Studies have shown that skin microbiota play a significant role in the health of the host and may play a role in disease. The epidermis of the skin is a two-way barrier, protecting the entire body from external insults and water loss. Tight junctions (TJs) are critical to this barrier. In this study, we investigated whether metabolites produced by human skin microbiota could impact TJ function in primary normal human epidermal keratinocytes (NHEKs). Skin swabs were collected from 4 body sites of 5 healthy participants and commensal bacteria were cultured in 6 different agars. The isolated bacteria were then identified using 16S rDNA sequencing. The effects of bacterial metabolites on TJ function were investigated by incubating monolayers of calcium-switched NHEKs with the cell-free supernatants of the bacteria and measuring transepithelial electrical resistance (TEER). The toxicity of the cell-free supernatants was measured using a tetrazolium reduction (MTT) assay. A total of 155 bacterial isolates were identified with a mean of 31 isolates per participant, belonging to 8 genera and 3 phyla. Initially, five Staphylococcus species were selected for study (S. epidermidis, S. hominis, S. capitis S. lugdunesis, and S. caprae). Metabolites produced by these bacteria were not toxic to differentiated NHEKs compared to control cells (N=3). The cell-free supernatant of S. hominis significantly increased the TEER in NHEKs such that it was 750 ohm.cm2 following 72h incubation compared with 517 ohm.cm2 in untreated NHEKs (N=6, P= 0.0006). However, the other staphylococci, had no impact on TEER in NHEKs. These data suggest that specific bacteria within the skin microbiota produce metabolites with the capacity to regulate the epidermal barrier via modulation of TJ function. The identification of such activities could open up new therapeutic approaches to treat skin conditions where the barrier is known to be aberrant.

ESDR110 - Metabolites of the skin commensal bacterium S. hominis enhance tight junction barrier integrity in primary human keratinocytes.

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING