背景:在西藏医学文献“四布益典”中广泛记载了刺槐(TT)的果实,治疗糖尿病已有一千多年的历史了。然而,TT对糖尿病的潜在机制和综合作用尚待研究。
目的:本研究旨在系统地阐明TT治疗糖尿病的潜在机制。并进一步研究水提取物的治疗效果,来自TT的小分子成分和糖类。
方法:基于UHPLC-Q-TOF-MS/MS,采用粪便代谢组学绘制代谢谱。扩增细菌16SrRNA基因的V3-V4高变区,探讨TT干预后肠道微生物组的结构变化,并分析差异菌群。通过GC-MS测定微生物代谢产物SCFA,BAs和色氨酸代谢物通过UPLC-TQ-MS定量。进行了Spearman相关分析,以全面研究内源性代谢物谱之间的关系,肠道微生物群及其代谢产物。
结果:TT对T2DM大鼠有明显的治疗作用,如改善的糖脂代谢和肠屏障完整性所证明的,改善炎症和缓解胰岛素抵抗。通过粪便代谢组学研究共筛选出24种内源性生物标志物,主要与色氨酸代谢有关,脂肪酸代谢,胆汁酸代谢,类固醇激素生物合成和花生四烯酸代谢。对微生物的研究表明,TT显着调节了18种差异细菌属,并逆转了糖尿病大鼠肠道微生物的紊乱。此外,TT显著改变了肠道微生物代谢产物的含量,血清和粪便样本.微生物群落之间的显著相关性,代谢物和T2DM相关指标被揭示。
结论:TT的多种成分调节生物体的代谢稳态和肠道菌群及其代谢产物的平衡,这可能介导TT的抗糖尿病能力。
BACKGROUND: The fruit of Tribulus terrestris L. (TT) is extensively documented in the Tibetan medical literature \'Si Bu Yi Dian\', has been used to treat diabetes mellitus for more than a thousand years. However, the underlying mechanisms and comprehensive effects of TT on diabetes have yet to be investigated.
OBJECTIVE: The aim of the study was to systemically elucidate the potential mechanisms of TT in treating diabetes mellitus, and further investigate the therapeutic effects of the water extract, small molecular components and saccharides from TT.
METHODS: Fecal metabolomics was employed to draw the metabolic profile based on UHPLC-Q-TOF-MS/MS. The V3-V4 hypervariable regions of the bacteria 16S rRNA gene were amplified to explore the structural changes of the intestinal microbiome after TT intervention and to analyze the differential microbiota. The microbial metabolites SCFAs were determined by GC-MS, and the BAs and tryptophan metabolites were quantified by UPLC-TQ-MS. Spearman correlation analysis was carried out to comprehensively investigate the relationship among the endogenous metabolites profile, intestinal microbiota and their metabolites.
RESULTS: TT exhibited remarkably therapeutic effect on T2DM rats, as evidenced by improved glucolipid metabolism and intestinal barrier integrity, ameliorated inflammation and remission in insulin resistance. A total of 24 endogenous biomarkers were screened through fecal metabolomics studies, which were mainly related to tryptophan metabolism, fatty acid metabolism, bile acid metabolism, steroid hormone biosynthesis and arachidonic acid metabolism. Investigations on
microbiomics revealed that TT significantly modulated 18 differential bacterial genera and reversed the disordered gut microbial in diabetes rats. Moreover, TT notably altered the content of gut microbiota metabolites, both in serum and fecal samples. Significant correlation among microbial community, metabolites and T2DM-related indicators was revealed.
CONCLUSIONS: The multiple components of TT regulate the metabolic homeostasis of the organism and the balance of intestinal microbiota and its metabolites, which might mediate the anti-diabetic capacity of TT.