High α-diversity of skin microbiome and mycobiome in Japanese patients with vitiligo.

BACKGROUND: Vitiligo is an acquired pigmentary disorder characterized by depigmented patches on the skin that majorly impact patients' quality of life. Although its etiology involves genetic and environmental factors, the role of microorganisms as environmental factors in vitiligo pathology remains under-researched. OBJECTIVES: Our study explored the presence of characteristic bacterial and fungal flora in vitiligo-affected skin and investigated their potential roles in vitiligo pathogenesis. METHODS: We sequenced bacterial 16S rRNA and the fungal ITS1 region from skin swabs collected at frequently affected sites, namely the forehead and back, of patients with vitiligo. We analyzed bacterial and fungal flora in lesional and non-lesional areas of patients with vitiligo compared with corresponding sites in age- and sex-matched healthy subjects. RESULTS: Our findings revealed elevated α-diversity in both bacterial and fungal flora within vitiligo lesions compared with healthy controls. Notably, bacterial flora exhibited a distinctive composition in patients with vitiligo, and the proportional representation of Enterococcus was inversely correlated with the degree of vitiligo progression. Gammaproteobacteria, Staphylococcus spp., and Corynebacterium spp. were more abundant in vitiligo patients, with notable Staphylococcus spp. prevalence during the stable phase on the forehead. Conversely, the proportion of Malassezia sympodialis was lower and that of Malassezia globosa was higher in the progressive phase on the back of vitiligo patients. CONCLUSION: Our study identified some characteristic bacterial and fungal groups associated with vitiligo activity and prognosis, highlighting the potential roles of microorganisms in pathogenesis and offering insights into personalized disease-management approaches.

Differences in the skin microbial community between patients with active and stable vitiligo based on 16S rRNA gene sequencing.

BACKGROUND/OBJECTIVE: Recent studies have described an association between altered skin microbial community and epidemiology of skin diseases, such as vitiligo, atopic dermatitis and psoriasis. In this study, we conducted microbiological analysis on patients at different stages of vitiligo to determine whether the dysbiosis is associated with disease progression. METHODS: To characterise the skin microbes in vitiligo patients, we profiled samples collected from 40 patients with active and stable vitiligo using the Novaseq sequencer. Alpha diversity was used to measure richness and uniformity, while Beta diversity (Non-Metric Multi-Dimensional Scaling) analysis was used to show the differences. Moreover, the species differences were evaluated by LEfSe analysis and the flora gene function was predicted using Statistical Analysis of Metagenomic Profiles (STAMP). RESULTS: The alpha diversity results showed no significant differences between active vitiligo and stable vitiligo, while beta diversity and LEfSe analysis results showed the differences in community composition. Streptomyces and Streptococcus were enriched in active vitiligo compared to stable vitiligo. In addition, the flora gene function of mixed acid fermentation was more pronounced in active vitiligo, while the function of lipid IVA biosynthesis was more significant in stable vitiligo. CONCLUSION: This study has shown the differences in epidermal microbes between active vitiligo and stable vitiligo. Our results suggest that maintaining the flora balance might be a potential therapeutic target for vitiligo.

Analysis of Matched Skin and Gut Microbiome of Patients with Vitiligo Reveals Deep Skin Dysbiosis: Link with Mitochondrial and Immune Changes.

Vitiligo is an autoimmune disease characterized by patchy, white skin owing to melanocyte loss. Commensal cutaneous or gut dysbiosis has been linked to various dermatological disorders. In this study, we studied the skin and gut microbiota of patients with vitiligo compared with those of healthy controls. We obtained swabs and biopsies from both lesional and nonlesional skin as well as stool and blood samples from each individual. We detected reduced richness and diversity of microbiota in the stools of subjects with vitiligo compared with the stools of the controls (P < 0.01). Skin swabs had greater α-diversity than biopsies (P < 0.001); swabs from lesional sites were primarily depleted of Staphylococcus compared with those from nonlesional sites (P < 0.02). Sampling deeper layers from the same patients showed differences in both α- and ß-diversity between samples with decreased richness and distribution of species (P < 0.01) in the lesional site. Biopsy microbiota from the lesional skin had distinct microbiota composition, which was depleted of protective Bifidobacterium and Bacteroides but was enriched in Proteobacteria, Streptococcus, Mycoplasma, and mtDNA (P < 0.001); the latter increased in the same patients with heightened innate immunity and stress markers in their blood (P < 0.05). These data describe vitiligo-specific cutaneous and gut microbiota and a link between skin dysbiosis, mitochondrial damage, and immunity in patients with vitiligo.

The impact of NBUVB on microbial community profiling in the lesional skin of vitiligo subjects.

BACKGROUND: The impact of NBUVB on the cutaneous microbiota of vitiligo patients remains to be fully elucidated. METHODS: To characterize the cutaneous microbiota in vitiligo patients, cutaneous samples from 60 patients with vitiligo and after NBUVB irradiation were profiled using the Illumina MiSeq platform. Alpha diversity estimations revealed higher microbiota diversity in samples from patients with lesional skin. Beta diversity (Principal Component Analysis (PCA)) analysis showed that the bacterial community structure segregated differently between different groups. RESULTS: There was a statistically significant increase in the Sobs, ACE, and Chao indices in the NB group compared with NF group, as determined by t-test. The alpha diversity have no significant difference between NF and DB group. At the phylum level, Firmicutes, Proteobacteria and Actinobacteria were the most predominant phyla. Propionibacterium and Pseudomonas were the most predominant genera in each group. In addition, Staphylococcus, Bacillus and Prevotella were enriched in DF group compared to DB group. Propionibacterium was enriched in DB group compared to DF group. CONCLUSIONS: Our studies indicate differences in microbial community dynamics of the lesional and non-lesional sites of vitiligo subjects, with greater diversity and higher association between microbial communities of the unaffected site. And NBUVB irradiation might eliminate these differences.

