Abstract
PURPOSE: Androgenetic alopecia (AGA) is characterized by perifollicular micro-inflammation, although its precise trigger remains elusive. Given that the hair follicle harbors a distinct microbiota which may modulate local immune responses, this study aimed to comprehensively profile the bacterial and fungal microbiome within the deep hair follicles of AGA patients versus healthy controls, and to evaluate the influence of disease severity, age, sex, and geographical environment. PATIENTS AND METHODS: We recruited 96 subjects (72 AGA patients and 24 healthy controls), collecting a total of 192 plucked hair follicle samples from the vertex and occipital scalp. Bacterial 16S rRNA (V3-V4) and fungal ITS regions were sequenced using the Illumina HiSeq platform. Bioinformatics pipelines were employed to analyze α- and β-diversity, as well as taxonomic composition, across multiple stratifications: disease stage, scalp region, age, sex, and geographical location. RESULTS: Bacterial community structure showed relative stability between groups. In contrast, fungal communities were markedly dysbiotic in AGA. A key finding was the significant depletion of the commensal yeast Malassezia in AGA follicles compared to controls (p < 0.01). Conversely, opportunistic taxa such as Thermomyces and Bifidobacterium were enriched in advanced disease stages. Notably, microbial α-diversity increased with both disease severity and age, indicating a disruption of the follicular niche ("niche collapse"). Male AGA patients exhibited distinct fungal shifts compared to females, and geographical location significantly shaped the follicular microbiome in patients but not in healthy controls. CONCLUSION: Androgenetic alopecia involves fungal dysbiosis with loss of commensal Malassezia and gain of opportunistic microbes. Driven by host and environmental factors, this reframes AGA as an ecological imbalance, opening avenues for microbiome-targeted therapies.