Abstract This study evaluated the effects of replacing dietary glucose with fructose on intestinal development in weaned pigs and assessed epithelial growth using a small intestinal organoid model. A total of 26 weaned pigs (Yorkshire × Landrace × Duroc, 21 days old) were randomly assigned to three groups: a control group (10 pigs, 3% glucose), a low-fructose (LF) group (8 pigs, 1.5% glucose + 1.5% fructose), and a high-fructose (HF) group (8 pigs, 3% fructose), with one pig per pen. The experimental period lasted 28 days, including a dietary transition on day 15. Results showed that dietary fructose did not affect growth performance (P 0.10). Fecal scores were not significantly different among treatments (0.05 P 0.1), although numerically lower values were observed in the LF group. The HF group had a greater relative length of the large intestine than the LF group (P 0.05), whereas the LF group showed reduced kidney weight (P 0.001). Regarding intestinal morphology, dietary fructose tended to reduce duodenal crypt depth and ileal villus height (0.05 P 0.1). Ileal malondialdehyde (MDA) levels were affected by dietary treatment (P 0.05), whereas digestive enzyme activities were not altered (P 0.10). At the molecular level, fructose significantly downregulated genes involved in carbohydrate metabolism (FBP1, FBP2, LDHA, PKM) and glucose transport (GLUT2) (P 0.05). Stem cell–associated genes (LGR5 and BMI1) and tight junction–related genes (OCLN and CLDN1) were significantly downregulated (P 0.05), whereas Ki67 expression was not significantly affected (P 0.10). In organoid cultures, fructose concentrations did not affect budding efficiency (P 0.10), but significantly affected the number of buds per organoid (P 0.05), with higher values observed at 1 mM and 5 mM. Overall, replacing dietary glucose with fructose did not impair growth performance, but altered oxidative status, epithelial-related gene expression, and intestinal epithelial responses in weaned pigs. These findings indicate that intestinal responses are sensitive to dietary monosaccharide composition under practical feeding conditions.
Wang et al. (2026) studied this question.