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

Gut Microbes. 2022 Jan-Dec;14(1):2128605. doi: 10.1080/19490976.2022.2128605.

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.

Keywords: Aromatic amine; Enterococcus faecalis; aromatic amino acid; aromatic amino acid decarboxylase; aromatic amino acid decarboxylase inhibitor; gut microbiota; peripheral serotonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aromatic-L-Amino-Acid Decarboxylases / genetics
  • Aromatic-L-Amino-Acid Decarboxylases / metabolism
  • Benserazide / pharmacology
  • Carbidopa*
  • Gastrointestinal Microbiome*
  • Humans
  • Mice
  • Phenethylamines
  • Serotonin / metabolism

Substances

  • Phenethylamines
  • Serotonin
  • Benserazide
  • Aromatic-L-Amino-Acid Decarboxylases
  • Carbidopa

Grants and funding

This work was supported by the Grants-in-aid from the Institution for Fermentation, Osaka (to M.S., T. Katayama., and S.K) under Grant [number K-25-04]; the Canon Foundation (to T. Koyanagi, S.O, and S.K) under Grant [number R15-0105].