重度特应性皮炎患者急性期和缓解期皮肤微生态研究
Skin microecology in patients with severe atopic dermatitis at acute and remission phases
摘要目的:探索重度特应性皮炎(AD)成人患者急性期及缓解期皮肤微生态结构和功能的变化特点。方法:采集2019年10月至2020年11月于广州市皮肤病防治所门诊就诊的4例成人重度AD患者急性期和缓解期5个部位(面颊、肘窝、手背、腹部、下肢)皮屑标本,利用第二代高通量测序技术进行宏基因组测序,构建皮肤微生物样本基因集,获得各个样本的物种注释信息并进行生物信息学数据分析。结果:4例重度AD患者皮肤中,共检测到18个门,37个纲,73个目,142个科,237个属,331个种。与急性期相比,缓解期AD患者皮肤微生物群落多样性上升,皮肤微生物的相对丰度发生变化( P < 0.05)。在微生物种水平上,金黄色葡萄球菌对AD急性期的影响程度最高,表皮葡萄球菌、奥斯陆莫拉菌、弗朗西丝菌、科氏葡萄球菌、沃氏葡萄球菌、球形马拉色菌以及限制性马拉色菌在AD缓解期富集(|lg线性判别分析值| > 2,Kruksal-Wallis检验,均 P < 0.05)。对微生物丰度差异基因行KEGG功能通路分析,共注释富集于355个功能通路,其中显著富集的通路38个(均 P < 0.05),主要涉及金黄色葡萄球菌感染、色氨酸代谢、组氨酸代谢、氮代谢、精氨酸和脯氨酸代谢、缬氨酸、亮氨酸和异亮氨酸生物合成与降解、脂肪酸降解及过氧化物酶体增殖物激活受体信号通路等。 结论:重度AD患者急性期和缓解期皮肤微生态结构存在显著差异,预测其可能与多个功能通路(如金黄色葡萄球菌感染、色氨酸代谢、组氨酸代谢、氮代谢等)水平相关。
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abstractsObjective: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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