Gut bacteria-derived 5-hydroxyindole is a potent stimulant of intestinal motility via its action on L-type calcium channels

Autor: Carmen Aranzamendi, Barbora Waclawiková, Sahar El Aidy, Sieger Adriaan Nelemans, Markus Schwalbe, Gertjan van Dijk, Amber Bullock
Přispěvatelé: Host-Microbe Interactions, Molecular Immunology, Van Dijk lab
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Male
Indoles
Muscle Physiology
Physiology
Stimulation
Pharmacology
Gut flora
Pathology and Laboratory Medicine
Biochemistry
5-Hydroxytryptophan
Feces
0302 clinical medicine
Aromatic Amino Acids
Medicine and Health Sciences
Biology (General)
Amino Acids
Voltage-dependent calcium channel
Organic Compounds
General Neuroscience
Gastrointestinal Motility Disorders
Tryptophanase
Tryptophan
Neurochemistry
Neurotransmitters
Chemistry
Physical Sciences
Enterochromaffin cell
Serotonin Production
Female
Anatomy
Pathogens
General Agricultural and Biological Sciences
Ion Channel Gating
Research Article
Muscle Contraction
Adult
Pathogen Motility
Biogenic Amines
Serotonin
Calcium Channels
L-Type
QH301-705.5
Colon
Virulence Factors
PH reduction
Gastroenterology and Hepatology
Biology
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Young Adult
Animals
Humans
L-type calcium channel
General Immunology and Microbiology
Bacteria
Gut Bacteria
Organic Chemistry
Organisms
Chemical Compounds
Biology and Life Sciences
Proteins
biology.organism_classification
Gastrointestinal Microbiome
Rats
Gastrointestinal Tract
030104 developmental biology
Gastrointestinal Motility
Digestive System
030217 neurology & neurosurgery
Neuroscience
Zdroj: PLoS Biology
PLOS BIOLOGY, 19(1):e3001070. PUBLIC LIBRARY SCIENCE
PLoS Biology, Vol 19, Iss 1, p e3001070 (2021)
ISSN: 1545-7885
1544-9173
Popis: Microbial conversion of dietary or drug substrates into small bioactive molecules represents a regulatory mechanism by which the gut microbiota alters intestinal physiology. Here, we show that a wide variety of gut bacteria can metabolize the dietary supplement and antidepressant 5-hydroxytryptophan (5-HTP) to 5-hydroxyindole (5-HI) via the tryptophanase (TnaA) enzyme. Oral administration of 5-HTP results in detection of 5-HI in fecal samples of healthy volunteers with interindividual variation. The production of 5-HI is inhibited upon pH reduction in in vitro studies. When administered orally in rats, 5-HI significantly accelerates the total gut transit time (TGTT). Deciphering the underlying mechanisms of action reveals that 5-HI accelerates gut contractility via activation of L-type calcium channels located on the colonic smooth muscle cells. Moreover, 5-HI stimulation of a cell line model of intestinal enterochromaffin cells results in significant increase in serotonin production. Together, our findings support a role for bacterial metabolism in altering gut motility and lay the foundation for microbiota-targeted interventions.
Databáze: OpenAIRE
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