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Gastrointestinal (GI) disturbances cause significant economic losses in the swine industry. Dietary-based approaches have been well applied to control the inflammation and optimize microbial colonization of the GI tract. This study aimed to screen differentially expressed (DE) RNAs in piglets supplied with arachidonic acid (ARA) or prebiotics in an acute dextran sodium sulfate (DSS) colitis model. Suckling pigs (n= 48) from 6 litters were randomly assigned into 4 diet groups: 0.5% ARA, 0.5% ARA+ PRE (4g/L galactooligosaccharide+ 4 g/L polydextrose), 2.5% ARA, and 2.5% ARA+ PRE. On day 17–21, half of the pigs (n= 24) were treated with 0.625 g DSS/kg BW to induce colitis. RNA samples (n= 48) were isolated from the mucosal layer of GI tract on day 22 for the gene expression analysis via RNAseq. The GLIMMIX procedure of SAS (v. 9.4) was used to fit the statistical models to gene counts, were the main …