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.
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DOI：
10.1016/j.isci.2020.101798
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发表时间：
2020-12-18
期刊：
影响因子：
5.8
通讯作者：
Kashyap PC
中科院分区：
文献类型：
--
作者：
Bhattarai Y;Jie S;Linden DR;Ghatak S;Mars RAT;Williams BB;Pu M;Sonnenburg JL;Fischbach MA;Farrugia G;Sha L;Kashyap PC
最近的研究强调了微生物代谢产物通过激活宿主受体在调节胃肠道（GI）生理学中的作用，突出了界间信号传导在治疗GI疾病中的潜力。在这项研究中，我们表明，色胺，一种源自大肠杆菌的细菌代谢产物，通过激活G蛋白偶联受体（GPCR）5-HT 4 R刺激粘液从杯状细胞释放。与用对照多形拟杆菌（Trp D-）定殖的小鼠相比，用优化以产生色胺（Trp D+）的工程化多形拟杆菌定殖的无菌小鼠在葡聚糖硫酸钠处理后表现出减少的体重减轻和增加的粘液释放。仅在雌性小鼠中观察到预防屏障破坏和降低疾病活动指数的额外有益作用，突出了细菌代谢物的性别特异性作用。这项研究证明了通过微生物产生的5-HT 4 GPCR激动剂精确调节粘液释放的潜力，作为治疗胃肠道炎症的治疗策略。色胺可增加结肠镜受体4依赖性结肠粘液释放细菌衍生色胺可减轻DSS结肠炎小鼠模型的体重减轻色胺在DSS结肠炎中的保护作用在雌性小鼠中更为明显色胺可降低结肠炎的严重程度和屏障破坏，特别是在雌性小鼠中
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. 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
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影响因子：
24.5
作者：
Swidsinski, Alexander;Loening-Baucke, Vera;Doerffel, Yvonne
通讯作者：
Doerffel, Yvonne
影响因子：
29.4
作者：
Spohn SN;Bianco F;Scott RB;Keenan CM;Linton AA;O'Neill CH;Bonora E;Dicay M;Lavoie B;Wilcox RL;MacNaughton WK;De Giorgio R;Sharkey KA;Mawe GM
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Mawe GM
可调表达工具在肠道微生物组中实现了单细胞应变的区别。
影响因子：
64.5
作者：
Whitaker WR;Shepherd ES;Sonnenburg JL
通讯作者：
Sonnenburg JL
影响因子：
15.8
作者：
Heazlewood CK;Cook MC;Eri R;Price GR;Tauro SB;Taupin D;Thornton DJ;Png CW;Crockford TL;Cornall RJ;Adams R;Kato M;Nelms KA;Hong NA;Florin TH;Goodnow CC;McGuckin MA
通讯作者：
McGuckin MA
影响因子：
24.5
作者：
PULLAN, RD;THOMAS, GAO;RHODES, J
通讯作者：
RHODES, J