Dysbiosis contributes to chronic constipation development via regulation of serotonin transporter in the intestine.

Dysbiosis contributes to chronic constipation development via regulation of serotonin transporter in the intestine.
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DOI:
10.1038/s41598-017-10835-8
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发表时间:
2017-09-04
期刊:
影响因子:
4.6
通讯作者:
Wang B
Wang B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cao H;Liu X;An Y;Zhou G;Liu Y;Xu M;Dong W;Wang S;Yan F;Jiang K;Wang B

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慢性便秘是一种常见的功能性胃肠道疾病,伴有肠道生态失调。然而,生态失调和便秘之间的因果关系仍然知之甚少。5-羟色胺转运蛋白(serotonintransporter,SERT)是一种跨膜转运蛋白,能从有效部位重新摄取过量的5-羟色胺(5-hydroxytryptamine,5-HT),终止其生理作用,参与调节胃肠运动。在这项研究中,来自便秘患者和健康对照的粪便微生物群被移植到抗生素耗尽小鼠模型中。接受来自便秘患者的粪便微生物群的小鼠表现出肠道水肿和异常排便参数的减少,包括颗粒排出频率、粪便重量和粪便含水量。粪菌群移植后,结肠组织SERT表达显著上调,5-HT含量降低,与胃肠通过时间呈负相关。此外,来自接受便秘患者粪便微生物群的小鼠的粪便微生物群也上调Caco-2细胞中的SERT。此外,FMT后肠道内梭菌、乳酸菌、脱硫弧菌、甲基杆菌数量减少,拟杆菌、阿克曼菌数量增加,也参与了FMT后肠道屏障功能的受损。总之,肠道生态失调可能上调SERT的表达,并有助于慢性便秘的发展。
Chronic constipation is a prevalent functional gastrointestinal disorder accompanied with intestinal dysbiosis. However, causal relationship between dysbiosis and constipation remains poorly understood. Serotonin transporter (SERT) is a transmembrane transport protein which re-uptakes excessive 5-hydroxytryptamine (5-HT) from effective location to terminate its physiological effects and involves in regulating gastrointestinal motility. In this study, fecal microbiota from patients with constipation and healthy controls were transplanted into the antibiotic depletion mice model. The mice which received fecal microbiota from patients with constipation presented a reducing in intestinal peristalsis and abnormal defecation parameters including the frequency of pellet expulsion, fecal weight and fecal water content. After fecal microbiota transplantation, the SERT expression in the colonic tissue was significantly upregulated, and the content of 5-HT was decreased which negatively correlated with the gastrointestinal transit time. Moverover, fecal microbiota from the mice which received fecal microbiota from patients with constipation also upregulated SERT in Caco-2 cells. Besides, this process accompanied with the decreased abundance of Clostridium, Lactobacillus, Desulfovibrio, and Methylobacterium and an increased tend of Bacteroides and Akkermansia, which also involved in the impairment of intestinal barrier after FMT. Taken together, intestinal dysbiosis may upregulate the SERT expression and contribute to the development of chronic constipation.
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