整合 16S rRNA 测序和非靶向代谢组学分析揭示多糖对 2 型糖尿病模型大鼠的保护机制。
Integrated 16S rRNA Sequencing and Untargeted Metabolomics Analysis to Reveal the Protective Mechanisms of Polysaccharide on Type 2 Diabetes Mellitus Model Rats.
机构信息
Department of Endocrinology and Metabolism, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China.
Department of Endocrinology and Metabolism, Chengde Medical University, Chengde, China.
出版信息
Curr Drug Metab. 2023;24(4):270-282. doi: 10.2174/1389200224666230406114012.
BACKGROUND
polysaccharide (PSP) can improve insulin resistance and inhibit oxidative stress. However, the detailed anti-diabetic mechanism of PSP is still poorly defined.
METHODS
In this study, the anti-diabetic, anti-inflammatory and anti-oxidative effects of PSP were evaluated on a type 2 diabetes mellitus (T2DM) rat model. Furthermore, we investigated the changes in gut microbiota and serum metabolites in T2DM rats after PSP treatment through 16S rRNA sequencing and untargeted metabolomics analyses.
RESULTS
Our results showed that PSP exhibited significant anti-diabetic, anti-inflammatory and anti-oxidative effects on T2DM model rats. In addition, 16S rRNA sequencing showed that PSP treatment decreased the ratio in the gut. At the genus level, PSP treatment increased the relative abundances of and while decreasing and . Untargeted metabolomics analysis revealed that PSP treatment could affect 20 metabolites, including hexanoylglycine, (±)5(6)-DiHET, ecgonine, L-cysteine-S-sulfate, epitestosterone, (±)12(13)-DiHOME, glutathione, L-ornithine, Dmannose 6-phosphate, L-fucose, L-tryptophan, L-kynurenine, serotonin, melatonin, 3-hydroxyanthranilic acid, xylitol, UDP-D-glucuronate, hydroxyproline, 4-guanidinobutyric acid, D-proline in T2DM model rats, these metabolites are associated with arginine and proline metabolism, tryptophan metabolism, amino sugar and nucleotide sugar metabolism, pentose and glucuronate interconversions, glutathione metabolism, arginine biosynthesis, ascorbate and aldarate metabolism pathways. Spearman correlation analysis results showed that the modulatory effects of PSP on the arginine and proline metabolism, tryptophan metabolism, and glutathione metabolism pathways were related to the regulation of and .
CONCLUSION
Our research revealed the therapeutic, anti-inflammatory and anti-oxidative effects of PSP on T2DM. The mechanisms of PSP on T2DM are associated with improving the dysbiosis of gut microbiota and regulating arginine and proline metabolism, tryptophan metabolism, and glutathione metabolism in serum.
背景
多糖（PSP）可以改善胰岛素抵抗和抑制氧化应激。然而，PSP 的详细抗糖尿病机制仍不清楚。
方法
在这项研究中，我们评估了 PSP 对 2 型糖尿病（T2DM）大鼠模型的抗糖尿病、抗炎和抗氧化作用。此外，我们通过 16S rRNA 测序和非靶向代谢组学分析，研究了 PSP 治疗后 T2DM 大鼠肠道微生物群和血清代谢物的变化。
结果
我们的结果表明，PSP 对 T2DM 模型大鼠具有显著的抗糖尿病、抗炎和抗氧化作用。此外，16S rRNA 测序显示，PSP 治疗降低了肠道中的 比值。在属水平上，PSP 治疗增加了 和 的相对丰度，同时降低了 和 的相对丰度。非靶向代谢组学分析显示，PSP 治疗可影响 20 种代谢物，包括己酰基甘氨酸、（±）5（6）-二氢表雄酮、ecgonine、L-半胱氨酸-S-硫酸酯、表睾酮、（±）12（13）-二氢同型 HOMe、谷胱甘肽、L-鸟氨酸、D-甘露糖 6-磷酸、L-岩藻糖、L-色氨酸、L-犬尿氨酸、血清素、褪黑素、3-羟基犬尿氨酸、木糖醇、UDP-D-葡萄糖醛酸、羟基脯氨酸、4-胍基丁酸、D-脯氨酸在 T2DM 模型大鼠中，这些代谢物与精氨酸和脯氨酸代谢、色氨酸代谢、氨基糖和核苷酸糖代谢、戊糖和葡萄糖醛酸转化、谷胱甘肽代谢、精氨酸生物合成、抗坏血酸和醛酸代谢途径有关。Spearman 相关分析结果表明，PSP 对精氨酸和脯氨酸代谢、色氨酸代谢和谷胱甘肽代谢途径的调节作用与对 和 的调节有关。
结论
本研究揭示了 PSP 对 T2DM 的治疗、抗炎和抗氧化作用。PSP 对 T2DM 的作用机制与改善肠道微生物群失调以及调节血清中精氨酸和脯氨酸代谢、色氨酸代谢和谷胱甘肽代谢有关。
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