Immunomonitoring and Microbiome Analysis in Alopecia Areata Patients Undergoing Fecal Microbiota Transplantation

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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.