109 Microbiome Alterations in Rosacea: A Multi-Site Analysis of Stool, Blood, and Skin Dysbiosis

Introduction: Staphylococcus aureus and Staphylococcus epidermidis are major contributors to skin dysbiosis and infections, e.g. folliculitis and intravascular catheter infections, forming biofilms that enhance their resistance to antibiotics and immune responses. Given that antibiotic resistance is a serious challenge, new solutions are constantly being explored. The endocannabinoid system is essential for maintaining skin homeostasis, regulating inflammation, and promoting skin regeneration. Cannabidiol has been shown to have antimicrobial properties and therapeutic effects on some pathophysiological skin conditions, e.g. chronic and uremic pruritus, by modulating the endocannabinoid system. However, cannabidiol has properties that limit its bioavailability when applied to the skin. Although it has an adequate molecular weight, its high logP value limits permeation into the skin’s deeper layers. To address these limitations and improve cannabidiol stability, it is proposed that it will be loaded in nanostructured lipid carriers. Since biofilms make infections more difficult to treat, studying nanostructured lipid carriers-cannabidiol's effects on these bacterial communities could provide insight into alternative or complementary therapeutic strategies. Objectives: By assessing nanostructured lipid carriers-cannabidiol’s ability to target these biofilms, researchers aim to explore its potential role in improving treatments for skin infections. Methodology: Six nanostructured lipid carriers formulations (three nanostructured lipid carriers- and three nanostructured lipid carriers+), with and without cannabidiol, were prepared using a modified melt emulsification method followed by ultrasonication, stored at 4ºC, and physicochemical properties were measured over 8 weeks. Results: With no significant change in zeta potential (ZP) (–29.91 to –29.93 mV; P = 0.9999), nanostructured lipid carriers-cannabidiol showed the highest stability. Although a statistically significant reduction in particle size was observed (224.14 to 213.24 nm; P < 0.0001), stability was not affected, with a low polydispersity index (0.2076±0.0133) indicating a homogenous particle distribution. FTIR spectra reveal the characteristic bands of cannabidiol, confirming cannabidiol’s encapsulation efficiency (%) higher than 99%. After 48 hours, treatment with nanostructured lipid carriers-cannabidiol resulted in a significant reduction in bacterial biofilm viability, with a decrease of approximately 2.5 and 1.5 log CFU/mL in S. aureus and S. epidermidis, respectively. Discussion: ... Conclusions: The results demonstrate the potential of nanostructured lipid carriers- to improve cannabidiol’s biofilm delivery and penetration. In conclusion, cannabidiol-loaded negatively charged nanostructured lipid carriers may be a promising strategy as anti-biofilm treatment.

BackgroundHuman papillomavirus (HPV) is the most frequent sexually transmitted virus, with high importance due its oncogenic risk. Previous studies have reported an association between genital dysbiosis and HPV infection in women and also in men co-infected with HPV and HIV. However, it remains to be determined whether penile skin dysbiosis is associated with HPV infection in men who are HIV-negative. This study characterizes the penile skin microbiota (PSM) of HPV-positive and HPV-negative men, hypothesizing that HPV infection is linked to dysbiotic anaerobic-dominated communities.MethodsA cross-sectional study was conducted on 103 sexually active HIV-negative men (70 HPV-negative, 33 HPV-positive). Those who tested HPV-positive were genotyped. The PSM of all samples was analyzed using 16S rRNA sequencing of the V4 region. Alpha and beta diversity were compared. Community State Types (CSTs) were identified using hierarchical clustering. Associations between CSTs and HPV status were tested adjusting for sexual preference.ResultsHPV-positive men exhibited significantly higher microbial richness than HPV-negative men (Chao1 p = .02), particularly those with high-risk genotypes (Chao1 p = .03). Five CSTs were identified, with CST-5 (dominated by Finegoldia and other anaerobes) showing a three-fold higher likelihood of HPV positivity (OR = 3.11, 95% CI: 1.22-8.22) compared to other CSTs. CST-5 also displayed reduced abundance of commensals like Corynebacterium and Staphylococcus.ConclusionsSubclinical HPV infection in HIV-negative men was associated with a dysbiotic PSM, characterized by an increased abundance of anaerobic bacteria alongside with a reduced proportion of facultative anaerobic genera. These findings suggest that PSM composition may influence HPV susceptibility or persistence. Longitudinal studies are needed to explore causality.

