title: 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.
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.
authors.affiliation: Department of Neonatology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215; Division of Translational Research, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. Electronic address: cmartin1@bidmc.harvard.edu.
authors.forename: Camilia R
authors.initials: CR
authors.lastname: Martin
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030. Electronic address: bstoll@bcm.edu.
authors.forename: Barbara
authors.initials: B
authors.lastname: Stoll
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. Electronic address: sfreedma@bidmc.harvard.edu.
authors.forename: Joanne
authors.initials: J
authors.lastname: Cluette-Brown
authors.affiliation: Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Texas Children's Hospital, 6621 Fannin St, Houston, TX 77030. Electronic address: axakinku@texaschildrens.org.
authors.forename: Adesola C
authors.initials: AC
authors.lastname: Akinkuotu
authors.affiliation: Division of Pediatric Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Texas Children's Hospital, 6621 Fannin St, Houston, TX 77030. Electronic address: oolutoye@bcm.edu.
authors.forename: Oluyinka O
authors.initials: OO
authors.lastname: Olutoye
authors.affiliation: Department of Pharmacy, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115. Electronic address: Kathleen.Gura@childrens.harvard.edu.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Gura
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Singh
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215.
authors.forename: Munir M
authors.initials: MM
authors.lastname: Zaman
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Perillo
authors.affiliation: Department of Surgery and the Vascular Biology Program, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115. Electronic address: Mark.Puder@childrens.harvard.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: Puder
authors.affiliation: Division of Translational Research, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215; Division of Gastroenterology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Freedman
authors.affiliation: USDA/ARS Children's Nutrition Research Center, Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030. Electronic address: Doug.Burrin@ars.usda.gov.
authors.forename: Doug
authors.initials: D
authors.lastname: Burrin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001647:Bile Acids and Salts; D001835:Body Weight; D004041:Dietary Fats / Q000097:blood*; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000097:blood*; D015118:Eicosapentaenoic Acid / Q000097:blood; D004750:Enteral Nutrition; D007082:Ileum / Q000378:metabolism*; D007408:Intestinal Absorption / Q000187:drug effects*; D008823:Micelles; D011897:Random Allocation; D012778:Short Bowel Syndrome / Q000628:therapy*; D013552:Swine
chemical_list: D001647:Bile Acids and Salts; D004041:Dietary Fats; D008823:Micelles; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid
keywords: Docosahexaenoic acid; Fat; Fatty acids; Intestinal adaptation; Piglet; Short bowel syndrome