Skin microbiome and causal relationships in three dermatological diseases: Evidence from Mendelian randomization and Bayesian weighting.

BACKGROUND: Atopic dermatitis (AD), psoriasis (PSO), rosacea, and other related immune skin diseases are affected by multiple complex factors such as genetic and microbial components. This research investigates the causal relationships between specific skin microbiota and these diseases by using Mendelian randomization (MR), and Bayesian weighted Mendelian randomization (BWMR). METHODS: We utilized genome-wide association study (GWAS) data to analyze the associations between various skin bacteria and three dermatological diseases. Single nucleotide polymorphisms (SNPs) served as instrumental variables (IVs) in MR methods, including inverse variance weighted (IVW), and MR Egger. BWMR was employed to validate results and address pleiotropy. RESULTS: The IVW analysis identified significant associations between specific skin microbiota and dermatological diseases. ASV006_Dry, ASV076_Dry, and Haemophilus_Dry were significantly positively associated with AD, whereas Kocuria_Dry was negatively associated. In PSO, ASV005_Dry was negatively associated, whereas ASV004_Dry, Rothia_Dry, and Streptococcus_Moist showed positive associations. For rosacea, ASV023_Dry was significantly positively associated, while ASV016_Moist, Finegoldia_Dry, and Rhodobacteraceae_Moist were significantly negatively associated. These results were corroborated by BWMR analysis. CONCLUSION: Bacterial species such as Finegoldia, Rothia, and Streptococcus play crucial roles in the pathogenesis of AD, PSO, and rosacea. Understanding these microbial interactions can aid in developing targeted treatments and preventive strategies, enhancing patient outcomes and quality of life.

Probiotics suppress LL37 generated rosacea-like skin inflammation by modulating the TLR2/MyD88/NF-κB signaling pathway.

Rosacea, a chronic inflammatory dermatological condition, is characterized by facial erythema and pustules. Recent investigations have delved into the interplay between the gut microbiota and rosacea pathogenesis, unveiling promising avenues for therapeutic intervention. In this study, we screened and isolated strains Ligilactobacillus salivarius 23-006 and Lacticaseibacillus paracasei 23-008 from the feces of healthy volunteers and evaluated the intervention effects of probiotics on rosacea by constructing an LL37 induced rosacea-like mouse model. Our results showed that both L. salivarius 23-006 and L. paracasei 23-008 were probiotic strains with favourable properties. In specific, we observed that both L. salivarius 23-006 and L. paracasei 23-008 alleviated skin lesions, reduced skin inflammatory infiltrates, and decreased the expression of inflammatory factors in mice, with the combination of L. salivarius 23-006 and L. paracasei 23-008 having the most significant effect. Moreover, the combination of strains reduced the expression of cathelicidin LL37 and rosacea-associated factors by inhibiting the TLR2/MyD88/NF-κB pathway. The 16S rRNA analysis showed that the combination enhanced the intestinal barrier, restored intestinal microbiota homeostasis, and up-regulated the abundance of Lactobacillus while down-regulating the abundance of Coprococcus and Oscillospira. We also explored the effects of postbiotics of L. salivarius 23-006 and L. paracasei 23-008 on rosacea. While postbiotics could also ameliorate the rosacea-like phenotype in mice via the TLR2/MyD88/NF-κB pathway, the effects were not as pronounced as those observed with probiotic treatment. However, the postbiotics still enhanced the intestinal barrier, up-regulated the Lactobacillus abundance, and modulated the intestinal microbiota. In conclusion, our study revealed that L. salivarius 23-006 and L. paracasei 23-008 improved rosacea by regulating the TLR2/MyD88/NF-κB pathway and intestinal microbiota, providing a theoretical basis for the treatment of rosacea.

Association between rosacea and helicobacter pylori infection: A meta-analysis.

