The nutrition–microbiota–gut–kidney axis in acute kidney injury: molecular mechanisms, candidate biomarkers, and investigational intervention strategies

Acute kidney injury (AKI) is a complex and heterogeneous clinical syndrome characterized by dynamic pathophysiological progression and high morbidity. Emerging evidence identifies the nutrition–microbiota–gut–kidney axis as a systemic and molecularly regulated network linking dietary inputs, microbial metabolism, intestinal barrier function, immune activation, and renal injury through metabolite-sensing receptors, inflammatory signaling pathways, and epithelial barrier regulators. In this context, gut microbiota-derived metabolites, including short-chain fatty acids, uremic toxins, bile acids, trimethylamine N-oxide, and indole-3-acetic acid, may act as mechanistic mediators and candidate biomarkers. This review synthesizes current evidence on the nutrition–microbiota–gut–kidney axis in AKI. We critically evaluate the directness of evidence across human AKI studies, experimental models, and indirect evidence from chronic kidney disease (CKD) and other disease settings, while distinguishing conventional nutritional management from microbiota-directed interventions. We also assess candidate biomarkers and the translational maturity of investigational microbiota- and metabolite-targeted strategies, with attention to acute injury, recovery, and AKI-to-CKD transition. Future biomarker-guided trial approaches are discussed, while computational decision-support methods are considered speculative directions requiring validation. The nutrition–microbiota–gut–kidney axis provides an integrative framework for understanding the mechanistic links among nutrition, microbial metabolism, intestinal dysfunction, and renal injury in AKI. Conventional nutritional management is an integral component of supportive care, whereas microbiota-guided nutritional strategies and microbiota- or metabolite-targeted interventions remain investigational and lack sufficient AKI-specific clinical evidence. Future translation will require prospective human studies, biomarker validation, stratified clinical trials, and rigorous safety assessment before these approaches can inform routine AKI management. The lower panels summarize microbiota-associated metabolic shifts linking homeostatic or dysbiotic gut communities with intestinal barrier function, systemic inflammation, renal recovery, and AKI-to-CKD transition. The upper panel presents a conceptual future translational framework in which longitudinal gut–kidney biomarkers may support patient stratification and the evaluation of investigational nutritional, microbiota-targeted, and metabolite-directed interventions. This framework is speculative and has not been clinically validated in AKI.