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 斑秃（AA）是一种常见的自身免疫性疾病，具有遗传易感性和 潜在的环境触发因素。当免疫系统攻击毛囊时就会发生 AA， 导致脱发。其表现可表现为炎症性、非疤痕性毛发 可能发生的部分脱发（斑片状脱发，AAP），头皮上的头发完全消失 （全秃，AT），或头皮和体毛完全脱落（普秃，AU）。我们的实验室 对 AA 的遗传学进行了广泛的研究，最近我们将注意力转向 调查可能在 AA 中发挥关键作用的环境触发因素。肠道 微生物组已被确定为自身免疫性疾病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，其多样性有助于维持几个基本过程 肠道稳态和健康。肠道微生物多样性最近已成为 潜在的免疫调节系统，具有引发生理或病理的能力 主机中的响应。虽然完全了解底层机制 仍然有点难以捉摸，越来越多的证据表明生态失调引起的破坏 肠道上皮屏障功能和全身免疫反应作为潜在因素 助长疾病。尽管 AA 和其他组织之间有许多共同点 自身免疫性疾病，迄今为止还没有关于其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 患者长期影响的机制 为了加强 AA 中强有力的临床试验的设计，并提供更多 通过开发新的治疗方式来有效地护理患者。在本提案中，我们将进行 对一组健康对照组的肠道微生物组进行观察性纵向研究 以及 AA 患者，并将生态失调与疾病发作或自发缓解相关联。这 通过提供信息，对于促进未来的临床试验设计将是非常宝贵的。 准确评估 AA 的自然史。