Bacteria Induce Skin Regeneration via IL‐1β Signaling

Environmental factors that enhance regeneration are largely unknown. We hypothesized that skin bacteria modulate regeneration. Here, we assessed low, medium, and high levels of bacterial burden in wound healing and Wound Induced Hair follicle Neogenesis (WIHN), a rare adult organogenesis model. WIHN levels and stem cell markers indeed correlated with bacterial counts, being lowest in germ free (GF) (fold= ‐17.9, n=13, p =1.9X10 ‐6 ), intermediate in conventional specific pathogen free (SPF), and highest even in mice infected with pathogenic Staphylococcus aureus (fold= 3.3, n=12, p =7.5X10 ‐5 ) (Figure 1). We identified IL‐1β and keratinocyte‐dependent IL‐1R‐MyD88 signaling as necessary and sufficient for bacteria to promote regeneration. Finally, in a small clinical trial, we found that a topical broad‐spectrum antibiotic slowed skin wound healing (Figure 2). These results demonstrate a novel role for IL‐1β to control morphogenesis and counter conventional notions that infection inhibits regeneration with a need for full sterility of small wounds.