Chronic kidney disease (CKD) is highly prevalent worldwide, with proteinuria serving as a key diagnostic and prognostic indicator. The concept of the "gut-kidney axis" suggests that gut microbiota dysbiosis may contribute to CKD pathogenesis; however, its relationship with proteinuria severity remains unclear. This study investigated dynamic changes in gut microbiota composition and function among CKD patients with varying levels of proteinuria, enrolling 148 participants: 54 healthy controls (HC), 49 CKD patients with mild proteinuria (PROUL), and 45 with massive proteinuria (PROUM). Fecal samples were analyzed using 16S rRNA gene sequencing to characterize microbiota structure, differential taxa, and functional potential, alongside clinical indicators and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Compared with HC, CKD patients exhibited significantly reduced gut microbiota ɑ-diversity (Chao1 and Shannon indices), which increased as proteinuria worsened. β-diversity also differed significantly among groups. The Faecalibacterium-dominated enterotype (beneficial) declined from 50. 0% (HC) to 40. 82% (PROUL) and 28. 9% (PROUM), whereas the Prevotella-dominated enterotype (potentially pathogenic) increased from 7. 4% (HC) to 20. 41% (PROUL) and 24. 4% (PROUM). With worsening proteinuria, probiotics, such as Akkermansia and Coprococcus, decreased progressively, while potentially pathogenic bacteria, including Enterobacteriaceae, Haemophilus, and Ruminococcus, were enriched. KEGG-based functional analysis indicated that microbiota nitrogen metabolism became increasingly overactivated from HC to PROUL and PROUM, whereas unsaturated fatty acid synthesis was inhibited. Enzymes such as fumarate reductase correlated with the degree of proteinuria. This study characterizes gut microbiota dysbiosis in CKD patients with varying proteinuria levels, revealing reduced probiotics, enrichment of pathogens, and metabolic dysfunction, which may contribute to the progression of renal injury. IMPORTANCEChronic kidney disease (CKD) affects nearly one billion people and remains a leading global cause of death; yet the molecular dialog between gut-microbiome imbalance and the severity of proteinuria is poorly defined. We profiled 148 participants-54 healthy controls, 49 CKD patients with mild proteinuria, and 45 with massive proteinuria-and uncovered a graded dysbiosis that intensifies as proteinuria worsens. Faecalibacterium-dominated enterotypes decline, whereas Prevotella-dominated communities expand; beneficial taxa, such as Akkermansia and Coprococcus, are progressively displaced by uremic-toxin producers (Enterobacteriaceae, Haemophilus). Concurrently, nitrogen metabolism pathways become hyperactive while unsaturated fatty acid synthesis is suppressed. These data illuminate the gut-kidney axis as a driver of CKD progression, deliver stage-specific microbial biomarkers for precision risk stratification, and identify tractable microecological targets for early intervention.
Wang et al. (Thu,) studied this question.