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 versus starting weight was 696 ± 425g in the DHA-ALT® group compared to 132 ± 278g 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=0.009; 0.7 ± 0.3 vs 0.2 ± 0.005, p=0.009, respectively). There were lower fecal losses of DHA and greater ileal tissue incorporation with DHA-ALT® versus the control. Morphometric analyses demonstrated an increase in proximal jejunum and distal ileum villus height in the DHA-ALT® group compared to controls (p=0.01). 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.

Effects of Intestinal Microbiota on Brain Development in Humanized Gnotobiotic Mice

“…Approximately 50 mg segments of brain were homogenized in 1.0 mL of Phosphate- Buffered Saline solution using a Fisher PowerGen 125 homogenizer. Five hundred microliters of the aliquot was removed and lipids were extracted using a modified Folch method 88 , 89 . Briefly, after the addition of an internal standard (30 μg of heptadecanoic acid), the sample was mixed with 3 ml of chloroform: methanol (2:1 v/v) and vortexed.…”

Early Enteral Administration of a Complex Lipid Emulsion Supplement Prevents Postnatal Deficits in Docosahexaenoic and Arachidonic Acids and Increases Tissue Accretion of Lipophilic Nutrients in Preterm Piglets

“…To evaluate our hypotheses, the preterm piglet model was used. We have shown previously that LCPUFA levels at birth and over the first postnatal week in the preterm pig model mirror the changes seen in preterm humans …”

Differential action of TGR5 agonists on GLP-2 secretion and promotion of intestinal adaptation in a piglet short bowel model

“…The pigs were immediately placed in individual cages in a heated (28 -30°C) room until the day of surgery. The surgical procedure involved manipulation of the bowel length and implantation of silicone catheters for intragastric formula feeding, jugular PN infusion, and carotid artery blood sampling, as previously described (36). Briefly, in the SBS groups, the pigs were subjected to an 80% mid-jejunoileal resection, with a remnant 20% representing the proximal jejunum (PJ) and DI, similar to that described previously in neonatal pigs (4,5).…”

“…We first tested the efficacy of the TGR5 agonists UA and OE to stimulate GLP-2 secretion in parenterally fed piglets. We further tested the capacity of these TGR5 agonists to increase GLP-2 secretion and promote intestinal adaptation in a neonatal pig model of massive mid-small bowel resection (4,5,36).…”