Virgin Coconut Oil Attenuates Diabetic Kidney Disease via Gut Microbiota‐Metabolism‐Inflammation Axis Modulation in Type 2 Diabetic Mice

Diabetic kidney disease (DKD) poses a significant global health challenge, necessitating novel therapeutic interventions. Virgin coconut oil (CO), rich in medium‐chain fatty acids (MCFAs), has emerging metabolic benefits, but its renoprotective potential and mechanistic basis remain unexplored. This study aimed to investigate the therapeutic effects of CO on DKD and elucidate its underlying molecular mechanisms through a multimodal approach. Network pharmacology and molecular docking were employed to predict CO's bioactive targets and pathways. Experimental validation was performed in a high‐fat diet/streptozotocin‐induced type 2 diabetic mouse model, with CO administered for 12 weeks. Systemic metabolic parameters (glucose, BUN, Scr, lipid profiles) and renal function were evaluated. Renal histopathology (H&E, Masson staining), inflammatory markers (TNF‐α, IL‐6), oxidative stress indicators (GSH‐Px, SOD, MDA), and fibrosis markers (TGF‐β, Collagen IV) were quantified. Gut microbiota composition (16S rRNA sequencing) and serum metabolomic profiling (LC–MS) were analyzed to identify systemic mechanisms. Computational analysis identified octanoic acid and decanoic acid of MCFAs as principal bioactive components targeting PPARα/γ and IL‐1β, modulating PPAR signaling and oxidative phosphorylation. In vivo, CO significantly ameliorated hyperglycemia, reduced uremic toxins, and improved lipid metabolism. Renal benefits included attenuated inflammation, restored redox balance, and suppressed fibrosis. Gut microbiota restructuring revealed decreased pro‐inflammatory Enterococcus and enriched probiotic Lactobacillus . Metabolomics identified CO‐mediated regulation of arachidonic acid metabolism and riboflavin pathways. Our findings demonstrate that CO exerts comprehensive renoprotection through a novel “gut microbiota‐metabolism‐inflammation” axis, suggesting its potential as a dietary intervention for DKD. These mechanistic insights warrant further clinical investigation of CO's therapeutic applications in diabetic complications.