Bacterially Derived Tryptamine Increases Mucus Release by Activating a Host Receptor in a Mouse Model of Inflammatory Bowel Disease

Bacterially Derived Tryptamine Increases Mucus Release by Activating a Host Receptor in a Mouse Model of Inflammatory Bowel Disease

Summary: Recent studies emphasize the role of microbial metabolites in regulating gastrointestinal (GI) physiology through activation of host receptors, highlighting the potential for inter-kingdom signaling in treating GI disorders. In this study, we show that tryptamine, a tryptophan-derived bacte...

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Main Authors: Yogesh Bhattarai, Si Jie, David R. Linden, Sayak Ghatak, Ruben A.T. Mars, Brianna B. Williams, Meng Pu, Justin L. Sonnenburg, Michael A. Fischbach, Gianrico Farrugia, Lei Sha, Purna C. Kashyap
Format: Article
Language:English
Published: Elsevier 2020-12-01
Series:iScience
Subjects:
Rodent Gastroenterology
Microbiology
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004220309950
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spelling doaj-b5bee85c22b34b76b33cddfd843fc1312020-12-19T05:09:56ZengElsevieriScience2589-00422020-12-012312101798Bacterially Derived Tryptamine Increases Mucus Release by Activating a Host Receptor in a Mouse Model of Inflammatory Bowel DiseaseYogesh Bhattarai0Si Jie1David R. Linden2Sayak Ghatak3Ruben A.T. Mars4Brianna B. Williams5Meng Pu6Justin L. Sonnenburg7Michael A. Fischbach8Gianrico Farrugia9Lei Sha10Purna C. Kashyap11Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USADivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USADepartment of Physiology and Biomedical Engineering, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USADivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USADivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USADepartment of Bioengineering and ChEM-H, Stanford University, CA 94305, USADivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USADepartment of Microbiology and Immunology, Stanford University, Stanford, CA 94304, USADepartment of Bioengineering and ChEM-H, Stanford University, CA 94305, USADivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USADepartment of Pharmacy, Department of Neuroendocrine Pharmacology, School of Pharmacy, China Medical University, 77 Pu He Road, Shenbei New District, Shenyang 110122, P.R. China; Corresponding authorDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA; Corresponding authorSummary: Recent studies emphasize the role of microbial metabolites in regulating gastrointestinal (GI) physiology through activation of host receptors, highlighting the potential for inter-kingdom signaling in treating GI disorders. In this study, we show that tryptamine, a tryptophan-derived bacterial metabolite, stimulates mucus release from goblet cells via activation of G-protein-coupled receptor (GPCR) 5-HT4R. Germ-free mice colonized with engineered Bacteroides thetaiotaomicron optimized to produce tryptamine (Trp D+) exhibit decreased weight loss and increased mucus release following dextran sodium sulfate treatment when compared with mice colonized with control B. thetaiotaomicron (Trp D-). Additional beneficial effects in preventing barrier disruption and lower disease activity index were seen only in female mice, highlighting sex-specific effects of the bacterial metabolite. This study demonstrates potential for the precise modulation of mucus release by microbially produced 5-HT4 GPCR agonist as a therapeutic strategy to treat inflammatory conditions of the GI tract.http://www.sciencedirect.com/science/article/pii/S2589004220309950Rodent GastroenterologyMicrobiology
collection DOAJ
language English
format Article
sources DOAJ
author Yogesh Bhattarai
Si Jie
David R. Linden
Sayak Ghatak
Ruben A.T. Mars
Brianna B. Williams
Meng Pu
Justin L. Sonnenburg
Michael A. Fischbach
Gianrico Farrugia
Lei Sha
Purna C. Kashyap
spellingShingle Yogesh Bhattarai
Si Jie
David R. Linden
Sayak Ghatak
Ruben A.T. Mars
Brianna B. Williams
Meng Pu
Justin L. Sonnenburg
Michael A. Fischbach
Gianrico Farrugia
Lei Sha
Purna C. Kashyap
Bacterially Derived Tryptamine Increases Mucus Release by Activating a Host Receptor in a Mouse Model of Inflammatory Bowel Disease
iScience
Rodent Gastroenterology
Microbiology
author_facet Yogesh Bhattarai
Si Jie
David R. Linden
Sayak Ghatak
Ruben A.T. Mars
Brianna B. Williams
Meng Pu
Justin L. Sonnenburg
Michael A. Fischbach
Gianrico Farrugia
Lei Sha
Purna C. Kashyap
author_sort Yogesh Bhattarai
title Bacterially Derived Tryptamine Increases Mucus Release by Activating a Host Receptor in a Mouse Model of Inflammatory Bowel Disease
title_short Bacterially Derived Tryptamine Increases Mucus Release by Activating a Host Receptor in a Mouse Model of Inflammatory Bowel Disease
title_full Bacterially Derived Tryptamine Increases Mucus Release by Activating a Host Receptor in a Mouse Model of Inflammatory Bowel Disease
title_fullStr Bacterially Derived Tryptamine Increases Mucus Release by Activating a Host Receptor in a Mouse Model of Inflammatory Bowel Disease
title_full_unstemmed Bacterially Derived Tryptamine Increases Mucus Release by Activating a Host Receptor in a Mouse Model of Inflammatory Bowel Disease
title_sort bacterially derived tryptamine increases mucus release by activating a host receptor in a mouse model of inflammatory bowel disease
publisher Elsevier
series iScience
issn 2589-0042
publishDate 2020-12-01
description Summary: Recent studies emphasize the role of microbial metabolites in regulating gastrointestinal (GI) physiology through activation of host receptors, highlighting the potential for inter-kingdom signaling in treating GI disorders. In this study, we show that tryptamine, a tryptophan-derived bacterial metabolite, stimulates mucus release from goblet cells via activation of G-protein-coupled receptor (GPCR) 5-HT4R. Germ-free mice colonized with engineered Bacteroides thetaiotaomicron optimized to produce tryptamine (Trp D+) exhibit decreased weight loss and increased mucus release following dextran sodium sulfate treatment when compared with mice colonized with control B. thetaiotaomicron (Trp D-). Additional beneficial effects in preventing barrier disruption and lower disease activity index were seen only in female mice, highlighting sex-specific effects of the bacterial metabolite. This study demonstrates potential for the precise modulation of mucus release by microbially produced 5-HT4 GPCR agonist as a therapeutic strategy to treat inflammatory conditions of the GI tract.
topic Rodent Gastroenterology
Microbiology
url http://www.sciencedirect.com/science/article/pii/S2589004220309950
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