Parenteral lipid emulsions induce unique ileal fatty acid and metabolomic profiles but do not increase the risk of necrotizing enterocolitis in preterm pigs

Authors: YAKAH, WILLIAM - Beth Israel Deaconess Medical Center; SINGH, PRATIBHA - Beth Israel Deaconess Medical Center; BROWN, JOANNE - Beth Israel Deaconess Medical Center; STOLL, BARBARA - Children'S Nutrition Research Center (CNRC); Burrin, Douglas - Doug; PREMKUMAR, MURALIDHAR - Baylor College Of Medicine; OTU, HASAN - University Of Nebraska; GU, XUESONG - Beth Israel Deaconess Medical Center; DILLON, SIMON - Beth Israel Deaconess Medical Center; LIBERMAN, TOWIA - Beth Israel Deaconess Medical Center; FREEDMAN, STEVEN - Beth Israel Deaconess Medical Center; MARTIN, CAMILIA - Beth Israel Deaconess Medical Center

Submitted to: American Journal of Physiology - Gastrointestinal and Liver Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/19/2020
Publication Date: 11/25/2020
Citation: Yakah, W., Singh, P., Brown, J., Stoll, B., Burrin, D.G., Premkumar, M., Otu, H., Gu, X., Dillon, S., Liberman, T., Freedman, S., Martin, C. 2020. Parenteral lipid emulsions induce unique ileal fatty acid and metabolomic profiles but do not increase the risk of necrotizing enterocolitis in preterm pigs. American Journal of Physiology - Gastrointestinal and Liver Physiology. https://doi.org/10.1152/ajpgi.00311.2020.
DOI: https://doi.org/10.1152/ajpgi.00311.2020

Interpretive Summary: In the U.S. each year, thousands of infants are born prematurely and have immature guts that cannot absorb enough food to sustain life. In order to nourish these babies, doctors use a life-saving therapy called total parenteral nutrition which provides critical nutrients given intravenously. In the U.S., most infants receive a lipid emulsion that is made from 100% soybean oil. Unfortunately, if babies remain on this soy emulsion for a long period, they develop parenteral nutrition-associated liver disease (PNALD), which can be life-threatening. New emulsions lipid emulsions are being approved that contain 100% fish oil or mixed oil emulsion and may provide a healthier alternative for premies. Another risk for these tiny babies is a disease call necrotizing enterocolitis (NEC) that can lead to surgery and death. The current study tested two new lipid emulsions in premature, newborn piglets to examine whether they can prevent NEC. One group received the soybean-oil based emulsion, while the others got either an emulsion based on pure-fish oil or a mixed oil emulsion that contained soybean oil, medium chain triglycerides and olive and fish oils for 8 days. The results showed that the type of lipid emulsion fed to newborn pigs did not influence the incidence of NEC. However, the profile of metabolites and protein in intestinal tissue provided key insights into the causes of the NEC disease.

Technical Abstract: Necrotizing enterocolitis (NEC) is a manifestation of maladaptive intestinal responses in preterm infants centrally medicated by unattenuated inflammation. Early in the postnatal period, preterm infants develop a deficit in arachidonic and docosahexaenoic acid, both potent regulators of inflammation. We hypothesized that the fatty acid composition of parenteral lipid emulsions uniquely induces blood and intestinal fatty acid profiles which, in turn, modifies the risk of NEC development. 42 Preterm pigs were randomized to receive one of three lipid emulsions containing 100% soybean oil (SO), 15% fish oil (MO15), or 100% fish oil (FO100) with enteral feedings over an 8-day protocol. Blood and distal ileum tissue were collected for fatty acid analysis. The distal ileum underwent histologic, proteomic, and metabolomic analyses. Eight pigs (3/14 SO (21 %), 3/14 MO15 (21%), and 2/14 FO100 (14%)) developed NEC. No differences in NEC risk were evident between groups despite differences in induced fatty acid profiles in blood and ileal tissue. Metabolomic analysis of NEC vs no NEC tissue revealed differences in tryptophan metabolism and arachidonic acid-containing glycerophospholipids. Proteomic analysis demonstrated no differences by lipid group; however, 15 proteins differentiated NEC vs no NEC in the domains of tissue injury, glucose uptake and chemokine signaling. Exposure to parenteral lipid emulsions induces unique intestinal fatty acid and metabolomic profiles, however, these profiles are not linked to a difference in NEC development. Metabolomic and proteomic analyses of NEC vs no NEC intestinal tissue provide mechanistic insights into the pathogenesis of NEC in preterm infants.