Transcriptome analysis reveals persistent effects of neonatal diet on the ileum gene expression in porcine neonates

Abstract

Mechanism(s) underlying long-lasting effects of human breast milk (HBM) on gut development and immune function have not been investigated. To differentiate between HBM and formula diet’s persistent effect on gene expression of a small intestine, piglets (n=15/group) were fed either HBM or dairy-based formula (FM) from postnatal day 2 to 21, followed by a soy free pig wean diet until day 51. Relative to HBM-fed, FM-fed had heavier small intestine (436±15.3 vs 362±45 g, p<0.05) but no change in the length. Transcriptome analysis revealed that the identified genes associated with cytokines (4↑, 9↓; i.e. CXCL8↓), Wnt (2↑, 9↓; CDHR2↓), gonadotropin releasing hormone receptor (1↑, 10↓; PRLR↓), EGF receptor (1↑, 7↓; CBL↓), cadherin (7↓; FRK↓) and endothelins (7↓; PRKG2↓) signaling were differentially expressed (2–5 fold) in ileum (IL) of FM-fed relative to HBM-fed. Moreover, the genes involved in biological processes such as cellular (84↑, 138↓; 2–12 fold), metabolic (71↑, 104↓; 2–17 fold), immune (14↑, 27↓; 2–10 fold) and developmental (16↑, 40↓ genes; 2–6.8 fold) were differentially expressed in IL of FM-fed relative to HBM-fed. Genes associated with T- (BRAF) and B-cell (BRAF, ITPR3 and FRK) activation were also decreased in IL of FM-fed relative to HBM-fed. NK, B and T-reg cells populations were reduced in mesenteric lymph nodes of FM-fed relative to HBM-fed. In summary, the data suggest a persistent effect of FM and HBM diets on small intestine and diet-driven changes in specific pathways of a small intestine. HBM may regulate these pathways to favor the gut development and immune function. However, FM may not harmonize it well and thereby delay the physiological process. Microbiome role is being evaluated to understand a specific mechanism.