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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: Formula diet alters ileal metagenome and transcriptome at weaning and during the postweaning period in a porcine model

Author
item ELOLIMY, AHMED - Arkansas Children'S Nutrition Research Center (ACNC)
item WASHAM, CHARITY - University Arkansas For Medical Sciences (UAMS)
item BYRUM, STEPHANIE - University Arkansas For Medical Sciences (UAMS)
item Chen, Celine
item Dawson, Harry
item BOWLIN, ANNE - Arkansas Children'S Nutrition Research Center (ACNC)
item RANDOLPH, CHRIST - Arkansas Children'S Hospital
item SARAF, MANISH - Arkansas Children'S Nutrition Research Center (ACNC)
item YERUVA, LAXMI - Arkansas Children'S Nutrition Research Center (ACNC)

Submitted to: mSystems
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/21/2020
Publication Date: 8/4/2020
Citation: Elolimy, A., Washam, C., Byrum, S., Chen, C.T., Dawson, H.D., Bowlin, A.K., Randolph, C., Saraf, M.K., Yeruva, L. 2020. Formula diet alters ileal metagenome and transcriptome at weaning and during the postweaning period in a porcine model. mSystems. 5:e00457-20. https://doi.org/10.1128/mSystems.00457-20.
DOI: https://doi.org/10.1128/mSystems.00457-20

Interpretive Summary: Breastfeeding is associated with positive health outcomes in terms of reduced infections, and these outcomes are coincident with breastfeeding-specific differences in the bacteria that naturally are present in the intestinal tract (gut microbiota). However, the mechanisms behind the positive health effects of breastfeeding, and how they associate with gut microbiota, are poorly understood. To address mechanisms, a piglet model was utilized, fed with either human breastmilk or cow's milk formula (MF) diet until day 21 and then weaned to solid diet until day 51 to recapitulate neonatal feeding in human infants. We evaluated small intestine ileal mucosal microbiota and gene expression. The data on ileal mucosal microbiota showed that MF piglets had higher levels of the bacterium called Helicobacter pylori. Additionally, gene expression data revealed that MF upregulated pathways involved in inflammation and cell death (apoptosis), whereas tight junctions (tissue structure) and pathogen detection systems were downregulated relative to the HM group. The MF impacts on small intestine were maintained over the postweaning period (d 51), as indicated by greater markers of inflammation pathways and apoptosis-associated systems in MF piglets. The current study demonstrates that MF might impact local intestinal inflammation, cell stress/apoptosis, and gut structure, and could suppress pathogen recognition in the small intestine compared with HM fed piglets. These are novel observations that highlight potential mechanisms driving the protective effects of breastmilk relative to formula diet.

Technical Abstract: Exclusive breastfeeding impacts the intestinal microbiome and is associated with a better immune function compared to milk formula (MF) feeding in infants yet with mechanisms poorly defined. The neonatal porcine model was used to evaluate the impact of MF on ileum microbial communities and gene expression relative to human milk (HM) fed piglets. Fifty-two Dutch Landrace male piglets were fed an isocaloric diet of either HM (n = 26) or MF (n = 26) from the day (d) 2 through d 21 of age and weaned to solid diet until day 51. Eleven piglets from each group were euthanized at d 21 while the remaining piglets (HM, n = 15; MF, n = 15) were euthanized at d 51 to collect ileal epithelium scrapings (EP) and ileal tissues (IL). The epithelial mucosa was subjected to shotgun metagenome sequencing, and EP and IL tissues were used for transcriptome analysis. At d 21, MF piglets had higher Helicobacter pylori. Additionally, transcriptome data revealed that MF upregulated pathways involved in inflammation, apoptosis, whereas tight junctions and pathogen detection systems were downregulated relative to the HM group. The MF impacts on small intestine were maintained over the postweaning period (d 51) as indicated by greater Dialister invisus bacteria relative to HM, and upregulation of inflammation pathways, and apoptosis-associated were observed. The current study demonstrates that MF might impact local intestinal inflammation, apoptosis, and tight junctions and might suppress pathogen recognition in the small intestine compared with HM.