Use of a novel docosahexaenoic acid formulation vs control in a neonatal porcine model of short bowel syndrome leads to greater intestinal absorption and higher systemic levels of DHA

Authors: MARTIN, CAMILIA - Beth Israel Deaconess Medical Center; STOLL, BARBARA - Children'S Nutrition Research Center (CNRC); CLUETTE-BROWN, JOANNE - Beth Israel Deaconess Medical Center; AKINKUOTU, ADESOLA - Baylor College Of Medicine; OLUTOYE, OLUYINKA - Baylor College Of Medicine; GURA, KATHLEEN - Boston Children'S Hospital; SINGH, PRATIBHA - Beth Israel Deaconess Medical Center; ZAMAN, MUNIR - Beth Israel Deaconess Medical Center; PERILLO, MICHAEL - Beth Israel Deaconess Medical Center; PUDER, MARK - Boston Children'S Hospital; FREEDMAN, STEVEN - Beth Israel Deaconess Medical Center; Burrin, Douglas - Doug

Submitted to: Nutrition Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/1/2017
Publication Date: 2/4/2017
Publication URL: https://handle.nal.usda.gov/10113/5801817
Citation: Martin, C.R., Stoll, B., Cluette-Brown, J., Akinkuotu, A.C., Olutoye, O.O., Gura, K., Singh, P., Zaman, M.M., Perillo, M.C., Puder, M., Freedman, S.D., Burrin, D.G. 2017. Use of a novel docosahexaenoic acid formulation vs control in a neonatal porcine model of short bowel syndrome leads to greater intestinal absorption and higher systemic levels of DHA. Nutrition Research. 39:51-60.

Interpretive Summary: Some infants are born with defects in Gastro Intestinal development or they experience disease early in life that requires surgical removal of part of the intestine. Although many infants recover from this surgery, some still need intravenous feeding of nutrition, called parenteral nutrition. The inability for the remaining intestine to function normally and support adequate growth is known as short bowel syndrome (SBS). Infants with SBS are at high risk for poor growth, liver disease and infection. Previous studies suggest that feeding certain fats, docosahexaenoic acid (DHA) and arachidonic acid (ARA), have been shown to enhance growth of the intestine, but these fats may not be digested effectively in these infants with SBS. The goal of this study was to use a pig model of SBS to test the absorption and intestinal growth capacity of a new chemical forms of DHA (DHA-ALT) compared to a standard form of DHA (Control). The results show that the novel DHA preparation resulted in increased absorption, increased intestinal tissue incorporation, and increased circulating blood levels of DHA. This study represents the first to show the benefit of a more bioavailable form of DHA in a relevant animal model of SBS.

Technical Abstract: Infants with short bowel syndrome (SBS) are at high risk for malabsorption, malnutrition, and failure to thrive. The objective of this study was to evaluate in a porcine model of SBS, the systemic absorption of a novel enteral Docosahexaenoic acid (DHA) formulation that forms micelles independent of bile salts (DHA-ALT). We hypothesized that enteral delivery of DHA-ALT would result in higher blood levels of DHA compared to a control DHA preparation due to improved intestinal absorption. SBS was induced in term piglets through a 75% mid-jejunoileal resection and the piglets randomized to either DHA-ALT or control DHA formulation (N=5 per group) for 4 postoperative days. The median +/- IQR difference in final vs starting weight was 696 +/- 425 g in the DHA-ALT group compared to 132 +/- 278 g in the controls (P=.08). Within 12 hours, median +/- IQR DHA and eicosapentaenoic acid plasma levels (mol%) were significantly higher in the DHA-ALT vs control group (4.1 +/- 0.3 vs 2.5 +/- 0.5, P=.009; 0.7 +/- 0.3 vs 0.2 +/- 0.005, P=.009, respectively). There were lower fecal losses of DHA and greater ileal tissue incorporation with DHA-ALT vs the control. Morphometric analyses demonstrated an increase in proximal jejunum and distal ileum villus height in the DHA-ALT group compared to controls (P=.01). In a neonatal porcine model of SBS, enteral administration of a novel DHA preparation that forms micelles independent of bile salts resulted in increased fatty acid absorption, increased ileal tissue incorporation, and increased systemic levels of DHA.