5-羟色胺(5-hydroxytryptamine,5-HT)是由一种占比不到肠上皮细胞数量1%的肠嗜铬(enterochromaffin,EC)细胞产生的神经递质,其中色氨酸羟化酶1(tryptophan hydroxylase 1,TPH1)是5-HT合成途径的限速酶。特定的益生菌能够调节EC中Tph1基因的表达,维持肠道正常的5-HT合成。然而,其作用机制尚不明确。该研究利用代谢物组学技术对益生菌发酵产物中的主要活性物质进行分析,并基于小肠类器官建立了代谢产物和Tph1基因表达之间的互作量效关系,明确了L-乳酸、乙酸是益生短双歧杆菌调节肠道5-HT合成的关键效应物质。研究结果明确了特定功能益生菌发挥生理作用的物质基础,为同类功能益生菌的定向筛选提供了理论支撑。
5-Hydroxytryptamine (5-HT) is a neurotransmitter produced by enterochromaffin cells (EC) that make up less than 1% of the number of intestinal epithelial cells, tryptophan hydroxylase (TPH1) is the rate-limiting enzyme in 5-HT synthesis pathway. Specific probiotics can regulate the expression of the Tph1 gene in intestinal chromaffin cells to maintain normal intestinal 5-HT synthesis. However, the mechanism of action remains unclear. In this study, metabolomics technology was used to analyze the main active substances in probiotic fermentation products. The interaction dose-effect relationship between the metabolites and the expression of the Tph1 gene was established based on the small intestinal organoids. We identified L-lactic acid and acetic acid as the essential effector substances in regulating intestinal 5-HT synthesis by probiotics. The results of this study clarified the material basis of the physiological function of probiotics and provided theoretical support for the targeted screening of similar functional probiotics.
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