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Objective:To investigate changes in skin microecological structures and functions between acute and remission phases in adult patients with severe atopic dermatitis (AD) .Methods:From October 2019 to November 2020, skin scale specimens were collected from 5 body sites (cheeks, cubital fossa, back of the hand, abdomen, lower limbs) of 4 adult patients with severe AD in the acute and remission phases, who visited the outpatient clinic of Guangzhou Institute of Dermatology. The next-generation high-throughput sequencing was performed for metagenomic sequencing to construct the microbial gene catalogue of these specimens, followed by gene annotation and bioinformatics analysis for each sample.Results:A total of 18 phyla, 37 classes, 73 orders, 142 families, 237 genera, and 331 species were identified in the skin specimens from the 4 patients with severe AD. The patients with AD in the remission phase showed significantly increased diversity of skin microbiota and markedly different relative abundance of skin microorganisms compared with those in the acute phase (both P < 0.05). At the microbial species level, Staphylococcus aureus showed the highest impact on the acute phase of AD, while Staphylococcus epidermidis, Moraxella osloensis, Francisella sp., Staphylococcus cohnii, Staphylococcus warneri, Malassezia globosa and Malassezia restricta were enriched in the remission phase of AD with the absolute value of the common logarithm of the linear discriminant analysis score > 2 (Kruksal-Wallis test, all P < 0.05). As KEGG pathway enrichment analysis showed, the differentially abundant genes were annotated into a total of 355 functional pathways, of which 38 pathways were significantly enriched (all P < 0.05), mainly involving Staphylococcus aureus infection, tryptophan metabolism, histidine metabolism, nitrogen metabolism, metabolism of arginine and proline, biosynthesis and degradation of valine, leucine and isoleucine, fatty acid degradation, peroxisome proliferator-activated receptor signaling pathway, etc. Conclusion:The skin microecological structure significantly differed between the acute and remission phases among the patients with severe AD, which may be related to multiple functional pathways, such as Staphylococcus aureus infection, tryptophan metabolism, histidine metabolism and nitrogen metabolism.
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Metagenomic analyses of humans and animals have showed that atopic dermatitis (AD) is associated with microbiome dysbiosis in the gut and skin. Decrease of microbial diversity can cause damage to skin barrier and aggravation of AD, and gut microbiome may be involved in the occurrence and development of AD through immune, metabolic and neuroendocrine pathways. This review summarizes the latest advances in the application of metagenomics in tmicrobiological research in and treatment of AD, possible mechanisms underlying microbiome-mediated pathogenesis of AD, and provides a theoretical reference for the microecological therapy of AD.
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Objective@#To identify differentially expressed genes in the transcriptome of the lesional versus nonlesional skin tissues of patients with moderate and severe atopic dermatitis (AD) , and to elucidate their roles in the pathogenesis of AD.@*Methods@#From July to October in 2016, lesional and nonlesional skin tissues were obtained from 5 outpatients of Han nationality with AD in Guangzhou Institute of Dermatology, Institute of Dermatology, Guangzhou Medical University. The next-generation high-throughput transcriptome-wide RNA sequencing (RNA-seq) was performed to identify differentially expressed genes, which were subjected to GO function annotation and KEGG pathway analysis. Real-time fluorescence-based quantitative PCR (qRT-PCR) was conducted to verify differences in candidate gene expression between lesional and nonlesional skin tissues.@*Results@#An average of 10.96 GBs sequence reads were acquired among 10 samples. A total of 21 729 genes were detected, including 19 268 known genes and 2 545 predicted novel genes. A total of 23 153 new transcripts were detected, of which 18 889 were new alternative splicing subtypes of known protein-coding genes, 2 545 were transcripts belonging to new protein-coding genes, and the remaining 1 719 belonged to long-stranded non-coding RNA. Totally, 78 differentially expressed genes were identified between the lesional and nonlesional skin tissues, including 69 upregulated and 11 downregulated genes in the lesional skin tissues. Among them, there were several genes known to be associated with AD inflammation (CXCL1/2/8, IL6/IL1β, MMP1, SERPINB4, S100A2, GZMB, OASL, OSM) and barrier (KRT16, FABP5, CYP1A1) and keratinocyte differentiation (IL-20) . GO analysis revealed that functions of 72 differentially expressed genes could be annotated. KEGG pathway analysis showed that the differentially expressed genes were grouped into 132 signaling pathways, of which 13 were significantly enriched, including the interleukin (IL) -17 pathway, NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, etc. qRT-PCR showed that the mRNA expression levels of candidate genes CXCL1, KRT6A, IL36A, SERPINB4 and PSAPL1 was consistent with the transcriptome sequencing results.@*Conclusions@#Differentially expressed genes and related important regulatory signaling pathways were identified between the lesional and nonlesional skin tissues of patients with AD at the transcriptional level, and the IL-17 pathway was found to be mostly enriched in AD lesions in patients of Han nationality. These findings provide an important basis for further study on the pathogenesis of AD..
ABSTRACT
Objective To identify differentially expressed genes in the transcriptome of the lesional versus nonlesional skin tissues of patients with moderate and severe atopic dermatitis(AD), and to elucidate their roles in the pathogenesis of AD. Methods From July to October in 2016, lesional and nonlesional skin tissues were obtained from 5 outpatients of Han nationality with AD in Guangzhou Institute of Dermatology, Institute of Dermatology, Guangzhou Medical University. The next-generation high-throughput transcriptome-wide RNA sequencing (RNA-seq) was performed to identify differentially expressed genes, which were subjected to GO function annotation and KEGG pathway analysis. Real-time fluorescence-based quantitative PCR(qRT-PCR)was conducted to verify differences in candidate gene expression between lesional and nonlesional skin tissues. Results An average of 10.96 GBs sequence reads were acquired among 10 samples. A total of 21729 genes were detected, including 19268 known genes and 2545 predicted novel genes. A total of 23153 new transcripts were detected, of which 18889 were new alternative splicing subtypes of known protein-coding genes, 2545 were transcripts belonging to new protein-coding genes, and the remaining 1719 belonged to long-stranded non-coding RNA. Totally, 78 differentially expressed genes were identified between the lesional and nonlesional skin tissues, including 69 upregulated and 11 downregulated genes in the lesional skin tissues. Among them, there were several genes known to be associated with AD inflammation (CXCL1/2/8, IL6/IL1β, MMP1, SERPINB4, S100A2, GZMB, OASL, OSM) and barrier (KRT16, FABP5, CYP1A1) and keratinocyte differentiation (IL-20). GO analysis revealed that functions of 72 differentially expressed genes could be annotated. KEGG pathway analysis showed that the differentially expressed genes were grouped into 132 signaling pathways, of which 13 were significantly enriched, including the interleukin(IL)-17 pathway, NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, etc. qRT-PCR showed that the mRNA expression levels of candidate genes CXCL1, KRT6A, IL36A, SERPINB4 and PSAPL1 was consistent with the transcriptome sequencing results. Conclusions Differentially expressed genes and related important regulatory signaling pathways were identified between the lesional and nonlesional skin tissues of patients with AD at the transcriptional level, and the IL-17 pathway was found to be mostly enriched in AD lesions in patients of Han nationality. These findings provide an important basis for further study on the pathogenesis of AD. .