Microbial homeostasis and dysbiosis in physiological and pathological skin.

Melatonin-mediated intestinal microbiota homeostasis improves skin barrier damage involvement of gut-skin axis dysfunction in aging mice.

0596 The role of skin dysbiosis in the progression of pediatric atopic dermatitis to asthma

In the last few decades, the number of studies on the microbiota and microbiome of living organisms inhabiting the skin has grown rapidly, and the contribution of the microbial community to the realization of skin functions and the pathogenesis of dermatoses is of great scientific and public interest. Understanding the contribution of skin dysbiosis to skin aging, sensitization, and the pathogenesis of chronic dermatoses has prompted the development of strategies aimed at correcting the skin microbiota. One of the directions of bacteriotherapy of skin diseases is the use of biotic complexes, which include metabiotics of human commensal bacteria and prebiotics. The use of biotic complexes allows to effectively modulate the skin microbiome and its barrier functions. A practical embodiment of the use of metabiotics of probiotic bacteria as part of biotic complexes was the development of active skin care systems containing lysates of probiotic microorganisms Lactococcus, Lactobacillus and Bifidobacterium and prebiotics trehalose and inulin. These products can be enhanced with active ingredients with proven efficacy, such as panthenol, jojoba oil, shea butter and others that provide skin cleansing, moisturizing and nourishing. The conducted studies have demonstrated the effectiveness and safety of products with enhanced formula as part of complex treatment of patients with atopic dermatitis. Their clinical effects are based on the restoration of the skin barrier (according to the dynamics of pH-metry, transepidermal water loss and skin elasticity), as well as normalization of the microbial composition of the skin (reduction in the frequency of identification of phylum, which belong to opportunistic microorganisms, and reduction in the frequency of identification of the Staphylococcaceae family, pathogenic representatives of which lead to increased inflammation and allergic reactions on the skin).

Epidermolysis bullosa (EB) is a group of rare, heterogeneous congenital conditions characterised by epidermal fragility, resulting in blister formation and lesions. Patients with EB are prone to developing cutaneous wounds. However, the composition of the EB skin microbiome in Chinese individuals remains poorly understood. The objective was to investigate the EB skin microbiome in Chinese individuals. The clinical symptoms and laboratory tests were collected for a total of 29 EB patients (23 Recessive Dystrophic EB, 3 EB simplex, 2 Kindler syndrome, and 1 Dominant Dystrophic EB). A total of 120 swabs were collected from 62 lesion sites, 29 non-lesion skin areas, and 29 nostrils. These samples underwent 16S rRNA amplicon sequencing and bacterial culture. The epidemiology of S. aureus was characterised, and its features were analysed using an animal model. Patients with EB exhibited a characteristic inflammatory response, marked by cutaneous lesions and elevated levels of C-reactive protein (CRP) and serum amyloid (SAA). Consistently, skin dysbiosis in EB patients was characterised by a predominance of S. aureus, particularly sequence type (ST) 7. Specifically, the abundance of S. aureus showed a positive correlation with EB severity and activity. Mechanistically, S. aureus isolated from lesional skin exhibited higher virulence due to increased accessory gene regulator (Agr) activity. Our study reported altered bacterial diversity and increased carriage of higher-virulence S. aureus in Chinese EB patients, which may potentially influence disease severity through microbiome alterations. Our findings suggested that maintaining the balance of the microbiome is crucial for optimising patient care.

