The mycotoxin deoxynivalenol affects nutrient absorption in human intestinal epithelial cells

Deoxynivalenol (DON) is a mycotoxin belonging to the tricothecene family that has many toxic effects in animals, including diarrhea and weight loss. Using the human epithelial intestinal cell line HT-29-D4 as an in vitro model, we studied the effect of DON on the uptake of different classes of nutrients, including sugars, amino acids and lipids. At low concentrations (below 10 mumol/L), DON selectively modulated the activities of intestinal transporters: the (D)-glucose/(D)-galactose sodium-dependent transporter (SGLT1) was strongly inhibited by the mycotoxin (50% inhibition at 10 mumol DON, P < 0.05), followed by the (D)-fructose transporter GLUT5 (42% inhibition at 10 mumol/L, P < 0.001), active and passive (L)-serine transporters (30 and 38% inhibition, respectively, at 10 mumol/L, P < 0.05). The passive transporters of (D)-glucose (GLUT) were slightly inhibited by DON (15% inhibition at 1 mumol/L, P < 0.01), whereas the transport of palmitate was increased by 35% at 10 mumol/L DON (P < 0.001). In contrast, the uptake of cholesterol was not affected by the mycotoxin. At high concentrations (100 mu mol/L), SGLT1 activity was inhibited by 76% (P < 0.01), whereas the activities of all other transporters were increased. The selective effects of DON on intestinal transporters were mimicked by cycloheximide and deoxycholate, suggesting that inhibition of protein synthesis and induction of apoptosis are the main mechanisms of DON toxicity in intestinal cells.