Bacteria induce skin regeneration

Wound Induced Hair follicle Neogenesis (WIHN) is a rare adult organogenesis model where stem cells form de novo hair follicles following full-thickness wounding. As wounds inevitably contact the skin microbiota, it is important to understand the role of the skin microbiome in WIHN. To do so, we modified bacterial burdens and tested WIHN. We used 3 levels of microbial burden to measure WIHN: For minimal bacteria loads, we used germ-free (GF) mice, applied antibiotic ointment (Neosporin) or frequent cage changes of standard specific pathogen free (SPF) mice housing. For intermediate bacterial loads and as a baseline comparator, we used standard SPF mice housing. For maximal bacteria loads, we injected each of the top three strains of SPF mice skin commensal bacteria to the wound bed early during wounding. We found that GF mice (fold= -14.4, n=5, p=3.5X10-5), mice treated with antibiotic (fold= -7.9, n=5, p=8.4X10-5) or mice in clean cages (fold= -2.8, n=4, p=0.015) have lower regeneration capacity respectively and lower stem cell marker expression. Increase commensal bacteria loads can enhance SPF mice regeneration capacity (fold=3.3, n=6, p=7.5X10-5) and also promote stem cell marker expression. Mice deficient in Myd88 (fold=-29.6, n=7, p=8.3X10-7) and IL1R deficient mice (fold=-9.4, n=5, p=0.4X10-4) have poor regeneration capacity, and are resistant to the ability of exogenous bacterial to enhance WIHN. Keratinocytes and Myeloid cell-specific Myd88 deficient mice have similar regeneration capacity to wild type mice. Taken together, these results demonstrate that commensal and exogenous bacterial burden enhance regeneration. This is mediated through IL1R- Myd88 signaling, but not in keratinocytes or myeloid cells. Future studies will define the cell type and cytokine responsible for activation of Myd88 and WIHN during commensal exposure.