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

Mengqi Wu¹Xin Zhou²Saiping Chen¹Yuqing Wang¹Bin Lu¹Aiping Zhang¹Yanqin Zhu¹Min Huang¹Jiarui Wang¹Junyi Liu¹Fenggui Zhu¹Hong Liu¹Riyang Lin^1,3*

• ¹Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Jiangsu Province, China
• ²Tianshui Wulin Street Community Heal Care Centre, Hangzhou, China
• ³Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Jiangsu Province, China

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.