CD4⁺ T cell count mediates the association between gut microbiota and diabetic kidney disease progression

Diabetic kidney disease (DKD) is the main cause of end-stage renal disease (ESRD). Gut microbiota dysbiosis can affect the DKD progression through pathways involving metabolism and inflammation. However, the dynamic evolution of gut microbiota along various DKD stages, and its interaction with immune cells and the DKD exacerbation remain unclear. This study aimed to explore the characteristics of gut microbiota alterations during DKD progression and evaluate whether CD4⁺ T cell count showed a statistically significant mediating association in this process.

A total of 157 patients with DKD were classified into early (n=34), middle (n=91) and late (n=32) stage groups according to clinical indicators. Fecal samples were collected for 16S rRNA sequencing to analyze the composition and diversity of the gut microbiota. Patients were further divided into low (n=22) and normal (n=44) CD4⁺ T cell count groups for comparative analysis. Mediation analysis was conducted to evaluate the relationship among gut microbiota, CD4⁺ T cells, and DKD progression.

The gut microbiota underwent significant changes at various stages of DKD. Thirty-five bacterial genera showed continuous changes in abundance during DKD progression. These bacterial genera were closely associated with renal function indicators and CD4⁺ T cell count. In addition, significant difference in the diversity and composition of gut microbiota were identified between the low and normal CD4⁺ T cell count groups, and were significantly related with renal injury markers. Mediation analysis showed that CD4⁺ T cell count mediated the association between 13 bacterial genera and the DKD progression.

The gut microbiota undergoes dynamic evolution during DKD progression, with CD4⁺ T cell count showing a significant mediating association between gut microbiota and DKD progression. These findings support a potential gut-immune-kidney association framework and warrant further investigation.