Enterorenal crosstalks in diabetic nephropathy and novel therapeutics targeting the gut microbiota

Yinhua Ni; Liujie Zheng; Sujie Nan; Lehui Ke; Zhengwei Fu; Juan Jin

doi:10.3724/abbs.2022140

Enterorenal crosstalks in diabetic nephropathy and novel therapeutics targeting the gut microbiota

Acta Biochim Biophys Sin (Shanghai). 2022 Oct 25;54(10):1406-1420. doi: 10.3724/abbs.2022140.

Authors

Yinhua Ni¹, Liujie Zheng¹, Sujie Nan¹, Lehui Ke¹, Zhengwei Fu¹, Juan Jin²

Affiliations

¹ College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
² Urology & Nephrology Center, Department of Nephrology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou 310014, China.

Abstract

The role of gut-kidney crosstalk in the progression of diabetic nephropathy (DN) is receiving increasing concern. On one hand, the decline in renal function increases circulating uremic toxins and affects the composition and function of gut microbiota. On the other hand, intestinal dysbiosis destroys the epithelial barrier, leading to increased exposure to endotoxins, thereby exacerbating kidney damage by inducing systemic inflammation. Dietary inventions, such as higher fiber intake, prebiotics, probiotics, postbiotics, fecal microbial transplantation (FMT), and engineering bacteria and phages, are potential microbiota-based therapies for DN. Furthermore, novel diabetic agents, such as glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-dependent glucose transporter-2 (SGLT-2) inhibitors, may affect the progression of DN partly through gut microbiota. In the current review, we mainly summarize the evidence concerning the gut-kidney axis in the advancement of DN and discuss therapies targeting the gut microbiota, expecting to provide new insight into the clinical treatment of DN.

Keywords: DPP-4 inhibitor; GLP-1 receptor agonist; SGLT-2 inhibitor; diabetic nephropathy; gut microbiota; microbiota-derived metabolites.

Publication types

Review

MeSH terms

Diabetes Mellitus*
Diabetic Nephropathies* / drug therapy
Dipeptidyl-Peptidase IV Inhibitors* / pharmacology
Dipeptidyl-Peptidase IV Inhibitors* / therapeutic use
Gastrointestinal Microbiome*
Humans
Kidney
Probiotics* / therapeutic use

Substances

Dipeptidyl-Peptidase IV Inhibitors

Grants and funding

This work was supported by the grants from the Natural Science Foundation of China of Zhejiang Province (No. LY19C110001 to Y.N.), the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China (No. LHDMZ22H050001), and the Key Project of Basic Scientific Research Operating Funds of Hangzhou Medical College (No. KYZD202002 to J.J.), and Innovative Research Team in University (No. IRT_17R97 to F.Z.).