Weaning comprises a challenging period for pigs, but dietary tools can be implemented to avoid excess antibiotics usage. Therefore, we tested the effect of a 17.6% crude protein (CP) diet on growth and diarrhoea and investigated the effect of a 15.5% CP diet post-weaning on tran-scriptomic responses, growth, and diarrhoea-related antibiotic treatments. At weaning, pigs were divided into five dietary treatment groups in a three-phase diet from weaning to 30 kg bodyweight. The diets included a positive control group (PC) with medicinal zinc oxide, a negative control group (NC), a 17.6% CP diet based on soy protein concentrate (SP), a 17.6% CP diet based on soybean meal (SB), and a 15.5% CP diet with additional amino acids (XLA). Growth performance and the occurrence of diarrhoea were similar between the SP and SB groups. The XLA pigs had a reduced weight gain and fewer antibiotics treatments caused by diarrhoea, as well as a reduced level of blood proteins. Intestinal tissue samples from the XLA pigs displayed decreased expression of genes involved in nutrient metabolism and immune responses relative to the PC group. In conclusion, a very low CP diet reduces antibiotics treatments, but also adapts gut nutrient metabolism and reduces growth performance.