Academic literature on the topic 'Skin dysbiosis'

<p>The human skin possesses a microenvironment conducive to the growth of the skin microbiome, which plays in many physiological functions in cutaneous immunity homeostasis and maturation. The microbiome composition depends on many variables, such as endogenous (host condition) or exogenous (environmental) factors and topographic location. Host-skin microbes’ interaction can be mutualism or pathogenicity. Dysbiosis or alteration in skin microbiota is associated with various dermatological diseases, including leprosy. Dysbiosis is driven by the alteration of the microbial communities themselves or due to the intrinsic features of the host. Leprosy is a chronic granulomatous disease caused by <em>Mycobacterium leprae</em> targeting the nerves and skin, leading to loss of sensation on the skin, with or without dermatologic lesions, and correlated with long term consequences, such as deformities or disability. Microvascular dysfunction and significant alterations in capillary structure due to invasion of <em>M. leprae</em> lead to altered hydration levels of the skin caused by disruption of blood flow; which changes the resident microbial community structure. The skin microbiome composition differences in leprosy patient’s skin lesions were observed; skin microbial diversity in the leprosy patients was lower than in healthy individuals. The diversity reduction was observed in freshly diagnosis leprosy patients, those at various stages of MDT, and post-MDT; indicated that both the interaction between skin microbial community and<strong> </strong><em>M. leprae</em> or the ongoing therapeutic regimen impacted the skin microbiome variation. </p><p> </p>

Background: To investigate the microbiome composition in individuals with and without rosacea and correlate findings to individual factors that may affect facial cutaneous and enteric microbiome composition. Methods: Participants with and without rosacea (as determined by a board-certified dermatologist) were surveyed regarding factors that may affect the facial cutaneous/enteric microbiome. Microbiome samples were collected, analyzed for 16S sequences, and mapped to an optimized version of existing databases. R was used to perform Mann-Whitney/Kruskal-Wallis test for categorical comparisons. Correlation between two continuous variables was determined with linear regression models. Primary Component Analysis (PCoA) plots employed Monte Carlo permutation test to estimate p-values. All p-values are adjusted for multiple comparisons with the false discovery rate (FDR algorithm) using Benjamini-Hochberg. Results: 84 individuals with rosacea and 44 controls were evaluated. Individuals with rosacea were more likely to currently own pets (p = 0.029) and consume more alcohol (p = 0.006). Absolute bacteria abundance were similar in facial cutaneous (p = 0.36) and enteral microbiome (p = 0.29). Facial cutaneous microbiome showed significantly decreased richness and evenness (OTU: p = 0.019; Shannon: p = 0.049) and a three to four-fold decrease in abundance of 8 distinct cutaneous bacterial genera in rosacea. Enteral microbiome analysis showed significant reduction in abundance of Ruminococcaceae (FDR = 0.002) and Blautia (FDR < 0.001) and increase in Prevotellaceae (FDR = 0.024) in rosacea. Conclusion: Environmental factors may alter relative abundances of specific microbial genera and lead to microbiome diversity. Further studies with increased sample sizes and higher severity cases may further elucidate the role of dysbiosis in rosacea.

Skin diseases, including acne, can be caused by a microbial imbalance (dysbiosis). The specific bacteria involved in acne dysbiosis are Cutibacterium (Propionibacterium) acnes and Staphylococcus epidermidis. Black garlic has better potential to be alternative antibiotic and chemical to curing ance and maintaining skin health, because it has antimicrobial potential and can inhibit the decrease in collagen deposition on the skin. These potentials can be alternative of antibiotics and chemicals to treat acne and maintain healthy skin. This study aimed to determine the antibacterial activity of black garlic extract against bacteria that cause acne dysbiosis. Garlic was aging with 3 variations of time (7, 14, and 21 days) then macerated with 70% alcohol and tested for antimicrobial activity to Cutibacterium acnes and Staphylococcus epidermidis with clindamycin as positive control. Black garlic extract provided inhibitory activity against Staphylococcus epidermidis and Cutibacterium acnes. The best recommendation time for aging garlic to prevent skin dysbiosis causes acne is 7 to 14 days.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that occurs in genetically predisposed individuals. It involves complex interactions among the host immune system, environmental factors (such as skin barrier dysfunction), and microbial dysbiosis. Genome-wide association studies (GWAS) have identified AD risk alleles; however, the associated environmental factors remain largely unknown. Recent evidence suggests that altered microbiota composition (dysbiosis) in the skin and gut may contribute to the pathogenesis of AD. Examples of environmental factors that contribute to skin barrier dysfunction and microbial dysbiosis in AD include allergens, irritants, pollution, and microbial exposure. Studies have reported alterations in the gut microbiome structure in patients with AD compared to control subjects, characterized by increased abundance of Clostridium difficile and decreased abundance of short-chain fatty acid (SCFA)-producing bacteria such as Bifidobacterium. SCFAs play a critical role in maintaining host health, and reduced SCFA production may lead to intestinal inflammation in AD patients. The specific mechanisms through which dysbiotic bacteria and their metabolites interact with the host genome and epigenome to cause autoimmunity in AD are still unknown. By understanding the combination of environmental factors, such as gut microbiota, the genetic and epigenetic determinants that are associated with the development of autoantibodies may help unravel the pathophysiology of the disease. This review aims to elucidate the interactions between the immune system, susceptibility genes, epigenetic factors, and the gut microbiome in the development of AD.

