The alternations of gut microbiota in diabetic kidney disease: insights from a triple comparative cohort.

BACKGROUND

Diabetic kidney disease (DKD) exhibits heterogeneous progression, implicating factors beyond hyperglycemia, such as gut microbiota dysbiosis. However, microbial distinctions among biopsy-confirmed pure DKD, DKD with non-diabetic renal disease (DKD+NDRD), and long-term diabetes without nephropathy (DM) remain unclear. This study aimed to identify gut microbial and functional biomarkers differentiating these groups.

METHODS

We enrolled 40 biopsy-confirmed participants classified into DKD (n=26), DM (n=8), and DKD+NDRD (n=6) groups. Gut microbiota was profiled using 16S rRNA sequencing. Microbial diversity, composition, and functional prediction (PICRUSt2 analysis) were compared among groups. Biomarkers were identified using LEfSe analysis.

RESULTS

No significant differences in alpha-diversity (Chao1, Shannon indices) or beta-diversity (PCoA/PCA) were observed among groups. Taxonomic analysis revealed distinct microbial signatures: DKD patients showed enrichment of Olsenella and reduced Faecalibacterium prausnitzii (a short-chain fatty acid producer), while DM patients exhibited higher Roseburia and Flavonifractor. The DKD+NDRD group was uniquely enriched in Prevotella_9. Functional prediction highlighted elevated pyruvate metabolism and bacterial toxin pathways in DKD, contrasting with enhanced linoleic acid metabolism in DM and attenuated endotoxin-related pathways in DKD+NDRD.

CONCLUSIONS

This study delineates gut microbiota profiles and functional shifts across DKD, DM, and DKD+NDRD. Key taxa (Olsenella, Prevotella_9) and metabolic pathways (pyruvate, toxin production) may serve as biomarkers for DKD progression and differential diagnosis. The findings underscore the gut-kidney axis's role in DKD pathogenesis and suggest microbiota-targeted interventions for precision management. Further validation in larger cohorts is warranted.