BACKGROUND AND OBJECTIVES: The potential association between rosacea and a heightened prevalence of Helicobacter pylori (HP) infection has been previously suggested. However, existing studies offer inconsistent results. This systematic review and meta-analysis aimed to elucidate the relationship between rosacea and HP infection. METHODS: We conducted comprehensive searches of PubMed, Embase, and Web of Science databases to identify relevant observational studies for our investigation. We utilized the random-effects model to aggregate the data to address the potential influence of heterogeneity among the studies on the outcome. RESULTS: Our analysis incorporated twenty-five datasets from 23 case-control and cross-sectional studies, encompassing 51,054 rosacea patients and 4,709,074 controls without skin disease. The pooled results revealed a significantly higher prevalence of HP infection in individuals with rosacea compared to controls (odds ratio [OR]: 1.51, 95% confidence interval [CI]: 1.17-1.95, p<0.001; I2 = 79%). Subgroup analysis indicated an increased prevalence of HP infection in rosacea studies that utilized one (OR: 1.72, 95% CI: 1.11-2.66, p = 0.02; I2 = 76%) or more tests for HP infection (OR: 2.26, 95% CI: 1.29-3.98, p = 0.005; I2 = 56%). However, this association was not observed in population-based studies that determined HP infection based on prescription records for HP eradication drugs (OR: 0.90, 95% CI: 0.76-1.07, p = 0.024; I2 = 54%). CONCLUSION: Rosacea may be significantly associated with a higher prevalence of HP infection. High-quality prospective studies with delicately controlled confounding factors are needed to determine if HP infection is a risk factor for rosacea.

Type I IFNs link skin-associated dysbiotic commensal bacteria to pathogenic inflammation and angiogenesis in rosacea.

Rosacea is a common chronic inflammatory skin disease with a fluctuating course of excessive inflammation and apparent neovascularization. Microbial dysbiosis with a high density of Bacillus oleronius and increased activity of kallikrein 5, which cleaves cathelicidin antimicrobial peptide, are key pathogenic triggers in rosacea. However, how these events are linked to the disease remains unknown. Here, we show that type I IFNs produced by plasmacytoid DCs represent the pivotal link between dysbiosis, the aberrant immune response, and neovascularization. Compared with other commensal bacteria, B. oleronius is highly susceptible and preferentially killed by cathelicidin antimicrobial peptides, leading to enhanced generation of complexes with bacterial DNA. These bacterial DNA complexes but not DNA complexes derived from host cells are required for cathelicidin-induced activation of plasmacytoid DCs and type I IFN production. Moreover, kallikrein 5 cleaves cathelicidin into peptides with heightened DNA binding and type I IFN-inducing capacities. In turn, excessive type I IFN expression drives neoangiogenesis via IL-22 induction and upregulation of the IL-22 receptor on endothelial cells. These findings unravel a potentially novel pathomechanism that directly links hallmarks of rosacea to the killing of dysbiotic commensal bacteria with induction of a pathogenic type I IFN-driven and IL-22-mediated angiogenesis.

Actinocatenispora comari sp. nov., an endophytic actinomycete isolated from aerial parts of Comarum salesowianum.

A novel actinomycete, designated NUM-2625T, was isolated as an endophytic bacterium in aerial parts of Comarum salesowianum, an endemic species in the Altai, Himalaya mountain chain area, collected from Khasagt Khairkhan Mountain in Mongolia. The 16S rRNA gene sequence of strain NUM-2625T showed the highest similarity to Actinocatenispora thailandica TT2-10T (99.4 %), Actinocatenispora sera KV-744T (99.3 %), and Actinocatenispora rupis CS5-AC17T (97.7 %). Chemotaxonomic properties of strain NUM-2625T were essentially consistent with those of the genus Actinocatenispora, such as the presence of meso-diaminopimelic acid as the diagnostic diamino acid of the peptidoglycan, MK-9(H4) and MK-9(H6) as the major menaquinones, and iso-C16 : 0, iso-C15 : 0, iso-C14 : 0 3-OH, and anteiso-C17 : 0 as the major fatty acids. Meanwhile, digital DNA-DNA hybridization and average nucleotide identity values revealed a low relatedness between strain NUM-2625T and the other type strains of the genus Actinocatenispora. In addition, strain NUM-2625T exhibited several phenotypic properties that could be used to distinguish it from its closest relatives. Based on the results of polyphasic analyses, strain NUM-2625T represents a novel species in the genus Actinocatenispora, for which the name Actinocatenispora comari sp. nov. is proposed. The type strain is NUM-2625T (=NBRC 114660T=TBRC 13496T).

