Disease ⇒ Atopy ⇒ Atopic Dermatitis {40000111} Record Keys Type:Disease Parent:Atopy Definition:Atopic Dermatitis Details Initialisation date:2020-09-06 Other Terms:Atopic eczema, AD, Infantile Eczema LinksWickipediaMerck Manual Meta Information MedDra ID:10014184 MedDra Level:pt ICD:[ ] Category:Dermatology Zone: Gut, Skin Mechanism:[ ] Notes: - Sufferers of AD tend to have higher proportions of Clostridia (including Clostridium difficile), Escherichia coli, and Staphylococcus aureus than do healthy controls, as well as lower numbers of healthy Bifidobacteria, Bacteroidetes, and Bacteroides. - The bacterium Roseomonas mucosa reduced the severity of atopic dermatitis in adults and children. - Most children in the study experienced substantial improvements in their skin and overall wellbeing following R. mucosa therapy. Encouragingly, the therapeutic bacteria stayed on the skin and continued to provide benefit after therapy stopped. - Seventeen of the 20 children experienced a greater than 50% improvement in eczema severity following treatment. Improvement occurred on all treated skin sites, including the inner elbows, inner knees, hands, trunk and neck. The scientists also observed increases in the skin’s barrier function—its ability to seal in moisture and keep out allergen.(3) - A specific set of lipids produced by R. mucosa strains isolated from healthy skin can induce skin repair processes and promote turnover of skin tissue. Study participants had increased levels of these lipids on their skin after treatment with R. mucosa. (4) - The abundance of S. aureus is greater in lesional than in non-lesional skin in AD, in a dose-dependent manner - with higher colonisation rates in severe eczema. - 62% of lesional skin samples produced at least one identifiable exotoxin. Exotoxins from S. aureus strains isolated from AD patients often have superantigenic properties and stimulate T-lymphocytes directly. - Children and young adults with AD had significantly lower gut concentrations of Bifidobacteria than controls (measured by stool sample analysis), and the concentration was inversely correlated with AD disease severity. - Low total gut and Bacteroidetes diversity at 1 month has been associated with the development of AD at 2 years of age. (5) - Faeclibacerium prausnitzii and Ruminococcus gnavus are increased in patients with AD, whereas Bacteroides fragilis and Streptococcus salivaris, are less abundantShared Reference Notes [1.1] - Skin dysbiosis in AD is characterized by increased abundance of Staphylococcus aureus. In the presence of this dysbiosis and barrier dysfunction, external stimuli such as infection, allergens, and mechanical injury lead to activation of skin keratinocytes to produce interleukin (IL)-33, IL-25, and thymic stromal lymphopoietin (TSLP), inducing differentiation of T helper type 2 (Th2) cells that secrete IL-4, IL-5, and IL-13 and resulting in Th2 inflammation. This inflammation can in turn activate keratinocytes, forming a vicious cycle that maintains skin inflammation in AD. - Skin dysbiosis in AD is characterized by increased abundance of Staphylococcus aureus. [1.2] - Corynebacterium simulans and Prevotella melaninogenica are positively and negatively correlated with AD severity, respectively. - The abundance of Prevotella melaninogenica decreased gradually with an increase in disease severity and increased after treatment. [1.3] - AD subjects is characterized by reduced microbial richness, depletion of #Cutibacterium acnes, #Dermacoccus and #Methylobacterium species. [1.4] [#Multiple Sclerosis] - Orally administered EDP1867, a gamma-irradiated strain of #Veillonella parvula, rapidly transits through the murine gut without colonization or alteration of the background microbiome flora. - In murine models of inflammatory disease including delayed-type hypersensitivity (DTH), atopic dermatitis, #Psoriasis, and experimental autoimmune encephalomyelitis (EAE), treatment with EDP1867 resulted in significant reduction in inflammation and immunopathology. [1.5] [#Staphylococcus aureus, #Staphylococcus epidermidis] - increased abundance of S. aureus with depletion of S. epidermidis and #Corynebacterium spp. among AD patients. - S. epidermidis, a commensal present on non–inflamed skin, appears to be S. aureus best antagonist. - less severe flares of AD had higher counts of S. epidermidis whereas the more severe flares were associated with S. aureus - #Malassezia spp. colonization increases with AD severity and has been detected in up to 90% of skin lesions. [#Staphylococcus aureus, #Staphylococcus lugdunensis] - #Staphylococcus hominis, S. lugdunensis and S. epidermidis produce several molecules capable of synergizing the innate antimicrobial response against S. aureus [1.6] [#Staphylococcus aureus] - samples where S. aureus was highly abundant, lower abundances of S. hominis and Cutibacterium acnes were observed. M. osloensis and M. luteus were more abundant in AD. - The flexures exhibited lower alpha-diversity and were colonized by S. aureus, accompanied by S. epidermidis in lesions. Malassezia