Abstract
BACKGROUND Alterations in gut homeostasis may contribute to the progression of diabetic nephropathy (DN). Resistant starch (RS) is a prebiotic fibre that promotes the production of butyrate by the gut microbiota. Butyrate acts as a ligand for G-protein-coupled-receptor (GPR)190a, decreasing intestinal inflammation and promoting gut epithelial barrier integrity in induced-colitis models. This study aimed to assess the effects of: (i) a diet supplemented with the physiological concentration of 12.5% RS and (ii) GPR109a deletion on the progression of DN.
METHODS Male mice that were homozygous for GPR109a deletion or their wildtype littermates were rendered diabetic with streptozotocin. Mice received either a control diet or an isocaloric diet containing 12.5% RS for 24 weeks. Renal injury was assessed by urine albumin and renal histology. Ileum histology was evaluated and gastrointestinal permeability was determined in vivo using the FITC-dextran test and ex vivo by expression of ileum tight junction proteins.
RESULTS Diabetes was associated with increased albuminuria, blood urea nitrogen, glomerulosclerosis index scores and urinary MCP-1, none of which were altered with RS supplementation or GPR109a deletion. Whilst diabetes was associated with alterations in intestinal morphology, intestinal permeability was unaltered and RS supplementation had no effect on intestinal permeability nor morphology. GPR109a deletion did not worsen DN or alter gastrointestinal homeostasis.
CONCLUSIONS Twenty-four weeks of supplementation of 12.5% RS does not protect against the development of DN in the STZ-induced diabetic mouse model. Further, GPR109a does not appear to play a critical role in intestinal homeostasis or in the development of DN.