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.

从父代R21提取 斑秃(AA)在美国影响多达680万人，在全球影响1.47亿人，终生 风险为2.1%，使其成为最常见的自身免疫性疾病之一。再生障碍性贫血导致严重的毁容和 对受影响的个体造成心理痛苦，并在所有皮肤中携带最高的情感负担之一 疾病，特别是在儿童和青少年中，他们的自我形象与他们的外表密切相关。 目前，AA的预后不可预测，也没有FDA批准的治疗方法。AA显示了几个 遗传和免疫病理与其他自身免疫疾病相似，表明相似 环境诱因以及导致终末器官毛囊损伤的炎症反应 (HF)，可能有共同的机制。虽然我们团队和其他人在以下方面取得了重大进展 了解再生障碍性贫血的遗传结构，全身自身免疫反应的环境触发因素 AA尚未确定。因此，我们最近将注意力转向了确定潜在的环境 触发，特别是微生物组。在我们的初步研究中，我们分析了肠道微生物群的组成 对26名再生障碍性贫血患者和10名健康受试者进行了研究，发现这些成分之间存在显著的差异 再生障碍性贫血患者和健康对照的肠道微生物群。我们观察到了一种过度的 再生障碍性贫血患者的氟米米特和类杆菌表达不足，这些发现也见于其他 自身免疫性疾病。C3H/HeJ小鼠再生障碍性贫血模型的初步研究 证明了用广谱抗生素鸡尾酒进行预治疗可以预防再生障碍性贫血 皮肤移植，表明肠道微生物群是再生障碍性贫血发病所必需的。此外，还发生了三起案件 文献报道慢性斑秃/泛发性脱发患者使用粪便治疗 微生物群移植(FMT)治疗无关的疾病，随后经历了显著的毛发再生。 综上所述，这些发现表明肠道微生物群在斑秃中发挥了意想不到的作用，并且 为这项辅助研究基金的母体研究提供了理论基础，题为《粪便微生物群 移植作为治疗斑秃患者的潜在方法“。本辅助研究的目的 Grant将在接受FMT的AA患者中进行微生物组分析和免疫学研究，以 了解环境因素的致病作用，如肠道成分的变化 微生物组，在FMT逆转AA的过程中。