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Research Project: Impact of Maternal Influence and Early Dietary Factors on Child Growth, Development, and Metabolic Health

Location: Arkansas Children's Nutrition Center

Title: Neonatal diet impacts the large intestine luminal metabolome at weaning and post-weaning in piglets fed formula or human milk

Author
item ROSA, FERNANDA - University Arkansas For Medical Sciences (UAMS)
item MATAZEL, KATELIN - Arkansas Children'S Nutrition Research Center (ACNC)
item BOWLIN, ANNE - University Arkansas For Medical Sciences (UAMS)
item WILLIAMS, KEITH - University Arkansas For Medical Sciences (UAMS)
item ELOLIMY, AHMED - University Arkansas For Medical Sciences (UAMS)
item Ferruzzi, Mario
item BODE, LARS - University Of California, San Diego
item YERUVA, LAXMI - University Arkansas For Medical Sciences (UAMS)

Submitted to: Frontiers in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/5/2020
Publication Date: 12/7/2020
Citation: Rosa, F., Matazel, K.S., Bowlin, A.K., Williams, K.D., Elolimy, A.A., Adams, S.H., Bode, L., Yeruva, L. 2020. Neonatal diet impacts the large intestine luminal metabolome at weaning and post-weaning in piglets fed formula or human milk. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2020.607609.
DOI: https://doi.org/10.3389/fimmu.2020.607609

Interpretive Summary: Exclusive breastfeeding is recommended to newborns during the first 6 months of life by the World Health Organization and American Academy of Pediatrics, however dairy-based infant formula is recommended as an alternative nutrition source to human milk. It has been shown that breastfeeding reduces the mortality rate in preterm babies and decreases the incidence of infections including respiratory tract infections and necrotizing enterocolitis in full term babies. Additionally, studies demonstrated the different gut microbiota composition in infants that were breastfed versus formula fed. However, due to limitations associated with sample collection from infants the impact of human milk (HM) feeding in comparison to milk formula (MF) diet on gut metabolism of neonates has not been fully investigated. We evaluated the abundance of metabolites in the cecum, proximal colon, distal colon, and in the rectum contents of piglets fed with either HM or MF (dairy based) diet during the first 21 days of life and solid diet from day 21 until day 51. This piglet model intended to mimic the neonatal feeding in human infants. Based on discriminant analysis we observed a clear separation in the metabolome due to diet (HM and MF) on day 21, but on day 51 the separation less distinguishable. Milk-formula feeding enhanced cholesterol level and the bile acid synthesis, and subsequently excretion relative to HM-diet at day 21. HM-diet fed piglets utilized fatty acids, polyamines and impacted immune system, while formula did not provide these as source. Also tryptophan metabolites that have been shown to reduce inflammation were higher in HM relative to MF-fed piglets at day 21. Human-milk diet also provided non-essential amino acids to be used by the body while providing the essential building blocks for protein metabolism. Overall, the current study demonstrates differential metabolic responses on energy utilization from HM and MF groups during the first 21 days of life while after the transition to solid food the energy source was resumed to carbohydrates in both groups. Together, these findings provide new insights regarding nutritional responses at the distal gastrointestinal tract, that can be used to strategically enhance infant nutrition based on the metabolic response.

Technical Abstract: The impact of human milk (HM) or dairy milk-based formula (MF) on the large intestine's metabolome was not investigated. Two-day old male piglets were randomly assigned to HM or MF diet (n = 26/group), from postnatal day (PND) 2 through 21 and weaned to a solid diet until PND 51. Piglets were euthanized at PND 21 and PND 51, luminal contents of the cecum, proximal (PC) and distal colons (DC), and rectum were collected and subjected to untargeted metabolomics. Data analyses were performed using Metaboanalyst. In comparison to MF, the HM diet resulted in higher levels of fatty acids in the lumen of the cecum, PC, DC, and rectum at PND 21. Glutamic acid was greater in the lumen of cecum, PC, and DC relative to the MF group at PND 21. Also, spermidine was higher in the DC and rectal contents of HM relative to MF at PND 21. MF diet resulted in greater abundances of amino acids in the cecal lumen relative to HM diet at PND 21. Additionally, several sugar metabolites were higher in various regions of the distal gut of MF fed piglets relative to HM group at PND 21. In contrast, at PND 51, in various regions there were higher levels of erythritol, maltotriose, isomaltose in HM versus MF fed piglets. This suggests a post weaning shift in sugar metabolism that is impacted by neonatal diet. The data suggest that infant diet type and host-microbiota interactions strongly impact the lower gut metabolome.