Human milk-fed piglets have a distinct small intestine and circulatory metabolome profile relative to that of milk formula-fed piglets

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

Submitted to: mSystems
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/19/2021
Publication Date: 2/9/2021
Citation: Rosa, F., Matazel, K.S., Elolimy, A.A., Adams, S.H., Bowlin, A., Williams, K.D., Bode, L., Yeruva, L. 2021. Human milk-fed piglets have a distinct small intestine and circulatory metabolome profile relative to that of milk formula-fed piglets. mSystems. https://doi.org/10.1128/mSystems.01376-20.
DOI: https://doi.org/10.1128/mSystems.01376-20

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. It has been shown that breastfed babies have decreased rates of infections including respiratory tract infections. Additionally, certain breastmilk components impact the early life intestinal tract colonization (gut microbiota) in infants. Infant formula is also recommended as nutrition source when breastfeeding is not an option. 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 the metabolites present in the small intestine, blood, and urine of neonates has not been fully investigated. We evaluated the abundance of metabolites in the small intestine contents, blood, and urine of piglets fed with either HM or MF (cow's based) diet until day 21 and weaned to a solid diet 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 based on diet was less abundant. The current study demonstrates differential metabolic responses to HM or MF not only during the exclusively milk feeding period but after the transition to solid food as well. Further these observations provide new insights regarding nutritional responses that can be used to strategically enhance infant nutrition based on the metabolic response.

Technical Abstract: The impact of human milk (HM) feeding in comparison to milk formula (MF) on gut bio-regional and circulatory metabolome patterns has not been fully investigated. Therefore, 2-day old male piglets were fed HM or MF (n = 26/group) from postnatal day (PND) 2 through 21, and were weaned to a solid diet until PND 51. The small intestine (GI) contents, serum, and urine were collected on subsets of piglets on PND 21 and on PND 51 and subjected to untargeted metabolomics analyses. The metabolome data assessment and the statistical analyses were performed with MetaboAnalyst software. Compared to MF, at PND 21 HM feeding resulted in higher abundance of fucose in the jejunum and urine, and greater concentration of myo-inositol in serum. In HM-fed piglets, 1,5-anhydroglucitol was higher in the duodenum, serum, and urine at PND 21; however, it was not detected at PND 51. In urine, the HM group had higher levels of kynurenic acid at PND 21. UDP-N-acetylglucosamine was higher in serum of HM versus MF group at PND 51. At PND 21 correlations between bacterial genera and altered metabolites in ileum revealed that Turicibacter and Campylobacter were positively correlated to maltotriose and panose. Ileal Campylobacter was negatively correlated to fumaric acid. At PND 51 no significant correlations were observed. The metabolites associated with the neonatal diets may serve as substrates and signals that contribute to the physiological effects of HM and MF during infancy, with a subset reflecting diet-associated differences in microbial metabolism and ecology.