Relationship between skin and gut microbiota dysbiosis and inflammatory skin diseases in adult patients: A systematic review

Background: Hidradenitis suppurativa (HS) is a chronic, disabling, and disfiguring inflammatory disease with a complex, incompletely elucidated pathogenesis. The role of skin dysbiosis in the development and progression of HS has not yet been clarified. Methods: We performed an observational, prospective culture-based study that included 40 HS patients and analyzed the bacterial load and diversity in HS skin lesions, their correlation with disease severity, and several host and environmental factors. Additionally, we investigated the prevalence of antibiotic resistance and determined the resistance profile of bacterial strains isolated from chronic HS lesions. Results: An impressive number and diversity of bacterial strains were isolated from both superficial and deep HS lesions. 201 aerobic and anaerobic bacterial strains were isolated, polymicrobial growth being detected in the majority of samples. The most frequently isolated bacteria were Staphylococcus epidermidis, Staphylococcus aureus, Staphylococcus lugdunensis, Peptoniphilus spp., and Enterococcus faecalis in superficial lesions and Staphylococcus epidermidis, Staphylococcus aureus, and Corynebacterium tuberculostearicum in deep lesions. A significantly higher bacterial density and diversity was found in male patients, regardless of the affected area and in patients with severe HS. The proportion of bacterial strains resistant to antibiotics was lower in our study (8.95%) compared to the previously reported data. Conclusions: Our findings indicate dysbiosis as a key player in the initiation and maintenance of the inflammatory process in HS. Further large-scale, prospective studies are required to comprehensively characterize the microbiological landscape of HS and shed light on its contribution in the pathogenesis of the disease.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder influenced by both genetic and environmental factors, collectively termed the exposome. Among these determinants, diet emerges as a pivotal component, with diverse nutrients, contaminants, and additives shaping immune responses, microbiota composition, and systemic inflammatory status. This literature review aimed to elucidate the interplay between dietary factors and skin dysbiosis in AD, providing insights into how these interactions may impact disease susceptibility and progression. A comprehensive search of PubMed and Scopus was conducted using relevant keywords and medical subject headings (MeSH). Studies published in English within the past 25 years were included, encompassing in vitro, in vivo, and ex vivo research, as well as reviews. Priority was given to frequently cited articles, reflecting significant contributions to current understanding. Findings suggest that dietary habits influence AD by modulating both gut and skin microbiota, immune pathways, and inflammatory processes. These insights underscore the importance of considering diet within a broader exposome framework, paving the way for targeted interventions to improve AD management. Further research is needed to clarify the mechanisms and optimize nutritional strategies, potentially informing preventive and therapeutic approaches for AD.

Objective This study aims to analyze the different therapeutic responses between topical antimicrobial–corticosteroid combination and topical corticosteroids alone on improving the skin microbiome and skin barrier of patients with atopic dermatitis (AD). Methods Forty patients with mild-to-moderate AD were randomly assigned to receive two kinds of treatment. Skin swabs were collected from the lesional sites and nearby nonlesional sites at baseline, after topical medication treatment and 2 weeks post-treatment, and were analyzed by DNA sequencing of the fungal internal transcribed spacer (ITS)1–5 rDNA gene and the V3V4 region of the bacterial 16S rRNA gene. Results According to our research analysis, both topical steroids alone and combination treatment of steroids and antimicrobials effectively improved the severity of AD and repaired skin barrier. AD lesions were characterized by a decreased sebum level, lower abundance of Cutibacterium and a higher abundance of Staphylococcus. A combined topical treatment with an antimicrobial and steroid showed better responses in increasing skin sebum level and restoring the skin bacterial microbiome, whereas topical steroid alone did not improve skin dysbiosis. Conclusion A combined therapy with antimicrobial and steroid helps to recover the skin microbiome. Further studies are necessary to explore the therapeutic effects of treatments aiming at balancing the microbiome.

Hypocrellin A-mediated photodynamic antibacterial activity against Cutibacterium acnes: An in vitro study.

