Differences in gut microbiota structure in patients with stages 4-5 chronic kidney disease Original paper

What was studied?

The study “Differences in gut microbiota structure in patients with stages 4–5 chronic kidney disease” examined how severe chronic kidney disease (CKD) alters gut microbial communities, a theme central to the gut–kidney axis. This work directly intersects with microbiome signature analysis by identifying specific bacterial shifts associated with advanced. Using 16S rDNA sequencing of the V3–V4 region, the researchers compared microbial richness, diversity, and taxa-level differences between patients with stage 4–5 CKD and healthy controls. The aim was to clarify how microbial disruption contributes to uremic toxin accumulation, systemic inflammation, and clinical deterioration.

Who was studied?

The study enrolled 39 patients with stage 4–5 CKD and 40 healthy adults, matched for age and sex, from Fujian Provincial Hospital in China. Patients met KDIGO criteria for CKD and were not receiving dialysis. Individuals with recent antibiotic use, gastrointestinal disorders, active infections, autoimmune disease, or conditions potentially altering the microbiome were excluded. Control participants had normal kidney function (eGFR >90 mL/min/1.73 m²) and no chronic diseases. Stool samples were collected under standardized conditions, processed per Human Microbiome Project guidelines, and sequenced to quantify microbial patterns.

Most important findings

Advanced CKD was associated with marked microbiome disruption, including reduced richness and diversity. Alpha diversity indices (Chao1, observed species, PD whole tree, Shannon, Simpson) were all significantly lower in CKD, reflecting broad ecological collapse. Beta diversity analyses (Unweighted and Weighted UniFrac) demonstrated clear separation between CKD and control samples, indicating distinct community structures. At the phylum and class levels (visualized in the stacked bar charts on page 5), controls were enriched in Bacteroidetes and Firmicutes, while CKD samples showed increased Proteobacteria and Gammaproteobacteria. Key taxa enriched in healthy controls included: Bacteroidia, Bacteroidales, Bacteroidetes, Clostridia, Clostridiales. Beneficial genera such as Prevotella, Faecalibacterium, Roseburia, and Ruminococcaceae members. These taxa are central producers of short-chain fatty acids (SCFAs), known to support intestinal integrity and immune modulation. In contrast, stage 4–5 CKD patients demonstrated significant increases in: Proteobacteria, Gammaproteobacteria, Enterobacteriaceae, Escherichia/Shigella, Enterococcus, Lactobacillales. These taxa are strongly associated with endotoxin production, uremic toxin generation (including indoxyl sulfate, p-cresol sulfate, and TMAO), and systemic inflammation. LEfSe analysis revealed high LDA scores for pathogenic or dysbiosis-associated taxa in CKD, confirming their dominant contribution to disease-related microbial signatures. Differential OTU heatmaps highlighted broad-scale microbial depletion alongside overrepresentation of facultative anaerobes typical of inflammatory states.

Key implications

This study strongly supports the concept of a microbial signature characteristic of advanced CKD, centered on loss of SCFA-producing commensals and overgrowth of uremic toxin–generating Proteobacteria. Such changes intensify systemic inflammation, impair gut barrier integrity, promote toxin accumulation, and accelerate CKD progression. The findings underscore the therapeutic importance of microbiome-based interventions—such as targeted probiotics, prebiotics, or fecal microbiota transplantation—to restore microbial balance and mitigate the gut-derived metabolic drivers of CKD progression.

Citation

Wu R, Ruan X-L, Ruan D-D, et al. Differences in gut microbiota structure in patients with stages 4–5 chronic kidney disease.Am J Transl Res. 2021;13(9):10056-10074