides critical insights into the complex host-microbial interactions that drive inflammatory skin diseases. Our study investigated dermal versus epidermal microbiota in lesional and non-lesional skin of 37 adult atopic dermatitis (AD) patients and 37 healthy controls. Skin biopsies were partitioned into epidermal and dermal compartments, while serial tape strips collected the superficial epidermis. Bacterial communities were analyzed by cultivation, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, confocal laser scanning microscopy, and metagenomic sequencing. We found that the effects of AD were evident across skin layers. The natural variation between skin layers and habitats diminishes in AD-affected skin, intensifying the impact of the microenvironment and host factors. A remarkably distinct dermal bacterial community was discovered among AD patients, being more conserved and providing a clearer difference between skin habitats, while the epidermis varied substantially. Importantly, comparisons between AD patients and controls revealed more genera differed when studying the dermal samples than the epidermal ones. Staphylococcus , Corynebacterium, and Cutibacterium genera differed with AD status across all samples, but Prevotella and Mitsuokella only differed in the dermis. In the dry and moist dermis, this translated into 14 and 61 gene pathways significantly varying with AD status, including many related to the biosynthesis of menaquinones (vitamin K2). These results suggest dermal sampling would allow for the role of the skin microbiome within AD pathogenesis to be better resolved since these communities are simpler and less prone to environmental contamination. IMPORTANCE: This study sheds light on the profound impact of skin microbiota's complex composition and distribution in atopic dermatitis (AD). The distinctive bacterial profile and activity, especially within the dermal skin compartment, vividly mirrored the cutaneous conditions in this inflamed microenvironment. The striking similarity in bacterial communities across different skin habitats in atopic skin underscores the high influence of atopic dermatitis—the genetic predisposition to an amplified immune response. This finding suggests that the dermal bacterial profile could be a valuable tool for longitudinally monitoring changes during the disease's relapsing phases, allowing for a precise categorization of patients into specific AD endotypes. Broadening the focus throughout the entire eczema-affected skin paves the way for treatments capable of modulating dermal biological factors, offering more effective management of AD. By further centering the interest in host-microbial interactions, we can refine personalized treatments, ultimately improving the lives of millions suffering from atopic dermatitis.

Several microbiome studies have recently demonstrated microbial dysbiosis in various chronic inflammatory skin diseases, and it is considered an important role in the pathogenesis. Although the role of skin dysbiosis in inflammatory skin diseases is debatable, the local microenvironment is considered essential concerning compositional changes and functional alterations of the skin microbiota. Indeed, various local nutrients (e.g., lipids), pH values, water, oxygen, and antimicrobial peptides may affect the level of skin dysbiosis in these skin diseases. In particular, in atopic dermatitis and hidradenitis suppurativa, significant changes in skin dysbiosis have been associated with local aberrant host immune changes. In this review, the potential pathogenic crosstalk between the host and the microbiota is reviewed in relation to the physical, chemical, and biological microenvironments of various chronic inflammatory skin diseases.

Needle reuse is a common practice and primary cause of customer compliance issues such as pain, bruising, clogging, injection site reactions (ISR), and associated lipodystrophy. This study aimed to characterize skin microflora at injection sites and establish microbial contamination of used pen injectors and needles. The second objective was to evaluate the risk of infections during typical and repeated subcutaneous injections. 50 participants with diabetes and 50 controls (n = 100) were sampled through tape strips and skin swabs on the abdomen and thigh for skin microflora. Used pen injectors and needles were collected after in‐home use and from the hospital after drug administration by health care professionals (HCPs). Samples were analyzed by conventional culture, matrix‐assisted laser desorption/ionization‐time of flight (MALDI‐TOF), mass spectrometry (MS), confocal laser scanning microscopy (CLSM), and 16S/ITS high throughput sequencing (HTS). A mathematical model simulated the risk of needle contamination during injections. Injection site populations were in 10² cells/cm² order, with increased viable bacteria and anaerobic bacteria on the skin in persons with diabetes (p = 0.05). Interpersonal variation dominated other factors such as sex or location. A higher prevalence of Staphylococcus aureus on abdominal skin was found in persons with diabetes than control skin (p ≤ 0.05). Most needles and cartridges (95% and 86%) contained no biological signal. The location of the device collection (hospital vs home‐use) and use regimen did not affect contamination. CLSM revealed scarcely populated skin microflora scattered in aggregates, diplo, or single cells. Our mathematical model demonstrated that penetrating bacteria colonies during subcutaneous injection is unlikely. These findings clarify the lack of documented skin infections from subcutaneous insulin injections in research. Furthermore, these results can motivate the innovation and development of durable, reusable injection systems with pharmacoeconomic value and a simplified and enhanced user experience for patients.

