Parenteral fish-oil containing lipid emulsions limit initial lipopolysaccharide-induced host immune responses in preterm pigs

Authors: YAKAH, WILLIAM - Beth Israel Deaconess Medical Center; RAMIRO-CORTIJO, DAVID - 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); KULKARNI, MADHUKIKA - Baylor College Of Medicine; OOSTERLOO, BERTHE - Children'S Nutrition Research Center (CNRC); Burrin, Douglas - Doug; MADDIPATI, KRISHNA - Wayne State University; FICHOROVA, RAINA - Harvard Medical School; FREEDMAN, STEVEN - Beth Israel Deaconess Medical Center; MARTIN, CAMILIA - Beth Israel Deaconess Medical Center

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/8/2021
Publication Date: 1/12/2021
Citation: Yakah, W., Ramiro-Cortijo, D., Singh, P., Brown, J., Stoll, B., Kulkarni, M., Oosterloo, B., Burrin, D.G., Maddipati, K., Fichorova, R., Freedman, S., Martin, C. 2021. Parenteral fish-oil containing lipid emulsions limit initial lipopolysaccharide-induced host immune responses in preterm pigs . Nutrients. 13(1):25. https://doi.org/10.3390/nu13010205.
DOI: https://doi.org/10.3390/nu13010205

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. Premies also have a significant risk for infection and the body responds with an inflammatory response that can become overwhelming. The current study tested two new lipid emulsions in premature, newborn pigs to examine whether they can reduce the markers of inflammation in premature pigs infused with bacteria toxin to simulate infection. 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 10 day and then pigs were treated with either a control saline or toxin. The results showed that the type of lipid emulsion containing omega-3 fatty acids reduced the toxin-induced inflammatory response. The results also suggest that ratio of arachidonic acid and docosahexaenoic acid may have an important influence on the response to infection in neonatal infants.

Technical Abstract: Multicomponent lipid emulsions are available for critical care of preterm infants. We sought to determine the impact of different lipid emulsions on early priming of the host and its response to an acute stimulus. Pigs delivered 7d preterm (n=59) were randomized to receive: 100% soybean oil (SO), mixed oil emulsion (SO, medium chain olive oil and fish oil) including 15% fish oil (MO15), or 100% fish oil (FO100) for 11 days. On day 11, pigs received an 8-hour continuous intravenous infusion of either lipopolysaccharide (LPS - lyophilized Escherichia coli) or saline. Plasma was collected for fatty acid, oxylipin, metabolomic, and cytokine analyses. At day 11, plasma omega-3 fatty acid levels in the FO100 groups showed the highest increase in eicosapentaenoic acid, EPA (0.1+/-0.0 to 9.7+/-1.9, p<0.001), docosahexaenoic acid, DHA (day 0=2.5+/-0.7 to 13.6+/-2.9, p<0.001), EPA and DHA-derived oxylipins, and sphingomyelin metabolites. In the SO group, levels of cytokine IL1B increased at the first hour of LPS infusion (296.6+/-308 pg/mL) but was undetectable in MO15, FO100, or in the animals receiving saline instead of LPS. Pigs in the SO group showed a significant increase in arachidonic acid (AA)-derived prostaglandins and thromboxanes in the first hour (p<0.05). No significant changes in oxylipins were observed with either fish-oil containing group during LPS infusion. Host priming with soybean oil in the early postnatal period preserves a higher AA:DHA ratio and the ability to acutely respond to an external stimulus. In contrast, fish-oil containing lipid emulsions increase DHA, exacerbate a deficit in AA, and limit acute LPS-induced inflammatory responses in preterm pigs.