Spatial Distribution and Functional Impact of Human Scalp Hair Follicle Microbiota

Human hair follicles (HFs) constitute a unique microbiota habitat that differs substantially from the skin surface. Traditional HF sampling methods fail to eliminate skin microbial contaminants or assess the HF microbiota incompletely, while microbiota functions in human HF physiology remain ill-explored. Therefore, we used laser-capture microdissection, metagenomic shotgun sequencing, and FISH to characterize the human scalp HF microbiota in defined anatomical compartments. This revealed significant compartment-, tissue lineage- and donor age-dependent variations in microbiota composition. Greatest abundance variations between HF compartments were observed for viruses, archaea, Staphylococcus epidermidis, Cutibacterium acnes and Malassezia restricta, with the latter two being surprisingly higher in the HF mesenchyme, and the most abundant viable HF epithelium colonizers (tested by propidium monoazide assay). Transfection of organ-cultured human scalp HFs with S. epidermidis-specific lytic bacteriophages ex vivo downregulated transcription of genes known to regulate HF growth and development, metabolism and melanogenesis, suggesting that selected microbial products can modulate HF functions. Indeed, treatment with butyrate, a bacterial metabolite of S. epidermidis amongst other HF microbiota, delayed catagen, promoted autophagy, mitochondrial activity, gp100, and dermcidin expression ex vivo. Thus, human HF microbiota show variations in spatial abundance and exert important modulatory effects on their host, inviting therapeutic targeting.