The microbiome plays an important role in a wide variety of skin disorders. Not only is the skin microbiome altered, but also surprisingly many skin diseases are accompanied by an altered gut microbiome. The microbiome is a key regulator for the immune system, as it aims to maintain homeostasis by communicating with tissues and organs in a bidirectional manner. Hence, dysbiosis in the skin and/or gut microbiome is associated with an altered immune response, promoting the development of skin diseases, such as atopic dermatitis, psoriasis, acne vulgaris, dandruff, and even skin cancer. Here, we focus on the associations between the microbiome, diet, metabolites, and immune responses in skin pathologies. This review describes an exhaustive list of common skin conditions with associated dysbiosis in the skin microbiome as well as the current body of evidence on gut microbiome dysbiosis, dietary links, and their interplay with skin conditions. An enhanced understanding of the local skin and gut microbiome including the underlying mechanisms is necessary to shed light on the microbial involvement in human skin diseases and to develop new therapeutic approaches.

(1) Background alteration of the skin microbiota, dysbiosis, causes skin barrier impairment resulting in disease development. Staphylococcus aureus, the main pathogen associated with dysbiosis, secretes several virulence factors, including α-toxin that damages tight junctions and compromises the integrity of the skin barrier. The use of members of the resident microbiota to restore the skin barrier, bacteriotherapy, represents a safe treatment for skin conditions among innovative options. The aim of this study is the evaluation of a wall fragment derived from a patented strain of Cutibacterium acnes DSM28251 (c40) alone and conjugated to a mucopolysaccharide carrier (HAc40) in counteracting S. aureus pathogenic action on two tight junction proteins (Claudin-1 and ZO-1) in an ex vivo porcine skin infection model. Methods: skin biopsies were infected with live S. aureus strains ATCC29213 and DSM20491. Tissue was pre-incubated or co-incubated with c40 and HAc40. (3) Results: c40 and HAc40 prevent and counteract Claudin-1 and Zo-1 damage (4) Conclusions: c40 and the functional ingredient HAc40 represent a potential non-pharmacological treatment of skin diseases associated with cutaneous dysbiosis of S. aureus. These findings offer numerous avenues for new research.

Atopic dermatitis (AD) is a common inflammatory dermatosis affecting up to 30% of children and 10% of adults worldwide. AD is primarily driven by an epidermal barrier defect which triggers immune dysregulation within the skin. According to recent research such phenomena are closely related to the microbial dysbiosis of the skin. There is growing evidence that cutaneous microbiota and bacterial biofilms negatively affect skin barrier function, contributing to the onset and exacerbation of AD. This review summarizes the latest data on the mechanisms leading to microbiome dysbiosis and biofilm formation in AD, and the influence of these phenomena on skin barrier function.

