Jin Peng, Peng Xiao-Han, Zhang Ying, Jiang Han, Zhao Yan-Lin, Du Yan, Tang Dao-Quan
Department of Pharmacy, Suining People's Hospital Affiliated to Xuzhou Medical University, Suining 221202, China.
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China.
J Pharm Biomed Anal. 2025 Nov 15;265:117065. doi: 10.1016/j.jpba.2025.117065. Epub 2025 Jul 16.
This study aims to explore the roles that the interplay between tryptophan (TRP) metabolism and gut microbiota plays in experimental type 2 diabetes mellitus (T2DM) mice treated with mulberry leaf extracts. Fecal and serum TRP metabolites were analyzed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) based targeted metabolomics approaches. Concurrently, gut microbiota composition was characterized through high-throughput sequencing of bacterial 16S rDNA. Mulberry leaf extracts administration demonstrated significant improvement in normalizing TRP-related metabolite concentrations in serum from T2DM mice. Affected metabolites comprised 5-hydroxyindoleacetic acid, kynurenic acid, 3-hydroxyanthranilic acid, indole-3-acetic acid, nicotinic acid, indole-3-acetamide, N-acetyl-5-hydroxytryptamine (NAS), 3-indoleglyoxylic acid (IGA), and indole-lactic acid. Concurrently, fecal analysis revealed enhanced levels of indole-3-propionic acid, nicotinic acid, indole acrylic acid (IA), IGA, and indole. These modifications coincided with measurable alterations in gut microbial composition, particularly affecting bacterial genera such as Streptococcus, Acinetobacter, Weissella, Lachnoclostridium, Klebsiella, Dorea, Leuconostoc, Rhodococcus, Flavonifractor, Peptococcaceae_unclassified, Erysipelatoclostridiaceae_unclassified, Lachnospiraceae_NK4A136_group, and Christensenellaceae_R-7_group. Correlation analyses identified that Christensenellaceae_R-7_group exhibited significant positive association with serum concentrations of IGA and NAS alongside fecal IA levels. Conversely, Flavonifractor displayed strong positive correlation with both serum nicotinic acid and fecal indole content. The ameliorative impact of mulberry leaf extracts on T2DM may be attributed to its modulatory effects on both gut microbiota dysbiosis and TRP metabolic pathway disturbances. This therapeutic mechanism appears to contribute substantially to the observed mitigation of diabetic symptoms, particularly through the restoration of microbial homeostasis and optimization of TRP-related biochemical processes within the organism.
本研究旨在探讨色氨酸（TRP）代谢与肠道微生物群之间的相互作用在接受桑叶提取物治疗的实验性2型糖尿病（T2DM）小鼠中所起的作用。使用基于超高效液相色谱-串联质谱（UHPLC-MS/MS）的靶向代谢组学方法分析粪便和血清中的TRP代谢物。同时，通过细菌16S rDNA的高通量测序来表征肠道微生物群的组成。给予桑叶提取物显示出显著改善T2DM小鼠血清中与TRP相关的代谢物浓度。受影响的代谢物包括5-羟吲哚乙酸、犬尿烯酸、3-羟基邻氨基苯甲酸、吲哚-3-乙酸、烟酸、吲哚-3-乙酰胺、N-乙酰-5-羟色胺（NAS）、3-吲哚乙醛酸（IGA）和吲哚乳酸。同时，粪便分析显示吲哚-3-丙酸、烟酸、吲哚丙烯酸（IA）、IGA和吲哚的水平有所升高。这些变化与肠道微生物组成的可测量改变同时发生，尤其影响了链球菌、不动杆菌、魏斯氏菌、毛螺菌属、克雷伯菌属、多雷氏菌属、明串珠菌属、红球菌属、黄酮分解菌属、消化球菌科未分类属、丹毒丝菌科未分类属、毛螺菌科NK4A136组和克里斯滕森菌科R-7组等细菌属。相关性分析确定，克里斯滕森菌科R-7组与血清IGA和NAS浓度以及粪便IA水平呈显著正相关。相反，黄酮分解菌属与血清烟酸和粪便吲哚含量均呈强正相关。桑叶提取物对T2DM的改善作用可能归因于其对肠道微生物群失调和TRP代谢途径紊乱的调节作用。这种治疗机制似乎对观察到的糖尿病症状缓解有很大贡献，特别是通过恢复微生物稳态和优化生物体内与TRP相关的生化过程。
