Previously either regarded as insignificant or feared as potential sources of infection, the bacteria living on our skin are increasingly recognized for their role in benefitting human health. Skin ...commensals modulate mucosal immune defenses and directly interfere with pathogens; however, their contribution to the skin’s physical integrity is less understood. Here, we show that the abundant skin commensal Staphylococcus epidermidis contributes to skin barrier integrity. S. epidermidis secretes a sphingomyelinase that acquires essential nutrients for the bacteria and assists the host in producing ceramides, the main constituent of the epithelial barrier that averts skin dehydration and aging. In mouse models, S. epidermidis significantly increases skin ceramide levels and prevents water loss of damaged skin in a fashion entirely dependent on its sphingomyelinase. Our findings reveal a symbiotic mechanism that demonstrates an important role of the skin microbiota in the maintenance of the skin’s protective barrier.
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•Commensal Staphylococcus epidermidis contributes to skin barrier homeostasis•S. epidermidis produces a sphingomyelinase that helps generate protective ceramides•Sphingomyelinase contributes to S. epidermidis skin colonization•S. epidermidis prevents skin dehydration via its sphingomyelinase activity
Ceramides are a key constituent of the skin barrier that prevent skin dehydration and aging. Zheng et al. show that the abundant skin commensal Staphylococcus epidermidis secretes a sphingomyelinase that facilitates host production of ceramides to help maintain skin integrity and prevent water loss of damaged skin.
In the regulation of inflammatory responses and skin homeostasis, the skin and its microbiota are closely related. Studies have reported that lactic acid bacteria extracts can improve the skin ...condition and microbiota. In our previous study, we developed probiotic lysates, which are efficacious in improvement of human skin cells and the skin barrier. The skin-moisturizing effect of Dermabiotics HDB (HDB) prepared with Lactiplantibacillus plantarum, and the correlation between changes in the skin microbiota and moisture contents, were evaluated and analyzed in clinical trials. The clinical parameters on the cheeks of 21 female participants were measured using biophysical tools before and after (2 weeks) using HDB or control. The skin microbes were collected and identified using 16s rRNA gene sequencing. HDB significantly improved moisture intensity, transepidermal water loss (TEWL), and hot flush level on the cheek. The beta-diversity of the skin microbiota was different from that of the control in the unweighted UniFrac principal coordinate analysis after using HDB. The genus Lawsonella demonstrated a positive correlation with TEWL and a negative correlation with the moisture contents of the keratin layer, regardless of the use of HDB and control. Conversely, after HDB use, the genus Staphylococcus was increased and associated with a lower hot flush level, while the genera of the phylum Proteobacteria tended to decrease, which is associated with an improved skin condition. Overall, HDB showed clinically proven effects, including skin moisturization with regulation of the skin microbiota.
The host-seeking activity of hematophagous arthropods is essential for arboviral transmission. Here, we demonstrate that mosquito-transmitted flaviviruses can manipulate host skin microbiota to ...produce a scent that attracts mosquitoes. We observed that Aedes mosquitoes preferred to seek and feed on mice infected by dengue and Zika viruses. Acetophenone, a volatile compound that is predominantly produced by the skin microbiota, was enriched in the volatiles from the infected hosts to potently stimulate mosquito olfaction for attractiveness. Of note, acetophenone emission was higher in dengue patients than in healthy people. Mechanistically, flaviviruses infection suppressed the expression of RELMα, an essential antimicrobial protein on host skin, thereby leading to the expansion of acetophenone-producing commensal bacteria and, consequently, a high acetophenone level. Given that RELMα can be specifically induced by a vitamin A derivative, the dietary administration of isotretinoin to flavivirus-infected animals interrupted flavivirus life cycle by reducing mosquito host-seeking activity, thus providing a strategy of arboviral control.
Psoriasis affects the health of myriad populations around the world. The pathogenesis is multifactorial, and the exact driving factor remains unclear. This condition arises from the interaction ...between hyperproliferative keratinocytes and infiltrating immune cells, with poor prognosis and high recurrence. Better clinical treatments remain to be explored. There is much evidence that alterations in the skin and intestinal microbiome play an important role in the pathogenesis of psoriasis, and restoration of the microbiome is a promising preventive and therapeutic strategy for psoriasis. Herein, we have reviewed recent studies on the psoriasis-related microbiome in an attempt to confidently identify the "core" microbiome of psoriasis patients, understand the role of microbiome in the pathogenesis of psoriasis, and explore new therapeutic strategies for psoriasis through microbial intervention.
Commensal fungi of the mammalian skin, such as those of the genus Malassezia, are associated with atopic dermatitis and other common inflammatory skin disorders. Understanding of the causative ...relationship between fungal commensalism and disease manifestation remains incomplete. By developing a murine epicutaneous infection model, we found Malassezia spp. selectively induce IL-17 and related cytokines. This response is key in preventing fungal overgrowth on the skin, as disruption of the IL-23-IL-17 axis compromises Malassezia-specific cutaneous immunity. Under conditions of impaired skin integrity, mimicking a hallmark of atopic dermatitis, the presence of Malassezia dramatically aggravates cutaneous inflammation, which again was IL-23 and IL-17 dependent. Consistently, we found a CCR6+ Th17 subset of memory T cells to be Malassezia specific in both healthy individuals and atopic dermatitis patients, whereby the latter showed enhanced frequency of these cells. Thus, the Malassezia-induced type 17 response is pivotal in orchestrating antifungal immunity and in actively promoting skin inflammation.
