Opapeju, F. O., Rodriguez-Lecompte, J. C., Rademacher, M., Krause, D. O. and Nyachoti, C. M. 2015. Low crude protein diets modulate intestinal responses in weaned pigs challenged with Escherichia coli K88. Can. J. Anim. Sci. 95: 71-78. Effects of dietary crude protein (CP) content on intestinal indicators of infection and diarrhea in pigs challenged with enterotoxigenic Escherichia coli (ETEC) K88 were investigated. Forty piglets [body weight (BW)=6.96±0.45, mean±SD], housed four per pen, were randomly allotted to two diets (five pens per diet): a 22.2% CP or a 17.3% CP supplemented with amino acids. Diets contained the same amount of standardized ileal digestible Lys, Met Cys, Thr, Trp based on the ideal amino acid ratio. Isoleucine and Val were added to the 17.3% CP diet up to the level in the 22.2% CP diet. All other nutrients were as per National Research Council (1998) specification. Three piglets per pen were serially slaughtered on days 3, 5, and 7 after weaning for evaluation of intestinal hydrolases (data reported elsewhere). On day 8 post-weaning, the remaining pigs were inoculated with 6 mL of ETEC suspension (10¹⁰ CFU mL^-1) and slaughtered 20 h later. Mucosal-associated ETEC was detected in higher counts (3.17±0.63 log₁₀ CFU g^-1 digesta) in 80% of pigs fed the 22.2% CP diet compared with 20% of those fed the 17.3% CP diet in which the counts were also lower (2.00±log₁₀ CFU g^-1 digesta). Pigs fed the 22.2% CP diet tended (P=0.09) to have fewer goblet cells with sialomucins in jejunal villi compared with those fed the 17.3% CP diet. The expression of toll-like receptors 4 and 5 was unaffected by diet but the expression of sodium-coupled glucose transporter 1 was higher (P=0.04) in the jejunum of pigs fed the 22.2% CP diet compared with those fed the 17.3% CP diet. The results suggest that feeding a low-CP diet decreases ETEC proliferation and attachment in the intestinal mucosa and this is accompanied by a reduced expression of sodium-coupled glucose transporter 1.