Diversity of Neurotransmitter-Producing Human Skin Commensals

Recent findings indicate that human microbiota can excrete trace amines, dopamine, and serotonin. These neurotransmitters (NTs) can either affect classical neurotransmitter signaling or directly trigger trace amine-associated receptors (TAARs), with still unclear consequences for host physiology. Compared to gut microbiota, less information is available on the role of skin microbiota in NT production. To explore this, 1909 skin isolates, mainly from the genera Staphylococcus, Bacillus, and Corynebacterium, were tested for NT production. Only 6.7% of the isolates were capable of producing NTs, all of which belonged to the Staphylococcus genus. Based on substrate specificity, we identified two distinct profiles among the NT producers. One group primarily produced tryptamine (TRY) and phenylethylamine (PEA), while the other mainly produced tyramine (TYM) and dopamine (Dopa). These differing production profiles could be attributed to the activity of two distinct aromatic amino acid decarboxylase enzymes, SadA and TDC, responsible for generating the TRY/PEA and TYM/Dopa product spectra, respectively. SadA and TDC orthologues differ in structure and size; SadA has approximately 475 amino acids, whereas the TDC type consists of about 620 amino acids. The genomic localization of the respective genes also varies: tdc genes are typically found in small, conserved gene clusters, while sadA genes are not. The heterologous expression of sadA and tdc in Escherichia coli yielded the same product spectrum as the parent strains. The possible effects of skin microbiota-derived NTs on neuroreceptor signaling in the human host remain to be investigated.