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ARS Home » Southeast Area » Little Rock, Arkansas » Microbiome and Metabolism Research Unit » Research » Publications at this Location » Publication #319594
Title: Formula diet alters small intestine morphology, microbial abundance and reduces VE-cadherin and IL-10 expression in neonatal porcine model

Author
item YERUVA, LAXMI - Arkansas Children'S Nutrition Research Center (ACNC)
item SPENCER, NICOLE - Arkansas Children'S Nutrition Research Center (ACNC)
item SARAF, MANISH - Arkansas Children'S Nutrition Research Center (ACNC)
item HENNINGS, LEAH - Arkansas Children'S Nutrition Research Center (ACNC)
item BOWLIN, ANNE - Arkansas Children'S Nutrition Research Center (ACNC)
item CLEVES, MARIO - Arkansas Children'S Nutrition Research Center (ACNC)
item MERCER, KELLY - Arkansas Children'S Nutrition Research Center (ACNC)
item CHINTAPPALLI, SREE - Arkansas Children'S Nutrition Research Center (ACNC)
item SHANKAR, KARTIK - Arkansas Children'S Nutrition Research Center (ACNC)
item RANK, ROGER - Arkansas Children'S Nutrition Research Center (ACNC)
item Badger, Thomas
item RONIS, MARTIN - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: BioMed Central (BMC) Gastroenterology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/15/2016
Publication Date: 3/22/2016
Citation: Yeruva, L., Spencer, N.E., Saraf, M.K., Hennings, L., Bowlin, A.K., Cleves, M., Mercer, K., Chintappalli, S.V., Shankar, K., Rank, R., Badger, T.M., Ronis, M.J. 2016. Formula diet alters small intestine morphology, microbial abundance and reduces VE-cadherin and IL-10 expression in neonatal porcine model. BioMed Central (BMC) Gastroenterology. 16:40. doi: 10.1186/s12876-016-0456-x.

Interpretive Summary: Our research is focused on understanding whether breast-fed children have any advantage in terms of gut development, immune function and also programming of growth and body composition. It has been suggested that breast-fed infants have advanced immune system development compared to formula-fed infants. It is well known that dietary factors in breast-milk and formulas can alter gut microbiota composition. However, does microbiota alone shape gut development and subsequent immune function in infants? And do breast-fed children have better immune responses to infections? In order to understand and address these questions ACNC had developed a piglet model of infant formula feeding. Preliminary data had demonstrated that gastrointestinal (GI) development and gut associated lymphoid tissue is highly developed in breast milk fed piglets in comparison to formula fed piglets. Formula diet induces pro-inflammatory signature in the GI tract. The differential effects of early diet on GI tract development and function are only partially characterized, and the long term health consequences and the mechanisms by which these occur are under investigation.

Technical 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 sowfed 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 proinflammatory, 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. 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.