2. Academic Validation
  3. Gut Microbiota-Produced Tryptamine Activates an Epithelial G-Protein-Coupled Receptor to Increase Colonic Secretion

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

  • Cell Host Microbe. 2018 Jun 13;23(6):775-785.e5. doi: 10.1016/j.chom.2018.05.004.
Yogesh Bhattarai 1,  Brianna B Williams 2,  Eric J Battaglioli 1,  Weston R Whitaker 3,  Lisa Till 4,  Madhusudan Grover 5,  David R Linden 4,  Yasutada Akiba 6,  Karunya K Kandimalla 7,  Nicholas C Zachos 8,  Jonathan D Kaunitz 9,  Justin L Sonnenburg 3,  Michael A Fischbach 2,  Gianrico Farrugia 10,  Purna C Kashyap 11
Affiliations

Affiliations

  • 1 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
  • 2 Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA 94305, USA.
  • 3 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94304, USA.
  • 4 Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
  • 5 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
  • 6 Department of Medicine, School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, CA 90073, USA; Brentwood Biomedical Research Institute, Los Angeles, CA 90073, USA.
  • 7 Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, USA.
  • 8 Department of Medicine, Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • 9 Department of Medicine, School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, CA 90073, USA; Brentwood Biomedical Research Institute, Los Angeles, CA 90073, USA; Department of Surgery, School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • 10 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA; Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL 32224, USA.
  • 11 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: kashyap.purna@mayo.edu.
PMID: 29902441 DOI: 10.1016/j.chom.2018.05.004
Abstract

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 the 5-HT4 receptor (5-HT4R), a G-protein-coupled receptor (GPCR) uniquely expressed in the colonic epithelium. Tryptamine increases both ionic flux across the colonic epithelium and 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-HT4R activation and is blocked by 5-HT4R antagonist and absent in 5-HT4R-/- mice. GF mice colonized by Bacteroides thetaiotaomicron engineered to produce tryptamine exhibit accelerated GI transit. Our study demonstrates an aspect of host physiology under control of a Bacterial metabolite that can be exploited as a therapeutic modality. VIDEO ABSTRACT.

Keywords

Bacteroides thetaiotaomicron; GI transit; IBS; constipation; genetically engineered; microbiome; motility; phage promoter; secretion; tryptophan.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z