RESUMO
Bacterial and food allergens are associated with immune-mediated food allergies via the gut-skin axis. However, there has been no data on the potential use of phages to rescue this pathological process. A human triple cell co-culture model incorporating colonocytes (T84 cells), macrophages (THP-1 cells), and hepatocytes (Huh7 cells) was established and infected with Pseudomonas aeruginosa PAO1 (P.a PAO1) in the absence or presence of its KPP22 phage in Dulbecco's Modified Eagle's Medium (DMEM), DMEM+ ovalbumin (OVA), or DMEM+ß-casein media. The physiological health of cells was verified by assessing cell viability and Transepithelial electrical resistance (TEER) across the T84 monolayer. The immune response of cells was investigated by determining the secretions of IL-1ß, IL-8, IL-22, and IL-25. The ability of P.a PAO1 to adhere to and invade T84 cells was evaluated. The addition of either OVA or ß-casein potentiated the P.a PAO1-elicited secretion of cytokines. The viability and TEER of the T84 monolayer were lower in the P.a PAO1+OVA group compared to the P.a PAO1 alone and PAO1+ß-casein groups. OVA and ß-casein significantly increased the adherence and invasion of P.a PAO1 to T84 cells. In the presence of the KPP22 phage, these disruptive effects were abolished. These results imply that: (1) food allergens and bacterial toxic effector molecules exacerbate each other's disruptive effects; (2) food allergen and bacterial signaling at the gut-skin mucosal surface axis depend on a network of bacteria-phage-eukaryotic host interactions; and (3) phages are complementary for the evaluation of pathobiological processes that occur at the interface between bacteria, host cellular milieu, and food antigens because phages intervene in P.a PAO1-, OVA-, and ß-casein-derived inflammation.
Assuntos
Alérgenos , Hipersensibilidade Alimentar , Humanos , Alérgenos/imunologia , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Pseudomonas aeruginosa/fisiologia , Bacteriófagos/fisiologia , Pele/imunologia , Pele/virologia , Pele/microbiologia , Citocinas/metabolismo , Técnicas de CoculturaRESUMO
A novel bacterial isolate A520T (A520T = CBAS 737T = CAIM 1944T) was obtained from the skin of bandtail puffer fish Sphoeroides spengleri (Tetraodontidae Family), collected in Arraial do Cabo (Rio de Janeiro, Brazil). A520T is Gram-stain-negative, flagellated and aerobic bacteria. Optimum growth occurs at 25-30 °C in the presence of 3% NaCl. The genome sequence of the novel isolate consisted of 4.5 Mb (4082 coding genes and G+C content of 41.1%). The closest phylogenetic neighbor was Pseudoalteromonas shioyasakiensis JCM 18891T (97.9% 16S rRNA sequence similarity, 94.8% Average Amino Acid Identity, 93% Average Nucleotide Identity and 51.8% similarity in Genome-to-Genome-Distance). Several in silico phenotypic features are useful to differentiate A520T from its closest phylogenetic neighbors, including trehalose, D-mannose, cellobiose, pyrrolidonyl-beta-naphthylamide, starch hydrolysis, D-xylose, lactose, tartrate utilization, sucrose, citrate, glycerol, mucate and acetate utilization, malonate, glucose oxidizer, gas from glucose, nitrite to gas, L-rhamnose, ornithine decarboxylase, lysine decarboxylase and yellow pigment. The genome of the novel species contains 3 gene clusters (~ 66.81 Kbp in total) coding for different types of bioactive compounds that could indicate ecological roles pertaining to the bandtail puffer fish host. Based on genome-based taxonomic approach, strain A520T (A520T = CBAS 737T = CAIM 1944T) is proposed as a new species, Pseudoalteromonas simplex sp. nov.
