Bhattarai Yogesh, Jie Si, Linden David R, Ghatak Sayak, Mars Ruben A T, Williams Brianna B, Pu Meng, Sonnenburg Justin L, Fischbach Michael A, Farrugia Gianrico, Sha Lei, Kashyap Purna C
Division 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.
iScience. 2020 Nov 13;23(12):101798. doi: 10.1016/j.isci.2020.101798. eCollection 2020 Dec 18.
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 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 (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.
最近的研究强调了微生物代谢产物通过激活宿主受体来调节胃肠道（GI）生理功能的作用，突出了跨界信号传导在治疗胃肠道疾病方面的潜力。在本研究中，我们发现色胺，一种由色氨酸衍生的细菌代谢产物，通过激活G蛋白偶联受体（GPCR）5-HT4R刺激杯状细胞释放黏液。与定殖对照菌（Trp D-）的小鼠相比，定殖了经工程改造优化以产生色胺的细菌（Trp D+）的无菌小鼠在接受葡聚糖硫酸钠处理后体重减轻减少，黏液释放增加。仅在雌性小鼠中观察到在预防屏障破坏和降低疾病活动指数方面的额外有益作用，突出了这种细菌代谢产物的性别特异性效应。本研究证明了微生物产生的5-HT4 GPCR激动剂精确调节黏液释放作为治疗胃肠道炎症性疾病的治疗策略的潜力。
