Related Experiment Video
Updated: Aug 15, 2025
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
The harmful intestinal microbial community accumulates during DKD exacerbation and microbiome-metabolome combined
Jin Shang1,2,3,4, Wen Cui1,2, Ruixue Guo1,2
1Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Objective:
Diabetic kidney disease (DKD) is one of the most prevalent complications of diabetes mellitus (DM) and is associated with gut microbial dysbiosis. We aim to build a diagnostic model to aid clinical practice and uncover a crucial harmful microbial community that contributes to DKD pathogenesis and exacerbation.
Design:
A total of 528 fecal samples from 180 DKD patients and 348 non-DKD populations (138 DM and 210 healthy volunteers) from the First Affiliated Hospital of Zhengzhou University were recruited and randomly divided into a discovery phase and a validation phase. The gut microbial composition was compared using 16S rRNA sequencing. Then, the 180 DKD patients were stratified into four groups based on clinical stages and underwent gut microbiota analysis. We established DKD mouse models and a healthy fecal microbiota transplantation (FMT) model to validate the effects of gut microbiota on DKD and select the potential harmful microbial community. Untargeted metabolome-microbiome combined analysis of mouse models helps decipher the pathogenetic mechanism from a metabolic perspective.
Results:
The diversity of the gut microbiome was significantly decreased in DKD patients when compared with that of the non-DKD population and was increased in the patients with more advanced DKD stages. The DKD severity in mice was relieved after healthy gut microbiota reconstruction. The common harmful microbial community was accumulated in the subjects with more severe DKD phenotypes (i.e., DKD and DKD5 patients and DKD mice). The harmful microbial community was positively associated with the serum injurious metabolites (e.g., cholic acid and hippuric acid).
Conclusion:
The fecal microbial community was altered markedly in DKD. Combining the fecal analysis of both human and animal models selected the accumulated harmful pathogens. Partially recovering healthy gut microbiota can relieve DKD phenotypes via influencing pathogens' effect on DKD mice's metabolism.
Insights
Diabetic kidney disease (DKD) is linked to gut microbial changes. Restoring healthy gut bacteria may improve DKD, targeting harmful microbes and their metabolites.
Area of Science:
- Microbiology
- Nephrology
- Metabolomics
Background:
- Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM), often associated with gut microbial dysbiosis.
- Understanding the gut microbiome's role is crucial for DKD diagnosis and treatment.
Purpose of the Study:
- To develop a diagnostic model for DKD using gut microbial data.
- To identify specific harmful microbial communities contributing to DKD pathogenesis and progression.
Main Methods:
- Analysis of 528 fecal samples from DKD patients and non-DKD individuals using 16S rRNA sequencing.
- Stratification of DKD patients by clinical stage for microbiota analysis.
- DKD mouse models and fecal microbiota transplantation (FMT) experiments to validate findings.
- Combined metabolome-microbiome analysis in mouse models.
Main Results:
- Gut microbiome diversity was reduced in DKD patients and correlated with disease severity.
- Healthy gut microbiota transplantation alleviated DKD severity in mouse models.
- A common harmful microbial community was identified in severe DKD cases and associated with injurious serum metabolites like cholic and hippuric acids.
Conclusions:
- Fecal microbial composition is significantly altered in DKD.
- Harmful gut pathogens contributing to DKD were identified through human and animal model analysis.
- Partial restoration of healthy gut microbiota shows potential to ameliorate DKD by modulating microbial metabolism.
