AbstractAtopic dermatitis is the most common inflammatory skin condition with a severe negative impact on patients’ quality of life. The etiology of AD is complex and depends on age, genetics, the immune system, environmental factors, and the skin microbiome, with a key role for pathogenic Staphylococcus aureus in the development of severe AD.

摘要特应性皮炎是最常见的炎症性皮肤病，对患者的生活质量有严重的负面影响。AD的病因复杂，取决于年龄，遗传学，免疫系统，环境因素和皮肤微生物组，致病性金黄色葡萄球菌在严重AD的发展中起关键作用。

However, the composition of the skin microbiome in mild AD is understudied. Here, using metagenomic shallow shotgun sequencing, we showed that mild AD lesions did not show a significant difference in the diversity of the skin microbiome compared to samples from non-AD patients and that the relative abundance of S.

然而，轻度AD中皮肤微生物组的组成尚未得到充分研究。在这里，使用宏基因组浅鸟枪测序，我们发现轻度AD病变与非AD患者的样本相比，皮肤微生物组的多样性没有显着差异，并且S的相对丰度。

aureus did not differ in these mild AD lesions. However, when we assessed other taxa, Mycobacterium ostraviense, Pedobacter panaciterrae_A and four Streptomyces species were identified with higher abundances in mild AD lesions and species of 15 genera were decreased in abundance. The highest fold decreases were observed for Paracoccus marcusii, Microbacterium lacticum, Micrococcus luteus, and Moraxella sp002478835.

金黄色葡萄球菌在这些轻度AD病变中没有差异。然而，当我们评估其他分类群时，在轻度AD病变中鉴定出具有较高丰度的ostraviense分枝杆菌，Pedobacter panaciterrae\u A和四种链霉菌，并且15属的物种丰度减少。对于marcusii副球菌，乳微杆菌，黄体微球菌和莫拉氏菌sp002478835，观察到最高的倍数降低。

These microbiome compositional insights are a first step towards novel microbiome-based diagnostics and therapeutics for early intervention at the stage of mild AD and provide a path forward for the functional study of species involved in this often-overlooked patient population..

这些微生物组组成的见解是朝着基于微生物组的新型诊断和治疗方法迈出的第一步，用于轻度AD阶段的早期干预，并为这一经常被忽视的患者群体中涉及的物种的功能研究提供了一条前进的道路。。

IntroductionAtopic dermatitis (AD) is a chronic inflammatory skin condition that affects approximately 20% of children and 3% of adults in Western countries1,2. The clinical diagnosis of AD is made based on the Hanifin and Rajkia criteria and the symptoms are characterized by flares of itchy, eczema lesions, and red and dry skin3.

引言特应性皮炎（AD）是一种慢性炎症性皮肤病，影响西方国家约20%的儿童和3%的成年人1,2。AD的临床诊断是根据Hanifin和Rajkia标准进行的，症状的特征是瘙痒，湿疹病变以及皮肤发红和干燥3。

AD can manifest in a different grade of severity, ranging from ‘mild’ to ‘severe’ which can be examined by validated severity assessment tools such as the Scoring AD (SCORAD) index or Eczema Area and Severity Index (EASI)4. However, the differences in pathophysiology between ‘mild’ and ‘severe’ AD are not well understood and depend on the site of the lesion.AD usually starts early during childhood and is a common first symptom in the so-called “atopic march”, describing the successive development of AD, allergic rhinitis, and asthma in atopic children5.

AD可以表现为不同程度的严重程度，从“轻度”到“严重”，可以通过经过验证的严重程度评估工具进行检查，例如评分AD（SCORAD）指数或湿疹面积和严重程度指数（EASI）4。然而，“轻度”和“重度”AD之间的病理生理学差异尚不清楚，并且取决于病变部位。AD通常在儿童早期开始，是所谓的“特应性游行”中常见的首发症状，描述了特应性儿童AD，过敏性鼻炎和哮喘的连续发展5。

The symptoms, which often cause insomnia and social insecurity, have a large impact on patients’ quality of life, even for mild AD symptoms6,7. In addition, the high prevalence creates a significant burden on health facilities8,9. The etiology of this skin condition is very complex, with the appearance influenced by genetic and immunological mechanisms, as well as environmental factors1.

