Influence of the Microbiome on the Natural History of Alopecia Areata

摘要 斑秃(AA)是一种常见的自身免疫性疾病，具有遗传易感性和 潜在的环境诱因。当免疫系统攻击毛囊时就会发生再生障碍性贫血， 导致脱发。其表现特征为炎症性、无疤痕的头发。 部分脱发(斑片性脱发，AAP)，头皮上完全没有毛发 脱发(全面性脱发，AT)或头皮和体毛完全脱落(全面性脱发，AU)。我们的实验室 对再生障碍性贫血的遗传学进行了广泛的研究，最近我们将注意力转向了 对可能在再生障碍性贫血中起关键作用的环境诱因进行调查。胆量 微生物组已被确认为自身免疫发展的潜在触发因素 一般的疾病。人类和其他哺乳动物的肠道微生物群落是 高度复杂，其多样性有助于保持以下几个基本过程 肠道动态平衡与健康。肠道中的微生物多样性最近已经成为一种 潜在的免疫调节系统，具有引起生理或病理的能力 主机中的响应。尽管对潜在的机制有一个完整的理解 仍然有些难以捉摸，越来越多的证据表明，生物失调导致的 肠道上皮屏障功能和全身免疫反应作为潜在因素 会导致疾病。尽管AA和其他公司之间有许多共同点 自身免疫性疾病，目前还没有关于长效作用的纵向研究。 再生障碍性贫血的肠道微生物群和不同的临床结局。有迫切的需要 了解微生物区系对再生障碍性贫血患者的长期影响的机制 为了加强再生障碍性贫血强大的临床试验的设计，并提供更多 通过开发新的治疗方式有效地护理病人。在这项提案中，我们将进行 一项对健康对照人群肠道微生物群的纵向观察性研究 和再生障碍性贫血患者一样，并将生物失调与疾病发作或自发缓解联系起来。这 信息将为未来的临床试验设计提供无价的帮助 准确评估再生障碍性贫血的自然历史。

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.