Vitamin A Attenuates High-Fat High-Sugar Diet-Associated Intestinal and Hippocampal Alterations in Wistar Rats: Implications for Gut-Brain Axis Dysfunction

High-fat high-sugar diets (HFHSD) are associated with metabolic disturbances, intestinal and hippocampal alterations, inflammation, and oxidative stress, which may contribute to gut-brain axis dysfunction. This study evaluated the effects of vitamin A on metabolic, inflammatory, and oxidative stress parameters and intestinal and hippocampal alterations in Wistar rats exposed to an HFHSD. Sixty Wistar rats (80–120 g) were randomly assigned to six groups (n = 10). Groups A–C received standard chow, whereas Groups D–F received an HFHSD containing 30% vegetable oil and 25% sucrose for 28 days. Vitamin A (500 or 1000 IU/kg/day) was administered orally to Groups B and C, respectively, and co-administered with the HFHSD in Groups E and F. Behavioural and cognitive performance were assessed using the Open Field Test, Y-maze, and Novel Object Recognition test. Blood glucose, adiponectin, leptin, TNF-α, IL-6, IL-10, malondialdehyde (MDA), and total antioxidant capacity (TAC), and hippocampal and ileal histopathology were evaluated. HFHSD increased body weight gain, feed intake, TNF-α, IL-6, and MDA, while blood glucose was numerically higher but not significantly different from controls. Adiponectin, leptin, IL-10, and TAC were reduced, accompanied by impaired locomotor and exploratory activity, cognitive deficits, and intestinal and hippocampal histopathological alterations. Vitamin A attenuated metabolic, inflammatory, oxidative, behavioural, and histopathological alterations. The 500 IU/kg dose showed greater improvement in several behavioural and histological outcomes, whereas 1000 IU/kg produced stronger effects on antioxidant status and glycaemic regulation. These findings indicate dose-specific differences in the effects of vitamin A, although the optimal dose and underlying mechanisms remain to be established.