这些症状通常会导致失眠和社会不安全感，即使对于轻度AD症状，也会对患者的生活质量产生很大影响6,7。此外，高流行率给卫生设施带来了沉重负担8,9。这种皮肤病的病因非常复杂，其外观受遗传和免疫机制以及环境因素的影响1。

Important genetic risk factors include mutations in genes encoding proteins for skin barrier integrity, such as loss-of-function mutations in the filaggrin gene10, or variants of several genes primarily involved in immune pathways, such as Interleukin-4 receptor (IL-4R), Interleukin-18 (IL-18), and Interleukin-31 (IL-31)11,12,13.

重要的遗传风险因素包括编码皮肤屏障完整性蛋白质的基因突变，例如聚丝蛋白基因10中的功能丧失突变，或主要参与免疫途径的几种基因的变体，例如白细胞介素-4受体（IL-4R），白细胞介素-18（IL-18）和白细胞介素-31（IL-31）11,12,13。

The complex immune dysregulation in AD includes an important role of T-helper (Th)-2 inflammation, with IL-4 and IL-13 involved in both acute and chronic AD lesions, and Th-1 inflammat.

AD中复杂的免疫失调包括T辅助（Th）-2炎症的重要作用，IL-4和IL-13参与急性和慢性AD病变，以及Th-1炎症。

Data availability

数据可用性

Datasets related to this article can be found at https://www.ebi.ac.uk/ena/browser/view/PRJEB63144 , with identification PRJEB63144, hosted at ENA, EMBL.

与本文相关的数据集可以在https://www.ebi.ac.uk/ena/browser/view/PRJEB63144，标识为PRJEB63144，位于EMBL的ENA。

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Ahannach, S. et al. Microbial enrichment and storage for metagenomics of vaginal, skin, and saliva samples. iScience 24, (2021).Download referencesAcknowledgementsFirst, we would like to thank all participants for donating samples. In addition, we would also like to thank the following colleagues of our research group for their contributions: Ines Tuyaerts, Nele Van de Vliet, and Leen Van Ham for their help with study preparations and Stijn Wittouck for his help with data-analyses and visualization.

。iScience 24，（2021）。下载参考文献致谢首先，我们要感谢所有参与者捐赠样本。此外，我们还要感谢我们研究小组的以下同事的贡献：Ines Tuyaerts，Nele Van de Vliet和Leen Van Ham在研究准备方面的帮助，以及Stijn Wittouck在数据分析和可视化方面的帮助。

L.D. was supported by Baekeland of VLAIO (HBC.2020.2873). IDB and JVM were supported by grants from Research Foundation – Flanders (Fonds Wetenschappelijk Onderzoek (FWO), respectively postdoctoral grant 12S4222N and SB grant 1S08523N). S.L. was supported by the European Research Council grant (Lacto-be 852600).Author informationAuthor notesShared senior authors: Margo Hagendorens, Sarah Lebeer and Julie Leysen. Authors and AffiliationsDepartment of Bioscience Engineering, University of Antwerp, Groenenborgerlaan 171, Antwerpen, B-2020, BelgiumLize Delanghe, Ilke De Boeck, Joke Van Malderen, Camille Nina Allonsius, Tim Van Rillaer, Peter A.

五十、 D.得到了VLAIO的Baekeland的支持（HBC。2020.2873）。IDB和JVM得到了法兰德斯研究基金会（Fonds Wetenschapelijk Onderzoek（FWO））的资助，分别是博士后资助12S4222N和SB资助1S08523N。S、 L.得到了欧洲研究理事会拨款（Lacto be 852600）的支持。作者信息作者笔记共享资深作者：玛戈·哈根多伦（MargoHagendorens）、莎拉·勒比尔（SarahLebeer）和朱莉·莱森（JulieLeysen）。。

Bron & Sarah LebeerUniversity Hospital Antwerp, Department of Pediatrics, University of Antwerp, Wilrijkstraat 10, Edegem, B-2650, BelgiumMargo HagendorensUniversity Hospital Antwerp, Department of Dermatology, University of Antwerp, Wilrijkstraat 10, Edegem, B-2650, BelgiumJulie LeysenYUN NV, Galileilaan 15, Niel, B-2845, BelgiumIngmar ClaesAuthorsLize DelangheView author publicationsYou can also search for this author in.

Bron＆Sarah LebeerUniversity Hospital安特卫普，儿科，安特卫普大学，Wilrijkstraat 10，Edegem，B-2650，BelgiumMargo HagendorensUniversity Hospital安特卫普，皮肤科，安特卫普大学，Wilrijkstraat 10，Edegem，B-2650，BelgiumJulie LeysenYUN NV，Galilelaan 15，Niel，B-2845，BelgiumIngmar ClaesAuthorsLize DelangheView作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarIlke De BoeckView author publicationsYou can also search for this author in

PubMed Google ScholarIlke De BoeckView作者出版物您也可以在

PubMed Google ScholarJoke Van MalderenView author publicationsYou can also search for this author in

PubMed Google ScholarJoke Van MalderenView作者出版物您也可以在

PubMed Google ScholarCamille Nina AllonsiusView author publicationsYou can also search for this author in

PubMed Google ScholarCamille Nina AllonsiusView作者出版物您也可以在

PubMed Google ScholarTim Van RillaerView author publicationsYou can also search for this author in

PubMed Google ScholarTim Van RillaerView作者出版物您也可以在

PubMed Google ScholarPeter A. BronView author publicationsYou can also search for this author in

PubMed Google ScholarPeter A.BronView作者出版物您也可以在

PubMed Google ScholarIngmar ClaesView author publicationsYou can also search for this author in

PubMed Google ScholarIngmar ClaesView作者出版物您也可以在

PubMed Google ScholarMargo HagendorensView author publicationsYou can also search for this author in

PubMed Google ScholarMargo HagendorensView作者出版物您也可以在

PubMed Google ScholarSarah LebeerView author publicationsYou can also search for this author in

PubMed Google ScholarSarah LebeerView作者出版物您也可以在

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PubMed Google ScholarJulie LeysenView作者出版物您也可以在

PubMed Google ScholarContributionsS.L., M.H. J.L., I.D.B., I.C. and L.D. worked on the conceptualization of the research project. The experiments were performed by J.V.M. and L.D. Data-analyses and visualization were performed by T.V.R. and L.D. Data interpretation was done by S.L., M.H., J.L., I.D.B., C.N.A., I.C., P.A.B., and L.D.

PubMed谷歌学术贡献。五十、 ，M.H.J.L.，I.D.B.，I.C.和L.D.致力于研究项目的概念化。实验由J.V.M.和L.D.进行。数据分析和可视化由T.V.R.和L.D.进行。数据解释由S.L.，M.H.，J.L.，I.D.B.，C.N.A.，I.C.，P.A.B.和L.D.完成。

The original draft was written by L.D. and S.L. All authors contributed to reviewing and editing of the paper. All authors proofread and approved the manuscript.Corresponding authorCorrespondence to.

原稿由L.D.和S.L.撰写。所有作者都为论文的审查和编辑做出了贡献。所有作者都校对并批准了手稿。对应作者对应。

Sarah Lebeer.Ethics declarations

莎拉·勒比尔。道德宣言

Competing interests

相互竞争的利益

S.L. was a member of the scientific advisory board of YUN NV until 2023. L.D. is affiliated with the university and her salary was funded by VLAIO through a Baekeland mandate in collaboration with YUN NV. I.C. is chief scientific officer at YUN NV. P.A.B. is a consultant for several companies in the food and health industry.

S、 L.是YUN NV科学顾问委员会的成员，直到2023年。五十、 。一、 是YUN NV的首席科学官。P、 A.B.是食品和健康行业几家公司的顾问。

The remaining authors declare no conflicts of interest..

其余作者声明没有利益冲突。。

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Reprints and permissionsAbout this articleCite this articleDelanghe, L., De Boeck, I., Van Malderen, J. et al. Mild atopic dermatitis is characterized by increase in non-staphylococcus pathobionts and loss of specific species.

转载和许可本文引用本文Delanghe，L.，De Boeck，I.，Van Malderen，J。等人。轻度特应性皮炎的特征是非葡萄球菌病原体的增加和特定物种的丧失。

Sci Rep 14, 23659 (2024). https://doi.org/10.1038/s41598-024-74513-2Download citationReceived: 11 January 2024Accepted: 26 September 2024Published: 10 October 2024DOI: https://doi.org/10.1038/s41598-024-74513-2Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

科学报告1423659（2024）。https://doi.org/10.1038/s41598-024-74513-2Download引文收到日期：2024年1月11日接受日期：2024年9月26日发布日期：2024年10月10日OI：https://doi.org/10.1038/s41598-024-74513-2Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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