ILC dysregulation and gut microbiota dysbiosis may drive kidney disease via the microbiota-gut-kidney axisGut bacteria imbalance may drive kidney disease inflammation

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.