Alterations of the Human Gut Microbiome in Chronic Kidney Disease Original paper

What was studied?

Alterations of the human gut microbiome in chronic kidney disease were investigated, focusing on how microbiome signatures shift as CKD progresses and whether these microbial changes can be used as non-invasive diagnostic markers. This study on chronic kidney disease gut microbiome evaluated 520 fecal samples from multiple cities in China and used 16S rRNA sequencing to map microbial shifts linked to renal dysfunction. The work emphasized identifying key microbial taxa, functional pathways, and operational taxonomic units (OTUs) that differentiate CKD from healthy states and explored how microbial alterations track with declining estimated glomerular filtration rate (eGFR).

Who was studied?

Participants included 489 individuals after exclusions: 159 adults with nondialysis CKD and 273 healthy controls from Zhengzhou, plus an independent cohort of 57 CKD patients from Hangzhou. Healthy controls were matched for age, sex, and BMI where possible. CKD staging followed KDIGO 2012 guidelines, and exclusion criteria eliminated confounding from antibiotics, probiotics, malignancies, liver disease, diabetes, or dialysis. Samples were stratified into discovery, validation, and independent diagnostic cohorts to ensure robust microbial comparisons and external verification.

Most important findings

CKD was associated with clear and progressive remodeling of gut microbial communities. Diversity markers (Shannon, Chao, ACE) were significantly reduced in CKD, with nonmetric multidimensional scaling and principal coordinate analysis showing distinct microbial clustering apart from healthy controls. At the phylum level, Proteobacteria, Actinobacteria, and Fusobacteria were significantly enriched, while Firmicutes and Verrucomicrobia were reduced. At the genus level, disease-associated increases included Klebsiella, Desulfovibrio, Veillonella, and Enterobacteriaceae members, whereas health-associated taxa such as Blautia, Roseburia, Lachnospira, and Faecalibacterium were depleted. Functional prediction via PICRUSt revealed elevations in tryptophan and phenylalanine metabolism—pathways leading to uremic toxins indoxyl sulfate and p-cresyl sulfate—as well as increased lipopolysaccharide biosynthesis. Arginine and proline metabolism showed substantial reductions.
A machine-learning classifier using five microbial markers achieved excellent diagnostic accuracy (AUC 0.9887 in discovery, 0.9512 in validation, 0.8986 in the external cohort). Progression analysis demonstrated a rising abundance of Akkermansia and Thalassospira in later CKD stages, with 13 OTUs correlating strongly with clinical indicators such as serum creatinine, blood urea nitrogen, and eGFR.

Key implications

This study demonstrates that CKD is characterized by a reproducible microbial signature reflecting both structural and functional disruptions in the gut ecosystem. Enrichment of urease- and indole-producing taxa suggests enhanced generation of microbial uremic toxins that accelerate kidney decline. Loss of short-chain-fatty-acid–producing genera indicates diminished epithelial support and heightened systemic inflammation. The strong cross-regional classifier performance underscores translational potential for microbiome-based, non-invasive CKD diagnostics, while taxa such as Akkermansia emerge as candidate microbial contributors to disease progression and promising therapeutic targets.

Citation

Ren Z, Fan Y, Li A, et al. Alterations of the human gut microbiome in chronic kidney disease. Advanced Science. 2020;7(20):2001936