Resistant Starch Ameliorates Heat Treated Diet-Induced Gut Permeability and Renal Dysfunction in Experimental Diabetes

Abstract:

Background/Aims: Heat treating foods leads to the formation of advanced glycation endproducts (AGEs) which contribute to chronic renal injury. Recent research implicates gut dysbiosis in the progression of diabetic nephropathy. This study investigates whether excess consumption of dietary AGEs causes gut dysbiosis, exacerbating renal injury in a type 2 diabetes mouse model. Methods: Six week old diabetic (db/db) and non-diabetic (db/h) mice were randomised (n=12/group) to receive a low AGE (LAGE, unbaked rodent chow) or a high AGE diet (HAGE, baked at 160°C for 1 hour), with or without resistant starch (RS) for 10 weeks. 24-hour urine was collected and albuminuria was measured. Intestinal permeability was assessed in vivo by the clearance of FITC-labelled dextran (500mg/kg body weight). Statistical differences were assessed by one-way ANOVA. Results: The high AGE diet exacerbated albuminuria in db/db mice (874.4±154.8 vs 536.2±96.5µg/24h, P<0.05, db/db HAGE vs db/db LAGE), and RS attenuated this AGE-induced increase (874.4±154.8 vs 515.5±71.9µg/24h, P<0.05, db/db HAGE vs db/db HAGE+RS). Db/db mice had greater gut permeability compared to db/h mice (2.38±0.32 vs 1.05±0.11µg/ml, P<0.01, db/db LAGE vs db/h LAGE). Db/db-HAGE-fed mice trended towards increased gut permeability (3.43±0.43 vs 2.38±0.32µg/ml, P=0.06, db/db HAGE vs db/db LAGE), an effect not observed in RS-fed db/db mice. Conclusions: Heat-treated diets led to increased intestinal permeability and worsening albuminuria in db/db mice. RS was protective against high AGE-induced albuminuria in db/db mice. These preliminary studies support the notion that dietary AGEs contribute to renal disease via alterations in gut homeostasis.