Integrated gut microbiota and fecal metabolomics reveal the renoprotective effect of Rehmanniae Radix Preparata and Corni Fructus on adenine-induced CKD rats

May 11, 2021Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

Gut bacteria and feces chemicals show kidney protection by Rehmanniae Radix Preparata and Corni Fructus in rats with kidney disease caused by adenine

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Abstract

CKD rats treated with Rehmanniae Radix Preparata and Corni Fructus exhibited significant changes in gut microbiota composition.

The treatment increased levels of beneficial bacteria such as Ruminococcaceae UCG-014 and Prevotellaceae_NK3B31_group.
A notable decrease in the opportunistic pathogen Desulfovibrio was observed following treatment.
Fecal metabolite analysis identified 15 metabolites linked to CKD, primarily involving amino acid, bile acids, and glycerophospholipid metabolism.
These findings suggest that gut flora and their metabolic products may influence the progression of CKD.

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Rehmanniae Radix Preparata (RR) and Corni Fructus (CF), well-known traditional Chinese medicines (TCMs), were generally used together in the clinical practices to treat chronic kidney disease (CKD) with synergistic effects for thousands of years, but their combination mechanism remains largely unknown so far. Recent evidences have implicated intestinal flora as potential targets for the therapy of CKD. In this study, the CKD rat model was induced by adenine. The levels of proteinuria, serum creatine (SCr), blood urea nitrogen (BUN) and creatinine clearance (Ccr) were used to assess the cooperation effect of RR and CF. Furthermore, high-throughput 16S ribosomal RNA (rRNA) gene sequencing combined with fecal metabonomics based on UPLC-Q-TOF-MS/MS were applied to explore the variations of intestinal flora and their metabolic profiles. 16S rRNA gene sequencing data indicated that CKD rats treated with RR, CF and RC showed the differences in the composition of gut microbiota. The abundance of beneficial bacteria including Ruminococcaceae UCG-014, Ruminococcus 1, Prevotellaceae_NK3B31_group, Lachnospiraceae NK4A136 group and Lachnospiraceae UCG-001 were elevated in various degrees, while the opportunistic pathogen such as Desulfovibrio was markedly decreased after the treatment. Moreover, fecal metabolite profiles revealed 15 different metabolites associated with CKD. These metabolites were mainly involved in the related metabolic pathways such as amino acid metabolism, bile acids metabolism and glycerophospholipid metabolism. The results implied that gut flora and their metabolites might play a vital role in the progress of CKD, which provided a potential target for the development of novel drugs for the therapy of CKD.

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Integrated gut microbiota and fecal metabolomics reveal the renoprotective effect of Rehmanniae Radix Preparata and Corni Fructus on adenine-induced CKD rats

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