The Ambivalent Role of Skin Microbiota and Adrenaline in Wound Healing and the Interplay between Them.

After skin injury, wound healing sets into motion a dynamic process to repair and replace devitalized tissues. The healing process can be divided into four overlapping phases: hemostasis, inflammation, proliferation, and maturation. Skin microbiota has been reported to participate in orchestrating the wound healing both in negative and positive ways. Many studies reported that skin microbiota can impose negative and positive effects on the wound. Recent findings have shown that many bacterial species on human skin are able to convert aromatic amino acids into so-called trace amines (TAs) and convert corresponding precursors into dopamine and serotonin, which are all released into the environment. As a stress reaction, wounded epithelial cells release the hormone adrenaline (epinephrine), which activates the β2-adrenergic receptor (β2-AR), impairing the migration ability of keratinocytes and thus re-epithelization. This is where TAs come into play, as they act as antagonists of β2-AR and thus attenuate the effects of adrenaline. The result is that not only TAs but also TA-producing skin bacteria accelerate wound healing. Adrenergic receptors (ARs) play a key role in many physiological and disease-related processes and are expressed in numerous cell types. In this review, we describe the role of ARs in relation to wound healing in keratinocytes, immune cells, fibroblasts, and blood vessels and the possible role of the skin microbiota in wound healing.