儿童期特应性皮炎与皮肤微生态的相关性研究

Atopic dermatitis(AD) is a chronic, recurrent, and pruritus inflammatory skin disorder which is most common in children. In recent years, the incidence rate increased significantly. AD is usually the initial manifestation of the “atopic march”, accompanied with allergic rhinitis and asthma, with drastic impacts on life quality of patients and the family. The pathogenesis of AD is still remains unclear, which include genetic susceptibility, immune imbalance, skin barrier dysfunction and infection. Among which, the skin barrier and infection factor are both related to the shift of skin microflora. The previous research mainly focused on the Staphylococcus aureus only, ignoring the relationship between the overall change of skin microflora with AD. How does other microbiome change when AD occurs? How does the skin microflora affect the occurrence and development of AD? At present, the microflora research in gut relying on metagenomics has been proceeded widely, but the research on the skin microflora has not been carried out yet. So this study aims to establish a high-throughout sequencing platform for skin microflora detection, to explore the characteristics of childhood AD and normal children's skin microflora, then further to discuss if the skin microflora regulating therapy which can make it back to the healthy microbiome structure, namely the targeted therapy of symbiotic microbiome, is possible to become the prevention and treatment methods for AD.

特应性皮炎（Atopic Dermatitis，AD）是儿童常见慢性、复发性、瘙痒性、炎症性皮肤病，近年发病率明显上升。其与过敏性鼻炎、哮喘称为“过敏性疾病三联征”，AD常为初始表现，严重影响患儿及家庭生活质量。目前AD病因及发病机制仍不明确，主要包括遗传易感性、免疫失衡、皮肤屏障破坏及感染因素。其中皮肤屏障及感染均涉及皮肤微生态变化，既往研究重点仅针对于金黄色葡萄球菌，而忽略了皮肤微生态的整体变化与AD的关系。AD发生时其他菌群如何变化？皮肤菌群如何影响AD的发生发展？目前依托于宏基因组学的肠道微生态研究已如火如荼，但对于皮肤微生态检测尚未开展。故本研究旨在建立高通量测序平台进行皮肤微生态菌群的检测，了解儿童期AD患儿及正常儿童皮肤菌群微生态的特点，探讨采用微生态调节皮肤微生物群使其回到健康的菌群结构状态，即进行自然共生菌结构的靶向治疗，是否可能成为AD的预防和诊治手段。

特应性皮炎（Atopic Dermatitis，简称AD）是儿童常见慢性、复发性皮肤病。AD患儿随着年龄增长，出现过敏性鼻炎、哮喘的几率明显增加，给家庭和社会造成了巨大的精神和经济负担。AD病因及发病机制至今不清，主要包括遗传背景易感性、免疫失衡、皮肤屏障破坏以及感染因素，且AD的严重程度与皮肤屏障的异常存在相关性。皮肤微生态菌群的研究是皮肤屏障研究的热点。.本项目共收集51个AD儿童和32个健康对照儿童的皮肤样本，并对经糠酸莫米松和莫匹罗星治疗2周前后的皮肤样本进行测试，结果发现：1、AD儿童与健康儿童的皮肤菌群组成显著不同：健康儿童的链球菌、副杆菌、不动杆菌、罗氏菌、梭状芽孢杆菌显著高于AD儿童，而葡萄球菌、假单胞菌、普氏菌、金黄杆菌、脱硫弧菌显著低于AD儿童（P<0.05）。2、明确AD患者菌群特点：根据Bray-Curtis分析，AD患者可分为金葡菌优势组（11个菌株）和非金葡菌优势组（假单胞菌或普氏菌）两组。金葡菌占优势的AD组患儿临床症状重，SCORAD评分高，微生物多样性显著降低。3、金葡菌与非金葡菌占主导的AD组患儿对临床治疗的反应存在差异：在临床治疗两周后，AD患者的皮肤微生物群发生了变化，与非金葡菌占主导的AD组相比，金葡菌占主导的AD组的皮肤微生物群发生了更为剧烈的变化。两组治疗后临床症状均有好转，SCORAD分数下降。金葡菌占主导的AD组治疗后金黄色葡萄球菌急剧减少，金黄色葡萄球菌丰度明显下降，多样性增加。.总之，本项目明确2-12岁健康儿童及AD患儿皮肤菌群微生态的特点，为日后探讨采用微生态调节皮肤微生物群使其回到健康的菌群结构状态，即进行自然共生菌结构的靶向治疗，是否可能成为AD的预防和诊治手段提供科学依据。并且成功建立高通量测序平台进行皮肤微生态菌群的检测，以后可将此平台应用到其他皮肤病与菌群的相关性研究中。