Gut bacterial aromatic amine production: aromatic amino acid decarboxylase and its effects on peripheral serotonin production

Abstract

Colonic luminal aromatic amines have been historically considered to be derived from dietary source, especially fermented foods; however, recent studies indicate that the gut microbiota serves as an alternative source of these amines. Herein, we show that five prominent genera of Firmicutes <i>(Blautia, Clostridium, Enterococcus, Ruminococcus</i>, and <i>Tyzzerella</i>) have the ability to abundantly produce aromatic amines through the action of aromatic amino acid decarboxylase (AADC). <i>In vitro</i> cultivation of human fecal samples revealed that a significant positive correlation between <i>aadc</i> copy number of <i>Ruminococcus gnavus</i> and phenylethylamine (PEA) production. Furthermore, using genetically engineered <i>Enterococcus faecalis</i>-colonized BALB/cCrSlc mouse model, we showed that the gut bacterial <i>aadc</i> stimulates the production of colonic serotonin, which is reportedly involved in osteoporosis and irritable bowel syndrome. Finally, we showed that human AADC inhibitors carbidopa and benserazide inhibit PEA production in <i>En. faecalis</i>.