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

• 批准号: 10414461
• 负责人: Angela M Christiano
• 金额: $ 7.8万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10414461
• 关键词: Adolescent; Affect; Alopecia Areata; Ancillary Study; Antibiotics; Appearance; Attention; Autoimmune Diseases; Autoimmune Responses; Bacteroides; C3H/HeJ Mouse; Child; Chronic; Development; Emotional; Environmental Risk Factor; FDA approved; Firmicutes; Genetic; Goals; Grant; Hair; Hair follicle structure; Immune; Immunologic Monitoring; Immunologics; Individual; Inflammatory Response; Link; Literature; Organ; Parents; Pathogenicity; Patients; Peripheral; Prognosis; Reporting; Role; Self Perception; Skin; Skin graft; cohort; experience; fecal transplantation; genetic architecture; gut microbiome; lifetime risk; microbiome; microbiome analysis; microbiome composition; mouse model; psychological distress; skin disorder

ABSTRACT from Parent R21 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.

父母R21的摘要 脱发Areata（AA）在美国影响多达680万人，在全球范围内影响1.47亿 2.1％的风险，使其成为最常见的自身免疫性疾病之一。 AA引起严重的毁容和 对受影响个人的心理困扰，并带来了所有皮肤中最高的情绪燃烧之一 疾病，特别是在自我形象与其外观紧密相关的儿童和青少年中。 目前，预后是不可预测的，并且没有FDA批准的AA治疗方法。 AA显示了几个 与其他自身免疫性条件的遗传和免疫病相似性，表明相似 环境触发器以及炎症反应导致最终器官损伤，毛囊 （HF）可能具有共同的机制。而我们的小组和其他人在 了解AA的遗传结构，这是系统性自身免疫反应的环境触发器 AA尚未确定。因此，我们最近将注意力转向确定潜在环境 特别是触发器，是微生物组。在我们的初步研究中，我们分析了肠道微生物组组成 由26名AA患者和10名健康受试者组成的队列，并发现组成之间的差异很大 AA患者的肠道微生物组和健康对照组的肠道微生物组。我们观察到了过多的代表 AA患者的固件和细菌的代表性不足，在其他发现中也可以看到 自身免疫性疾病。我们对AA的良好C3H/HEJ鼠标模型的其他初步研究 证明与广谱抗生素鸡尾酒的预处理可导致防止AA 皮肤移植，表明AA发作需要肠道微生物组。此外，有三种情况是 在接受粪便治疗的慢性脱发/环球病患者的文献中报道了 微生物群移植（FMT）对于随后进行了重大改革的无关疾病。 综上所述，这些发现表明肠道微生物组在脱发区域的意外作用，以及 提供了该辅助研究赠款的父母研究的基本原理，标题为“粪便菌群 移植作为脱发患者的潜在治疗”。该辅助研究的目的 授予是为了对正在接受FMT的AA患者进行微生物组分析和免疫学研究，以便为了 了解环境因素的致病作用，例如肠道组成的变化 微生物组，在FMT的AA反转中。