Gut Microbiota-Produced Tryptamine Activates an Epithelial G-Protein-Coupled Receptor to Increase Colonic Secretion

Autor: Brianna B. Williams, Eric J. Battaglioli, Yogesh Bhattarai, David R. Linden, Justin L. Sonnenburg, Jonathan D. Kaunitz, Yasutada Akiba, Madhusudan Grover, Purna C. Kashyap, Weston R. Whitaker, Michael A. Fischbach, Karunya K. Kandimalla, Lisa Till, Gianrico Farrugia, Nicholas C. Zachos
Rok vydání: 2017
Předmět:
0301 basic medicine
Tryptamine
microbiome
5-HT4
129 Strain
Gut flora
Oral and gastrointestinal
Epithelium
chemistry.chemical_compound
Feces
Mice
genetically engineered
Cell Movement
Receptors
Receptor
Mice
Knockout
biology
Microbiota
Tryptamines
Specific Pathogen-Free Organisms
secretion
motility
Medical Microbiology
GI transit
Bacteroides thetaiotaomicron
Signal Transduction
Serotonin
Mice
129 Strain
Colon
Knockout
Immunology
Primary Cell Culture
Motility
Microbiology
Article
03 medical and health sciences
Sex Factors
Virology
IBS
Animals
Humans
Secretion
tryptophan
G protein-coupled receptor
Bacteria
Intestinal Secretions
constipation
biology.organism_classification
phage promoter
Molecular biology
Gastrointestinal Microbiome
030104 developmental biology
Monoamine neurotransmitter
chemistry
Parasitology
Receptors
Serotonin
5-HT4
Digestive Diseases
Digestive System
Zdroj: Cell host & microbe, vol 23, iss 6
ISSN: 1934-6069
Popis: Tryptamine, a tryptophan-derived monoamine similar to 5-hydroxytryptamine (5-HT), is produced by gut bacteria and is abundant in human and rodent feces. However, the physiologic effect of tryptamine in the gastrointestinal (GI) tract remains unknown. Here, we show that the biological effects of tryptamine are mediated through 5-HT(4) receptor (5-HT(4)R), a G-protein coupled receptor (GPCR) uniquely expressed in the colonic epithelium. Tryptamine increases ionic flux across the colonic epithelium and increases fluid secretion in colonoids from germ free (GF) and humanized (ex-GF colonized with human stool) mice consistent with increased intestinal secretion. The secretory effect of tryptamine is dependent on 5-HT(4)R activation and is blocked by 5-HT(4)R antagonist and absent in 5-HT(4)R(−/−) mice. GF mice colonized by Bacteroides thetaiotaomicron engineered to produce tryptamine exhibit accelerated gastrointestinal transit. Our study demonstrates an aspect of host physiology under control of a bacterial metabolite that can be exploited as a therapeutic modality.
Databáze: OpenAIRE
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