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
Affiliations
Yuta Sugiyama
Faculty of Bioresources and Environmental Sciences, Ishikawa Prefectural University, Nonoichi, 921-8836, Japan
Yumiko Mori
Department of Clinical Laboratory Sciences, Faculty of Health Sciences, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan
Misaki Nara
Faculty of Bioresources and Environmental Sciences, Ishikawa Prefectural University, Nonoichi, 921-8836, Japan
Yusuke Kotani
Department of Clinical Laboratory Sciences, Faculty of Health Sciences, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan
Emiko Nagai
Faculty of Bioresources and Environmental Sciences, Ishikawa Prefectural University, Nonoichi, 921-8836, Japan
Hiroki Kawada
Faculty of Bioresources and Environmental Sciences, Ishikawa Prefectural University, Nonoichi, 921-8836, Japan
Mayu Kitamura
Department of Clinical Laboratory Sciences, Faculty of Health Sciences, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan
Rika Hirano
Faculty of Biology-Oriented Science and Technology, Kindai University, Kinokawa, Japan
Hiromi Shimokawa
Faculty of Biology-Oriented Science and Technology, Kindai University, Kinokawa, Japan
Akira Nakagawa
Faculty of Bioresources and Environmental Sciences, Ishikawa Prefectural University, Nonoichi, 921-8836, Japan
Hiromichi Minami
Faculty of Bioresources and Environmental Sciences, Ishikawa Prefectural University, Nonoichi, 921-8836, Japan
Aina Gotoh
Graduate School of Biostudies, Kyoto University, Kyoto, Japan
Mikiyasu Sakanaka
Faculty of Bioresources and Environmental Sciences, Ishikawa Prefectural University, Nonoichi, 921-8836, Japan
Noriho Iida
Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan
Takashi Koyanagi
Faculty of Bioresources and Environmental Sciences, Ishikawa Prefectural University, Nonoichi, 921-8836, Japan
Takane Katayama
Faculty of Bioresources and Environmental Sciences, Ishikawa Prefectural University, Nonoichi, 921-8836, Japan
Shigefumi Okamoto
Department of Clinical Laboratory Sciences, Faculty of Health Sciences, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan
Shin Kurihara
Faculty of Bioresources and Environmental Sciences, Ishikawa Prefectural University, Nonoichi, 921-8836, Japan
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.
