Dysregulation of the gut microbiota/gut hormone axis contributes to the pathogenesis of irritable bowel syndrome (IBS). Melatonin plays a beneficial role in gut motility and immunity. However, altered expression of local mucosal melatonin in IBS and its relationship with the gut microbiota remain unclear. Therefore, we aimed to detect the colonic melatonin levels and microbiota profiles in patients with diarrhea-predominant IBS (IBS-D) and explore their relationship in germ-free (GF) rats and BON-1 cells. Thirty-two IBS-D patients and twenty-eight healthy controls (HCs) were recruited. Fecal specimens from IBS-D patients and HCs were separately transplanted into GF rats by gavage. The levels of colon mucosal melatonin were assessed by immunohistochemical methods, and fecal microbiota communities were analyzed using 16S rDNA sequencing. The effect of butyrate on melatonin synthesis in BON-1 cells was evaluated by ELISA. Melatonin levels were significantly increased and negatively correlated with visceral hypersensitivity in IBS-D patients. GF rats inoculated with fecal microbiota from IBS-D patients had high colonic melatonin levels. Butyrate-producing Clostridium cluster XIVa species, such as Roseburia species and Lachnospira species, were positively related to colonic mucosal melatonin expression. Butyrate significantly increased melatonin secretion in BON-1 cells. Increased melatonin expression may be an adaptive protective mechanism in the development of IBS-D. Moreover, some Clostridium cluster XIVa species could increase melatonin expression via butyrate production. Modulation of the gut hormone/gut microbiota axis offers a promising target of interest for IBS in the future.
?研究问题：IBS患者肠道黏膜褪黑素水平与肠道菌群之间的关系尚不清楚。?研究方法：纳入32名符合罗马III诊断标准的IBS-D患者和 28 名健康志愿者，并应用无菌雄性 Sprague-Dawley（SD） 大鼠，分别以 IBS-D 患者和对照者的粪便进行粪菌移植。结肠黏膜褪黑素的表达水平应用免疫组织化学方法进行检测。肠道菌群采用16S rDNA 测序分析。此外，使用丁酸钠干预 BON-1 细胞系，并用 ELISA 方法检测细胞上清中的褪黑素水平。?主要结果1：IBS-D 患者结肠黏膜褪黑素水平显著高于健康对照组，并且与内脏敏感性呈显著负相关。?主要结果2：移植 IBS-D 患者菌群的大鼠结肠黏膜褪黑素水平显著高于移植健康志愿者菌群的大鼠。?主要结果3：IBS-D患者伴有显著的肠道菌群紊乱。?主要结果4：产丁酸的梭菌 XIVa 簇的 Roseburia 和Lachnospira 菌群与结肠黏膜褪黑素的水平显著正相关。?主要结果5：丁酸可以显著促进 BON-1 细胞褪黑素的释放。?数据链接：http://bigd.big.ac.cn/gsa. (GSA: CRA001604)





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