Bovine Osteopontin Modifies the Intestinal Transcriptome of Formula-Fed Infant Rhesus Monkeys to Be More Similar to Those That Were Breastfed

Abstract

Background: Osteopontin (OPN) is a multifunctional protein found in human milk at high concentration.Objective: The impact of supplemental bovine OPN on growth, body composition, and the jejunal transcriptome was assessed.Methods: Newborn rhesus monkeys were randomly assigned to be breastfed (n = 4) or to receive formula [formula fed (FF), n = 6] or formula supplemented with 125 mg/L of bovine OPN (bOPN, n = 6) for 3 mo. Jejunal mRNA was extracted and subjected to microarray analysis.Results: Growth was similar among all the treatment groups, but breastfed monkeys were ∼25% leaner at 3 mo. Pairwise comparisons demonstrated that 1017 genes were differentially expressed between breastfed and FF groups, 217 between breastfed and bOPN groups, and 119 between FF and bOPN groups. The data were also analyzed with the use of weighted gene coexpression network analysis, which revealed 6 modules of coexpressed genes that differed among the 3 treatments. Nearly 50% of genes were assigned to one module in which breastfed differed from FF and bOPN expression was intermediate. This module was enriched for genes related to cell adhesion and motility, cytoskeletal remodeling, wingless and integration site signaling, and neuronal development. Most of these canonical pathways centered on integrins, which are receptors for OPN.Conclusions: The intestinal transcriptome of breastfed and FF monkeys differs, but bovine OPN at levels similar to human milk shifts gene expression profiles to be more similar to breastfed monkeys.