Assuntos
Composição de Bases , DNA Bacteriano , Filogenia , Pseudoalteromonas , RNA Ribossômico 16S , Pele , Tetraodontiformes , Animais , Pseudoalteromonas/genética , Pseudoalteromonas/classificação , Pseudoalteromonas/isolamento & purificação , RNA Ribossômico 16S/genética , Tetraodontiformes/microbiologia , DNA Bacteriano/genética , Pele/microbiologia , Genoma Bacteriano , Brasil , Técnicas de Tipagem Bacteriana , Ácidos Graxos/química , Ácidos Graxos/análise , Análise de Sequência de DNARESUMO
BACKGROUND: Treatment failure (TF) in leprosy following multidrug therapy (MDT) presents a significant challenge. The current World Health Organization (WHO) fixed-duration MDT regimen, based on lesion count, might not be adequate. Leprosy lacks clear-cut objective cure criteria, and the predictive value of post-MDT histopathological findings remains uncertain. This study aims to identify predictive factors for TF among leprosy patients who have completed the WHO-recommended MDT. METHODS: An analysis was conducted on 80 individuals from a national leprosy reference center, comprising 40 TF cases (with a mean relapse at 13.0 months) and 40 controls (with a mean of 113.1 months without disease signs). Various epidemiological and clinical-laboratory parameters were assessed post-MDT. RESULTS: In skin samples, the presence of foamy granuloma (OR = 7.36; 95%CI2.20-24.60; p = 0.0012) and histological bacillary index (hBI) ≥ 1+ (OR = 1.55; 95%CI1. 22-1.99; p = 0.0004) were significantly associated with TF, with odds ratios of 7.36 and 1.55, respectively. Individuals who experienced TF had a mean hBI of 3.02+ (SD ± 2.02), while the control group exhibited a mean hBI of 1.8+ (SD ± 1.88). An hBI ≥ 3 + showed a sensitivity of 73% and a specificity of 78% for TF detection (AUC: 0.75; p = 0.0001). Other histopathological features like epithelioid granulomas, and skin changes did not show significant associations (p > 0.05). Additionally, higher anti-phenolic glycolipid-I (anti-PGL-I) ELISA index (EI) levels were linked to a 1.4-fold increased likelihood for TF (OR = 1.4; 95%CI1.13-1.74; p = 0.0019). A mean EI of 4.48 (SD ± 2.80) was observed, with an EI ≥ 3.95 showing a sensitivity of 79% and a specificity of 59% for TF detection (AUC: 0.74; p = 0.0001). Moreover, the presence of Mycobacterium leprae (M. leprae) DNA in real-time polymerase chain reaction (qPCR) was associated with a 3.43-fold higher likelihood of TF. Multivariate regression analysis indicated that concurrent presentation of neural/perineural lymphocytic infiltrate, foamy granuloma, hBI ≥ 1+, and EI ≥ 1 markedly increased the likelihood of TF by up to 95.41%. CONCLUSION: Persistence of nerve-selective lymphocytic infiltrate, foamy granulomas, and bacilli in skin biopsies, and elevated EI post-MDT, may serve as predictive factors for identifying individuals at higher probability of TF.
Assuntos
Hanseníase , Falha de Tratamento , Humanos , Hanseníase/tratamento farmacológico , Hanseníase/patologia , Hanseníase/diagnóstico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Mycobacterium leprae/genética , Mycobacterium leprae/isolamento & purificação , Pele/patologia , Pele/microbiologia , Diagnóstico Precoce , Hansenostáticos/uso terapêutico , Adulto Jovem , Idoso , AdolescenteRESUMO
Amphibians face the threat of decline and extinction, and their health is crucially affected by the microbiota. Their health and ecological adaptability essentially depend on the diverse microbial communities that are shaped by unique host traits and environmental factors. However, there is still limited research on this topic. In this study, cutaneous (C) and gut (G) microbiota in Rana amurensis (A) and R. dybowskii (D) was analyzed through 16S amplicon sequencing. Groups AC and DC significantly differed in alpha diversity, while the gut groups (AG and DG) showed no such differences. Analyses of Bray-Curtis dissimilarity matrix and unweighted UniFrac distances showed significant differences in cutaneous microbiota between groups AC and DC, but not between groups AG and DG. Stochastic processes significantly influenced the assembly of cutaneous and gut microbiota in amphibians, with a notably higher species dispersal rate in the gut. The predominant phyla in the skin of R. amurensis and R. dybowskii were Bacteroidetes and Proteobacteria, respectively, with significant variations in Bacteroidota. Contrarily, the gut microbiota of both species was dominated by Firmicutes, Proteobacteria, and Bacteroidetes, without significant phylum-level differences. Linear discriminant analysis effect size (LEfSe) analysis identified distinct microbial enrichment in each group. Predictive analysis using phylogenetic investigation of communities by reconstruction of unobserved states 2 (PICRUSt2) revealed the significant functional pathways associated with the microbiota, which indicates their potential roles in immune system function, development, regeneration, and response to infectious diseases. This research underscores the critical impact of both host and environmental factors in shaping amphibian microbial ecosystems and emphasizes the need for further studies to explore these complex interactions for conservation efforts.
