The role of microbial metabolites in diabetic kidney disease
Ting Zhu,
Bi-Ying Hu,
Yi-Qing Zhang,
Ze-Yu Zhang,
Kai-Wen Cai,
Lei Lei,
Bo Hu,
Xiao-Hua Wang,
Chun Tang,
Yong-Ping Lu,
Zhi-Hua Zheng
Affiliations
Ting Zhu
Department of Nephrology, Center of Kidney and Urology, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
Bi-Ying Hu
Department of Nephrology, the First Affiliated Hospital of Jinan University, Guangzhou, China
Yi-Qing Zhang
Department of Nephrology, Center of Kidney and Urology, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
Ze-Yu Zhang
Department of Nephrology, the First Affiliated Hospital of Jinan University, Guangzhou, China
Kai-Wen Cai
Department of Nephrology, Center of Kidney and Urology, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
Lei Lei
Department of Nephrology, Center of Kidney and Urology, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
Bo Hu
Department of Nephrology, the First Affiliated Hospital of Jinan University, Guangzhou, China
Xiao-Hua Wang
Department of Nephrology, Center of Kidney and Urology, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
Chun Tang
Department of Nephrology, Center of Kidney and Urology, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China; Corresponding author.
Yong-Ping Lu
Department of Nephrology, Center of Kidney and Urology, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China; Department of Nephrology, the First Affiliated Hospital of Jinan University, Guangzhou, China; Corresponding author. Department of Nephrology, Center of Kidney and Urology, the seventh affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Zhi-Hua Zheng
Department of Nephrology, Center of Kidney and Urology, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China; Corresponding author.
Background: Growing evidence suggests a complex bidirectional interaction between gut microbes, gut-derived microbial metabolites, and diabetic kidney disease (DKD), known as the “gut-kidney axis” theory. The present study aimed to characterize the role of microbial metabolites in DKD. Methods: Six-week-old db/db and littermate db/m mice were raised to 20 weeks old. The serum, urine, feces, liver, perinephric fat, and kidney were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based metabolomic analyses. Results: The db/db mice showed obvious pathological changes and worse renal functions than db/m mice. Indoleacetaldehyde (IAld) and 5-hydroxy-l-tryptophan (5-HTP) in kidney samples, and serotonin (5-HT) in fecal samples were increased in the db/db group. Phosphatidylcholine (PC), phosphatidate (PA), and 1-acylglycerophosphocholine (lysoPC) were decreased in liver and serum samples of the db/db group, while PC and lysoPC were decreased in kidney and perinephric fat samples. Suggested metabolomic homeostasis was disrupted in DKD mice, especially glycerophospholipid and tryptophan metabolism, which are closely related to the gut microbiome. Conclusions: Our findings reveal the perturbation of gut microbial metabolism in db/db mice with DKD, which may be useful for building a bridge between the gut microbiota and the progression of DKD and provide a theoretical basis for the intestinal treatment of DKD.