Information on skin barrier in horses is limited. A study on the epidermal ultrastructure of normal and allergic horses documented disorganized amorphous intercellular lipids in the stratum corneum of allergic samples. These findings are similar to atopic canine and human skin. Currently, there is no published study comparing skin barrier function parameters between normal and allergic horses; thus, the functional implications of the ultrastructural changes are unknown. In normal horses, body location, gender, breed, and ambient conditions affect skin barrier parameters, such as Transepidermal Water Loss. Skin microbiome studies on normal horses have highlighted the importance of season and environmental conditions, since horses housed together share similar microbiomes. Skin dysbiosis and predominance of staphylococcus have been described in horses with pastern dermatitis. Transcriptomic studies of the epidermis of normal and allergic horses have found that lesional allergic skin has substantial transcriptomic differences when compared with healthy skin, namely downregulation of genes of tight junctions, keratins, and upregulation of serine proteases and IL-13. Keratinocytes harvested from horses with insect bite hypersensitivity show upregulation of IL-31 gene expression under stimulation. While more research is clearly needed, preliminary results seem to support skin barrier differences between normal and allergic horses.

Staphylococcus epidermidis is an opportunistic bacterium that causes acne vulgaris. Under conditions of skin dysbiosis, S. epidermidis can form biofilms, which is resistant to antibiotics, thus it is necessary to develop antibiofilm agents. This study examines the activity of a lotion with the addition of palmarosa essential oil (C. martini) as an antibiofilm agent against S. epidermidis. This study is designed to determine the minimum inhibitory concentration (MIC) of palmarosa essential oil against S. epidermidis and evaluate the inhibition and degradation activity of S. epidermidis biofilms by palmarosa essential oil and lotion with added palmarosa essential oil. MIC testing and antibiofilm activity were conducted using the 96-well plate microdilution method. This study employed a completely randomized design (CRD) with 6 variations of essential oil concentrations in the lotion (0, 0.5, 1, 2, 2.5, and 3 times the MIC) and 5 replications of analysis. Based on the research, it was found that palmarosa essential oil has minimum inhibition concentration (MIC) at 2 mg/mL against S. epidermidis, while lotion with the addition of 6 mg/mL or equal to 3 MIC palmarosa essential oil showed 44.36% inhibition activity and 39.92% degradation activity against S. epidermidis biofilms.

091 Neonatal skin dysbiosis and altered Th2/Th17 signaling are associated with the development of infantile atopic dermatitis

Acne is a multifactorial inflammatory disease with a robust microbial component and numerous correlations with dysbiosis states. Furthermore, various factors are recognized as triggers for skin dysbiosis, including the use of certain cosmetics. Based on these arguments, we hypothesized that using photoprotective formulations could trigger dysbiosis and the occurrence of acne manifestations. To verify this assumption, six volunteers between 19 and 23 years of age, meeting all the inclusion criteria, received two applications a day of a non-commercial sunscreen formulation developed with the sun filters ethylhexyl methoxycinnamate, ethylhexyl salicylate, methyl anthranilate, and octocrylene dispersed in a base gel, with an estimated protection factor of 28.8. The pure base gel was used as a control. The samples were applied to an area delimited by a standard template (15 cm2) in an amount corresponding to 30mg (2mg cm2) for ten days. At two points in time, pre- and post-sample applications, the facial skin surface was swabbed to collect extracted DNA and processed to verify divergent degrees of 16S RNA coding sequences. The data obtained allowed us to determine the abundance of different bacterial entities at the genus and species levels. The results showed that critical species of the acne process, such as Cutibacterium acnes and Staphylococcus epidermidis, seem to tolerate the evaluated formulation well and are not significantly affected by the formulation, suggesting no interference of its use concerning dysbiosis induction. These findings refute the idea that photoprotectors may cause skin dysbiosis in men.

Infection is the most common complication of atopic dermatitis (AtD). In particular, some patients with AtD exhibit increased susceptibility to skin infections of bacterial, viral, and fungal etiologies. In some cases, infections can even be systemic. Bacterial skin infections are more common than viral and fungal ones. An especially severe infection caused by the herpes virus is herpetic eczema, which can cause life-threatening complications. Infections of fungal etiology are represented mainly by the Malassezia species, especially in patients with dermatitis of the head and neck. The review focuses on the pathophysiological mechanisms identified to date that are thought to predispose to skin infections. The main ones are impaired skin barrier function, complex immunological changes, as well as poorly understood factors such as environmental exposure and skin dysbiosis. The review also includes the clinical characteristics of patients with various skin infections, as well as appropriate treatment for complications of AtD.