Assuntos
Bactérias , Microbioma Gastrointestinal , Filogenia , RNA Ribossômico 16S , Ranidae , Pele , Animais , Pele/microbiologia , Ranidae/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , RNA Ribossômico 16S/genética , Microbiota , BiodiversidadeRESUMO
Leprosy is a chronic infectious disease that mainly affects the skin and peripheral nerves, it can also invade deeper tissues and organs, including mucous membranes, lymph nodes, testes, eyes, and internal organs. Severe cases can result in deformities and disabilities. We encountered the case of a 39-year-old male with unexplained fever, headache and rash. The patient's lesions were taken for histopathological examination and slit skin smear analysis. Further, the patient was detected of Mycobacterium leprae (M.leprae) nucleic acid sequences in the cerebrospinal fluid (CSF) and plasma, and M.leprae gene targets in the skin lesion tissue and blood. The patient was eventually diagnosed with multibacillary leprosy and type II leprosy reaction. These results suggest the possibility of bacteremia in patients with leprosy to some extent, and observation implies the potential invasion of CSF by M.leprae or its genetic material.
Assuntos
Febre de Causa Desconhecida , Mycobacterium leprae , Humanos , Masculino , Adulto , Mycobacterium leprae/genética , Febre de Causa Desconhecida/etiologia , Febre de Causa Desconhecida/diagnóstico , Hanseníase/diagnóstico , Hanseníase/líquido cefalorraquidiano , Bacteriemia/diagnóstico , Pele/patologia , Pele/microbiologia , Hanseníase Multibacilar/diagnósticoAssuntos
Interleucina-33 , Necroptose , Proteínas Quinases , Proteína Serina-Treonina Quinases de Interação com Receptores , Staphylococcus aureus , Animais , Camundongos , Interleucina-33/metabolismo , Interleucina-33/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Humanos , Proteínas Quinases/metabolismo , Pele/metabolismo , Pele/microbiologia , Pele/patologia , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/imunologia , Masculino , FemininoRESUMO
BACKGROUND: Cutaneous infectious granulomas (CIG) are localized and chronic skin infection caused by a variety of pathogens such as protozoans, bacteria, worms, viruses and fungi. The diagnosis of CIG is difficult because microbiological examination shows low sensitivity and the histomorphological findings of CIG caused by different pathogens are commonly difficult to be distinguished. OBJECTIVE: The objective of this study is to explore the application of mNGS in tissue sample testing for CIG cases, and to compare mNGS with traditional microbiological methods by evaluating sensitivity and specificity. METHODS: We conducted a retrospective study at the Department of Dermatology of Sun Yat-sen Memorial Hospital, Sun Yat-sen University from January 1st, 2020, to May 31st, 2024. Specimens from CIG patients with a clinical presentation of cutaneous infection that was supported by histological examination were retrospectively enrolled. Specimens were delivered to be tested for microbiological examinations and mNGS. RESULTS: Our data show that mNGS detected Non-tuberculosis mycobacteria, Mycobacterium tuberculosis, fungi and bacteria in CIG. Compared to culture, mNGS showed a higher positive rate (80.77% vs. 57.7%) with high sensitivity rate (100%) and negative predictive value (100%). In addition, mNGS can detect more pathogens in one sample and can be used to detect variable samples including the samples of paraffin-embedded tissue with shorter detective time. Of the 21 patients who showed clinical improvement within a 30-day follow-up, eighteen had their treatments adjusted, including fifteen who continued treatment based on the results of mNGS. CONCLUSIONS: mNGS could provide a potentially rapid and effective alternative detection method for diagnosis of cutaneous infectious granulomas and mNGS results may affect the clinical prognosis resulting from enabling the patients to initiate timely treatment.
