Influence of the Microbiome on the Natural History of Alopecia Areata

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.