Gut Microbiota Dysbiosis and Metabolite Imbalance Mediate Diabetic Kidney Disease Inflammation: Mechanisms and Intervention Strategies Targeting Gut-Kidney Axis and NF-κB/NLRP3 Pathways

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. Keywords: inflammation, diabetic kidney disease, intestinal microecology, traditional Chinese medicine, immune function, bacterial communities