Assuntos
Granuloma , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Granuloma/microbiologia , Granuloma/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Bactérias/isolamento & purificação , Bactérias/genética , Bactérias/classificação , Idoso , Sensibilidade e Especificidade , Fungos/isolamento & purificação , Fungos/genética , Fungos/classificação , Adulto Jovem , Metagenômica/métodos , Dermatopatias Infecciosas/diagnóstico , Dermatopatias Infecciosas/microbiologia , Adolescente , Pele/microbiologia , Pele/patologia , CriançaRESUMO
Candida auris is a pathogenic yeast frequently exhibiting multidrug resistance and thus warrants special attention. The prompt detection and proper identification of this organism are needed to prevent its spread in healthcare facilities. The authors of this paper had previously developed LAMPAuris, a loop-mediated isothermal amplification assay, for the specific detection of C. auris. LAMPAuris is evaluated in this report for its ability to identify C. auris from five clades and to detect it from clinical specimens. A total of 103 skin swab samples were tested in comparison with a culture-based method and C. auris-specific SYBR green qPCR. The results show that the LAMPAuris assay had specificities ranging from 97 to 100% and sensitivities ranging from 66 to 86%. The lower sensitivity could be attributed to DNA degradation caused by the prolonged storage of the samples. In conclusion, LAMPAuris proved to be a rapid and reliable method for identifying C. auris and for detecting it in clinical specimens. Fresh specimens should ensure better yield and higher sensitivities.
Assuntos
Candida auris , Candidíase , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Sensibilidade e Especificidade , Humanos , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Candidíase/diagnóstico , Candidíase/microbiologia , Candida auris/genética , Candida auris/isolamento & purificação , Pele/microbiologia , Fatores de Tempo , Candida/isolamento & purificação , Candida/genética , Candida/classificaçãoRESUMO
Atopic dermatitis (AD) is a common and recurrent skin disease characterized by skin barrier dysfunction, inflammation and chronic pruritus, with wide heterogeneity in terms of age of onset, clinical course and persistence over the lifespan. Although the pathogenesis of the disease are unclear, epidermal barrier dysfunction, immune and microbial dysregulation, and environmental factors are known to be critical etiologies in AD pathology. The skin microbiota represents an ecosystem consisting of numerous microbial species that interact with each other as well as host epithelial cells and immune cells. Although the skin microbiota benefits the host by supporting the basic functions of the skin and preventing the colonization of pathogens, disruption of the microbial balance (dysbiosis) can cause skin diseases such as AD. Although AD is a dermatological disease, recent evidence has shown that changes in microbiota composition in the skin and intestine contribute to the pathogenesis of AD. Environmental factors that contribute to skin barrier dysfunction and microbial dysbiosis in AD include allergens, diet, irritants, air pollution, epigenetics and microbial exposure. Knowing the microbial combination of intestin, as well as the genetic and epigenetic determinants associated with the development of autoantibodies, may help elucidate the pathophysiology of the disease. The skin of patients with AD is characterized by microbial dysbiosis as a result of reduced microbial diversity and overgrowth of the pathogens such as Staphylococcus aureus. Recent studies have revealed the importance of building a strong immune response against microorganisms during childhood and new mechanisms of microbial community dynamics in modulating the skin microbiome. Numerous microorganisms are reported to modulate host response through communication with keratinocytes, specific immune cells and adipocytes to improve skin health and barrier function. This growing insight into bioactive substances in the skin microbiota has led to novel biotherapeutic approaches targeting the skin surface for the treatment of AD. This review will provide an updated overview of the skin microbiota in AD and its complex interaction with immune response mechanisms, as well as explore possible underlying mechanisms in the pathogenesis of AD and provide insights into new therapeutic developments for the treatment of AD. It also focuses on restoring skin microbial homeostasis, aiming to reduce inflammation by repairing the skin barrier.