L'hidradénite suppurée (HS) est une dermatose chronique, débilitante et suppurative des plis. Sa physiopathologie reste mal comprise et seule la chirurgie est curative au prix d'exérèses parfois délabrantes. Les études sont limitées du fait de l'absence de modèle animal de la maladie, de son hétérogénéité et de son caractère multifactoriel. Plusieurs études ont montré le rôle de la dysbiose cutanée dans l'inflammation chronique de la maladie pouvant être causée par une altération de sécrétion de peptides antimicrobiens (PAMs) liée au dysfonctionnement kératinocytaire. La thérapie photodynamique (PDT) a montré un rationnel dans le traitement des dermatoses inflammatoires. Cependant la faible pénétrance du PS limite l'action thérapeutique et donc sa pertinence dans l'HS due aux trajets fistuleux parfois profonds.La première partie des résultats a permis de caractériser notre modèle in vitro de lignée kératinocytaire humain immortalisé HaCaT, muté sur le gène de la Nicastrine (modèle HS), où nous observons des troubles de la différenciation kératinocytaire notamment morphologique et protéique par rapport à la lignée sauvage. Dans un second temps, nous avons évalué le sécrétome de nos milieux de culture, où nous observons la présence de cytokines pro-inflammatoires de la voie TH1 et TH17 (IL-1β, IL-17a, IL-23 et IFN-γ) ainsi qu'un défaut de sécrétion IL-10 dans notre modèle KO à l'état basal par rapport à la lignée sauvage ce qui pourrait participer au déséquilibre de la réponse inflammatoire. Par ailleurs, nous montrons un changement du profil d'expression des marqueurs de différenciation kératinocytaire, dans notre modèle in vitro d'HS, exposé à une inflammation induite (TNF-α + IL-6 + LPS), qui s'apparente à un profil de kératinocytes de la couche basale, caractérisé par une capacité proliférative élevée et une survie cellulaire prolongée. Ces propriétés pourraient être la cause de l'acanthose épidermique décrite dans l'HS qui est responsable de l'occlusion folliculaire ainsi que des cicatrices hypertrophiques caractéristiques de la maladie. Nous observons, à partir de test de blessure, que notre lignée HaCaT KO présente une meilleure capacité de cicatrisation que la lignée WT et que l'induction de la différenciation augmente cette capacité. Les caractéristiques présentaient par notre lignée HaCaT KO s'apparentent à un état d'activation kératinocytaire décrit en particulier lors du processus de cicatrisation où les kératinocytes suivent une voie de différenciation épithéliale alternative leur permettant d'acquérir des capacités de migration et de prolifération.Dans un second temps, nous avons testé l'effet de la PDT sur notre modèle in vitro. Nous observons une plus grande efficacité et sélectivité de la PDT au BdM sur notre lignée HaCaT KO par rapport à la PDT au 5-ALA. Nous avons également obtenu, en parallèle, l'autorisation du comité de protection des personnes pour la réalisation de l'étude clinique ImoHS afin de pouvoir évaluer la réponse immunitaire locale et systémique, à partir de prélèvements sanguins et d'explants cutanés issus de patients HS. Dans ce cadre, nous avons mis au point un nouveau dispositif d'illumination de PDT pour le traitement d'explants cutanés humains (modèle ex vivo). Nous avons également mis au point et validé notre stratégie d'analyse d'étude des sous-groupes des cellules lymphoïdes innées par cytométrie de flux à partir du sang de donneur sain.Le projet de thèse a permis de mieux caractériser le modèle in vitro d'HS et l'impact de la différentiation et de l'inflammation sur les HaCaT KO. Nous avons également mis en évidence l'efficacité de la PDT au BdM sur notre modèle in vitro d'HS. L'autorisation obtenue pour la mise en place de l'étude clinique ImoHS, nous permettra par son côté translationnel, de valider nos résultats obtenus sur un modèle ex vivo
Hidradenitis suppurativa (HS) is a chronic, debilitating and suppurative dermatosis affecting the folds. Its pathophysiology remains poorly understood, and only surgery is curative, although it can cause significant tissue damage. Studies are limited by the absence of animal models of the disease, its heterogeneity and multifactorial nature. Several studies have demonstrated the role of cutaneous dysbiosis in the chronic inflammation of the disease, which may be caused by altered secretion of antimicrobial peptides (AMPs) linked to keratinocyte dysfunction. Photodynamic therapy (PDT) has been shown to be a rational treatment for inflammatory dermatoses. However, the low penetrance of the photosensitizer (PS) limits its therapeutic action and therefore its relevance in HS due to deep fistulous tracts.The first part of the results allowed us to characterize our in vitro model of the immortalized human keratinocyte line HaCaT, mutated on the Nicastrin gene (HS model), where we observe disturbances in morphological and protein keratinocyte differentiation compared with the wild-type line. Secondly, we assessed the secretome of our culture media, where we observed the presence of pro-inflammatory cytokines of the TH1 and TH17 pathways (IL-1β, IL-17a, IL-23 and IFN-γ) as well as a defect in IL-10 secretion in our KO control model compared with the wild-type line, which could be involved in the imbalance of the inflammatory response. Furthermore, we show a change in the expression profile of keratinocyte differentiation markers, in our in vitro HS model, exposed to induced inflammation (TNF-α + IL-6 + LPS), which resembles a basal layer keratinocyte profile, characterized by high proliferative capacity and prolonged cell survival. These properties could be the cause of the epidermal acanthosis described in HS, which is responsible for the follicular occlusion and hypertrophic scarring characteristic of the disease. Based on wounding tests, we have observed that our HaCaT KO line has a better wound healing capacity than the WT line, and that induction of differentiation enhances this capacity. The characteristics displayed by our HaCaT KO line are like a state of keratinocyte activation described during the healing process, where keratinocytes follow an alternative epithelial differentiation pathway enabling them to acquire migration and proliferation capacities.Secondly, we tested the effect of PDT on our in vitro model. We observed greater efficacy and selectivity of methylene blue PDT on our HaCaT KO line, compared with 5-ALA PDT. At the same time, we obtained the authorization of the French Committee for the Protection of Individuals to conduct the ImoHS clinical study, to evaluate the local and systemic immune response, using blood samples and skin explants from HS patients. In this context, we have developed a new PDT illumination device for the treatment of human skin explants (ex vivo model). We also developed and validated our analysis strategy for studying innate lymphoid cell subgroups by flow cytometry from healthy donor blood.The thesis project enabled us to better characterize the in vitro HS model and the impact of differentiation and inflammation on HaCaT KOs. We also demonstrated the efficacy of methylene blue PDT on our in vitro HS model. The authorization obtained to set up the ImoHS clinical trial will enable us, through its translational aspect, to validate our results obtained on an ex vivo model

