Chronic kidney disease and the gut microbiome Original paper

What was reviewed?

This review article examined the gut–kidney axis in chronic kidney disease (CKD), using the focus keyphrase chronic kidney disease gut microbiome to explore how progressive renal dysfunction reshapes intestinal microbial ecology and triggers systemic toxicity. The authors synthesized evidence on how elevated urea, altered colonic physiology, dietary restrictions, and slowed intestinal transit disrupt microbial balance. A central theme is dysbiosis-driven production of gut-derived uremic solutes—particularly indoxyl sulfate and p-cresyl sulfate—whose accumulation worsens renal, cardiovascular, and metabolic health. The review also covered metaproteomic and metagenomic tools that characterize microbiome function with species-level and protein-level precision. Visuals underscore the feedback loop in which CKD increases uremic solutes, further injuring the gut barrier and kidneys, outlining taxa increased (e.g., Enterobacteriaceae, Actinobacteria) or decreased (e.g., Lactobacillus, Bifidobacterium) in CKD and ESRD.

Who was reviewed?

The review synthesized findings from human subjects with CKD, end-stage renal disease (ESRD), and hemodialysis or peritoneal dialysis dependence, as well as multiple animal models, including 5/6 nephrectomy and adenine-induced CKD rats. It also incorporated metaproteomic studies in human stool samples, clinical trials of synbiotics and oral adsorbents, and experimental models exploring dietary fiber, resistant starch, and microbial metabolites. Collectively, the reviewed populations represent diverse CKD etiologies, treatment modalities, and stages of renal impairment, allowing broad identification of microbiome-specific signatures relevant to clinical translation.

Most important findings

CKD generates a distinct dysbiosis marked by expansion of urease-, uricase-, and indole- and p-cresyl–producing bacteria, driven largely by urea diffusion into the gut lumen. This dysbiosis elevates gut-derived toxins such as indoxyl sulfate and p-cresyl sulfate, which exhibit strong protein binding and are minimally dialyzable. These solutes damage renal tubules, impair endothelial repair, promote oxidative stress, and disrupt metabolic pathways, including insulin sensitivity. They also correlate with vascular stiffness, atherosclerosis severity, and mortality. Page 2’s diagram highlights how these toxins weaken the gut barrier by reducing tight-junction proteins (claudin-1, occludin, ZO-1), increasing permeability, and systemic inflammation. SCFA-producing taxa contract in CKD, diminishing butyrate levels crucial for colonocyte energy, Treg homeostasis, and epithelial integrity. Metaproteomic work reveals functionally active but low-abundance species such as Ruminococcus bromii, whose abundance increases with resistant starch supplementation and may slow CKD progression. Therapeutic studies show mixed outcomes: synbiotics reduce p-cresyl sulfate, resistant starch improves renal and inflammatory markers in animal models, while AST-120 trials show limited benefit.

Key implications

The review establishes the gut microbiome as both a driver and amplifier of CKD progression. Dysbiosis increases production of toxic solutes, undermines epithelial integrity, propagates systemic inflammation, and worsens cardiovascular risk. These data support microbiome-targeted therapies—dietary fiber, resistant starch, synbiotics, and possibly metaproteomic-guided precision approaches. Restoring SCFA-producing taxa and strengthening the gut barrier emerge as central therapeutic strategies, with implications for personalized microbial signature profiling in clinical nephrology.

Citation

Hobby GP, Karaduta O, Dusio GF, Singh M, Zybailov BL, Arthur JM. Chronic kidney disease and the gut microbiome.Am J Physiol Renal Physiol. 2019;316:F1211–F1217. doi:10.1152/ajprenal.00298.2018