Assuntos
Dermatite Atópica , Disbiose , Pele , Staphylococcus aureus , Dermatite Atópica/microbiologia , Dermatite Atópica/imunologia , Humanos , Staphylococcus aureus/imunologia , Staphylococcus aureus/fisiologia , Pele/microbiologia , Pele/imunologia , Pele/patologia , Disbiose/microbiologia , Disbiose/imunologia , Microbiota/imunologia , Animais , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologiaAssuntos
Microbioma Gastrointestinal , Fototerapia , Psoríase , Pele , Psoríase/terapia , Psoríase/tratamento farmacológico , Humanos , Pele/microbiologia , Adulto , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Recent advances have increased the importance of the human microbiome, including the skin microbiome. Despite the hand microbiome research, the factors affecting the composition of the hand microbiome and their personal characteristics are incompletely known. OBJECTIVES: Despite changing environmental factors and personal variation, we aimed to indicate the interpersonal distinction between skin microbiota using simple and rapid molecular methods. METHODS: Over a non-consecutive 10-day period, samples were taken from 10 adult individuals, and ribotyping analysis of the 16S and 23S genes of S. epidermidis was performed on each skin sample. Additionally, EcoRI and HindIII enzyme reactions and variable number tandem repeat (VNTR) reactions of S. epidermidis obtained from DNA samples were performed. The skin microbiomes of individuals were evaluated along with the microbiome profiles left on the surfaces they touched. RESULTS: In the environmental samples taken, it has been observed that people preserve their core skin microbiota characters and carry them to their environment. It was determined that the highest similarity rate was 77.14%, and the lowest similarity rate was 31.74%. CONCLUSION: Our study showed that the core skin microbiota retains its characteristics and leaves traces in environments. The fact that the personal microbiome remains unchanged despite environmental differences and has characteristic features has shown that it can be used in forensic sciences to distinguish individuals from each other. These results with simple and rapid methods further increased the importance and significance of the study. The findings indicate that personal skin microbiota can provide a significant contribution to criminal investigations by increasing accuracy and reliability, especially in forensic analyses.
Assuntos
Microbiota , Pele , Humanos , Microbiota/genética , Pele/microbiologia , Adulto , Masculino , Feminino , Staphylococcus epidermidis/isolamento & purificação , Staphylococcus epidermidis/genética , Ribotipagem/métodos , Dermatoglifia , RNA Ribossômico 16S/genética , Adulto Jovem , Repetições MinissatélitesRESUMO
Malassezia, the most abundant fungal commensal on the mammalian skin, has been linked to several inflammatory skin diseases such as atopic dermatitis, seborrheic dermatitis and psoriasis. This study reveals that epicutaneous application with Malassezia globosa (M. globosa) triggers skin inflammation in mice. RNA-sequencing of the resulting mouse lesions indicates activation of Interleukin-17 (IL-17) signaling and T helper 17 (Th17) cells differentiation pathways by M. globosa. Furthermore, our findings demonstrate a significant upregulation of IL-23, IL-23R, IL-17A, and IL-22 expressions, along with an increase in the proportion of Th17 and pathogenic Th17 cells in mouse skin exposed to M. globosa. In vitro experiments illustrate that M. globosa prompts human primary keratinocytes to secrete IL-23 via TLR2/MyD88/NF-κB signaling. This IL-23 secretion by keratinocytes is shown to be adequate for inducing the differentiation of pathogenic Th17 cells in the skin. Overall, these results underscore the significant role of Malassezia in exacerbating skin inflammation by stimulating IL-23 secretion by keratinocytes and promoting the differentiation of pathogenic Th17 cells.
Assuntos
Diferenciação Celular , Interleucina-23 , Queratinócitos , Malassezia , Células Th17 , Malassezia/imunologia , Queratinócitos/microbiologia , Queratinócitos/imunologia , Queratinócitos/metabolismo , Células Th17/imunologia , Animais , Interleucina-23/metabolismo , Humanos , Camundongos , Transdução de Sinais , NF-kappa B/metabolismo , Receptor 2 Toll-Like/metabolismo , Interleucina-17/metabolismo , Pele/microbiologia , Pele/patologia , Pele/imunologia , Modelos Animais de Doenças , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Células Cultivadas , Camundongos Endogâmicos C57BL , Interleucina 22RESUMO
Staphylococcus aureus is the most common cause of skin and soft tissue infections (SSTIs) with Methicillin-Resistant S. aureus (MRSA) strains being a major contributor in both community and hospital settings. S. aureus relies on metabolic diversity and a large repertoire of virulence factors to cause disease. This includes α-hemolysin (Hla), an integral player in tissue damage found in various models, including SSTIs. Previously, we identified a role for the Spx adapter protein, YjbH, in the regulation of several virulence factors and as an inhibitor of pathogenesis in a sepsis model. In this study, we found that YjbH is critical for tissue damage during SSTI, and its absence leads to decreased proinflammatory chemokines and cytokines in the skin. We identified no contribution of YjbI, encoded on the same transcript as YjbH. Using a combination of reporters and quantitative hemolysis assays, we demonstrated that YjbH impacts Hla expression and activity both in vitro and in vivo. Additionally, expression of Hla from a non-native promoter reversed the tissue damage phenotype of the ΔyjbIH mutant. Lastly, we identified reduced Agr activity as the likely cause for reduced Hla production in the ΔyjbH mutant. This work continues to define the importance of YjbH in the pathogenesis of S. aureus infection as well as identify a new pathway important for Hla production.
