Toxic microbiome and progression of chronic kidney disease: insights from a longitudinal CKD-Microbiome Study Original paper

What was studied?

This original research article examined how the toxic microbiome in chronic kidney disease (CKD) contributes to disease severity and progression, with a particular focus on gut-derived uraemic toxins (UTs), microbial functional capacity, and diet. The study integrates shotgun metagenomics, multiomics profiling, dietary assessment, and faecal microbiota transplantation (FMT) experiments. Because the work seeks to define a microbiome signature relevant to CKD, it directly supports efforts to develop a microbiome signatures database. The authors compared 240 non-dialysis CKD patients with healthy controls to identify microbial species producing UT precursors—such as tryptophan- and tyrosine-derived indoles and phenols—and evaluated how these species contribute to increased UT levels and renal injury.

Who was studied?

The main human cohort consisted of 240 adults with non-dialysis CKD stages 2–5 from the French CKD-REIN cohort, with extensive clinical, dietary, toxin, and microbiome characterisation. A subset of 103 patients was followed for approximately three years to assess longitudinal microbiome changes and CKD progression. Matched healthy controls came from the Milieu Intérieur cohort. An independent Belgian CKD cohort (n=79) validated key microbial associations. Animal experiments used CKD model mice receiving FMT from either CKD patients or healthy donors to test causality.

Most important findings

The study identified a distinct CKD-associated gut microbiome, characterised by a marked enrichment of UT precursor-producing species, especially members of Enterocloster, Hungatella, Desulfovibrionaceae, Alistipes, and Intestinimonas. These microbes carry genes involved in kynurenine, indole, phenylacetylglutamine, p-cresyl sulfate, and TMAO synthesis pathways. Multiple figures visually demonstrate strong correlations between these microbial species and serum UT levels. Species depleted in CKD—most prominently Faecalibacterium prausnitzii—correlated negatively with UT concentrations and kidney fibrosis in both humans and mice. Longitudinal analysis showed progressive loss of species richness, increased toxic species ratio, and rising UT levels over three years (Figure 6, page 11). Dietary patterns influenced this trajectory: increased vegetable intake, lower protein consumption, and stable probiotic use reduced the toxic species ratio, while reductions in fibre intake increased it. Causality experiments revealed that transplanting CKD microbiota into CKD mice increased renal fibrosis and UT levels compared with transplantation of healthy stool, confirming a functional toxic role of the CKD microbiome.

Key implications

This study demonstrates that the CKD gut microbiome is not merely altered but functionally toxic, actively driving the production of indole- and phenol-derived UTs that accelerate CKD progression. Microbial species such as Desulfovibrio fairfieldensis, Hungatella spp., and Enterocloster spp. emerge as key contributors to a toxic microbial ecosystem. Conversely, beneficial species—including Faecalibacterium prausnitzii—represent potential therapeutic targets. Diet appears to be a modifiable factor capable of reducing UT-producing taxa, suggesting that plant-based, low-protein dietary interventions may meaningfully modulate dysbiosis. The findings support the integration of microbiome signatures into CKD risk stratification and highlight UT-producing pathways as targets for clinical trial development.

Citation

Laiola M, Koppe L, Larabi A, et al. Toxic microbiome and progression of chronic kidney disease: insights from a longitudinal CKD-Microbiome Study.Gut. 2025;74:1624–1637. doi:10.1136/gutjnl-2024-334634