Cutaneous microbial composition is driven by the microenvironment of the skin, as well as by internal and external factors. Local changes in the microenvironment can affect the configuration of the community, which may lead toward an imbalance of microbiota. Alterations in the microbial profile are common in both inflammatory skin diseases and chronic infections. A shift in balance within the microbiota, toward limited variation and a greater abundance of specific pathogens, may further worsen the pathogenicity of the diseases. These alterations may be prevented by topical treatment of probiotic solutions stimulating a balanced multispecies community. Compositional variations may further constitute potential biomarkers to predict flares or monitor efficacy during therapy. New approaches such as machine learning may contribute to this prediction of microbial alterations prior to the development of chronic infections and flares. This review provides insight into the composition and distribution of a healthy community of microorganisms in the skin and draws parallels with the community in chronic infections and chronic inflammatory skin diseases such acne vulgaris and Hidradenitis Suppurativa. We discuss the potential role of specific species in the pathogenesis and the possible prevention of disease exacerbation.

Post-surgical infections arise due to various contributing factors. Most important is the presence of potential pathogenic microorganisms in the skin complemented by the patient's health status. Cutibacterium acnes is commonly present in the pilosebaceous glands and hair follicle funnels in human skin. After surgical intervention, these highly prevalent, slow-growing bacteria can be found in the deeper tissues and in proximity of implants. C. acnes is frequently implicated in post-surgical infections, often resulting in the need for revision surgery. This review summarizes the current understanding of microbial dynamics in shoulder surgical infections. In particular, we shed light on the contribution of C. acnes to post-surgical shoulder infections as well as their colonization and immune modulatory potential. Despite being persistently found in post-surgical tissues, C. acnes is often underestimated as a causative organism due to its slow growth and the inefficient detection methods. We discuss the role of the skin environment constituted by microbial composition and host cellular status in influencing C. acnes recolonization potential. Future mapping of the individual skin microbiome in shoulder surgery patients using advanced molecular methods would be a useful approach for determining the risk of post-operative infections.

The ability of bacteria to aggregate and form biofilms impairs phagocytosis by polymorphonuclear leukocytes (PMNs). The aim of this study was to examine if the size of aggregates is critical for successful phagocytosis and how bacterial biofilms evade phagocytosis. We investigated the live interaction between PMNs andPseudomonas aeruginosa,Staphylococcus aureus,Escherichia coliandStaphylococcus epidermidisusing confocal scanning laser microscopy. Aggregate size significantly affected phagocytosis outcome and larger aggregates were less likely to be phagocytized. Aggregates ofS. epidermidiswere also less likely to be phagocytized than equally-sized aggregates of the other three species. We found that only aggregates of approx. 5 μm diameter or smaller were consistently phagocytosed. We demonstrate that planktonic and aggregated cells of all four species significantly reduced the viability of PMNs after 4 h of incubation. Our results indicate that larger bacterial aggregates are less likely to be phagocytosed by PMNs and we propose that, if the aggregates become too large, circulating PMNs may not be able to phagocytose them quickly enough, which may lead to chronic infection.