Assuntos
Proteínas de Bactérias , Toxinas Bacterianas , Regulação Bacteriana da Expressão Gênica , Proteínas Hemolisinas , Staphylococcus aureus , Transativadores , Proteínas Hemolisinas/metabolismo , Proteínas Hemolisinas/genética , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/imunologia , Toxinas Bacterianas/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Staphylococcus aureus/patogenicidade , Staphylococcus aureus/imunologia , Staphylococcus aureus/genética , Camundongos , Animais , Transativadores/genética , Transativadores/metabolismo , Infecções Cutâneas Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/imunologia , Infecções Cutâneas Estafilocócicas/patologia , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/imunologia , Pele/microbiologia , Pele/patologia , Pele/imunologia , Fatores de Virulência/genética , Humanos , Infecções dos Tecidos Moles/microbiologia , Infecções dos Tecidos Moles/imunologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Citocinas/metabolismo , Citocinas/imunologia , Citocinas/genéticaRESUMO
Objectives: There is evidence from observational studies that human microbiota is linked to skin appendage Disorders (SADs). Nevertheless, the causal association between microbiota and SADs is yet to be fully clarified. Methods: A comprehensive two-sample Mendelian randomization (MR) was first performed to determine the causal effect of skin and gut microbiota on SADs. A total of 294 skin taxa and 211 gut taxa based on phylum, class, order, family, genus, and ASV level information were identified. Summary data of SADs and eight subtypes (acne vulgaris, hidradenitis suppurativa, alopecia areata, rogenic alopecia, rosacea, rhinophyma, seborrhoeic dermatitis, and pilonidal cyst) were obtained from the FinnGen consortium. We performed bidirectional MR to determine whether the skin and gut microbiota are causally associated with multiple SADs. Furthermore, sensitivity analysis was conducted to examine horizontal pleiotropy and heterogeneity. Results: A total of 65 and 161 causal relationships between genetic liability in the skin and gut microbiota with SADs were identified, respectively. Among these, we separately found 5 and 11 strong causal associations that passed Bonferroni correction in the skin and gut microbiota with SADs. Several skin bacteria, such as Staphylococcus, Streptococcus, and Propionibacterium, were considered associated with multiple SADs. As gut probiotics, Bifidobacteria and Lactobacilli were associated with a protective effect on SAD risk. There was no significant heterogeneity in instrumental variables or horizontal pleiotropy. Conclusions: Our MR analysis unveiled bidirectional causal relationships between SADs and the gut and skin microbiota, and had the potential to offer novel perspectives on the mechanistic of microbiota-facilitated dermatosis.
Assuntos
Microbioma Gastrointestinal , Análise da Randomização Mendeliana , Dermatopatias , Pele , Humanos , Microbioma Gastrointestinal/genética , Pele/microbiologia , Dermatopatias/microbiologia , Predisposição Genética para DoençaRESUMO
Follicular skin disorders, including hidradenitis suppurativa (HS), frequently coexist with systemic autoinflammatory diseases, such as inflammatory bowel disease (IBD) and its subtypes, Crohn's disease and ulcerative colitis. Previous studies suggest that dysbiosis of the human gut microbiome may serve as a pathogenic link between HS and IBD. However, the role of the microbiome (gut, skin, and blood) in the context of IBD and various follicular disorders remains underexplored. Here, we performed a systematic review to investigate the relationship between follicular skin disorders, IBD, and the microbiome. Of the sixteen included studies, four evaluated the impact of diet on the microbiome in HS patients, highlighting a possible link between gut dysbiosis and yeast-exclusion diets. Ten studies explored bacterial colonization and HS severity with specific gut and skin microbiota, including Enterococcus and Veillonella. Two studies reported on immunological or serological biomarkers in HS patients with autoinflammatory disease, including IBD, and identified common markers including elevated cytokines and T-lymphocytes. Six studies investigated HS and IBD patients concurrently. Our systematic literature review highlights the complex interplay between the human microbiome, IBD, and follicular disorders with a particular focus on HS. The results indicate that dietary modifications hold promise as a therapeutic intervention to mitigate the burden of HS and IBD. Microbiota analyses and the identification of key serological biomarkers are crucial for a deeper understanding of the impact of dysbiosis in these conditions. Future research is needed to more thoroughly delineate the causal versus associative roles of dysbiosis in patients with both follicular disorders and IBD.
