How do Host Genetic Factors Affect Gut Microbiome in the Development of Atopic Dermatitis?
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ABSTRACT:
SUBMITTER: Yoo Y
PROVIDER: S-EPMC7984947 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
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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.
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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.
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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.
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Project description:Imbalance of the immune system caused by alterations of the gut microbiome is considered to be a critical factor in the pathogenesis of infant eczema, but the exact role of the gut microbiome in adult atopic dermatitis (AD) patients remains to be clarified. To investigate the differences of the gut microbiome between adult AD patients and healthy individuals, stool samples of 234 adults, containing 104 AD patients and 130 healthy subjects, were collected for 16S rRNA gene amplicon. Altered structure and metabolic dysfunctions of the gut microbiome were identified in adult AD patients. Our results illustrated that the adult AD patients were more likely to have allergies, particularly non-food allergies. In addition, the gut microbiome composition of the AD and normal groups were considerably different. Moreover, Romboutsia and Clostridi-um_sensu_stricto_1 was enriched in the normal group, whereas Blautia, Butyricicoccus, Lachnoclostridium, Eubacterium_hallii_group, Erysi-pelatoclostridium, Megasphaera, Oscillibacter, and Flavonifractor dominated in the AD group. Additionally, purine nucleotide degradation pathways were significantly enriched in the AD group, and the enrichment of proteinogenic amino acid biosynthesis pathways was found in the normal group. This study provides insights into new therapeutic strategies targeting the gut microbiome for AD and evidence for the involvement of the gut-skin axis in AD patients.
| S-EPMC10454836 | 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.
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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.
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Project description:Probiotics often acquire potentially adaptive mutations in vivo, gaining new functional traits through gut selection. While both the host and microbiome can contribute to probiotics' genetic evolution, separating the microbiome and the host's contribution to such selective pressures remains challenging. Here, we introduced germ-free (GF) and specific pathogen-free (SPF) mouse models to track how probiotic strains, i.e., Lactiplantibacillus plantarum HNU082 (Lp082) and Bifidobacterium animalis subsp. lactis V9 (BV9), genetically evolved under selection pressures derived from host factors alone and both host and microbial ecological factors. Notably, compared to the genome of a probiotic strain before consumption, the host only elicited <15 probiotic mutations in probiotic genomes that emerged in the luminal environment of GF mice, while a total of 840 mutations in Lp082 mutants and 21,579 mutations in BV9 were found in SPF mice, <0.25% of those derived from both factors that were never captured by other experimental evolution studies, indicating that keen microbial competitions exhibited the predominant evolutionary force in shaping probiotic genetic composition (>99.75%). For a given probiotic, functional genes occurring in potentially adaptive mutations induced by hosts (GF mice) were all shared with those found in mutants of SPF mice. Collectively, the native microbiome consistently drove a more rapid and divergent genetic evolution of probiotic strains in seven days of colonization than host factors did. Our study further laid a theoretical foundation for genetically engineering probiotics for better gut adaptation through in vitro artificial gut ecosystems without the selection pressures derived from host factors.
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Project description:Atopic dermatitis (AD) has been shown to be closely related to gut dysbiosis mediated through the gut-skin axis, and thus the gut microbiome has recently been explored as a potential therapeutic target for the treatment of AD. Contrasting and varying efficacy have been reported since then. In order to investigate the determining factor of probiotics responsiveness in individuals with AD, we initiated the analysis of 41 AD patients with varying disease severity in Hong Kong, whereas the severity was assessed by Eczema Area and Severity Index (EASI) by board certified dermatologist. 16S rRNA sequencing on the fecal samples from AD patients were performed to obtain the metagenomics profile at baseline and after 8 weeks of oral administration of a novel E3 probiotics formula (including prebiotics, probiotics and postbiotics). While EASI of the participants were significantly lower after the probiotics treatment (p < 0.001, paired Wilcoxon signed rank), subjects with mild AD were found to be more likely to respond to the probiotics treatment. Species richness among responders regardless of disease severity were significantly increased (p < 0.001, paired Wilcoxon signed rank). Responders exhibited (1) elevated relative abundance of Clostridium, Fecalibacterium, Lactobacillus, Romboutsia, and Streptococcus, (2) reduced relative abundance of Collinsella, Bifidobacterium, Fusicatenibacter, and Escherichia-Shigella amid orally-intake probiotics identified using the machine learning algorithm and (3) gut microbiome composition and structure resembling healthy subjects after probiotics treatment. Here, we presented the gut microbiome dynamics in AD patients after the administration of the E3 probiotics formula and delineated the unique gut microbiome signatures in individuals with AD who were responding to the probiotics. These findings could guide the future development of probiotics use for AD management.
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