Gut Dysbiosis, Uremic Toxins, and NLRP3 Signaling in Chronic Kidney Disease: From Mechanistic Evidence to Clinical Biomarker Evaluation.

@article{donathmiklos2026dysbiosis,
  title = {{Gut Dysbiosis, Uremic Toxins, and NLRP3 Signaling in Chronic Kidney Disease: From Mechanistic Evidence to Clinical Biomarker Evaluation.}},
  author = {Imola Donath-Miklos and Oana Știrbu and Romana Olivia Popețiu and Adrian Silviu Crișan and Paula Alexandra Vulciu and Roxana Andra Coman and Cecilia Roberta Avram and Darius Radu Roman and Radmila-Anca Bugari and Dana Zdremțan and Maria Orodan and Luminița Pilat and Larisa Alexandra Rus and Cristina Georgiana Firu and Mihai Cătălin Roșu and Simona Maria Borta},
  journal = {Diagnostics (Basel, Switzerland)},
  year = {2026},
  month = sep,
  doi = {10.3390/diagnostics16193084},
  url = {https://europepmc.org/article/MED/42882239},
  note = {CC BY},
}

TY  - JOUR
TI  - Gut Dysbiosis, Uremic Toxins, and NLRP3 Signaling in Chronic Kidney Disease: From Mechanistic Evidence to Clinical Biomarker Evaluation.
AU  - Imola Donath-Miklos
AU  - Oana Știrbu
AU  - Romana Olivia Popețiu
AU  - Adrian Silviu Crișan
AU  - Paula Alexandra Vulciu
AU  - Roxana Andra Coman
AU  - Cecilia Roberta Avram
AU  - Darius Radu Roman
AU  - Radmila-Anca Bugari
AU  - Dana Zdremțan
AU  - Maria Orodan
AU  - Luminița Pilat
AU  - Larisa Alexandra Rus
AU  - Cristina Georgiana Firu
AU  - Mihai Cătălin Roșu
AU  - Simona Maria Borta
PY  - 2026
DA  - 2026/09/23
JO  - Diagnostics (Basel, Switzerland)
DO  - 10.3390/diagnostics16193084
UR  - https://europepmc.org/article/MED/42882239
AB  - Chronic kidney disease (CKD) is associated with intestinal dysbiosis, barrier dysfunction, uremic toxin accumulation, and systemic inflammation. This narrative review critically evaluates the gut-kidney axis, focusing on the distinction between NLRP3 [Nucleotide-binding Oligomerization Domain (NOD)-like receptor pyrin domain-containing protein 3] inflammasome priming and direct activation. It also examines the diagnostic and prognostic relevance of related biomarkers. Preclinical studies, clinical investigations, systematic reviews, meta-analyses, and relevant clinical trials within the past decade were considered. CKD-associated barrier dysfunction increases exposure to lipopolysaccharides and gut-derived metabolites. Lipopolysaccharide (LPS)-mediated TLR4/NF-κB (Toll-like receptor 4/nuclear factor kappa B) signaling provides well-supported inflammasome priming. Indoxyl sulfate acts predominantly as a priming stimulus, although its effects vary among cell types. Direct NLRP3 activation by p-cresyl sulfate has not been demonstrated. Trimethylamine N-oxide has the strongest experimental evidence for inflammasome activation. Candidate biomarkers include these metabolites, microbial profiles, intestinal permeability markers, and inflammasome-related mediators. However, their interpretation is limited by dependence on renal clearance, assay heterogeneity, absent standardized thresholds, and uncertain added value beyond estimated glomerular filtration rate and urinary albumin-to-creatinine ratio. Interventional studies remain small and predominantly use surrogate endpoints. The gut-toxin-inflammasome axis is mechanistically plausible, but evidence for priming is substantially stronger than that for direct activation. Its biomarkers remain research tools and require assay harmonization, prospective validation, and demonstration of independent clinical value before routine implementation.
SN  - 2075-4418
ER  -