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•The skin commensal yeast Malassezia drives type 17 immunity in the skin•Malassezia-specific human memory T cells display a Th17 phenotype•Mice deficient in IL-17AF or IL-23 show uncontrolled Malassezia growth on the skin•In the disrupted skin, IL-23 and IL-17AF promote Malassezia-induced inflammation
The skin commensal yeast Malassezia is associated with common skin disorders like atopic dermatitis, but how the mammalian host responds to Malassezia remains unclear. Using an epicutaneous infection model in mice, Sparber et al. demonstrate that the IL-23-IL-17 pathway controls fungal colonization and also drives Malassezia-induced inflammation in atopy-like skin.
Psoriasis is a chronic skin inflammation influenced by dysregulated skin microbiota, with the role of microbiota in psoriasis gaining increasing prominence. Bacterial extracellular vesicles (bEVs) ...serve as crucial regulators in the interaction between hosts and microbiota. However, the mechanism underlying the therapeutic potential of bEVs from commensal bacteria in psoriasis remains unclear. Here, we investigated the therapeutic role of Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs) in psoriasis treatment. To prolong the active duration of CA-EVs, we encapsulated them in gelatin methacrylate (GelMA) to fabricate hydrogel microspheres (CA-EVs@GHM) with sustained release properties. As GelMA degraded, CA-EVs were gradually released, maintaining a high concentration in mouse skin even 96 hours post-treatment. In human keratinocyte cells (HaCaT), CA-EVs@GHM enhanced resistance to Staphylococcus aureus (S. aureus), promoted proliferation and migration of HaCaT cells exposed to S. aureus, and significantly reduced the expression of inflammatory genes such as interleukin (IL)-6 and C-X-C motif chemokine ligand 8 (CXCL8). In vivo, CA-EVs@GHM, more potent than CA-EVs alone, markedly attenuated proinflammatory gene expression, including tumor necrosis factor (TNF), Il6, Il17a, Il22 and Il23a in imiquimod (IMQ)-induced psoriasis-like mice, and restored skin barrier function. 16S rRNA sequencing revealed that CA-EVs@GHM might provide therapeutic effects against psoriasis by restoring microbiota diversity on the back skin of mice, reducing Staphylococcus colonization, and augmenting lipid metabolism. Furthermore, flow cytometry analysis showed that CA-EVs@GHM prevented the conversion of type 2 innate lymphoid cells (ILC2) to type 3 innate lymphoid cells (ILC3) in psoriasis-like mouse skin, reducing the pathogenic ILC3 population and suppressing the secretion of IL-17 and IL-22. In summary, our findings demonstrate that the long-term sustained release of CA-EVs alleviated psoriasis symptoms by controlling the transformation of innate lymphoid cells (ILCs) subgroups and restoring skin microbiota homeostasis, thus offering a promising therapy for psoriasis treatment. STATEMENT OF SIGNIFICANCE: Cutibacterium acnes, which is reduced in psoriasis skin, has been reported to promote skin homeostasis by regulating immune balance. Compared to live bacteria, bacterial extracellular vesicles (bEVs) are less prone to toxicity and safety concerns. bEVs play a pivotal role in maintaining bacterial homeostasis and modulating the immune system. However, bEVs without sustained release materials are unable to function continuously in chronic diseases. Therefore, we utilized hydrogel microspheres to encapsulate Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs), enabling long term sustained release. Our findings indicate that, CA-EVs loaded gelatin methacrylate hydrogel microspheres (CA-EVs@GHM) showed superior therapeutic effects in treating psoriasis compared to CA-EVs. CA-EVs@GHM exhibited a more significant regulation of pathological type 3 innate lymphoid cells (ILC3) and skin microbiota, providing a promising approach for microbiota-derived extracellular vesicle therapy in the treatment of skin inflammation.
Hair follicles (HFs) function as hubs for stem cells, immune cells, and commensal microbes, which must be tightly regulated during homeostasis and transient inflammation. Here we found that ...transmembrane endopeptidase ADAM10 expression in upper HFs was crucial for regulating the skin microbiota and protecting HFs and their stem cell niche from inflammatory destruction. Ablation of the ADAM10-Notch signaling axis impaired the innate epithelial barrier and enabled Corynebacterium species to predominate the microbiome. Dysbiosis triggered group 2 innate lymphoid cell-mediated inflammation in an interleukin-7 (IL-7) receptor-, S1P receptor 1-, and CCR6-dependent manner, leading to pyroptotic cell death of HFs and irreversible alopecia. Double-stranded RNA-induced ablation models indicated that the ADAM10-Notch signaling axis bolsters epithelial innate immunity by promoting β-defensin-6 expression downstream of type I interferon responses. Thus, ADAM10-Notch signaling axis-mediated regulation of host-microbial symbiosis crucially protects HFs from inflammatory destruction, which has implications for strategies to sustain tissue integrity during chronic inflammation.
