Fructose enhances intestinal development and barrier function while driving hepatic lipogenesis and inflammation in broilers.

To test the effects of fructose on the intestinal health, nutrient metabolism, and production performance of broilers, both in vitro and in vivo studies were conducted. In vitro, treatment with 5 mM fructose increased the size of intestinal organoids from broilers (P < 0.05). For in vivo trial, 96 one-day-old male AA broilers with similar body weights were randomly divided into 2 treatment groups (control and fructose) with 6 replicates of 8 birds each. All birds received the same commercial diet, with the control group receiving tap water and the fructose group receiving 1 % fructose in water for 42 days. Fructose supplementation had no effects on body weight, feed intake or FCR throughout the trial (P > 0.05). It increased the dressed percentage of the broilers (P < 0.05), without affecting other carcass characteristics or abdominal fat index. Apparent digestibility of dietary crude fat was reduced by fructose (P < 0.05), while crude protein digestibility remained unchanged (P > 0.05). However, fructose enhanced hepatic lipids synthesis, as evidenced by upregulated expression of ACC1 and Srebf1 (P < 0.05) and suppressed fatty acids oxidation through reduced CPT1 expression and lower serum palmitoylcarnitine levels (P < 0.05). Liver inflammation was also increased, indicated by elevated expression of IL-1β and higher serum concentrations of pro-inflammatory mediators such as 5-HETE (P < 0.05). Fructose improved intestinal morphology, including increased villus height to crypt depth ratio and lengthening of the duodenum and ileum (P < 0.05). Tight junction gene expression was also upregulated, indicating enhanced barrier integrity. Fructose influenced the intestinal microbiota and serum metabolites of broilers. Gut microbiota composition was altered by fructose, as shown by significant differences in microbial structure (ANOSIM, P < 0.05). Fructose reduced the relative abundance of Firmicutes while increasing Bacteroidota, resulting in a lower Firmicutes-to-Bacteroidota ratio (P < 0.05). Enrichment analysis showed fructose-associated bacteria were positively correlated with intestinal morphology, while control-associated taxa were linked to fat metabolism. Serum metabolomics analysis revealed distinct clustering between groups, with differentially abundant metabolites (VIP > 1, P < 0.05) enriched in lipid metabolic pathways. In conclusion, supplementation with 1% fructose via drinking water enhanced intestinal development and microbial composition in broilers without affecting growth performance. However, it reduced dietary fat digestibility and induced hepatic lipogenesis and inflammation. These findings suggest the need for further research to optimize its use for promoting gut health without compromising liver function or nutrient utilization.