Abstract
Breastfeeding is associated with a variety of positive health outcomes in children and is recommended exclusively for the first 6 months of life; however, 50–70 % of infants in the US are formula-fed. To test the hypothesis that immune system development and function in neonates and infants are significantly influenced by diet, 2-day old piglets were fed soy or milk formula (n = 6/group/gender) until day 21 and compared to a sow-fed group (n = 6/gender). Histomorphometric analyses of ileum, jejunum and Peyer’s patches were carried out, to determine the inflammation status, mRNA and protein expression of pro-inflammatory, anti-inflammatory and growth-related chemokines and cytokines. In formula-fed animals, increases in ileum and jejunum villus height and crypt depth were observed in comparison to sow-fed animals (jejunum, p < 0.01 villus height, p < 0.04 crypt depth; ileum p < 0.001 villus height, p < 0.002 crypt depth). In formula-fed the lymphoid follicle size (p < 0.01) and germinal centers (p < 0.01) with in the Peyer’s patch were significantly decreased in comparison to sow-fed, indicating less immune education. In ileum, formula diet induced significant up-regulation of AMCFII, IL-8, IL-15, VEGFA, LIF, FASL, CXCL11, CCL4, CCL25 and down-regulation of IL-6, IL-9, IL-10, IL-27, IFNA4, CSF3, LOC100152038, and LOC100736831 at the transcript level. We have confirmed some of the mRNA data by measuring protein, and significant down-regulation of anti-inflammatory molecule IL-10 in comparison to sow-fed piglets was observed. To further determine the membrane protein expression in the ileum, VE-cadherin, occludin, and claudin-3, Western blot analyses were conducted. Sow fed piglets showed significantly more VE-Cadherin, which associated with levels of calcium, and putrescine measured. It is possible that differences in GI tract and immune development are related to shifts in the microbiome; notably, there were 5-fold higher amounts of Lactobacillaceae spp and 3 fold higher Clostridia spp in the sow fed group in comparison to milk formula-fed piglets, whereas in milk formula-fed pigs Enterobacteriaceae spp was 5-fold higher. In conclusion, formula diet alters GI morphology, microbial abundance, intestinal barrier protein VE-cadherin and anti-inflammatory molecule IL-10 expression. Further characterization of formula effects could lead to modification of infant formula to improve immune function, reduce inflammation and prevent conditions such as allergies and infections.
Highlights
Breastfeeding is associated with a variety of positive health outcomes in children and is recommended exclusively for the first 6 months of life; 50–70 % of infants in the US are formula-fed
Studies conducted in rats and guinea pigs demonstrated that early diet influences the development of the gastrointestinal (GI) tract mucosal epithelium, gut-associated lymphoid tissue (GALT), the microbiota acquired in early life, and the mucosal immune response and tolerance
It is suggested that components of neonatal diet dictate the microbiome composition and diversity, which could play a role in GI tract membrane protein expression and inflammation status and metabolic signaling
Summary
Breastfeeding is associated with a variety of positive health outcomes in children and is recommended exclusively for the first 6 months of life; 50–70 % of infants in the US are formula-fed. Several studies have indicated that formula feeding has a negative impact on immediate and long-term health of children [3,4,5,6], suggesting that the complex mixture of nutrients and bioactive components in breast milk have a beneficial impact on health and disease outcomes. Many of these studies have noted increased gastrointestinal (GI) and/or upper respiratory infections, and prevalence of ear infections in formula fed infants [3,4,5,6], yet few have identified a pathophysiological basis for these outcomes. Given the widespread use of infant formulas and the effects of these formulas on development and function of the GI tract, it is imperative to develop a better understanding of the implication for the short- and long-term health consequences in children
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