Exploring the Therapeutic Potential of Fermented Apple Juice and Sidr Leaves Powder on Gut Microbiota Modulation and Neuropathy Relief in Diabetic Rats

Diabetes and its complications, particularly diabetic neuropathy, represent major health risks. This study investigated the potential of natural nutrients and bioactive compounds specifically fresh and fermented apple juice and sidr leaf powder to improve gut microbiota and alleviate neuropathy in diabetic rats. Seventy adult male Sprague–Dawley rats (180 ± 20 g) were assigned to six groups (11 rats each), while the diabetic control group (15 rats). Diabetes was induced by feeding a high-sucrose, high-fat (HSHF) diet and administering streptozotocin (45 mg/kg, intraperitoneally) during the 4th week. The groups included: healthy control; diabetic control; diabetic rats receiving fresh or fermented apple juice (2 ml/kg body weight/day); rats fed an HSHF diet containing 5% sidr leaf powder; and rats receiving both sidr powder and fermented apple juice. Supplementation with fresh or fermented apple juice, sidr leaves, or their combination significantly improved (P ≤ 0.05) neurological responses, blood glucose, serum insulin, inflammatory markers, oxidative stress indicators, brain-derived neurotrophic factor levels, apoptotic markers, fecal microbiota composition, short-chain fatty acid production, and the balance of Firmicutes and Bacteroidetes. These treatments also enhanced brain nerve growth factor gene expression. The beneficial effects are attributed to the high nutritional and bioactive profiles of apple juice and sidr leaves, with fermentation further increasing the biological activity and bioavailability of active constituents. Notably, the combination of sidr powder and fermented apple juice produced the greatest improvement across all measured parameters.