Discovery and Characterization of Gut Microbiota Decarboxylases that Can Produce the Neurotransmitter Tryptamine

作者：Williams, Brianna B.; Van Benschoten, Andrew H.; Cimermancic, Peter; Donia, Mohamed S.; Zimmermann, Michael; Taketani, Mao; Ishihara, Atsushi; Kashyap, Purna C.; Fraser, James S.; Fischbach, Michael A.^*

来源：Cell Host & Microbe, 2014, 16(4): 495-503.

DOI：10.1016/j.chom.2014.09.001

• 5-PHOSPHATE-DEPENDENT HISTIDINE-DECARBOXYLASE
• IRRITABLE-BOWEL-SYNDROME
• TNBS-INDUCED COLITIS
• DEPENDENT ENZYMES
• ALPHA-FLUOROMETHYLHISTIDINE
• XENORHABDUS-NEMATOPHILUS
• DOPA DECARBOXYLASE
• SEROTONIN
• MICE
• REVEALS

Several recent studies describe the influence of the gut microbiota on host brain and behavior. However, the mechanisms responsible for microbiota-nervous system interactions are largely unknown. Using a combination of genetics, biochemistry, and crystallography, we identify and characterize two phylogenetically distinct enzymes found in the human microbiome that decarboxylate tryptophan to form the beta-arylamine neurotransmitter tryptamine. Although this enzymatic activity is exceedingly rare among bacteria more broadly, analysis of the Human Microbiome Project data demonstrate that at least 10% of the human population harbors at least one bacterium encoding a tryptophan decarboxylase in their gut community. Our results uncover a previously unrecognized enzymatic activity that can give rise to host-modulatory compounds and suggests a potential direct mechanism by which gut microbiota can influence host physiology, including behavior.

• 出版日期2014-10-8