Flavonoids Derived from Opuntia ficus-indica Fruit Alleviate Renal Injury in Diabetic Nephropathy Mice by Altering Gut Microbiota and Promoting the Production of SCFAs

Diabetic nephropathy (DN) represents a severe microvascular complication of diabetes mellitus with limited therapeutic options, many of which are accompanied by considerable adverse effects. <i>Opuntia ficus-indica</i> (OFI) fruit, rich in vitamins, dietary fiber, and fatty acids, contains numerous bioactive compounds, including phytosterols, polysaccharides, and flavonoids that demonstrate significant potential in diabetes management. The flavonoid fraction derived from OFI fruit (OFI-F) has exhibited pronounced anti-inflammatory, antioxidant, and gut microbiota modulatory properties. However, the efficacy of OFI-F in ameliorating DN and its underlying mechanisms remain inadequately elucidated. This investigation examined the therapeutic potential of OFI-F in DN and explored its mechanistic pathways. Our findings demonstrate that OFI-F administration significantly attenuated renal injury and intestinal barrier dysfunction in the DN murine model. OFI-F intervention resulted in multiple beneficial outcomes in DN mice, including the mitigation of weight loss, reduction in hyperglycemia, decrease in renal coefficient index, and the attenuation of renal injury. An analysis of gut microbiota composition revealed that OFI-F administration favorably modulated the intestinal microbial community by enhancing the abundance of beneficial bacteria while concomitantly reducing populations of potentially pathogenic bacteria. Additionally, OFI-F treatment promoted the production of short-chain fatty acids (SCFAs), which contributed substantially to renoprotection and inflammatory resolution. Antibiotic intervention studies further confirmed the indispensable role of gut microbiota in mediating the renoprotective effects of OFI-F. In conclusion, this study provides compelling evidence supporting the therapeutic potential of OFI-F in DN management through the concurrent modulation of gut microbiota and renal function, offering a promising nutraceutical approach for alleviating renal injury in DN.