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Research Article Volume 17 Issue 2
The enteric microbiota-kidney axis: a novel paradigm in the management of Hepatorenal syndrome
Mega Obukohwo OYOVWI, , Eseroghene Cecilia ADEGOR, Ejayeta JEROH, Rotu Arientare RUME, Odomero Thomas OLOMO, Aisuodionoe Eromosele Michael, Onose ALUYA
Received: June 01, 2026 | Published: July 14, 2026
Citation: OYOVWI MO, ADEGOR EC, JEROH E,et al. The enteric microbiota-kidney axis: a novel paradigm in the management of Hepatorenal syndrome. Gastroenterol Hepatol Open Access. 2026;17(2):47-53. DOI: 10.15406/ghoa.2026.17.00635
Abstract
Background: Hepatorenal syndrome (HRS) in cirrhosis carries high mortality, yet vasoconstrictor-based therapy remains incompletely effective. Evidence from clinical and preclinical studies indicates that gut-derived uremic toxins may directly contribute to renal injury, potentially through mechanisms beyond hemodynamic changes.
Aim: This review examines the “Enteric Microbiota-Kidney Axis” as a conceptual framework for understanding renal dysfunction in cirrhosis and evaluates the evidence supporting this paradigm.
Methods: A narrative synthesis of literature from PubMed, Scopus, and Web of Science (2015–2025) was performed, focusing on gut microbiota alterations, uremic toxin production, renal injury mechanisms, and therapeutic interventions in cirrhosis.
Results: Cirrhotic dysbiosis is characterized by depletion of butyrate-producing genera (Roseburia, Faecalibacterium, Coprococcus) and enrichment of urease-positive Proteobacteria (Escherichia-Shigella, Klebsiella). These compositional shifts may drive overproduction of indoxyl sulfate (IS) and p-cresyl sulfate (PCS). The mechanisms by which IS induces oxidative stress involve binding to the aryl hydrocarbon receptor (AhR) in proximal tubular epithelial cells, leading to downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), increased NADPH oxidase 4 (NOX4)-induced reactive oxygen species production, and activation of inflammatory transcription factors. Clinical cohort studies have suggested that elevated serum IS may predict HRS development, though these findings require validation. Randomized controlled trials in chronic kidney disease patients have demonstrated that synbiotic administration may stabilize renal function and that AST-120 reduces serum indoxyl sulfate levels, but these findings have not been confirmed in cirrhotic populations. Preclinical studies of phage therapy have shown efficacy against carbapenem-resistant Klebsiella pneumoniae in infection models, though direct relevance to HRS remains uncertain.
Conclusion: The enteric microbiota-kidney axis represents a testable conceptual framework for understanding hepatorenal syndrome, but current evidence is largely hypothesis-generating. High-quality randomized controlled trials in cirrhotic populations are needed before microbiome-directed therapies can be recommended for HRS management.
Keywords: Gut-kidney axis; hepatorenal syndrome; dysbiosis; indoxyl sulfate; p-cresyl sulfate; synbiotics; cirrhosis
©2026 OYOVWI, et al. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.
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