Fruit and Vegetable Supplemented-Diet Ameliorates Dextran Sodium Sulfate (DSS)-Induced Colitis by Modulating Host Transcriptome and Gut Metagenome Response

<b>Background/Objectives</b>: Dietary intake of fruits and vegetables (FVs) has been inversely associated with a lower risk of ulcerative colitis. Using a pig model, we evaluated the effect of FV supplementation on dextran sulfate sodium (DSS)-induced colitis. <b>Methods</b>: Six-week-old pigs were fed a grower diet (negative control), grower diet + 4% DSS (positive control), half-FV diet + DSS, or full-FV diet + DSS. FV levels matched half or full daily recommendations from the Dietary Guidelines for Americans (DGA). Clinical signs were monitored; proximal colon contents (PCs) and mucosa (PCM) were analyzed for metagenome, transcriptome and histopathology. <b>Results</b>: Full-FV pigs showed no diarrhea, less fecal occult blood (FOB), crypt hyperplasia, but no changes in gene expression or microbiome diversity (<i>p</i> < 0.05). Half-FV pigs had increased FOB, differentially expressed genes (DEGs) linked to tissue remodeling, crypt/goblet cell hyperplasia and two cases of diarrhea (<i>p</i> < 0.05). DSS controls showed reduced immune-related DEGs, altered microbiome, PCM erosion, FOB, and persistent diarrhea in one pig (<i>p</i> < 0.05). <b>Conclusions</b>: A three-week full-FV diet conferred protection against DSS-induced colitis, with a dose-dependent protection of intestinal tissue and gut metagenome under inflammatory challenge.