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度普利尤单抗治疗而非环孢素治疗可使中重度特应性皮炎患者的微生物组向健康皮肤菌群转变。

Dupilumab but not cyclosporine treatment shifts the microbiome toward a healthy skin flora in patients with moderate-to-severe atopic dermatitis.

机构信息

Center for Inflammatory Skin Diseases, Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.

出版信息

Allergy. 2023 Aug;78(8):2290-2300. doi: 10.1111/all.15742. Epub 2023 Apr 18.

DOI:10.1111/all.15742
PMID:37032440
Abstract

BACKGROUND

Atopic dermatitis (AD) patients display an altered skin microbiome which may not only be an indicator but also a driver of inflammation. We aimed to investigate associations among AD patients' skin microbiome, clinical data, and response to systemic therapy in patients of the TREATgermany registry.

METHODS

Skin swabs of 157 patients were profiled with 16S rRNA gene amplicon sequencing before and after 3 months of treatment with dupilumab or cyclosporine. For comparison, 16s microbiome data from 258 population-based healthy controls were used. Disease severity was assessed using established instruments such as the Eczema Area and Severity Index (EASI).

RESULTS

We confirmed the previously shown correlation of Staphylococcus aureus abundance and bacterial alpha diversity with AD severity as measured by EASI. Therapy with Dupilumab shifted the bacterial community toward the pattern seen in healthy controls. The relative abundance of Staphylococci and in particular S. aureus significantly decreased on both lesional and non-lesional skin, whereas the abundance of Staphylococcus hominis increased. These changes were largely independent from the degree of clinical improvement and were not observed for cyclosporine.

CONCLUSIONS

Systemic treatment with dupilumab but not cyclosporine tends to restore a healthy skin microbiome largely independent of the clinical response indicating potential effects of IL-4RA blockade on the microbiome.

摘要

背景

特应性皮炎(AD)患者的皮肤微生物组发生改变,这种改变不仅是炎症的标志物,也可能是其驱动因素。我们旨在研究 TREATgermany 登记处 AD 患者的皮肤微生物组、临床数据与全身性治疗应答之间的关联。

方法

在接受度普利尤单抗或环孢素治疗 3 个月前后,对 157 例患者的皮肤拭子进行 16S rRNA 基因扩增子测序。为了进行比较,使用了 258 例基于人群的健康对照者的 16s 微生物组数据。使用 Eczema Area and Severity Index(EASI)等现有工具评估疾病严重程度。

结果

我们证实了先前报道的金黄色葡萄球菌丰度与 AD 严重程度(通过 EASI 评估)之间的相关性,以及细菌 alpha 多样性与 AD 严重程度之间的相关性。度普利尤单抗治疗使细菌群落向健康对照组的模式转变。金黄色葡萄球菌,尤其是金黄色葡萄球菌的相对丰度在病变和非病变皮肤上均显著降低,而人葡萄球菌的丰度增加。这些变化在很大程度上独立于临床改善程度,在环孢素治疗中未观察到。

结论

与环孢素相比,全身性使用度普利尤单抗治疗往往会使皮肤微生物组恢复健康,这在很大程度上与临床反应无关,表明 IL-4RA 阻断对微生物组可能具有潜在影响。

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