Microbiome-Metabolomics Analysis Reveals the Protection Mechanism of α-Ketoacid on Adenine-Induced Chronic Kidney Disease in Rats

Bibliographic Details
Title: Microbiome-Metabolomics Analysis Reveals the Protection Mechanism of α-Ketoacid on Adenine-Induced Chronic Kidney Disease in Rats
Authors: Yenan Mo, Huang Sun, Lei Zhang, Wenjia Geng, Lixin Wang, Chuan Zou, Yuchi Wu, Chunlan Ji, Xusheng Liu, Zhaoyu Lu
Source: Frontiers in Pharmacology, Vol 12 (2021)
Publisher Information: Frontiers Media S.A., 2021.
Publication Year: 2021
Collection: LCC:Therapeutics. Pharmacology
Subject Terms: chronic kidney disease, α-ketoacid, metabolic profiles, microbiota, reno-protective, Therapeutics. Pharmacology, RM1-950
More Details: Objectives: As nitrogen-free precursors of corresponding essential amino, α-ketoacid have been widely prescribed to end-stage renal disease patients together with a low protein diet However, the impact of α-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 α-ketoacid treatment in an adenine-induced CKD rat model.Design: Rats in the treatment groups were given solution of compound α-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.Results:α-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, α-ketoacid significantly improved intestinal barrier and increased the abundance of Methanobrevibacter, Akkermansia, Blautia and Anaerositipes while reduced the abundance of Anaerovorax and Coprococcus_3 at the genus level. In addition, our results also demonstrated that α-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.Conclusion:α-Ketoacid has a reno-protective effect against adenine-induced CKD, which may be mediated regulation of serum metabolic profiles via affecting intestinal microbial community.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1663-9812
Relation: https://www.frontiersin.org/articles/10.3389/fphar.2021.657827/full; https://doaj.org/toc/1663-9812
DOI: 10.3389/fphar.2021.657827
Access URL: https://doaj.org/article/7750d45eac744a7c9b50acde3638f2b7
Accession Number: edsdoj.7750d45eac744a7c9b50acde3638f2b7
Database: Directory of Open Access Journals
More Details
ISSN:16639812
DOI:10.3389/fphar.2021.657827
Published in:Frontiers in Pharmacology
Language:English