Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China.
Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Nutrients. 2021 Dec 28;14(1):117. doi: 10.3390/nu14010117.
Intestinal melatonin exerts diverse biological effects on the body. Our previous research showed that the abundance of the butyrate-producing bacteria, , is positively related to the expression of colonic mucosal melatonin. However, the detailed relationship is unclear. Therefore, we aimed to explore whether regulates intestinal melatonin and its underlying mechanisms. Male Sprague-Dawley germfree rats were orally administered with or without . treatment significantly increased the intestinal melatonin level. The concentrations of propionate and butyrate in the intestinal contents were significantly elevated after gavage of . Propionate or butyrate treatment increased melatonin, 5-hydroxytryptamine (5-HT), arylalkylamine N-acetyltransferase (AANAT), and phosphorylated cAMP-response element-binding protein (p-CREB) levels. When pretreated with telotristat ethyl, the inhibitor of tryptophan hydroxylase (TPH), or siRNA of , or 666-15, i.e., an inhibitor of CREB, propionate, or butyrate, could not promote melatonin production in the pheochromocytoma cell line BON-1. Metabolomics analysis showed that propionate and butyrate stimulation regulated levels of some metabolites and some metabolic pathways in BON-1 cell supernatants. In conclusion, propionate and butyrate, i.e., metabolites of , can promote intestinal melatonin synthesis by increasing 5-HT levels and promoting p-CREB-mediated transcription, thereby offering a potential target for ameliorating intestinal diseases.
肠道褪黑素对人体有多种生物学作用。我们之前的研究表明，产生丁酸的细菌丰度与结肠黏膜褪黑素的表达呈正相关。然而，其具体关系尚不清楚。因此，我们旨在探讨是否可以调节肠道褪黑素及其潜在机制。雄性 Sprague-Dawley 无菌大鼠经口给予或不给予 处理。结果发现，处理组大鼠肠道褪黑素水平显著升高。灌胃 后，肠道内容物中丙酸和丁酸的浓度明显升高。丙酸或丁酸处理可增加褪黑素、5-羟色胺（5-HT）、芳基烷基胺 N-乙酰基转移酶（AANAT）和磷酸化 cAMP 反应元件结合蛋白（p-CREB）水平。用色氨酸羟化酶（TPH）抑制剂托洛司他乙酯（telotristat ethyl）、 或 CREB 抑制剂 666-15 预处理后，丙酸、丁酸或 不能促进嗜铬细胞瘤细胞系 BON-1 中褪黑素的产生。代谢组学分析显示，丙酸和丁酸刺激可调节 BON-1 细胞上清液中某些代谢物和代谢途径的水平。总之， 产生的丙酸和丁酸可以通过增加 5-HT 水平和促进 p-CREB 介导的 转录来促进肠道褪黑素的合成，为改善肠道疾病提供了一个潜在的靶点。
