Characterization of metal(loid)s and antibiotic resistance in bacteria of human gut microbiota from chronic kidney disease subjects Original paper

What was studied?

This study investigated chronic kidney disease microbiome resistance, focusing on how metal(loid) exposure and antibiotic pressure shape resistance phenotypes in gut bacteria of CKD patients. The authors characterized bacterial isolates from stool samples across CKD stages, examining their tolerance to arsenic, cadmium, mercury, and lead, as well as their antibiotic resistance patterns. They used culture-based selection on media supplemented with metal(loid)s, followed by antibiotic susceptibility testing and 16S rRNA amplicon sequencing to identify taxa enriched under these selective pressures. Additionally, qPCR targeting a panel of resistance genes evaluated the abundance of microbial genetic determinants associated with both antibiotic and metal(loid) resistance. The study provides mechanistic insight into how progressive renal dysfunction, combined with common exposures such as contaminated tap water and frequent antibiotic use, drives dysbiosis and shapes the gut resistome.

Who was studied?

Participants included sixteen adults divided into four groups: healthy controls and individuals with CKD stages 3, 4, and 5. Each group contained four subjects. All CKD participants were classified based on estimated glomerular filtration rate (eGFR) criteria, and stage 5 subjects included individuals receiving renal replacement therapy. Participants with confounding gastrointestinal, inflammatory, malignant, or immune disorders were excluded to ensure that microbiome shifts reflected CKD pathophysiology rather than unrelated comorbidities. Stool samples—processed aerobically on YCFAm medium—served as the biological source for microbiological isolation, phenotyping, and genomic analyses. Clinical and anthropometric parameters were recorded, although the main analytic focus remained on microbial behavior and genetic signatures.

Most important findings

A central finding is that CKD3 subjects retained a broader range of metal(loid)-resistant bacteria, predominantly Firmicutes and Proteobacteria, mirroring patterns. These isolates frequently displayed co-resistance to antibiotics—including ampicillin, ciprofloxacin, cefazolin, gentamicin, and ceftazidime—especially when metal(loid)s were present at sublethal concentrations. Bacillus spp. and Pseudomonas spp. were consistently enriched, showing multidrug-resistant phenotypes under arsenic and lead exposure. Notably, qPCR revealed a progressive loss of resistance gene diversity across CKD stages. Stage 3 samples retained cadA2k, cadA3k, and arsC (metal resistance) and genes such as strB, floR, arr2, and acrB (antibiotic resistance), while stage 5 samples showed marked depletion, retaining only qnrB1, dhfr1, floR, merA, and cadA2k.

A representative summary of microbial–gene associations is shown below:

Key implications

Findings highlight a clinically relevant pattern: early CKD stages show greater microbial diversity and richer resistome profiles, while advanced stages display microbiome depletion and reduced genetic determinants of resistance. This suggests that declining renal function—and its metabolic consequences, including uremia and altered gut transit—compresses microbial diversity and selectively reduces gene carriage. The presence of cadA and arsC in CKD3 subjects supports their potential use as early-stage biomarkers of environmental metal exposure and gut dysbiosis severity. From a clinical standpoint, the co-selection of metal and antibiotic resistance underlines the need to consider environmental toxicants when evaluating antibiotic-resistant infections in CKD patients. These results support integrating resistome analysis into CKD microbiome assessment, particularly for detecting hidden environmental exposures that may influence disease trajectory.

Citation

Miranda MV, González FC, Paredes-Godoy OS, Maulén MA, Vásquez CC, Díaz-Vásquez WA. Characterization of metal(loid)s and antibiotic resistance in bacteria of human gut microbiota from chronic kidney disease subjects. Biological Research. 2022;55:23. doi:10.1186/s40659-022-00389-z