Short-Chain Fatty Acids and Functional Adaptations in the Neonatal Intestine

182 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2004.Intestinal adaptation following massive loss of absorptive surface area is an important process that results in enhanced intestinal function to compensate for reduced absorptive capacity. Short-chain fatty acids (SCFA) are known to enhance this adaptive process in adult animal models, and data from our lab indicates that butyrate (Bu) results in marked changes in glucose transport in the intestine within minutes. We hypothesized that SCFA and Bu would enhance glucose transport and transporter gene expression in a neonatal pig model of massive small bowel resection. Two-day-old neonatal pigs underwent 80% jejunoileal massive small bowel resection, and were fed via total parenteral nutrition (TPN). Piglets were randomized to receive the following treatments: (1) control TPN; and isoenergetic, isonitrogenous TPN supplemented with; (2) SCFA (36 mM acetate, 15 mM propionate, 9 mM Bu, for a total of 60 mM SCFA); (3) 9 mM Bu (9Bu); or (4) 60 mM Bu (60Bu). Piglets were further randomized to examine acute (4 h, 12 h, 24 h) and chronic (3 d, 7 d) adaptations. With SCFA and Bu treatments, improvements in glucose, amino acid, and dipeptide transport were observed in the proximal small intestine (duodenum and jejunum), but not ileum. Transport of certain nutrients (glucose and arginine) was enhanced in the colon by SCFA and Bu. Whenever effects were observed with the SCFA group, similar effects were also observed with Bu group(s), indicating that Bu is the main SCFA responsible for these changes. Using a microarray approach with isolated jejunal epithelia, 9Bu was found to affect expression of nearly one-third of the >10,000 total genes examined. This included induced expression of several nutrient transporter genes, indicating that Bu enhances expression of nutrient transporters in the intestinal epithelia. In addition, studies examining peptide transporter (PepT1) protein indicated that 9Bu induces trafficking of PepT1 to the brush-border membrane. Therefore, Bu enhances intestinal adaptation in a neonatal pig model, probably by increasing transcription of nutrient transporters, as well as increasing trafficking of specific transporters to the brush-border membrane. Butyrate offers great promise as a nutritional therapy for neonatal short-bowel syndrome patients.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD