How do Host Genetic Factors Affect Gut Microbiome in the Development of Atopic Dermatitis?
Ontology highlight
ABSTRACT:
SUBMITTER: Yoo Y
PROVIDER: S-EPMC7984947 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The determining factors of the composition of the gut microbiome are one of the main interests in current science. In this work, we compared the effect of diet shift (DS) from heavily relying on meatatarian diets to vegetarian diets and physical exercise (EX) on the composition of the gut microbiome after 3 months. Although both DS and EX affected the composition of the gut microbiome, the patterns of alteration were different. The α-diversity analyzed by InvSimpson, Shannon, Simpson, and Evenness showed that both EX and DS affected the microbiome, causing it to become more diverse, but EX affected the gut microbiome more significantly than DS. The β-diversity analyses indicated that EX and DS modified the gut microbiome in two different directions. Co-occurrence network analysis confirmed that both EX and DS modified the gut microbiome in different directions, although EX modified the gut microbiome more significantly. Most notably, the abundance of Dialister succinatiphilus was upregulated by EX, and the abundances of Bacteroides fragilis, Phascolarctobacterium faecium, and Megasphaera elsdenii were downregulated by both EX and DS. Overall, EX modulated the composition of the gut microbiome more significantly than DS, meaning that host factors are more important in determining the gut microbiome than diets. This work also provides a new theoretical basis for why physical exercise is more health-beneficial than vegetarian diets.
| S-EPMC8707884 | biostudies-literature
Project description:Recent advances in sequencing technologies have revealed the diversity of microbes that reside on the skin surface which has enhanced our understanding on skin as an ecosystem, wherein the epidermis, immune cells and the microbiota engage in active dialogues that maintain barrier integrity and functional immunity. This mutual dialogue is altered in atopic dermatitis (AD), in which an impaired epidermal barrier, the skin microbial flora and aberrant immunity can form a vicious cycle that leads to clinical manifestations as eczematous dermatitis. Microbiome studies have revealed an altered microbial landscape in AD and genetic studies have identified genes that underlie barrier impairment and immune dysregulation. Shifting from the long-standing notion that AD was mediated by conventional allergic responses, emerging data suggest that it is a disorder of an altered host-microbial relationship with sophisticated pathophysiology. In this review, we will discuss recent advancements that suggest the roles of the skin microbiota in AD pathophysiology, genetic factors that mediate barrier impairment, dysbiosis and inflammation. Studies in mice, classic AD and monogenic disorders that manifest as AD collectively facilitate our understanding of AD pathophysiology and provide a foundation for novel therapeutic strategies.
| S-EPMC6626296 | biostudies-literature
Project description:Large individual differences in susceptibility to arsenic-induced diseases are well-documented and frequently associated with different patterns of arsenic metabolism. In this context, the role of the gut microbiome in directly metabolizing arsenic and triggering systemic responses in diverse organs raises the possibility that gut microbiome phenotypes affect the spectrum of metabolized arsenic species. However, it remains unclear how host genetics and the gut microbiome interact to affect the biotransformation of arsenic. Using an integrated approach combining 16S rRNA gene sequencing and HPLC-ICP-MS arsenic speciation, we demonstrate that IL-10 gene knockout leads to a significant taxonomic change of the gut microbiome, which in turn substantially affects arsenic metabolism.
| S-EPMC3997221 | biostudies-literature
Project description:The gut microbiome plays a significant role in health and disease, and there is mounting evidence indicating that the microbial composition is regulated in part by host genetics. Heritability estimates for microbial abundance in mice and humans range from (0.05-0.45), indicating that 5-45% of inter-individual variation can be explained by genetics. Through twin studies, genetic association studies, systems genetics, and genome-wide association studies (GWAS), hundreds of specific host genetic loci have been shown to associate with the abundance of discrete gut microbes. Using genetically engineered knock-out mice, at least 30 specific genes have now been validated as having specific effects on the microbiome. The relationships among of host genetics, microbiome composition, and abundance, and disease is now beginning to be unraveled through experiments designed to test causality. The genetic control of disease and its relationship to the microbiome can manifest in multiple ways. First, a genetic variant may directly cause the disease phenotype, resulting in an altered microbiome as a consequence of the disease phenotype. Second, a genetic variant may alter gene expression in the host, which in turn alters the microbiome, producing the disease phenotype. Finally, the genetic variant may alter the microbiome directly, which can result in the disease phenotype. In order to understand the processes that underlie the onset and progression of certain diseases, future research must take into account the relationship among host genetics, microbiome, and disease phenotype, and the resources needed to study these relationships.
| S-EPMC8295090 | biostudies-literature
Project description:ImportanceKnowledge about factors associated with persistence of atopic dermatitis (AD) during childhood is sparse.ObjectiveTo explore heritable, environmental, and clinical factors associated with persistent AD based on 13 years' follow-up of an at-risk birth cohort.Design, setting, and participantsIn the Copenhagen Prospective Study on Asthma in Childhood 2000 (COPSAC2000) clinical birth cohort study, 411 children born to mothers with asthma were followed up until the age of 13 years at a clinical research unit in Copenhagen, Denmark, from August 1998 to June 2015. Atopic dermatitis was diagnosed prospectively during close clinical follow-up according to the criteria of Hanifin and Rajka. Data were gathered on parental history, social circumstances, and environmental factors through parent interviews. The cohort was followed up with biannual visits to the clinic until the age of 7 years and were seen again at age 13 years. Data were analyzed from August 2015 to January 2018.Main outcomes and measuresAtopic dermatitis was diagnosed using Hanifin and Rajka major and minor criteria, and severity was determined by Scoring Atopic Dermatitis (SCORAD) index, with possible scores from 0 to 83, with higher scores indicating more severe AD.ResultsOf the 411 children in the cohort, 203 (49.4%) were male and 186 (45.3%) were diagnosed with AD before the age of 13 years; 40 of 166 children (24.1%) had persistent AD at the age of 13 years, and 126 (76.0%) experienced remission. Factors associated with persistent AD to age 13 years included heritability, environmental exposures, asthma and allergic sensitization, clinical presentation at the time of diagnosis, the composition of Hanifin and Rajka diagnostic minor criteria, and AD severity according to SCORAD. A higher AD genetic risk score was associated with an increased the risk for persistent AD (multivariable odds ratio [OR], 1.8; 95% CI, 1.1-2.9; P = .02), together with paternal asthma (multivariable OR, 3.7; 95% CI, 1.2-11.5; P = .02); paternal AD (multivariable OR, 6.2; 95% CI, 1.17-23.2; P = .007), and higher social circumstances (multivariable OR, 1.6; 95% CI, 1.0-2.5; P = .05). Particular clinical presentations at time of diagnosis were also associated with specific minor criteria of Hanifin and Rajka (Dennie-Morgan and anterior neck folds, white dermographism, intolerance to wool, itching when sweating, tendency to skin infection, food intolerance, and food allergy) (OR, 2.6; 95% CI, 1.1-6.2; P = .03) as well as increased severity at diagnosis (OR, 1.1; 95% CI, 1.0-1.1; P = .007).Conclusions and relevanceIn a birth cohort of children at risk for asthma who received close clinical follow-up to age 13 years, known genetic AD risk variants, paternal asthma and AD, high social circumstances, diagnostic minor criteria, and disease severity at onset were associated with persistent AD at age 13 years. These findings may be applied in clinical practice to evaluate the likely disease course for individual patients.
| S-EPMC6439574 | biostudies-literature
Project description:Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers. We find that atopic dermatitis and psoriasis can be classified by distinct microbes, which differ from healthy volunteers microbiome composition. Atopic dermatitis is dominated by a single microbe (Staphylococcus aureus), and associated with a disease relevant host transcriptomic signature enriched for skin barrier function, tryptophan metabolism and immune activation. In contrast, psoriasis is characterized by co-occurring communities of microbes with weak associations with disease related gene expression. Our work provides a basis for biomarker discovery and targeted therapies in skin dysbiosis.
| S-EPMC6795799 | biostudies-literature
Project description:BACKGROUND:Disease flares of established atopic dermatitis (AD) are generally associated with a low-diversity skin microbiota and Staphylococcus aureus dominance. The temporal transition of the skin microbiome between early infancy and the dysbiosis of established AD is unknown. METHODS:We randomly selected 50 children from the Cork Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE) longitudinal birth cohort for microbiome sampling at 3 points in the first 6 months of life at 4 skin sites relevant to AD: the antecubital and popliteal fossae, nasal tip, and cheek. We identified 10 infants with AD and compared them with 10 randomly selected control infants with no AD. We performed bacterial 16S ribosomal RNA sequencing and analysis directly from clinical samples. RESULTS:Bacterial community structures and diversity shifted over time, suggesting that age strongly affects the skin microbiome in infants. Unlike established AD, these patients with infantile AD did not have noticeably dysbiotic communities before or with disease and were not colonized by S aureus. In comparing patients and control subjects, infants who had affected skin at month 12 had statistically significant differences in bacterial communities on the antecubital fossa at month 2 compared with infants who were unaffected at month 12. In particular, commensal staphylococci were significantly less abundant in infants affected at month 12, suggesting that this genus might protect against the later development of AD. CONCLUSIONS:This study suggests that 12-month-old infants with AD were not colonized with S aureus before having AD. Additional studies are needed to confirm whether colonization with commensal staphylococci modulates skin immunity and attenuates development of AD.
| S-EPMC5207796 | biostudies-literature
Project description:Atopic dermatitis (AD) is a chronic multifactorial inflammatory skin disease. The pathogenesis of AD remains unclear, but the disease results from dysfunctions of skin barrier and immune response, where both genetic and environmental factors play a key role. Recent studies demonstrate the substantial evidences that show a strong genetic association with AD. As for example, AD patients have a positive family history and have a concordance rate in twins. Moreover, several candidate genes have now been suspected that play a central role in the genetic background of AD. In last decade advanced procedures similar to genome-wide association (GWA) and single nucleotide polymorphism (SNP) have been applied on different population and now it has been clarified that AD is significantly associated with genes of innate/adaptive immune systems, human leukocyte antigens (HLA), cytokines, chemokines, drug-metabolizing genes or various other genes. In this review, we will highlight the recent advancements in the molecular genetics of AD, especially on possible functional relevance of genetic variants discovered to date.
| S-EPMC4791162 | biostudies-literature
Project description:BACKGROUND:Atopic dermatitis (AD) is a chronic inflammatory disease caused by the complex interaction of genetic, immune and environmental factors. There have many recent discoveries involving the genetic and epigenetic studies of AD. METHODS:A retrospective PubMed search was carried out from June 2009 to June 2016 using the terms "atopic dermatitis", "association", "eczema", "gene", "polymorphism", "mutation", "variant", "genome wide association study", "microarray" "gene profiling", "RNA sequencing", "epigenetics" and "microRNA". A total of 132 publications in English were identified. RESULTS:To elucidate the genetic factors for AD pathogenesis, candidate gene association studies, genome-wide association studies (GWAS) and transcriptomic profiling assays have been performed in this period. Epigenetic mechanisms for AD development, including genomic DNA modification and microRNA posttranscriptional regulation, have been explored. To date, candidate gene association studies indicate that filaggrin (FLG) null gene mutations are the most significant known risk factor for AD, and genes in the type 2 T helper lymphocyte (Th2) signaling pathways are the second replicated genetic risk factor for AD. GWAS studies identified 34 risk loci for AD, these loci also suggest that genes in immune responses and epidermal skin barrier functions are associated with AD. Additionally, gene profiling assays demonstrated AD is associated with decreased gene expression of epidermal differentiation complex genes and elevated Th2 and Th17 genes. Hypomethylation of TSLP and FCER1G in AD were reported; and miR-155, which target the immune suppressor CTLA-4, was found to be significantly over-expressed in infiltrating T cells in AD skin lesions. CONCLUSIONS:The results suggest that two major biologic pathways are responsible for AD etiology: skin epithelial function and innate/adaptive immune responses. The dysfunctional epidermal barrier and immune responses reciprocally affect each other, and thereby drive development of AD.
| S-EPMC5069938 | biostudies-literature
Project description:Skin Microbiome in Atopic Dermatitis
| PRJEB21789 | ENA