Dermoscopy of papulopustular rosacea and comparison of dermoscopic features in patients with or without concomitant Demodex folliculorum.

BACKGROUND: The dermoscopic findings of papulopustular rosacea include tiny papules and pustules, follicular plugs and follicular dilatation. Demodex tails and Demodex follicular openings are dermoscopic indicators that are mainly found in primary demodicosis and, less frequently, in rosacea. AIM: To describe the dermoscopic features of papulopustular rosacea and to investigate the differential dermoscopic features between patients with and without concomitant Demodex infestation. METHODS: We conducted a prospective study of patients with almost-clear, mild or moderate papulopustular rosacea. For each patient, dermoscopic images were taken and a standardized skin surface biopsy was performed. RESULTS: In this group of 60 patients, the most frequent dermoscopic findings were yellow dots, vascular polygons and follicular scales. Patients with moderate rosacea had more Demodex follicular openings compared with patients with mild rosacea (P = 0.02), while patients with mild rosacea had a higher frequency of follicular scales than did patients with almost-clear rosacea (P = 0.01). Patients with moderate rosacea had higher rates of Demodex follicular openings (P = 0.02), follicular scales (P < 0.001), follicular annular pigmentation (P = 0.001) and follicular pustules (P < 0.001) compared with patients with almost-clear rosacea. No significant dermoscopic differences were observed between patients with and without concomitant Demodex infestation. CONCLUSIONS: Papulopustular rosacea has specific dermoscopic findings. In our opinion, dermoscopy is not sufficient by itself for the diagnosis of Demodex proliferation in rosacea.

Evidence of Barrier Deficiency in Rosacea and the Importance of Integrating OTC Skincare Products into Treatment Regimens.

BACKGROUND: Rosacea, an inflammatory skin disease that leads to an impaired skin barrier function commonly involves the face. Symptoms of rosacea can be bothersome and include pain, stinging, burning, itching, and facial flushing. This review explored skin barrier impairment in rosacea and reduced symptomatology when using over the counter (OTC) skincare products. METHODS: Nine dermatologists (the panel) completed a survey on OTC products they recommend for rosacea. The survey results were summarized, presented, and discussed during the online meeting, together with the results of a literature review. The outcome of these discussions, coupled with the panel's expert opinion and experience, is shown in the current review. RESULTS: Addressing barrier dysfunction by use of moisturizer and cleanser formulations that restore skin hydration, normalize skin pH, restore the microbiome, and skin lipids can assist in improving rosacea signs and symptoms. The panel's consensus was that in addition to the use of prescription medications, skincare recommendations are a crucial part of successful rosacea therapy. In addition to occlusives and humectants, barrier restoring ingredients such as ceramides, hyaluronic acid, and niacinamide were considered beneficial. Equally important was the absence of potentially irritating substances. CONCLUSIONS: The use of OTC products can improve rosacea symptomatology and signs. As adjuncts, these products are recommended before and during prescription therapy and as part of a maintenance regimen. J Drugs Dermatol. 20(4):384-392. doi:10.36849/JDD.5861 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL fTEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Oral Sarecycline for Treatment of Papulopustular Rosacea: Results of a Pilot Study of Effectiveness and Safety.

