Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease.

Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease.
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糖尿病肾病血清代谢物和肠道菌群的特征

DOI:
10.3389/fphar.2022.872988
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发表时间:
2022
影响因子:
5.6
通讯作者:
Li, Ping
Li, Ping
中科院分区:
医学2区
文献类型:
--
作者:
Zhang, Bo;Wan, Yuzhou;Zhou, Xuefeng;Zhang, Haojun;Zhao, Hailing;Ma, Liang;Dong, Xi;Yan, Meihua;Zhao, Tingting;Li, Ping

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循环代谢物的紊乱和肠道微生物群的紊乱参与糖尿病肾病(DKD)的进展。然而,关于血清代谢物与肠道微生物群之间的关系及其与DKD的关系的研究有限。本研究采用链脲佐菌素联合单侧肾切除诱导的实验性DKD大鼠模型,采用非靶向代谢组学和16 S rRNA基因测序技术,探讨代谢特征与肠道菌群结构和功能的关系。140种血清代谢物以及大鼠肠道微生物群的组成和功能发生了显著变化。这些变化主要与碳水化合物、脂质和氨基酸代谢有关。在这些途径中,异麦芽糖,D-甘露糖,半乳糖酸,柠檬酸和前列腺素B2显着上调。3-(2-羟乙基)吲哚、3-甲基吲哚和吲哚丙烯酸下调,是DKD模型中的关键代谢产物。此外,这三个吲哚的水平恢复后,与传统的中草药治疗糖肾方。在属水平上,结瘤真杆菌群、乳杆菌和粪杆菌在DKD的进展中参与代谢紊乱最多。值得注意的是,循环脂质代谢产物与DKD相关参数有很强的相关性,尤其与系膜基质面积呈负相关。血脂指标(TG和TC)和UACR与某些微生物属直接相关。总之,本研究证实了DKD进展中的异常循环代谢物和肠道微生物群。我们还确定了治疗DKD的潜在代谢和微生物靶点。
Disturbance of circulating metabolites and disorders of the gut microbiota are involved in the progression of diabetic kidney disease (DKD). However, there is limited research on the relationship between serum metabolites and gut microbiota, and their involvement in DKD. In this study, using an experimental DKD rat model induced by combining streptozotocin injection and unilateral nephrectomy, we employed untargeted metabolomics and 16S rRNA gene sequencing to explore the relationship between the metabolic profile and the structure and function of gut microbiota. Striking alterations took place in 140 serum metabolites, as well as in the composition and function of rat gut microbiota. These changes were mainly associated with carbohydrate, lipid, and amino acid metabolism. In these pathways, isomaltose, D-mannose, galactonic acid, citramalic acid, and prostaglandin B2 were significantly upregulated. 3-(2-Hydroxyethyl)indole, 3-methylindole, and indoleacrylic acid were downregulated and were the critical metabolites in the DKD model. Furthermore, the levels of these three indoles were restored after treatment with the traditional Chinese herbal medicine Tangshen Formula. At the genera level, g_Eubacterium_nodatum_group, g_Lactobacillus, and g_Faecalibaculum were most involved in metabolic disorders in the progression of DKD. Notably, the circulating lipid metabolites had a strong relationship with DKD-related parameters and were especially negatively related to the mesangial matrix area. Serum lipid indices (TG and TC) and UACR were directly associated with certain microbial genera. In conclusion, the present research verified the anomalous circulating metabolites and gut microbiota in DKD progression. We also identified the potential metabolic and microbial targets for the treatment of DKD.
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