Formula Diet Alters the Ileal Metagenome and Transcriptome at Weaning and during the Postweaning Period in a Porcine Model.

Abstract

Exclusive breastfeeding impacts the intestinal microbiome and is associated with a better immune function than is seen with milk formula (MF) feeding in infants and yet with mechanisms poorly defined. The porcine model was used to evaluate the impact of MF on ileum microbial communities and gene expression relative to human milk (HM)-fed piglets. Fifty-two Dutch Landrace male piglets were fed an isocaloric diet of either HM (n = 26) or MF (n = 26) from day 2 through day 21 of age and weaned to a solid diet until day 51. Eleven piglets from each group were euthanized at day 21, while the remaining piglets (HM, n = 15; MF, n = 15) were euthanized at day 51 to collect ileal epithelium (EP) scrapings and ileal (IL) tissues. The epithelial mucosa was subjected to shotgun metagenome sequencing, and EP and IL tissues were used for transcriptome analysis. On day 21, transcriptome data revealed that the levels of pathways involved in inflammation and apoptosis were significantly higher in MF piglets than in HM piglets, whereas the levels of tight junctions and pathogen detection systems were lower in MF piglets than in HM piglets. The MF impacts on the small intestine were maintained over the postweaning period (day 51) as indicated by higher levels of Dialister invisus bacteria and higher levels of expression of genes associated with inflammation and apoptosis pathways relative to HM group. The current study demonstrated that MF might impact local intestinal inflammation, apoptosis, and tight junctions and might suppress pathogen recognition in the small intestine compared with HM.IMPORTANCE Exclusive human milk (HM) breastfeeding for the first 6 months of age in infants is recommended to improve health outcomes during early life and beyond. When women are unable to provide sufficient HM, milk formula (MF) is often recommended as a complementary or alternative source of nutrition. Previous studies in piglets demonstrated that MF alters the gut microbiome and induces inflammatory cytokine production. The links between MF feeding, gut microbiome, and inflammation status are unclear due to challenges associated with the collection of intestinal samples from human infants. The current report provides the first insight into MF-microbiome-inflammation connections in the small intestine compared with HM feeding using a porcine model. The present results showed that, compared with HM, MF might impact immune function through the induction of ileal inflammation, apoptosis, and tight junction disruptions and likely compromised immune defense against pathogen detection in the small intestine relative to piglets that were fed HM.