Tryptophol, a regulator of barrier function

Skin Barrier function is regulated at least in part, by tryptophan metabolites produced by the skin microbiota. To date the contribution of individual species to barrier function has not been addressed. Here, we analysed the tryptophan metabolite production of species and strains isolated from healthy volunteers along with the ability of the bacterial cell free supernatants to enhance the barrier function of human keratinocyte monolayers . Of 7 common skin isolates tested, the cell free supernatants of three were able to enhance barrier function as measured using transepithelial electrical resistance (TEER). These were Micrococcus luteus, Staphylococcus aureus and S. hominis. Using S. hominis as a model organism, we investigated a further 6 strains and showed that all but one of these enhanced TEER. Analysis of the metabolites produced by species and strains by mass spectrometry indicated that only those strains able to produce tryptophol enhanced TEER. The S. hominis strain that was unable to augment TEER contained mutations in genes essential for tryptophol biosynthesis within its genome. Finally, tryptophol at high dose augmented TEER in keratinocytes. These data point to species and strain-dependent effects on keratinocyte barrier function and identify tryptophol as a regulator of barrier function in keratinocytes.