The pig whipworm Trichuris suis is important in swine production because of its negative effects on pig performance and, notably, to some humans with inflammatory bowel disease as a therapeutic agent that modulates inflammation. The proximal colon of T. suis-infected pigs exhibited general inflammation around day 21 after inoculation with infective eggs that is transcriptionally characterized by markers of type-2 immune activation, inflammation, cellular infiltration, tissue repair enzymes, pathways of oxidative stress, and altered intestinal barrier function. Prominent gene pathways involved the Th2-response, de novo cholesterol synthesis, fructose and glucose metabolism, basic amino acid metabolism, and bile acid transport. Upstream regulatory factor analysis implicated the bile acid/farnesoid X receptor in some of these processes. Metabolic analysis indicated changes in fatty acids, antioxidant capacity, biochemicals related to methylation, protein glycosylation, extracellular matrix structure, sugars, Krebs cycle intermediates, microbe-derived metabolites and altered metabolite transport. Close to 1,200 differentially expressed genes were modulated in the proximal colon of pigs with a persistent adult worm infection that was nearly 90% lower in pigs that had expelled worms. The results support a model to test diets that favorably alter the microbiome and improve host intestinal health in both pigs and humans exposed to Trichuris.