Bacterially Derived Tryptamine Increases Mucus Release by Activating a Host Receptor in a Mouse Model of Inflammatory Bowel Disease
| العنوان: | Bacterially Derived Tryptamine Increases Mucus Release by Activating a Host Receptor in a Mouse Model of Inflammatory Bowel Disease |
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| المؤلفون: | Justin L. Sonnenburg, Lei Sha, Yogesh Bhattarai, Purna C. Kashyap, Brianna B. Williams, Meng Pu, Ruben A. T. Mars, Sayak Ghatak, Michael A. Fischbach, David R. Linden, Gianrico Farrugia, Si Jie |
| المصدر: | iScience iScience, Vol 23, Iss 12, Pp 101798-(2020) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Tryptamine, Agonist, medicine.drug_class, Metabolite, 02 engineering and technology, Pharmacology, Inflammatory bowel disease, Microbiology, Article, 03 medical and health sciences, chemistry.chemical_compound, medicine, lcsh:Science, Receptor, G protein-coupled receptor, Multidisciplinary, Chemistry, Rodent Gastroenterology, 021001 nanoscience & nanotechnology, medicine.disease, Mucus, 030104 developmental biology, lcsh:Q, 0210 nano-technology, Bacteroides thetaiotaomicron |
| الوصف: | 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. Graphical Abstract Highlights • Tryptamine increases serotonin-receptor4-dependent colonic mucus release • Bacterially derived tryptamine attenuates weight loss in DSS colitis mouse model • Protective effect of tryptamine in DSS colitis is more pronounced in female mice • Tryptamine reduces colitis severity and barrier disruption specifically in female mice Rodent Gastroenterology; Microbiology |
| تدمد: | 2589-0042 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7aea3e0f12b981f448a844bd641b6f40 https://pubmed.ncbi.nlm.nih.gov/33299969 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7aea3e0f12b981f448a844bd641b6f40 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 25890042 |
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