Mo Yenan, Sun Huang, Zhang Lei, Geng Wenjia, Wang Lixin, Zou Chuan, Wu Yuchi, Ji Chunlan, Liu Xusheng, Lu Zhaoyu
The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Emergency, TCM-Integrated Hospital, Southern Medical University, Guangzhou, China.
Front Pharmacol. 2021 May 11;12:657827. doi: 10.3389/fphar.2021.657827. eCollection 2021.
As nitrogen-free precursors of corresponding essential amino, -ketoacid have been widely prescribed to end-stage renal disease patients together with a low protein diet However, the impact of -ketoacid on intestinal microbiota in chronic kidney disease (CKD) individuals is unknown. The study aims at investigating the variation in the intestinal microbiota and metabolic profile in response to -ketoacid treatment in an adenine-induced CKD rat model. Rats in the treatment groups were given solution of compound -ketoacid tablets. At the end of the study, blood, feces, colon tissues and kidney tissues were collected and processed for biochemical analyses, histological and western blot analyses, 16S rRNA sequence and untargeted metabolomic analyses. -Ketoacid treatment reduced serum creatinine, blood urea nitrogen and 24 h urine protein, and alleviated tubular atrophy, glomerulosclerosis and interstitial fibrosis in adenine-induced CKD rats. Moreover, -ketoacid significantly improved intestinal barrier and increased the abundance of , while reduced the abundance of and at the genus level. In addition, our results also demonstrated that -ketoacid significantly reduced the concentrations of indoxyl sulfate, betaine, choline and cholesterol. Spearman's correlation analysis revealed that the abundance of Coprococcus_3 was positively correlated with serum level of betaine, trimethylamine N-oxide, indoxyl sulfate, cholic acid and deoxycholic acid. -Ketoacid has a reno-protective effect against adenine-induced CKD, which may be mediated regulation of serum metabolic profiles via affecting intestinal microbial community.
作为相应必需氨基酸的无氮前体，α-酮酸已与低蛋白饮食一起广泛应用于终末期肾病患者。然而，α-酮酸对慢性肾脏病（CKD）患者肠道微生物群的影响尚不清楚。本研究旨在探讨腺嘌呤诱导的CKD大鼠模型中，α-酮酸治疗对肠道微生物群和代谢谱的影响。治疗组大鼠给予复方α-酮酸片溶液。在研究结束时，收集血液、粪便、结肠组织和肾脏组织，进行生化分析、组织学和蛋白质印迹分析、16S rRNA测序和非靶向代谢组学分析。α-酮酸治疗降低了腺嘌呤诱导的CKD大鼠的血清肌酐、血尿素氮和24小时尿蛋白，并减轻了肾小管萎缩、肾小球硬化和间质纤维化。此外，α-酮酸显著改善了肠道屏障，增加了[具体菌属1]的丰度，同时在属水平上降低了[具体菌属2]和[具体菌属3]的丰度。此外，我们的结果还表明，α-酮酸显著降低了硫酸吲哚酚、甜菜碱、胆碱和胆固醇的浓度。Spearman相关性分析显示，Coprococcus_3的丰度与血清甜菜碱、氧化三甲胺、硫酸吲哚酚、胆酸和脱氧胆酸水平呈正相关。α-酮酸对腺嘌呤诱导的CKD具有肾脏保护作用，这可能是通过影响肠道微生物群落来调节血清代谢谱介导的。