Assuntos
Disbiose , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/microbiologia , Disbiose/microbiologia , Microbiota , Hidradenite Supurativa/microbiologia , Pele/microbiologia , Dermatopatias/microbiologiaRESUMO
BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with unclear etiology. Growing evidence suggests the microbiome plays a role in SLE pathogenesis. However, findings are inconsistent across studies due to factors like small sample sizes and geographical variations. A comprehensive meta-analysis is needed to elucidate microbiome alterations in SLE. OBJECTIVE: This study aimed to provide a systematic overview of microbiota dysbiosis across body sites in SLE through a meta-analysis of alpha diversity indices, beta diversity indices, and abundance taxa of microbiome. METHODS: A literature search was conducted across four databases to identify relevant studies comparing SLE patients and healthy controls. Extracted data encompassed alpha and beta diversity metrics, as well as bacterial, fungal, and viral abundance across gut, oral, skin, and other microbiota. Study quality was assessed using the Newcastle-Ottawa Scale. Standardized mean differences and pooled effect sizes were calculated through meta-analytical methods. RESULTS: The analysis showed reduced alpha diversity and distinct beta diversity in SLE, particularly in the gut microbiota. Taxonomic analysis revealed compositional variations in bacteria from the gut and oral cavity. However, results for fungi, viruses, and bacteria from other sites were inconsistent due to limited studies. CONCLUSIONS: This meta-analysis offers a comprehensive perspective on microbiome dysbiosis in SLE patients across diverse body sites and taxa. The observed variations underscore the microbiome's potential role in SLE pathogenesis. Future research should address geographical variations, employ longitudinal designs, and integrate multi-omics approaches.
Assuntos
Disbiose , Microbioma Gastrointestinal , Lúpus Eritematoso Sistêmico , Lúpus Eritematoso Sistêmico/microbiologia , Humanos , Disbiose/microbiologia , Microbiota , Pele/microbiologia , Bactérias/classificação , Bactérias/isolamento & purificação , Boca/microbiologiaRESUMO
Numerous studies have established a strong association between Malassezia and various skin disorders, including atopic dermatitis. Finding appropriate methods or medications to alleviate Malassezia-induced skin damage is of notable public interest. This study aimed to evaluate the therapeutic effect of the exopolysaccharide EPS1, produced by Paenibacillus polymyxa, on Malassezia restricta-induced skin damage. In vitro assays indicated that EPS1 reduced the expression of pro-inflammatory cytokine genes in TNF-α-induced HaCaT cells. In a murine model, EPS1 was found to mitigate clinical symptoms, reduce epidermal thickness and mast cell infiltration, improve skin barrier function, decrease pro-inflammatory cytokine levels associated with type 17 inflammation, enhance Tregs in the spleen, upregulate the transcription of Treg-related genes in skin lesions, and modulate the skin microbiota. This study is the first to report the alleviating effect of Paenibacillus exopolysaccharide on Malassezia-induced skin inflammation and its impact on the skin microbiota. These findings support the potential of Paenibacillus exopolysaccharides as consumer products and therapeutic agents for managing Malassezia-induced skin damage by improving skin barrier function, modulating immune responses, and influencing skin microbiota.
