Feed efficiency is a trait of interest in pigs as it contributes to lowering the ecological and economical costs of pig production. A divergent genetic selection experiment from a Large White pig population was performed for 10 generations, leading to pig lines with relative low- (LRFI, more efficient) and high- (HRFI, less efficient) residual feed intake (RFI). The meals of pigs from the LRFI line are shorter and less frequent as compared to the HRFI line. We hypothesised that these differences in feeding behaviour could be related to differential sensing and absorption of nutrients in the intestine. We investigated the duodenum transcriptomic response and DNA methylation profile to short term feed intake in LRFI and HRFI lines (n=24). We identified 1,106 differentially expressed genes between the two lines, notably affecting pathways of the transmembrane transport activity and related to mitosis or chromosome separation. The LRFI line showed a greater transcriptomic response to feed intake, with 2,222 differentially expressed genes before and after a meal, as compared to 61 differentially expressed genes in the HRFI line. Feed intake affected genes from both anabolic and catabolic pathways in the pig duodenum, such as autophagy and rRNA production. We noted that several nutrient transporter genes were differentially expressed between lines and/or by short term feed intake. Duodenal DNA methylation profiles were not altered by feed intake. However differences in DNA methylation profiles could be identified between LRFI and HRFI. Altogether, our findings highlighted that the genetic selection for feed efficiency in pigs changed the transcriptome profiles of the duodenum, and notably its response to feed intake.