Antibiotics Drive Microbial Imbalance and Vitiligo Development in Mice.

Vitiligo is impacted by environmental triggers. We studied the contribution of the microbiome in FH mice, in which depigmentation is mediated by tyrosinase-reactive T cells. The mice received oral antibiotics and were monitored for depigmentation. The microbiome was studied in fecal and skin samples using 16S rRNA analysis. The resulting T-cell distributions were evaluated. In untreated mice, pigment loss did not expand to the pelage, whereas mice in the ampicillin group were approximately 1/3 depigmented at 30 weeks. In contrast to models of autoimmunity that are less dependent on IFN-γ, ampicillin but not neomycin treatment correlated with accelerated disease and reduced bacteria in the fecal pellets. Modified cytokine patterns in the tissue and serum suggest a response that transcends the gut. Ampicillin-induced depigmentation was accompanied by gut but not skin dysbiosis, and reduced T cell numbers in both sites. Neomycin induced a redistribution of gut T cells and an accumulation of skin regulatory T cells. This treatment spurred a Bacteroides-dominated population of fecal bacteria. Reduced diversity is prominent particularly after ampicillin treatment, when the gut is dominated by Pseudomonas species. In line with current concepts relating the microbiome and the immune system, we predict that dietary measures might promote skin health and delay vitiligo onset.

Relationship between Helicobacter pylori infection and vitiligo: a prospective study.

BACKGROUND: Helicobacter pylori is a worldwide bacteria that may affect several extra-gastric systems, including the endocrine, hematologic, vascular, respiratory, immune, and skin. Several skin diseases, including chronic urticaria, alopecia areata, psoriasis, and systemic lupus erythematosis have been found to be associated with H. pylori infection. AIM: To our knowledge, there are no data showing an association between H. pylori and vitiligo. Therefore, in this study, we wanted to evaluate the relationship between H. pylori and vitiligo. METHODS: This study is a prospective study carried out in our Gastroenterology and Dermatology and Venereology departments of the Ankara Education and Research Hospital (Ankara, Turkey) between July 2013 and December 2013. Seventy-nine consecutive patients with vitiligo and 72 patients with telogen effluvium (TE) were recruited from the dermatology outpatient clinic. A total of 133 patients with vitiligo (n=68) and TE (n=65) [excluding 18 patients who had suspicious urea breath test (UBT) results] were included in the study. All individuals were tested for H. pylori IgG and CagA. Also, a UBT was performed to detect the presence of H. pylori infection. RESULTS: There were significantly higher rates of H. pylori positivity, H. pylori CagA, and IgG in serum in the vitiligo group than in the TE group (p<0.05). The number of patients with dyspepsia was significantly higher in the vitiligo group than in the TE group. No statistically significant relationship was seen between H. pylori positivity, CagA, H. pylori IgG, dyspepsia, and the Vitiligo Disease Activity score (p>0.05). Also, when patients with vitiligo were divided into localized and generalized types of vitiligo, there was no association between vitiligo involvement pattern and H. pylori positivity, CagA, H. pylori IgG, and dyspepsia (p>0.05). CONCLUSION: Additional studies are necessary to evaluate the effect of H. pylori eradication on the clinical course of vitiligo. Further studies are also needed to explain the relationship between H. pylori and the pathogenesis of vitiligo.

Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling.

Lymphodepletion with total body irradiation (TBI) increases the efficacy of adoptively transferred tumor-specific CD8(+) T cells by depleting inhibitory lymphocytes and increasing homeostatic cytokine levels. We found that TBI augmented the function of adoptively transferred CD8(+) T cells in mice genetically deficient in all lymphocytes, indicating the existence of another TBI mechanism of action. Additional investigation revealed commensal gut microflora in the mesenteric lymph nodes and elevated LPS levels in the sera of irradiated mice. These findings correlated with increased dendritic cell activation and heightened levels of systemic inflammatory cytokines. Reduction of host microflora using antibiotics, neutralization of serum LPS using polymyxin B, or removal of LPS signaling components using mice genetically deficient in CD14 and TLR4 reduced the beneficial effects of TBI on tumor regression. Conversely, administration of microbial ligand-containing serum or ultrapure LPS from irradiated animals to nonirradiated antibody-lymphodepleted mice enhanced CD8(+) T cell activation and improved tumor regression. Administration of ultrapure LPS to irradiated animals further enhanced the number and function of the adoptively transferred cells, leading to long-term cure of mice with large B16F10 tumors and enhanced autoimmune vitiligo. Thus, disruption of the homeostatic balance between the host and microbes can enhance cell-based tumor immunotherapy.

[Disturbances in the intestinal microflora and immune system in children with vitiligo]. / Narusheniia mikroflory kishechnika i immunnoi sistemy u detei, bol'nykh vitiligo.

A total of 91 children, aged 3-16 years, with vitiligo were examined. These examinations showed that the total number of T lymphocytes decreased irrespective of the degree of intestinal dysbacteriosis. The average number of T suppressors increased as dysbiotic changes in the intestine became more profound. The amount of natural killers, B lymphocytes, as well as the content of IgG and IgA (p < 0.001), increased irrespectively of the degree of intestinal dysbacteriosis. Thus the unbalance of the immunity system and dysbiotic changes in the intestine of children having vitiligo were Inter-related.