Assuntos
Malassezia , Microbiota , Polissacarídeos Bacterianos , Pele , Malassezia/efeitos dos fármacos , Animais , Camundongos , Pele/microbiologia , Pele/efeitos dos fármacos , Pele/imunologia , Humanos , Polissacarídeos Bacterianos/farmacologia , Microbiota/efeitos dos fármacos , Citocinas/metabolismo , Paenibacillus , Modelos Animais de Doenças , Células HaCaTRESUMO
Staphylococcus aureus acts both as a colonizing commensal bacterium and invasive pathogen. Nasal colonization is associated with an increased risk of infection caused by the identical strain. In patients with atopic dermatitis (AD), the degree of S. aureus colonization is associated with the severity of the disease. Here, we comparatively analyzed the in vivo transcriptional profile of S. aureus colonizing the nose and non-diseased skin (non-lesional skin) as opposed to the diseased skin (lesional skin-defined here as infection) of 12 patients with AD. The transcriptional profile during the asymptomatic colonization of the nose closely resembled that of the lesional skin samples for many of the genes studied, with an elevated expression of the genes encoding adhesion-related proteins and proteases. In addition, the genes that modify and remodel the cell wall and encode proteins that facilitate immune evasion showed increased transcriptional activity. Notably, in a subgroup of patients, the global virulence regulator Agr (accessory gene regulator) and downstream target genes were inactive during nasal colonization but upregulated in the lesional and non-lesional skin samples. Taken together, our results demonstrate a colonization-like transcriptional profile on diseased skin and suggest a role for the peptide quorum sensing system Agr during the transition from asymptomatic nasal colonization to skin colonization/infection.
Assuntos
Dermatite Atópica , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Pele , Infecções Estafilocócicas , Staphylococcus aureus , Dermatite Atópica/microbiologia , Dermatite Atópica/genética , Humanos , Staphylococcus aureus/genética , Pele/microbiologia , Pele/metabolismo , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/genética , Feminino , Masculino , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Adulto , Transcriptoma , Infecções Cutâneas Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/genética , Mucosa Nasal/microbiologia , TransativadoresRESUMO
Although antibiotics induce sizable perturbations in the human microbiome, we lack a systematic and quantitative method to measure and predict the microbiome's response to specific antibiotics. Here, we introduce such a method, which takes the form of a microbiome response index (MiRIx) for each antibiotic. Antibiotic-specific MiRIx values quantify the overall susceptibility of the microbiota to an antibiotic, based on databases of bacterial phenotypes and published data on intrinsic antibiotic susceptibility. We applied our approach to five published microbiome studies that carried out antibiotic interventions with vancomycin, metronidazole, ciprofloxacin, amoxicillin, and doxycycline. We show how MiRIx can be used in conjunction with existing microbiome analytical approaches to gain a deeper understanding of the microbiome response to antibiotics. Finally, we generate antibiotic response predictions for the oral, skin, and gut microbiome in healthy humans. Our approach is implemented as open-source software and is readily applied to microbiome data sets generated by 16S rRNA marker gene sequencing or shotgun metagenomics. IMPORTANCE: Antibiotics are potent influencers of the human microbiome and can be a source for enduring dysbiosis and antibiotic resistance in healthcare. Existing microbiome data analysis methods can quantify perturbations of bacterial communities but cannot evaluate whether the differences are aligned with the expected activity of a specific antibiotic. Here, we present a novel method to quantify and predict antibiotic-specific microbiome changes, implemented in a ready-to-use software package. This has the potential to be a critical tool to broaden our understanding of the relationship between the microbiome and antibiotics.
Assuntos
Antibacterianos , Bactérias , Microbiota , RNA Ribossômico 16S , Humanos , Antibacterianos/farmacologia , Microbiota/efeitos dos fármacos , Microbiota/genética , RNA Ribossômico 16S/genética , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/classificação , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Metagenômica/métodos , Testes de Sensibilidade Microbiana/métodos , Pele/microbiologia , Boca/microbiologia , SoftwareRESUMO
Interleukin (IL) 17 is a proinflammatory cytokine belonging to a structurally related group of cytokines known as the IL-17 family. It has been profoundly studied for its contribution to the pathology of autoimmune diseases. However, it also plays an important role in homeostasis and the defense against extracellular bacteria and fungi. IL-17 is important for epithelial barriers, including the skin, where some of its cellular targets reside. Most of the research work on IL-17 has focused on its effects in the skin within the context of autoimmune diseases or sterile inflammation, despite also having impact on other skin conditions. In recent years, studies on the role of IL-17 in the defense against skin pathogens and in the maintenance of skin homeostasis mediated by the microbiota have grown in importance. Here we review and discuss the cumulative evidence regarding the main contribution of IL-17 in the maintenance of skin integrity as well as its protective or pathogenic effects during some skin infections.