BACKGROUND: Cutaneous rosacea is a common inflammatory skin disorder that often presents with facial papulopustular lesions that are frequently bothersome to patients. Studies have shown oral sarecycline to be effective and safe for acne, with a low risk of side effects that are historically associated with other tetracycline-class drugs such as doxycycline and minocycline, in addition to offering a reduced risk of emergence of resistant bacteria due to its narrow-spectrum of antibiotic activity. Oral sarecycline is FDA-approved for the treatment of acne (2018). OBJECTIVE: A pilot study to evaluate the efficacy and safety of oral sarecycline in papulopustular rosacea. METHODS: A 12-week, prospective, parallel-group, investigator-blinded, controlled pilot study was completed evaluating once-daily sarecycline, using weight-based oral dosing as recommended for acne vs control (multivitamin tablet), for the treatment of moderate-to-severe papulopustular rosacea in adult subjects (n=102), aged ≥18 years. The primary efficacy endpoint was Investigator's Global score (IGA; clear or almost clear) and percent reduction in inflammatory lesion count at week 12. Safety and tolerability assessments were performed as well. RESULTS: A total of 102 subjects were randomized; 97 completed the study. At week 12, IGA improvement was significantly greater for oral sarecycline when compared to the control (P<0.0001). Furthermore, absolute and percent reductions in inflammatory lesion counts were significantly greater in the sarecycline group for all weeks (4, 8, and 12) when compared to the control (P<0.001). Significant improvement in facial burning, erythema, and pruritus was reported in the sarecycline group, when compared to the control (P<0.05). No serious AEs were reported. CONCLUSION: Sarecycline was effective, safe, and well-tolerated for treating papulopustular rosacea in adults with marked superiority in efficacy compared to subjects in the control group. With its narrow-spectrum activity, oral sarecycline may be a good option for the treatment of papulopustular rosacea. Additional studies are warranted to confirm the positive results of this pilot study.

Interactions between immune system and the microbiome of skin, blood and gut in pathogenesis of rosacea.

The increasingly wide use of next-generation sequencing technologies has revolutionised our knowledge of microbial environments associated with human skin, gastrointestinal tract and blood. The collective set of microorganisms influences metabolic processes, affects immune responses, and so directly or indirectly modulates disease. Rosacea is a skin condition of abnormal inflammation and vascular dysfunction, and its progression is affected by Demodex mites on the skin surface. When looking into the effects influencing development of rosacea, it is not only the skin microbiome change that needs to be considered. Changes in the intestinal microbiome and their circulating metabolites, as well as changes in the blood microbiome also affect the progression of rosacea. Recent research has confirmed the increased presence of bacterial genera like Acidaminococcus and Megasphera in the intestinal microbiome and Rheinheimera and Sphingobium in the blood microbiome of rosacea patients. In this review we discuss our current knowledge of the interactions between the immune system and the skin, gut and blood microbiome, with particular attention to rosacea diagnostic opportunities.

Comparison of the skin microbiota in acne and rosacea.

Acne and rosacea, despite their similar clinical presentations, follow distinct clinical courses, suggesting that fundamental differences exist in their pathophysiology. We performed a case-control study profiling the skin microbiota in rosacea and acne patients compared to matched controls. Nineteen rosacea and eight acne patients were matched to controls by age ± 5 years, sex and race. DNA was extracted from facial skin swabs. The V3V4 region of the bacterial 16S rRNA gene was sequenced using Illumina MiSeq and analysed using QIIME/Metastats 2.0 software. The mean relative abundance of Cutibacterium acnes in rosacea with inflammatory papules and pustules (20.454% ±16.943%) was more similar to that of acne (19.055% ±15.469%) than that of rosacea without inflammatory papules and pustules (30.419% ±21.862%). C acnes (P = .048) and Serratia marcescens (P = .038) were significantly enriched in individuals with rosacea compared to acne. Investigating the differences between the skin microbiota in acne and rosacea can provide important clues towards understanding the disease progression in each condition.

Microbiota in Rosacea.

