Neonatal diet composition modulates ileum mitochondrial function in a neonatal pig model

Abstract

BackgroundThe composition of postnatal diet (i.e., breastmilk vs. formula) has a strong influence on a variety of physiological outcomes in infants, but the impact on bioenergetics and mitochondrial function remains an open question. In a published study (1), early ingestion of dairy‐based infant formula vs. human breast milk differently modulated liver mitochondrial function and gut microbiota in rodents. However, the effects on bioenergetics in other tissues, including the gut, and the persistent effect after weaning remain unknown. In the current study we used a piglet model to determine the effects of these two milk types on bioenergetics phenotypes in the ileum.MethodsNeonatal piglets were fed isocaloric diets of either human breast milk (n=9) or a dairy‐based infant formula (n=9) from 48 hours post‐delivery until day 21, followed by an ad libitum solid diet until day 51. Subsequently, ileum biopsies were collected for evaluation of permeabilized cell mitochondrial function by high resolution respirometry, following a substrate and inhibitor protocol. In addition, gene expression for a key regulator of mitogenesis and mitochondrial function, peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1α) was assessed.ResultsATP‐linked respiration tended to be increased in the ileum of piglets fed a dairy‐based infant formula compared to those fed with human breast milk, even at 4 weeks of post‐weaning neonatal diet (10.4 +/− 2.2 vs. 5.8 +/− 0.9 pmol·s−1·mg−1; p=0.07). Cytochrome c oxidase (COX) activity was significantly elevated in the formula compared to the human breast milk (23.3 +/− 4.8 vs. 9.9 +/− 1.8 pmol·s−1·mg−1; p=0.02). Thus, the substrate control ratio for succinate relative to COX was significantly lower in the dairy fed group (0.07 +/− 0.02 vs. 0.14 +/− 0.02; p=0.03). Interestingly, PGC‐1α gene expression tended to be elevated (2.3 fold, p=0.06) in ileum of formula‐fed piglets compared to those fed human breast milk.ConclusionWe conclude that different milk diets may have a sustained impact on ileum bioenergetics in neonatal piglets, even a month after discontinuation of the milk diets. Future efforts are needed to understand the implications of these novel findings on infant tissue function and whole‐body macronutrient metabolism.Support or Funding InformationFunded by USDA ARS Project 6026 51000 010 05S. FEDER and FEDER funds through the Operational Programme Competitiveness Factors ‐ COMPETE and UID/NEU/04539/2013.