species were absent on the neck in AD. [1.7] - #Vitamin D-associated 3-hydroxyisobutyric acid and glutamine were positively correlated with atopic disease-associated succinic acid and alanine, respectively. - hippuric acid was negatively correlated with atopic disease-associated formic acid, which was positively correlated with #Vitamin D level. - Absolute eosinophil count (AEC) was positively correlated with serum D. pteronyssinus- and D. farinae -specific IgE level [1.8] [#Staphylococcus aureus] - S. aureus, a dominant species among the family of Staphylococcae, can be 100 times more abundant in AD skin compared to normal healthy skin. - AD is associated with a depletion in the coagulase-negative staphylococcal species (CoNS), such as S. epidermidis, S. hominis, and other skin commensal bacterial communities, including Streptococcus salivarius, Propionibacterium, Streptococcus, Acinetobacter, Corynebacterium, Prevotella and Proteobacteria. - AD patients exhibit abundant S. aureus in their gut microbiota [1.9] [#Allergy] [#High fibre diet] - Epidemiological evidence indicates that children suffering from allergies have lower levels of dietary fibre-derived short-chain fatty acids (SCFA). Using an experimental model of AD-like skin inflammation, - a fermentable fibre-rich diet alleviates systemic allergen sensitization and disease severity. - particularly butyrate, which strengthens skin barrier function by altering mitochondrial metabolism of epidermal keratinocytes and the production of key structural components. - children and infants suffering from AD, or prone to develop allergic sensitization later in childhood43, exhibit a gut microbiota characterized by a reduced capacity to produce SCFA, particularly #Butyrate. - the skin of patients with atopic dermatitis is characterized by a higher prevalence of S. aureus [1.11] - Supplement #Lactobacillus rhamnosus > increase #Butyrate production > reduce atopic symptoms [1.12] [#Staphylococcus epidermidis] - S. epidermidis is also frequently detectable in the skin of patients with the inflammatory skin disease atopic dermatitis (AD) and some studies reported a significantly higher presence of S. epidermidis in severe AD as compared to mild AD. - Various S. epidermidis skin-derived isolates activated the proinflammatory transcription factor NF-kappaB and induced expression of AD-associated proinflammatory cytokines in human primary keratinocytes and 3D skin equivalents. [1.13] - Increased richness and abundance of #Staphylococcus, Lactococcus, and #Alternaria were found in atopics. - #Staphylococcus and #Alternaria formed robust mixed-species biofilms (based on XTT and SEM) that were resistant to antifungals/antimicrobials. - their biofilm supernatant was capable of influencing keratinocytes biology (pro-inflammatory cytokines and structural proteins), suggesting an additive effect on AD-associated host response. [1.14] [#Natural Skin Microbiome] - skin colonization by commensal #Staphylococci species has been associated with lower incidence of AD in babies, suggesting these bacteria may also play a role in the disease development. - in #Infants > #Staphylococcus epidermidis was found protective against AD as well as in older populations [1.15] [#Staphylococcus aureus] [1.16] - #Nitrosomonas eutropha B244 provided fast-acting itch relief, with significant reductions in itch observed within one week of treatment. - The study found that the Worst Itch Numeric Rating Scale (WI-NRS) score was reduced by 34% with B244 compared to the placebo. [1.17] [#Antimicrobial peptides] - Atopic skin exhibits lower levels of certain HDPs such as #Dermcidin, human beta-defensin-2 (hBD-2), human beta-defensin-3 (hBD-3), and #Cathelicidin, as well as increased expression of #RNAse7 and S100A7 - Patients with AD exhibit decreased expression of #Antimicrobial peptides (AMPs) which is linked to increased colonization by #Staphylococcus aureus. [#Staphylococcus aureus] [#Ceramides] - The lesional skin of AD patients shows higher prevalence of S.aureus (up to 70%) than nonlesional skin of the same patients (39%) - The enzyme ceramidase secreted by S. aureus lowers lipid and fatty acid levels and makes the skin permeable to allergens. - Lower fatty acid levels also lead to decreased formation of phospholipid hydrolysis products in sebum and sweat, which increase skin surface pH and further promote S. aureus growth. - Alpha toxin secreted by S. aureus is cytotoxic to keratinocytes and alters the integrity of E-cadherin, compromising barrier function [1.18] - Allergic infants are more frequently colonised that those who are not allergic by adult-like Bifidobacterium (such as B. adolescentis), while in healthy infants the Bifidobacterium population was dominated by B. bifidum. - The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including Staphylococcus epidermidis and Staphylococcus homini. These AMPs were strain-specific, highly potent, selectively killed S. aureus, and synergized with the human AMP LL-37. [1.19] [#Infantile eczema] [#Faecalibacterium prausnitzii] - #Faecalibacterium