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•ADAM10-Notch axis bolsters epithelial innate immunity in IFN-responsive HF cells•Lack of ADAM10-Notch axis leads to follicular dysbiosis predominated by C. mastitidis•Dysbiosis triggers ILC2-mediated inflammation that depends on IL-7R, S1P1R, and CCR6•HFs undergo pyroptotic cell death, resulting in irreversible alopecia
Host symbiosis with commensal microorganisms must be maintained during homeostasis and inflammation. Sakamoto et al. show that the innate epithelial barrier bolstered by ADAM10-Notch signaling in type I interferon-responsive upper hair follicles was crucial for regulating the follicular microbiome, inhibition of which led to downregulation of β-defensin-6, dysbiosis, and inflammatory destruction of hair follicles mediated by innate lymphoid cells.
Background
Atopic dermatitis (AD) is a multifactorial inflammatory skin disease and an altered skin microbiota with an increase of Staphylococcus aureus has been reported. However, the role of fungi ...remains poorly investigated.
Objectives
We aimed to improve the understanding of the fungal skin microbiota, the mycobiota, in AD in relation to the bacterial colonization.
Methods
Skin swabs of 16 AD patients and 16 healthy controls (HC) from four different skin sites, that is antecubital crease, dorsal neck, glabella and vertex from multiple time points were analysed by DNA sequencing of the internal transcribed spacer region 1 (ITS1) and 16S rRNA gene for fungi and bacteria, respectively.
Results
Malassezia spp. were the predominant fungi in all subjects but with a decreased dominance in severe AD patients in favour of non‐Malassezia fungi, for example Candida spp. For bacteria, a decrease of Cutibacterium spp. in AD patients in favour of Staphylococcus spp., particularly S. aureus, was observed. Further, both bacterial and fungal community compositions of severe AD patients significantly differed from mild‐to‐moderate AD patients and HC with the latter two having overall similar microbiota showing some distinctions in bacterial communities.
Conclusions
We conclude that severe AD is associated with a pronounced dysbiosis of the microbiota with increased fungal diversity. Potentially infectious agents, for example Staphylococcus and Candida, were increased in severe AD.
During this study, 690 swabs were taken from different sites divided as the following: First, 350 swabs from surgical instruments, doctor gloves, and antiseptics before beginning cesarean surgery to ...ensure their sterilization. Second, 310 swabs from 70 skins (out of 100) of female patients attending Al-Elwiya Educational Maternity Hospital were taken at the site of cesarean surgery incision before and after sterilization with 10% povidone-iodine and 10% povidone-iodine mixed with 70% ethanol to detect the efficiency of antiseptics and any bacterial invasion might cause post operative infections. Furthermore, 30 swabs from infected surgical sites were taken from 30 female patients with post operative cesarean infections to detect the causative bacterial pathogen. The result of 350 swabs that were all taken from different surgical instruments, doctor gloves, and antiseptics before surgery in all groups showed negative growth culture. The bacterial isolates were primary identified by phenotypic examinations and biochemical tests and final identification by VITEK -2 system. Staphylococcus epidermidis was revealed to be the prevalent bacterial species from all skin sample sources, while Staphylococcus aureus was dominant in surgical site infections. Sterilization with 10% povidone iodine mixed with 70% ethanol showed less bacterial load on skin with a significant decrease in the numbers of isolated bacteria in comparison to use 10% povidone iodine solution alone.
Commensal organisms that constitute the skin microbiota play a pivotal role in the orchestration of cutaneous homeostasis and immune competence. This balance can be promptly offset by the expansion ...of the opportunistic pathogen Staphylococcus aureus, which is responsible for the majority of bacterial skin infections. S. aureus carriage is also known to be a precondition for its transmission and pathogenesis. Recent reports suggest that skin-dwelling coagulase-negative staphylococci (CoNS) can prime the skin immune system to limit the colonization potential of invaders, and they can directly compete through production of antimicrobial molecules or through signaling antagonism. We review recent advances in these CoNS colonization resistance mechanisms, which may serve to aid development of pharmacologic and probiotic intervention strategies to limit S. aureus skin colonization and disease.
Emerging evidence shows that cutaneous host defense relies upon extensive host/commensal cooperation. Resident commensals serve as the 'true' first line of defense at the skin’s surface.Skin commensals, including coagulase-negative staphylococci (CoNS), fortify cutaneous immune competence by broadening the functional repertoire of the skin’s innate and adaptive immune cell networks in a manner that bolsters effector responses against pathogenic microbes, while sparing members of the normal flora.CoNS can employ a diverse array of tactics that directly counter both the carriage and invasion of the common dermatopathogen S. aureus.The therapeutic efficacy of quorum-sensing inhibition has emerged as a promising paradigm for both pharmacologic and probiotic interventions aimed at mitigating S. aureus-induced disease.
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