Abstract
BACKGROUND/OBJECTIVES: Diabetic nephropathy (DN) is a major complication of diabetes and a leading cause of end-stage renal disease, a condition associated with high mortality risks. Recently, supplementation with probiotics and postbiotics has been attracting attention. Especially, metabolites of natural products bioconverted by beneficial bacteria have emerged as a novel therapeutic intervention for metabolic diseases, including diabetes, due to the enhanced bioavailability of their metabolites. This study investigated the alleviating effects of metabolites derived from guava leaf extract bioconverted by Limosilactobacillus fermentum (GBL) on renal inflammation in type 2 diabetic mice. METHODS: For this purpose, diabetes was induced in male C57BL/6J mice by a high-fat diet and streptozotocin injection (80 mg/kg BW) twice. Subsequently, mice with fasting blood glucose levels higher than 300 mg/dL were administered metabolites of L. fermentum (LF) (50 mg/kg BW/day) or guava leaf extract bioconverted by L. fermentum (GBL) (50 mg/kg BW/day) by oral gavage for 15 weeks. RESULTS: GBL demonstrated potential in alleviating hyperglycemia-induced DN in diabetic mice. It markedly improved hyperglycemia, glucose tolerance, and morphological alterations, which might stem from activation of key regulators of energy metabolism. GBL uniquely reduced advanced glycation end products (AGEs) and suppressed nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-driven inflammatory pathways, which significantly alleviated oxidative stress and apoptosis. CONCLUSIONS: This highlights the distinct therapeutic efficacy of GBL in addressing DN, primarily through its effects on renal inflammation. Taken together, GBL can be used as a promising nutraceutical to mitigate hyperglycemia and its associated renal inflammation, thereby alleviating the progression of DN.