Necrotising enterocolitis (NEC), short bowel syndrome (SBS) and intra-uterine growth restriction (IUGR) are three conditions associated with intestinal dysfunction in newborn infants, particularly those born preterm. Piglet (Sus scrofa) models have recently been developed for NEC, SBS and IUGR, and tissue proteomic analyses have identified unknown pathways and new prognostic disease markers. Intestinal heat shock proteins, iron metabolism proteins and proteins related to amino acid (e.g., arginine) and glucose metabolism are consistently affected by NEC progression and some of these proteins are also affected by SBS and IUGR. Parallel changes in some plasma and urinary proteins (e.g., haptoglobin, globulins, complement proteins, fatty acid binding proteins) may mirror the intestinal responses and pave the way to biomarker discovery. Explorative non-targeted proteomics provide ideas about the cellular pathways involved in intestinal adaptation during the critical neonatal period. Proteomics, combined with other -omics techniques, help to get a more holistic picture of intestinal adaptation during NEC, SBS and IUGR. Explorative -omics research methods also have limitations and cannot replace, but only supplement, classical hypothesis-driven research that investigate disease mechanisms using a single or few endpoints. This article is protected by copyright. All rights reserved.