Abstract
OBJECTIVE: Chronic unresolved inflammation is a core driver of diabetic kidney disease (DKD) progression, with gut microbiota dysbiosis and metabolite imbalance (via gut-kidney axis) as key pathogenic triggers. This review systematically elucidates the pathological link between gut microbiota-metabolite-axis dysfunction and DKD-related inflammation (centered on NF-κB/NLRP3 pathways) and summarizes multi-target intervention strategies-including traditional Chinese medicine (TCM), SGLT2 inhibitors, probiotics/prebiotics-targeting this axis. METHODS: Literature search was conducted on PubMed using keywords ["Gut microbiota" or "Gut microflora" or "Gut microbiota metabolites"], ["Diabetic kidney disease" or "Diabetic nephropathy" or "DKD"], ["immune regulation"], ["intestinal barrier"], [inflammation"], ["Traditional Chinese Medicine" or "TCM"], without date restrictions. Articles that do not meet the requirements are excluded. RESULTS: Gut microbiota dysbiosis in DKD is characterized by reduced SCFA-producing bacteria (Ruminococcaceae, Lachnospiraceae) and enriched pathogenic Proteobacteria, leading to metabolite imbalance: insufficient beneficial metabolites (SCFAs, IPA) and accumulation of harmful metabolites (TMAO, phenyl sulfate, BCAAs). This imbalance impairs intestinal barrier (ZO-1/Occludin downregulation), promotes endotoxin (LPS) translocation, and activates NF-κB (p65 phosphorylation) and NLRP3 inflammasome (NLRP3/ASC/caspase-1 complex), exacerbating renal inflammation via pro-inflammatory cytokines (IL-1β, TNF-α, IL-6). Intervention strategies (including TCM) suppress this cascade: TCM (eg, Astragalus membranaceus, Xiaoyaosan) reshapes microbiota, strengthens intestinal barrier, and inhibits NF-κB/NLRP3; SGLT2 inhibitors and probiotics/prebiotics complement via SCFA elevation and TMAO reduction. Clinically, these interventions lower UACR, improve eGFR, and correlate with reduced serum IL-1β/TNF-α. CONCLUSION: Gut microbiota-metabolite-intestinal barrier axis dysfunction is a pivotal pathological mechanism of DKD inflammation, mediated by NF-κB/NLRP3 pathways. Multi-pronged interventions targeting this axis effectively resolve inflammation, providing promising therapeutic approaches for DKD.