Introduction Diabetic kidney disease (DKD) is a major complication of diabetes mellitus (DM). Although dysbiosis of the gut microbiota in DKD has been reported, the specific microbial species associated with disease progression from DM to DKD remain insufficiently defined. Methods We conducted shotgun metagenomic sequencing on fecal samples from 55 healthy participants, 47 patients with DM, and 38 patients with DKD. Gut microbiota diversity, composition, and functional pathways were compared across groups; correlations with glycemic and renal indices were evaluated. Results Overall alpha-diversity showed no significantly difference between DKD and healthy controls; however, the simpson’s index was higher in DKD than in DM (p 0.05). There was a difference in beta-diversity between DKD and the healthy control (p = 0.002), but no significant difference was observed between the DKD and DM group. Bacteria significantly enriched in DM/DKD include Mediterraneibacter , Enterocloster , Shigella , Limosilactobacillus , and Thomasclavelia , which showed positive correlations with glycemic indicators (HbA1c, fasting blood glucose) and renal indicators (BUN, UACR). In contrast, health-enriched bacteria, Phocaeicola , Faecalibacterium , Lachnospira , Agathobacter , Odoribacter , and Paraprevotella were negatively correlated with these parameters. Functional analysis revealed that compared to the DM group, the DKD group enriched pathways related to aromatic amino acid biosynthesis (phenylalanine, tyrosine, tryptophan), biofilm formation, and lipopolysaccharide biosynthesis. Gut microbial shifts along the DM–DKD correlates with adverse glycemic and renal phenotypes, as well as functional characteristics associated with inflammation and barrier injury. These findings suggest that microbially driven metabolic and structural pathways represent potential targets for mitigating the progression of DKD. Conclusion This study elucidates the distinct characteristics of the gut microbiota in DKD patients and highlights potential microbial markers involved in the progression from DM to DKD.
Yu et al. (2026) studied this question.