Le dioxyde d’azote (NO2), en tant que second polluant atmosphérique le plus meurtrier en Europe est un des plus préoccupants pour la santé humaine selon l’Agence Européenne de l’Environnement. Il est notamment connu pour être responsable de maladies cardiovasculaires, respiratoires ainsi que pour contribuer au vieillissement cutané et au développement de la dermatite atopique. Des facteurs endogènes à l’hôte tels que le microbiote cutané interviennent également dans cette pathologie. En effet, de nombreuses pathologies cutanées sont corrélées à un déséquilibre (dysbiose) du microbiote bactérien, un acteur essentiel du maintien de l’homéostasie de la peau. Or, il est fortement soupçonné que l’effet des polluants sur la peau implique des mécanismes d’action directe mais également un mécanisme d’action indirecte lié à l’altération du microbiote cutané par le polluant. En conséquence, il est pertinent d’aborder l’effet du NO2 gazeux (gNO2) sur le microbiote cutané bactérien. Cette thèse a donc pour objectif d’évaluer l’impact physiologique, morphologique et moléculaire du NO2 sur des souches bactériennes commensales d’espèces représentatives du microbiote cutané (Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus capitis, Pseudomonas fluorescens, Corynebacterium tuberculostearicum). Selon l’espèce, des réponses différentes au stress nitrosant généré par le gNO2 ont ainsi été mises en évidence ainsi qu’une tolérance plus importante au gNO2 pour certaines d’entre elles. Ces travaux suggèrent par conséquent que le NO2 pourrait contribuer à la formation d’un état dysbiotique du microbiote cutané et participer à l’action indirect du polluant sur la peau
Nitrogen dioxide (NO2), as the second most deadly air pollutant in Europe, is one of the most of concern for human health according to the European Environment Agency. It is notably known to be responsible for cardiovascular and respiratory diseases and also contributes to skin aging and atopic dermatitis. Host endogenous factors such as the cutaneous microbiota are also involved in this pathology, which is common in urban and suburban areas. Indeed, many skin pathologies are correlated to an imbalance (dysbiosis) of the bacterial microbiota, an essential player in the preservation of skin homeostasis. However, it is strongly presumed that the effect of pollutants on the skin involves direct mechanisms of action but also an indirect mechanism linked to the alteration of the cutaneous microbiota by the pollutant. Consequently, it is relevant to address the effect of gaseous NO2 (gNO2) on the cutaneous microbiota. This thesis aims to assess the physiological, morphological and molecular impact of gNO2 on commensal bacterial strains of representative species of the cutaneous microbiota (Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus capitis, Pseudomonas fluorescens, Corynebacterium tuberculostearicum). Depending on the species, different responses to gNO2-generated nitrosative stress were thus highlighted as well as a higher tolerance to gNO2 for some of them. This work therefore suggests that gNO2 could contribute to the formation of a dysbiotic state of the cutaneous microbiota and participate in the pollutant indirect action on the skin

‘Microbiota and microbiome in humans’ examines the microbiota and microbiome in humans. Humans could not have evolved to their current sophistication without the help of bacteria, both for their ability to obtain energy in their cells through mitochondria and also more directly in their ability to maximize the nutrients obtained from food and their primary defence against serious infection. Microbiome exist on the skin, in the vagina, the mouth, and the gut. Many infections result from the disruption of the microbiome, or dysbiosis. Probiotics and faecal transplants play a role in achieving a more balanced microbiota.