Rosacea is a complex facial skin condition associated with abnormal inflammation and vascular dysfunction. Next to the known trigger factors, the role of microbiota in the development and aggravation of rosacea continues to raise interest. Demodex folliculorum mites, Helicobacter pylori, Staphylococcus epidermidis, Chlamydia pneumoniae, and the Demodex-associated bacterium, Bacillus oleronius are microbes that have been linked with rosacea. However, the results of studies which assessed their involvement in the disease have been inconsistent and inconclusive. Microbiological research in many different disciplines exploded in recent years as methods to analyze complex microbial communities at the taxonomic and phylogenetic levels became available. Here, we provide an update on the microorganisms implicated in rosacea and review the potential pathogenic role of microbes in the development of rosacea.

Rosacea is associated with conjoined interactions between physical barrier of the skin and microorganisms: A pilot study.

BACKGROUND: Rosacea is a common condition characterized by transient or persistent central facial erythema, and often papules and pustules. Currently, the role of bacterium in the development and progression of rosacea remains controversial. This study aimed to investigate the difference in the physiological conditions and microorganisms between the lesional and non-lesional areas of papulopustular rosacea. METHODS: Twenty-five French patients with papulopustular rosacea were enrolled in this pilot study. Each patient was subjected to clinical assessment, and the skin barrier function was tested in lesional and non-lesional areas. In addition, samples from the lesional and non-lesional areas were collected for bacterial culturing. RESULTS: Of all subjects included in the study, a lower skin conductivity was measured in lesional areas than in non-lesional areas (43.5 ± 12.4 vs. 57.2 ± 11.6 U, P < .05), and a higher transepidermal water loss (TEWL) value was found in lesional areas than in non-lesional areas (17.2 ± 5.9 vs. 14.2 ± 4.1 g/(m2  h), P < .05). We found a lower TEWL in lesions in rosacea patients with bacterial dysbiosis than in those with bacterial balance (P < .05). In addition, there were significant differences in the skin conductivity and TEWL between lesional and non-lesional areas in patients with bacterial dysbiosis (P < .001), and no significant differences were seen in patients with bacterial balance (P < .05). CONCLUSION: The results of the present study demonstrate that the physiological features of rosacea are closely associated with the interactions between the host and the microorganisms.

[THE ROLE OF HELICOBACTER PYLORI IN ROSACEA AND PATHOGENETIC TREATMENT].

Rosacea is a chronic, recurrent skin disease. It may be aggravated by various factors. An increased incidence of rosacea has been reported in those who carry the stomach bacterium Helicobacter pylori. The purpose of this study was determination of the relationship of this infection with rosacea and to investigate effectiveness of eradication therapy of H. pylori. As our results showed, 80.9% of study patients were infected with H. pillory. There was correlation between infection rates and rosacea severity. In most cases the positive test results for H. Pylori was found in patients with moderate to severe form of disease. The results of the treatment of different forms of rosacea confirmed the effectiveness of the eradication therapy of H. Pylori, regarding as one of the pathogenic cause of rosacea and the way in the choice of treatment. More wide studies of pathophysiological aspects of causes of rosacea will be promising and help in treating rosacea. These data indicate the important role of H.Pylori in the development of rosacea and recommend taking into account in the therapy of this dermatosis.

Characterization and Analysis of the Skin Microbiota in Rosacea: A Case-Control Study.

