Department of Gastrointestinal Microbiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
Department of Molecular Systems Biology, Helmholtz Centre for Enviromental Research -UFZ, Leipzig, Germany.
Sci Rep. 2019 Feb 4;9(1):1177. doi: 10.1038/s41598-018-38018-z.
Peripheral serotonin (5-hydroxytryptamine: 5-HT) synthesized in the intestine by enterochromaffin cells (ECs), plays an important role in the regulation of peristaltic of the gut, epithelial secretion and promotes the development and maintenance of the enteric neurons. Recent studies showed that the indigenous gut microbiota modulates 5-HT signalling and that ECs use sensory receptors to detect dietary and microbiota-derived signals from the lumen to subsequently transduce the information to the nervous system. We hypothesized that Clostridium ramosum by increasing gut 5-HT availability consequently contributes to high-fat diet-induced obesity. Using germ-free mice and mice monoassociated with C. ramosum, intestinal cell lines and mouse organoids, we demonstrated that bacterial cell components stimulate host 5-HT secretion and program the differentiation of colonic intestinal stem progenitors toward the secretory 5-HT-producing lineage. An elevated 5-HT level regulates the expression of major proteins involved in intestinal fatty acid absorption in vitro, suggesting that the presence of C. ramosum in the gut promotes 5-HT secretion and thereby could facilitates intestinal lipid absorption and the development of obesity.
肠道中的肠嗜铬细胞（enterochromaffin cells，ECs）合成的外周血清素（5-羟色胺：5-HT），在肠道蠕动、上皮分泌的调节中发挥重要作用，并促进肠神经元的发育和维持。最近的研究表明，本土肠道微生物群调节 5-HT 信号，而 ECs 使用感觉受体来检测腔室中来自饮食和微生物群的信号，随后将信息转导至神经系统。我们假设 C. ramosum 通过增加肠道 5-HT 的可利用性，从而有助于高脂肪饮食诱导的肥胖。使用无菌小鼠和单定植 C. ramosum 的小鼠、肠细胞系和小鼠类器官，我们证明了细菌细胞成分刺激宿主 5-HT 分泌，并使结肠肠干细胞祖细胞向分泌 5-HT 的谱系分化。升高的 5-HT 水平调节参与体外肠道脂肪酸吸收的主要蛋白的表达，这表明肠道中 C. ramosum 的存在促进 5-HT 分泌，从而促进肠道脂质吸收和肥胖的发展。
