Diabetic kidney disease (DKD) is leading causes and one of the fastest growing causes of chronic kidney disease worldwide, and leads to high morbidity and mortality. Emerging evidences have revealed gut microbiota dysbiosis and related metabolism dysfunction play a dominant role in DKD progression and treatment through modulating inflammation. Our previous studies showed that Tangshen Formula (TSF), a Chinese herbal prescription, exhibited anti-inflammatory effect on DKD, but underlying mechanism that involved gut microbiota and related metabolism in aged model remained obscure. Here, BTBR ob/ob mice were used to establish aged DKD model, and 16S rRNA sequence and untargeted metabolomic analyses were employed to investigate the correlation between colonic microbiota and serum metabolism. The aged ob/ob mice exhibited obvious glomerular and renal tubule injury and kidney function decline in kidney, while TSF treatment significantly attenuated these abnormalities. TSF also exhibited potent anti-inflammatory effect in aged ob/ob mice indicating by reduced proinflammatory factor IL-6 and TNF-α, MCP-1 and COX-2 in serum, kidney and intestine, which suggested the involvement of gut microbiota with TSF effect. The 16S rDNA sequencing of the colonic microbiome and untargeted serum metabolomics analysis revealed significant differences in gut microbiota structure and serum metabolomic profiles between WT and ob/ob mice. Notably, TSF treatment reshaped the structure of gut microbiota and corrected the disorder of metabolism especially tryptophan metabolism and arginine biosynthesis. TSF increased and genera and decreased and genera, and further elevated tryptophan, 5-hydroxyindoleacetate, glutamic acid, aspartate and reduced 4-hydroxy-2-quinolinecarboxylic acid, indole-3-acetic acid, xanthurenic acid, glutamine. Further correlation analysis indicated that disturbed gut microbiota was linked to tryptophan metabolism and arginine biosynthesis to regulate inflammation in aged DKD. Our data revealed that TSF attenuated renal inflammation by modulating gut microbiota and related amino acid metabolism in aged DKD model, highlighting gut microbiota and related metabolism functioned as potential therapeutic target for DKD in elderly patients.

中文翻译：

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糖肾方通过调节肠道菌群组成及相关氨基酸代谢减轻老年糖尿病肾病炎症损伤

糖尿病肾病 (DKD) 是全球慢性肾病的主要原因，也是增长最快的原因之一，导致高发病率和死亡率。新的证据表明，肠道微生物群失调和相关代谢功能障碍通过调节炎症在 DKD 进展和治疗中发挥着主导作用。我们之前的研究表明，汤肾方（TSF）这种中药方剂对 DKD 具有抗炎作用，但在老年模型中涉及肠道菌群和相关代谢的潜在机制仍不清楚。本研究使用BTBR ob/ob小鼠建立老年DKD模型，并采用16S rRNA序列和非靶向代谢组学分析来研究结肠微生物群与血清代谢之间的相关性。老年ob/ob小鼠表现出明显的肾小球和肾小管损伤以及肾脏肾功能下降，而TSF治疗显着减弱了这些异常。 TSF 还在老年 ob/ob 小鼠中表现出有效的抗炎作用，表明血清、肾脏和肠道中的促炎因子 IL-6 和 TNF-α、MCP-1 和 COX-2 减少，这表明肠道微生物群与 TSF 相关影响。结肠微生物组的 16S rDNA 测序和非靶向血清代谢组学分析揭示了 WT 和 ob/ob 小鼠的肠道微生物群结构和血清代谢组谱存在显着差异。值得注意的是，TSF治疗重塑了肠道菌群结构，纠正了代谢紊乱，特别是色氨酸代谢和精氨酸生物合成的紊乱。 TSF增加和属和减少和属，并进一步升高色氨酸、5-羟基吲哚乙酸、谷氨酸、天冬氨酸和还原型4-羟基-2-喹啉甲酸、吲哚-3-乙酸、黄嘌呤酸、谷氨酰胺。进一步的相关分析表明，肠道菌群紊乱与色氨酸代谢和精氨酸生物合成有关，从而调节老年 DKD 的炎症。我们的数据显示，TSF 通过调节老年 DKD 模型中的肠道微生物群和相关氨基酸代谢来减轻肾脏炎症，强调肠道微生物群和相关代谢是老年 DKD 患者的潜在治疗靶点。