Immunomonitoring and Microbiome Analysis in Alopecia Areata Patients Undergoing Fecal Microbiota Transplantation

接受粪便微生物群移植的斑秃患者的免疫监测和微生物组分析

基本信息

批准号：
10392950
负责人：
Angela M Christiano
金额：
$ 28.23万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10392950
关键词：
Adolescent Affect Alopecia Areata Ancillary Study Antibiotics Appearance Attention Autoimmune Diseases Autoimmune Responses Bacteroides Biopsy C3H/HeJ Mouse Celiac Disease Cells Child Chronic Clinical Clinical Data Complex Development Disease Emotional Environmental Risk Factor FDA approved Firmicutes Gene Expression Gene Expression Profile Gene Expression Profiling Genetic Genetic Diseases Goals Grant Hair Hair follicle structure Human Immune Immunologic Monitoring Immunologics Individual Inflammatory Response Inherited Insulin-Dependent Diabetes Mellitus Link Literature Organ Outcome Parents Pathogenicity Patients Peripheral Persons Plasma Population Prognosis Reporting Role Sampling Scalp structure Self Perception Skin Skin graft T-Lymphocyte cohort experience fecal transplantation gene discovery genetic architecture gut dysbiosis gut microbiome lifetime risk longitudinal analysis microbiome microbiome analysis microbiome composition mouse model novel novel marker psychological distress response biomarker skin disorder

项目摘要

ABSTRACT Alopecia areata (AA) affects as many as 6.8 million people in the U.S. and 147 million worldwide, with a lifetime risk of 2.1%, making it one of the most common autoimmune diseases. AA causes significant disfigurement and psychological distress to affected individuals and carries one of the highest emotional burdens amongst all skin diseases, particularly among children and adolescents whose self-image is so closely linked to their appearance. At present, the prognosis is unpredictable and there is no FDA approved treatment for AA. AA shows several genetic and immunopathogenic similarities to other autoimmune conditions, suggesting that similar environmental triggers as well as the inflammatory responses leading to damage in the end-organ, the hair follicle (HF), may have common mechanisms. While our group and others have made significant advances in understanding the genetic architecture of AA, the environmental triggers of systemic autoimmune response in AA have not been identified. Therefore, we recently turned our attention to determining potential environmental triggers, in particular, the microbiome. In our Preliminary Studies we analyzed the gut microbiome composition of a cohort of 26 AA patients and 10 healthy subjects, and found striking dissimilarities between the composition of the gut microbiome of AA patients and those of healthy controls. We observed an overrepresentation of firmicutes and an underrepresentation of bacteroides in AA patients, findings which are also seen in other autoimmune diseases. Our additional Preliminary Studies on the well-established C3H/HeJ mouse model of AA demonstrated that pre-treatment with a wide-spectrum antibiotic cocktail results in protection against AA after skin grafting, suggesting the gut microbiome is required for the onset of AA. In addition, three cases have been reported in the literature of patients with chronic alopecia areata/universalis who were treated with a fecal microbiota transplant (FMT) for unrelated conditions, who subsequently experienced significant regrowth of hair. Taken together, these findings suggest an unexpected role of the gut microbiome in alopecia areata, and provided the rationale for the Parent Study of this Ancillary Studies Grant, entitled “Fecal Microbiota Transplantation as a Potential Treatment for Patients with Alopecia Areata”. The purpose of this Ancillary Studies grant is to conduct microbiome analysis and immunological studies in AA patients undergoing FMT, in order to understand the pathogenic role of environmental factors, such as changes in the composition of the gut microbiome, in the reversal of AA by FMT.

抽象的斑秃 (AA) 影响着美国多达 680 万人和全球 1.47 亿人，影响其一生 AA 的风险为 2.1%，使其成为最常见的自身免疫性疾病之一，会导致严重的毁容和损伤。给受影响的人带来心理困扰，是所有皮肤中情绪负担最重的皮肤之一疾病，尤其是儿童和青少年，他们的自我形象与其外表密切相关。目前，AA 的预后是不可预测的，并且还没有 FDA 批准的 AA 治疗方法。与其他自身免疫性疾病的遗传和免疫病理相似性，表明相似的环境触发因素以及导致终末器官毛囊受损的炎症反应（HF），可能有共同的机制，而我们的小组和其他人在这方面取得了重大进展。了解 AA 的遗传结构、系统性自身免疫反应的环境触发因素因此，我们最近将注意力转向确定潜在的环境。在我们的初步研究中，我们分析了肠道微生物组的组成。对 26 名 AA 患者和 10 名健康受试者组成的队列进行了研究，发现其成分之间存在显着差异我们观察到 AA 患者和健康对照者肠道微生物组的比例过高。 AA 患者中厚壁菌门和类杆菌代表性不足，这一发现在其他患者中也有发现我们对成熟的 AA C3H/HeJ 小鼠模型进行了额外的初步研究。使用广谱抗生素混合物进行预处理可在治疗后产生针对 AA 的保护作用植皮，表明肠道微生物组是 AA 发病所必需的。此外，还发现了 3 例病例。文献报道了接受粪便治疗的慢性斑秃/普秃患者针对不相关的病症进行微生物移植（FMT），随后头发显着再生。综上所述，这些发现表明肠道微生物组在斑秃中发挥着意想不到的作用，并且提供了这项辅助研究补助金的家长研究的基本原理，题为“粪便微生物群移植作为斑秃患者的潜在治疗方法”。拨款旨在对接受 FMT 的 AA 患者进行微生物组分析和免疫学研究，以便了解环境因素的致病作用，例如肠道成分的变化微生物组，通过 FMT 逆转 AA。