A low-protein calorie-restricted diet mitigates kidney injury in diabetic mice by modulating the gut-kidney axis
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Background: Dietary interventions are a promising strategy for restoring microbial balance in chronic kidney disease. Research indicates that a low-protein calorie-restricted (LPCR) diet can reduce renal injury in diabetic rodents. However, it is unclear whether the beneficial effects of LPCR diet in mice with diabetic kidney disease (DKD) are mediated through the modulation of the gut microbiota. Methods: A mouse model of diabetes was established using high-fat diet combined with streptozotocin injection. Diabetic mice were randomly divided into four groups: normal protein (NP, 20% protein), caloric restriction (CR, 30% restriction), low protein (LP, 13% protein), and LPCR (13% protein, 30% restriction). After five weeks of intervention, blood and urine samples were collected for relevant analyses, faecal samples for gut microbiota analysis, and kidney tissues for histological and immunohistochemical assays,as well as Western blot analysis. Results: LPCR diet significantly improved fasting blood glucose levels and lipid profiles ( p < 0.01) and mitigated kidney damage in diabetic mice. Additionally, LPCR diet ameliorated gut microbiota dysbiosis, significantly suppressing the increase in Firmicutes/Bacteroidetes ratio ( p < 0.05) and decreasing serum trimethylamine oxide(TMAO) levels ( p < 0.01). Compared to the NP group, the LPCR group exhibited significant reductions in serum TNF-α levels and the expression of ASC, NLRP3, and IL-1β in kidney tissue ( p < 0.01). Conclusion: LPCR diet exerts renoprotective effects in mice with DKD, possibly by modulating the gut-kidney axis to reduce circulating TMAO levels, thereby inhibiting NLRP3 inflammasome activation in kidney tissue.