Gut Microbiome

Gut microbiota biomarkers of chronic kidney disease progression identified by 16S rDNA sequencing and machine learning.

TL;DR

An integrative analysis using 16S rDNA sequencing and machine learning identified stage-specific gut microbial biomarkers and functional pathways implicated in CKD progression, supporting the mechanistic role of the gut-kidney axis and the potential for microbiota-based interventions and early diagnostic approaches.

Key Findings

Significant differences in microbial composition, richness, and diversity were found among CKD stage groups and healthy controls.

  • Fecal samples were collected from 27 participants: 6 with stage II CKD, 5 with stage III CKD, 7 with stage IV CKD, and 9 healthy controls.
  • 16S rDNA sequencing was used to analyze microbial composition following quality control of sequencing data.
  • Both microbial richness and diversity metrics showed significant differences among the groups.

Ten differential microbial taxa were identified across CKD stages, with Actinobacteriota and Bifidobacterium showing the highest relative abundances.

  • Actinobacteriota (phylum level) and Bifidobacterium (genus level) were the most abundant differential taxa identified.
  • The ten differential taxa were identified through comparative analysis across stage II, III, and IV CKD groups and healthy controls.
  • These taxa were identified following 16S rDNA sequencing and quality control of fecal sample data.

Machine learning methods identified six microbial biomarkers capable of distinguishing CKD patients from healthy individuals, all with AUC values exceeding 0.7.

  • Three machine learning techniques were employed: Lasso regression, the Boruta algorithm, and K-fold cross-validation.
  • Six microbial biomarkers were identified, including Eubacterium eligens and Lactococcus.
  • All six biomarkers exhibited AUC values exceeding 0.7, indicating their potential diagnostic utility.
  • The machine learning pipeline was designed to highlight the most informative microbial features for distinguishing CKD from healthy status.

Species driving force analysis revealed increasing numbers of microbial interaction relationships with advancing CKD stage, with 26, 27, and 39 interactions identified in stage II, III, and IV CKD compared to controls, respectively.

  • Microbial network analysis via species driving force analysis was used to uncover interaction relationships.
  • Stage II CKD showed 26 microbial interaction relationships compared to controls.
  • Stage III CKD showed 27 microbial interaction relationships compared to controls.
  • Stage IV CKD showed the greatest number at 39 microbial interaction relationships compared to controls, suggesting increasing microbial network complexity with disease progression.

The study identified stage-specific gut microbial biomarkers and functional pathways implicated in CKD progression, supporting the mechanistic role of the gut-kidney axis.

  • Integrative analysis combined 16S rDNA sequencing with multiple machine learning techniques and microbial network analysis.
  • Stage-specific biomarkers were identified across CKD stages II, III, and IV.
  • Findings underscore the potential for microbiota-based interventions and early diagnostic approaches in CKD.
  • The authors conclude their results support the mechanistic role of the gut-kidney axis in CKD pathogenesis.

What This Means

This research suggests that the bacteria living in the gut change in specific ways as chronic kidney disease (CKD) progresses through its stages. By analyzing stool samples from 27 people — including patients with stage II, III, and IV CKD and healthy individuals — researchers used genetic sequencing to identify which gut bacteria were present and how their communities differed between groups. They found significant shifts in the diversity and makeup of gut bacteria across CKD stages, with certain bacteria like Actinobacteriota and Bifidobacterium standing out as particularly notable. Using artificial intelligence and statistical tools (machine learning), the researchers then identified six specific bacterial markers that could distinguish CKD patients from healthy people with reasonable accuracy (all with AUC scores above 0.7, where 1.0 would be perfect). Two of these were Eubacterium eligens and Lactococcus. The study also found that as CKD worsened, the interactions between different bacterial species became more complex, rising from 26 interaction relationships in stage II to 39 in stage IV. This research suggests that gut bacteria may play a role in how CKD develops and worsens — a concept known as the 'gut-kidney axis.' The identified bacterial markers could potentially be developed into non-invasive tools to detect or monitor CKD at earlier stages. The findings also raise the possibility that targeting gut bacteria through diet, probiotics, or other interventions might one day help slow kidney disease progression, though further research in larger populations is needed before any clinical applications could be considered.

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Citation

Zhang Y, Zhang M, Liu S, Li X. (2026). Gut microbiota biomarkers of chronic kidney disease progression identified by 16S rDNA sequencing and machine learning.. Renal failure. https://doi.org/10.1080/0886022X.2026.2667649