is significantly increased in the microbiota of patients with atopic dermatitis and eczema, and this genus represents only a single known species, F prausnitzii. - participants with AD were more likely to have #Schizophrenia or schizoaffective disorder. - AD was significantly associated with #Schizophrenia and schizoaffective disorder even after adjusting for demographics and comorbidities. [1.21] - elevations in #Butyric acid shifted the immune response away from a type 2 response that is characteristic of atopic dermatitis, to a type 1 immune response [#Short Chain Fatty Acid] - The G protein-coupled receptor (GPCR) GPR43 is an SCFA receptor which has also been implicated in mouse models of atopic dermatitis [1.22] [#humanized Galactooligosaccharides] - In #Infants, GOS reduces the risk of atopic dermatitis and eczema [1.23] - #Asthma, #Allergic rhinitis (or hay fever), #Food Allergy, and atopic dermatitis (or eczema) can share many common etiological mechanisms characterized by aberrant type-2 inflammatory responses and elevated IgE [1.24] [#Cutibacterium acnes] - patients with atopic dermatitis have a decrease of C. acnes and a decrease of TAG46:2, TAG48:2, TAG50:2, and TAG50:3 that correlates with higher TEWL. - TAGs (TAG46, TAG48, and TAG50) were increased with increased exposure to C. acnes. [1.25] [1.26] - lower alpha diversity concurrently or prospectively linked to conditions including #Asthma, atopic dermatitis, #Food Allergy, and type 1 diabetes, while others have found no association [1.27] - depletion of #Bacteroides and an enrichment of #Clostridium sensu stricto 1 in the gut microbiome of #Infants with eczema at 1 year old. [#Infants] - alterations in the infant gut microbiota precede the development of eczema. [1.28] [#Inflamatory bowel disease] - Among #Adult participants, the scientists found that those with atopic dermatitis had a 34% increased risk of IBD, a 36% higher risk of #Crohn’s disease, and a 32% increased risk of #Ulcerative Colitis. [#Crohn’s disease, #Inflamatory bowel disease, #Ulcerative Colitis] - #Children with Atopic Dermatitis had a 44% increased risk of IBD and a 74% increased risk of CD, which increased with worsening AD; however, they did not have increased risk of UC except for those with severe AD. [1.29] [#Clostridioides difficile] [#Short Chain Fatty Acid] - gut microbiome structure in patients with AD > increased abundance of Clostridium difficile and decreased abundance of short-chain fatty acid (SCFA)-producing bacteria such as #Bifidobacterium. [#Staphylococcus aureus, #Staphylococcus epidermidis] - The genus #Delftia, increased after #Balneotherapy, is instead known to degrade organic pollutants and includes both environmental and opportunistic pathogenic strains. - #Delftia was previously associated with a reduction of S. epidermidis and a consequent increase in S. aureus on the skin of patients with atopic dermatitis [1.31] [#Hidradenitis suppurativa, #Psoriasis] [1.32] [#Infantile eczema] [#Antibiotic Therapy, #Infants, #Mother-infant] - maternal antibiotic use was not associated with food allergies, atopic dermatitis, or eczema. [1.33] [#Faecalibacterium prausnitzii] - F. prausnitzii is a well-known microbiomarker of inflammatory diseases, which has been reported to be reduced in the gut microbiome of atopic dermatitis and #Psoriasis patients. [1.34] - The α diversity in the gut microbiota of AD patients was markedly decreased. #Escherichia-#Shigella (15.8 %) was the predominant genus, whereas the relative level of #Bacteroides pectinophilus was markedably elevated [1.35] - AD #Infants skin microbiota composition in early life preceding AD onset was predominantly driven by the enrichment of #Pseudomonas stutzeri and reduction of #Staphylococcus and #Corynebacterium species. - This bacterial signature was linked with lower natural moisturizing factors [NMF] (PCA, Urocanic acid-cis) and higher #Antimicrobial peptides [AMPs] (alpha and beta defensin) levels. [1.36] [#Allergy, #Atopy] - In #Children with AD, there was a significantly lower #Vitamin D level at age 2 and 4, but a significantly higher prevalence of food and mite sensitization at all ages in comparison with HC. - #Vitamin D level was found to be inversely related to the prevalence of allergen sensitization at age 4 [1.37] - patients with atopic dermatitis were associated with a higher risk of headache disorder (#Migraine) [1.38] [#Roseomonas mucosa] - In 15 #Children with AD, R. mucosa treatment was associated with amelioration of disease severity, improvement in epithelial barrier function, reduced #Staphylococcus aureus burden on the skin, and a reduction in topical steroid requirements without severe adverse events. - Skin improvements and colonization by R. mucosa persisted for up to 8 months after cessation of treatment. [#Roseomonas mucosa] - The production of #Sphingolipids by R. mucosa, cholinergic signaling, and #Flagellin expression may have contributed to therapeutic impact through induction of a TNFR2-mediated epithelial-to-mesenchymal transition. References Notes[ ]
