Influence of the Microbiome on the Natural History of Alopecia Areata

微生物组对斑秃自然史的影响

• 批准号: 10585677
• 负责人: Angela M Christiano
• 金额: $ 25.33万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10585677
• 关键词: Adrenal Cortex Hormones; Alopecia; Alopecia Areata; Attention; Autoimmune Diseases; Biological Markers; Clinical; Clinical Trials; Clinical Trials Design; Complex; Cross-Sectional Studies; DNA; Data; Development; Disease; Disease remission; Environmental Risk Factor; Exhibits; FDA approved; Flare; Future; Genetic Predisposition to Disease; Genetic study; Goals; Growth; Hair; Hair follicle structure; Health; Human; Image; Immune response; Immune system; Inflammatory; Intestines; Investigation; Knowledge; Long-Term Effects; Longitudinal Studies; Longitudinal, observational study; Maintenance; Mammals; Mediating; Modality; Natural History; Organ; Outcome; Pathogenesis; Pathologic; Patient Care; Patients; Physiological; Play; Process; Recurrent disease; Research Design; Role; Scalp structure; Severities; Severity of illness; Skin; Sodium Chloride; Spontaneous Remission; Standardization; Swab; System; T-Lymphocyte; Therapeutic; Time; Visit; Waxes; Weight; beta diversity; cohort; design; dysbiosis; effective therapy; gastrointestinal epithelium; gut dysbiosis; gut microbiome; immunoregulation; improved; indexing; innovation; insight; intestinal homeostasis; longitudinal analysis; microbial; microbial community; microbial signature; microbiome; microbiome composition; microbiome signature; microbiota; operational taxonomic units; psychologic; rRNA Genes; response; skin disorder; timeline; tool

ABSTRACT Alopecia Areata (AA) is a common autoimmune disease with a genetic predisposition and potential environmental triggers. AA occurs when the immune system attacks the hair follicle, resulting in hair loss. Its presentation can be characterized as inflammatory, non-scarring hair loss that can occur as a partial (patchy alopecia, AAP), complete absence of hair on the scalp (alopecia totalis, AT), or total loss of scalp and body hair (alopecia universalis, AU). Our lab has extensively studied the genetics of AA, and we have recently turned our attention to the investigation of environmental triggers that may play a crucial role in AA. The gut microbiome has been identified as a potential trigger for the development of autoimmune diseases in general. The intestinal microbial community in humans and other mammals is highly complex, and its diversity contributes to several essential processes that maintain intestinal homeostasis and health. Microbial diversity in the gut has recently emerged as a potential immunomodulatory system with the capacity to elicit physiologic or pathologic responses in the host. Although a complete understanding of the underlying mechanisms remains somewhat elusive, mounting evidence suggests dysbiosis-induced disruption of the gut epithelial barrier function and the systemic immune response as potential factors contributing to disease. Despite the many commonalities between AA and other autoimmune diseases, there are no longitudinal studies to date on the long-term effects of the gut microbiome and different clinical outcomes in AA. There is an urgent need to understand the mechanisms underlying the long-term effects of the microbiota on AA patients in order to enhance the design of well-powered clinical trials in AA, and to provide more effective patient care by developing new treatment modalities. In this proposal, we will conduct an observational longitudinal study of the gut microbiome in a cohort of healthy controls as well as AA patients, and correlate dysbiosis with disease flare or spontaneous remission. This information will be invaluable to facilitate clinical trials design in the future by providing an accurate assessment of the natural history of AA.

抽象的 脱发Areata（AA）是一种常见的自身免疫性疾病，具有遗传易感性和 潜在的环境触发器。当免疫系统攻击毛囊时，就会发生AA 导致脱发。它的呈现可以被描述为炎症性，无刺的头发 可以作为部分（斑点脱发，AAP）发生的损失，头皮上完全没有头发 （脱发，AT）或头皮和身体头发的总损失（环球无菌，au）。我们的实验室 已经广泛研究了AA的遗传学，我们最近将注意力转向了 对可能在AA中起关键作用的环境触发者的调查。肠道 微生物组已被确定为自身免疫性发展的潜在触发因素 一般疾病。人类和其他哺乳动物的肠道微生物群落是 高度复杂，其多样性有助于维护的几个基本过程 肠内稳态和健康。肠道中的微生物多样性最近出现了 潜在的免疫调节系统具有生理或病理的能力 主机中的响应。虽然对基本机制有完整的理解 仍然难以捉摸，越来越多的证据表明营养不良引起的破坏 肠上皮屏障功能和全身免疫反应作为潜在因素 促进疾病。尽管AA与其他人之间有许多共同点 自身免疫性疾病，迄今为止没有关于长期影响的纵向研究 AA中的肠道微生物组和不同的临床结果。迫切需要 了解微生物群对AA患者的长期影响的基础机制 为了增强AA中动力良好的临床试验的设计，并提供更多 通过开发新的治疗方式，有效的患者护理。在此提案中，我们将进行 肠道微生物组在一系列健康对照组中的观察纵向研究 以及AA患者，并将营养不良与疾病爆发或自发缓解相关。这 通过提供一个信息，信息将在未来通过提供一个信息来促进临床试验设计。 准确评估AA的自然史。