BACKGROUND: The efficacy of antibiotics in rosacea treatment suggests a role for microorganisms in its pathophysiology. Growing concern over the adverse effects of antibiotic use presents a need for targeted antimicrobial treatment in rosacea. OBJECTIVE: We performed a case-control study to investigate the skin microbiota in patients with rosacea compared to controls matched by age, sex, and race. METHODS: Nineteen participants with rosacea, erythematotelangiectatic, papulopustular, or both, were matched to 19 rosacea-free controls. DNA was extracted from skin swabs of the nose and bilateral cheeks of participants. Sequencing of the V3V4 region of the bacterial 16S ribosomal RNA gene was performed using Illumina MiSeq and analyzed using QIIME/MetaStats 2.0 software. RESULTS: Compared with controls, skin microbiota in erythematotelangiectatic rosacea was depleted in Roseomonas mucosa (p = 0.004). Papulopustular rosacea was enriched in Campylobacter ureolyticus (p = 0.001), Corynebacterium kroppenstedtii (p = 0.008), and the oral flora Prevotella intermedia (p = 0.001). The highest relative abundance of C. kroppenstedtii was observed in patients with both erythematotelangiectatic and papulopustular rosacea (19.2%), followed by papulopustular (5.06%) and erythematotelangiectatic (1.21%) rosacea. C. kroppenstedtii was also associated with more extensive disease, with the highest relative abundance in rosacea affecting both the cheeks and nose (2.82%), followed by rosacea sparing the nose (1.93%), and controls (0.19%). CONCLUSIONS: The skin microbiota in individuals with rosacea displays changes from that of healthy skin, suggesting that further studies examining a potential role for the skin microbiota in the pathophysiology of rosacea may be warranted.

The Use of Oral Antibiotics in the Management of Rosacea

Rosacea is common inflammatory facial dermatosis. Rosacea has variable manifestations including facial flushing, central facial erythema, telangiectasias, and papulopustular lesions. Treatment of rosacea is challenging given the varied manifestations and incompletely understood etiology, but the treatment of papulopustular presentations often relies on oral antibiotics. Tetracyclines, specifically doxycycline, are the most commonly prescribed antibiotics for rosacea. Other antibiotics that can be used include macrolides, commonly azithromycin, and rarely, metronidazole. This paper will review the evidence for the use of antibiotics in the treatment of rosacea. J Drugs Dermatol. 2019;18(6):506-513.

The microbiome in dermatology.

The skin supports a delicate ecosystem of microbial elements. Although the skin typically acts as a barrier, these microbes interact with the internal body environment and imbalances from the "healthy" state that have been linked to several dermatologic diseases. Understanding the changes in microbial flora in disease states allows for the potential to treat by restoring equilibrium. With the rising popularity of holistic and natural consumerism, prebiotics, probiotics, symbiotic, and other therapies are under study to find alternative treatments to these skin disorders through manipulation or supplementation of the microbiome.

Analysis of the effect of temperature on protein abundance in Demodex-associated Bacillus oleronius.

A potential role for bacteria in the induction of rosacea has been suggested. The aim of this work was to characterise the effect of temperature on the production of immunostimulatory proteins by Bacillus oleronius-a bacterium to which rosacea patients show sera reactivity and which was originally isolated from a Demodex mite from a rosacea patient. The affected skin of rosacea patients is at a higher temperature than unaffected skin, and it was postulated that this might alter the protein expression pattern of B. oleronius. B. oleronius growth was reduced at 37°C compared to 30°C but resulted in increased expression of the immune-reactive 62kDa protein (1.65 fold [P < 0.05]). Proteomic analysis revealed increased abundance of a wide range of proteins involved in the stress response (e.g. stress proteins [21.7-fold increase], phosphocarrier protein HPr [438.5-fold increase], 60 kDa chaperonin [12.6-fold increase]). Proteins decreased in abundance after growth at 37°C included ferredoxin (325-fold decrease) and peptidase (244-fold decrease). This work indicates that the increased skin temperature of rosacea patients may alter the growth and protein production pattern of B. oleronius and lead to the greater production of immuo-stimulatory proteins.

Rosacea Pathogenesis.

Rosacea is a chronic inflammatory skin disorder that is not fully understood but involves the complex interplay of genetic factors, immune dysregulation, neurovascular dysregulation, presence of microorganisms, and environmental factors. Increased activation of the immune system occurs through multiple stimuli, including increased levels of cathelicidin and kallikrein 5, Toll-like receptor 2, matrix metalloproteinases, and mast cells within the skin. Their effects are enhanced by the presence of microorganisms and external triggers, such as UV radiation.