Psoriasis is a common chronic inflammatory skin disease, associated with significant morbidity and a considerable negative impact on the patients' quality of life. The complex pathogenesis of psoriasis is still incompletely understood. Genetic predisposition, environmental factors like smoking, alcohol consumption, psychological stress, consumption of certain drugs, and mechanical trauma, as well as specific immune dysfunctions, contribute to the onset of the disease. Mounting evidence indicate that skin dysbiosis plays a significant role in the development and exacerbation of psoriasis through loss of immune tolerance to commensal skin flora, an altered balance between Tregs and effector cells, and an excessive Th1 and Th17 polarization. While the implications of skin dysbiosis in psoriasis pathogenesis are only starting to be revealed, the progress in the characterization of the skin microbiome changes in psoriasis patients has opened a whole new avenue of research focusing on the modulation of the skin microbiome as an adjuvant treatment for psoriasis and as part of a long-term plan to prevent disease flares. The skin microbiome may also represent a valuable predictive marker of treatment response and may aid in the selection of the optimal personalized treatment. We present the current knowledge on the skin microbiome changes in psoriasis and the results of the studies that investigated the efficacy of the different skin microbiome modulation strategies in the management of psoriasis, and discuss the complex interaction between the host and skin commensal flora.

Abstract Introduction Atopic Dermatitis (AD) is a chronic relapsing inflammatory skin condition that is evolvingly perceived as a systemic disease, particularly when severe. The therapeutic ladder for managing AD has undergone substantial expansion in the last decade as new pathways are revealed, yet 75% of patients are not satisfied with their management of AD. While patients may report symptom relief, AD often requires ongoing treatment, increased dosage, or alternating regimens. For those patients who appear to respond well over a prolonged period, it is unclear whether they will tolerate treatment cessation. Objective To evaluate the current therapeutic options available for AD from the standpoint of their disease-modifying vs. disease-suppressing capabilities. Methods A systematic review of the literature was performed using academic research databases including PubMed and Embase between 1994 and 2024. The studies extracted from the search included, but were not limited to, randomized placebo-controlled trials, systematic reviews, cross-sectional studies, observational studies, case series, case reports, and retrospective studies. Current and emerging therapies for the treatment of AD were assessed for their ability to modify underlying disease mechanisms, and/or induce disease remission. Results Although several of the drugs that are currently approved for AD target the pathogenic Th2 axis, Janus Kinase (JAK) inhibitors have the most supporting evidence for their ability to modify underlying disease mechanisms. Inhibiting distinct JAK families hinders the downstream effects of multiple cytokines involved in AD at once. In some case reports, patients treated with selective JAK-1 inhibitors for up to 6 months did not experience disease recurrence following cessation during a several-month follow-up period. Similar studies of certain biological agents have shown prolonged periods of remission after discontinuation of dupilumab, tralokinumab, and lebrikizumab. This suggests that they may also drive long-lasting cellular changes, especially when implemented in early disease. Targeting OX40 or its ligand, the OX40L, may also hold promise for modifying AD. Studies have additionally indicated that there may be a therapeutic window of opportunity for maximal treatment impact in AD. Early intervention shortly after pediatric onset of disease may lead to improved long-term control and reduced comorbidity development. Novel disease-modifying strategies are currently being investigated in clinical trials for their capacity to correct skin and gut dysbiosis, restore epidermal barrier integrity, and alter innate and adaptive immune responses. Conclusions Recent progress in drug development has greatly advanced symptom control in patients with AD. However, only a few, if any, therapeutic strategies have demonstrated long-term disease modification. There is an unmet need to study the rate of recurrence upon cessation of current AD therapies. Future research should prioritize the development of therapeutic interventions for AD that not only treat symptoms but also modify the underlying disease pathology over time.