Gut bacterial aromatic amine production: aromatic amino acid decarboxylase and its effects on peripheral serotonin production
Yuta Sugiyama, Yumiko Mori, Misaki Nara, Yusuke Kotani, Emiko Nagai, Hiroki Kawada, Mayu Kitamura, Rika Hirano, Hiromi Shimokawa, Akira Nakagawa, Hiromichi Minami, Aina Gotoh, Mikiyasu Sakanaka, Noriho Iida, Takashi Koyanagi, Takane Katayama, Shigefumi Okamoto, Shin Kurihara
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 (Blautia, Clostridium, Enterococcus, Ruminococcus, and Tyzzerella) have the ability to abundantly produce aromatic amines through the action of aromatic amino acid decarboxylase (AADC). In vitro cultivation of human fecal samples revealed that a significant positive correlation between aadc copy number of Ruminococcus gnavus and phenylethylamine (PEA) production. Furthermore, using genetically engineered Enterococcus faecalis-colonized BALB/cCrSlc mouse model, we showed that the gut bacterial aadc 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 En. faecalis.