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先天性鱼鳞病中独特的皮肤微生物群落结构。

Distinct skin microbiome community structures in congenital ichthyosis.

机构信息

A*STAR Skin Research Labs, Agency for Science, Technology and Research, 8A Biomedical Grove, #06-10 Immunos, Singapore, 138648, Singapore.

Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

出版信息

Br J Dermatol. 2022 Oct;187(4):557-570. doi: 10.1111/bjd.21687. Epub 2022 Jul 4.

Abstract

BACKGROUND

The ichthyoses are rare genetic keratinizing disorders that share the characteristics of an impaired epidermal barrier and increased risk of microbial infections. Although ichthyotic diseases share a T helper (Th) 17 cell immune signature, including increased expression of antimicrobial peptides, the skin microbiota of ichthyoses is virtually unexplored.

OBJECTIVES

To analyse the metagenome profile of skin microbiome for major congenital ichthyosis subtypes.

METHODS

Body site-matched skin surface samples were collected from the scalp, upper arm and upper buttocks of 16 healthy control participants and 22 adult patients with congenital forms of ichthyosis for whole metagenomics sequencing analysis.

RESULTS

Taxonomic profiling showed significant shifts in bacteria and fungi abundance and sporadic viral increases across ichthyosis subtypes. Cutibacterium acnes and Malassezia were significantly reduced across body sites, consistent with skin barrier disruption and depletion of lipids. Microbial richness was reduced, with specific increases in Staphylococcus and Corynebacterium genera, as well as shifts in fungal species, including Malassezia. Malassezia globosa was reduced at all body sites, whereas M. sympodialis was reduced in the ichthyotic upper arm and upper buttocks. Malassezia slooffiae, by contrast, was strikingly increased at all body sites in participants with congenital ichthyosiform erythroderma (CIE) and lamellar ichthyosis (LI). A previously undescribed Trichophyton species was also detected as sporadically colonizing the skin of patients with CIE, LI and epidermolytic ichthyosis subtypes.

CONCLUSIONS

The ichthyosis skin microbiome is significantly altered from healthy skin with specific changes predominating among ichthyosis subtypes. Skewing towards the Th17 pathway may represent a response to the altered microbial colonization in ichthyosis. What is already known about this topic? The skin microbiome of congenital ichthyoses is largely unexplored. Microbes play an important role in pathogenesis, as infections are common. The relative abundances of staphylococci and corynebacteria is increased in the cutaneous microbiome of patients with Netherton syndrome, but extension of these abundances to all congenital ichthyoses is unexplored. What does this study add? A common skin microbiome signature was observed across congenital ichthyoses. Distinct microbiome features were associated with ichthyosis subtypes. Changes in microbiome may contribute to T helper 17 cell immune polarization. What is the translational message? These data provide the basis for comparison of the microbiome with lipidomic and transcriptomic alterations in these forms of ichthyosis and consideration of correcting the dysbiosis as a therapeutic intervention.

摘要

背景

鱼鳞病是一种罕见的遗传性角化障碍,其特征为表皮屏障受损和微生物感染风险增加。虽然鱼鳞病存在 Th17 细胞免疫特征,包括抗菌肽表达增加,但鱼鳞病的皮肤微生物组几乎未被探索。

目的

分析主要先天性鱼鳞病亚型的皮肤微生物组宏基因组谱。

方法

从 16 名健康对照参与者和 22 名成人先天性鱼鳞病患者的头皮、上臂和上臀部采集部位匹配的皮肤表面样本,进行全宏基因组测序分析。

结果

分类分析显示,细菌和真菌丰度显著变化,病毒零星增加,跨越鱼鳞病亚型。整个身体部位的痤疮丙酸杆菌和马拉色菌显著减少,与皮肤屏障破坏和脂质耗竭一致。微生物丰富度降低,葡萄球菌和棒状杆菌属增加,以及真菌物种变化,包括马拉色菌。所有部位的球状马拉色菌减少,而上肢和上臀部的融合马拉色菌减少。相反,先天性鱼鳞病性红皮病(CIE)和层状鱼鳞病患者的所有部位的 slooffiae 马拉色菌均显著增加。在 CIE、LI 和表皮松解性鱼鳞病患者中,还检测到一种以前未描述的 Trichophyton 种偶尔定植在皮肤中。

结论

鱼鳞病的皮肤微生物组与健康皮肤有显著差异,特定变化在鱼鳞病亚型中占主导地位。向 Th17 途径倾斜可能代表对鱼鳞病改变的微生物定植的反应。

已知的相关信息

先天性鱼鳞病的皮肤微生物组在很大程度上尚未被探索。微生物在发病机制中起着重要作用,因为感染很常见。 Netherton 综合征患者的皮肤微生物组中葡萄球菌和棒状杆菌的相对丰度增加,但这些丰度扩展到所有先天性鱼鳞病尚未被探索。

本研究新增内容

在所有先天性鱼鳞病中观察到共同的皮肤微生物组特征。特定的微生物组特征与鱼鳞病亚型相关。微生物组的变化可能有助于 Th17 细胞免疫极化。

临床意义

这些数据为比较这些形式的鱼鳞病的微生物组与脂质组学和转录组学改变提供了基础,并考虑将菌群失调作为一种治疗干预。

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Inherited ichthyosis: Non-syndromic forms.遗传性鱼鳞病:非综合征型
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