ILC dysregulation and gut microbiota dysbiosis may drive kidney disease via the microbiota-gut-kidney axis

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Frontiers in Medicine Published June 2, 2026 Medically reviewed June 2, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider targeting gut microbiota-ILC interaction for future kidney disease therapies

This narrative review examines the potential link between immune cell dysregulation and chronic kidney disease. The authors propose that ILC dysregulation represents a novel immune mechanism underpinning microbiota-gut-kidney axis dysfunction. They highlight gut microbiota dysbiosis, gut-derived metabolic signals, and uremic toxins such as indoxyl sulfate and kynurenine as relevant factors in this context.

The review notes that the specific immune mechanisms connecting alterations in the gut milieu to renal inflammation remain poorly defined. Consequently, the evidence is currently limited by a lack of clarity on these biological pathways. The authors do not report specific adverse events or sample sizes as this is a conceptual synthesis rather than a primary trial.

Practice relevance is directed toward future research directions. The authors recommend focusing on developing novel therapeutic strategies that target the gut microbiota-ILC interaction. Potential approaches mentioned include dietary interventions, probiotics, or immunomodulators for the treatment of kidney diseases. Clinicians should interpret these findings as hypotheses requiring further validation before clinical application.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedJun 2026

View Original Abstract ↓

BackgroundThe progression of chronic kidney disease (CKD) is closely linked to gut microbiota dysbiosis and the consequent accumulation of harmful microbial metabolites, forming a vicious cycle called “gut-kidney axis.” However, the specific immune mechanisms connecting these alterations in the gut milieu to renal inflammation remain poorly defined. Innate lymphoid cells (ILCs), with their tissue-resident nature, plasticity, and potential migratory capacity, are poised to be critical mediators in this process.ObjectiveThis review aims to systematically elucidate the mechanisms by which ILCs, in response to gut-derived metabolic signals, regulate kidney disease through the gut-kidney axis.MethodsWe synthesized evidence from both preclinical and clinical studies, with a focus on: ① the functions of distinct ILC subsets in kidney disease; ② the dual effects—detrimental or protective—of individual ILC subsets and their secreted factors on renal function and morphology; ③ experimental evidence linking ILC activity to the disruption of gut-kidney homeostasis.ConclusionWe propose that ILC dysregulation represents a novel immune mechanism underpinning “microbiota-gut-kidney axis” dysfunction. This review integrates existing evidence to formulate a central working model that positions the aryl hydrocarbon receptor (AHR) as a pivotal node connecting gut microbial metabolism to ILC-mediated immunity in the kidney. The trans-tissue migration of ILCs, their sensing of uremic toxins (e.g., indoxyl sulfate and kynurenine), and their synergy with adaptive immunity collectively contribute to renal injury. Future research should focus on developing novel therapeutic strategies that target the gut microbiota-ILC interaction—such as dietary interventions, probiotics, or immunomodulators—for the treatment of kidney diseases.