title: Dietary supplementation with orotate and uracil increases adaptive growth of jejunal mucosa after massive small bowel resection in rats.
abstract: BACKGROUND
  Massive small-bowel resection (SBR) increases adaptive growth of residual intestine in animal models of short-bowel syndrome (SBS). Pyrimidine nucleotides are critical for DNA and RNA synthesis, but no previous study has evaluated whether supplementation of pyrimidines or their precursors in the diet enhances adaptive gut growth after SBR. This study determined growth responses in jejunal mucosa after 7 days of dietary supplementation with uracil, or its precursor, orotate, after massive SBR in rats.
  
  
  METHODS
  Sprague-Dawley rats ( approximately 200 g) underwent 80% jejunoileal resection (RX) or ileal transection (TX; control). Rats were pair-fed a purified (AIN-93G) powdered diet supplemented with or without 1% (wt/wt) orotate or uracil until killing at 7 days postsurgery. Defined jejunal segments were obtained for analysis of mucosal villus height (VH), crypt depth (CD), total mucosal height, bromodeoxyuridine (BrdU) incorporation, an index of cell proliferation, and full-thickness DNA and protein content as measures of intestinal adaptive growth.
  
  
  RESULTS
  Jejunal VH increased significantly with SBR, as expected, and orotate further stimulated this response. Jejunal CD and total mucosal height increased significantly with both orotate and uracil supplementation compared with resected animals receiving standard diet. Orotate administration also increased jejunal DNA content compared with the increase observed with SBR alone. Finally, orotate, but not uracil, supplementation increased BrdU incorporation compared with resected rats fed standard or uracil-supplemented diet after SBR.
  
  
  CONCLUSIONS
  Supplementation of oral diet with the pyrimidine precursor orotate and uracil stimulated adaptive jejunal growth after massive SBR in rats. Dietary orotate had more potent growth-stimulatory effects than uracil in this animal model. Dietary supplementation with orotate and uracil represents a novel nutrition approach to enhance small-bowel mucosal adaptive growth and absorptive capacity in SBS.
authors.affiliation: Department of Medicine and the Center for Clinical and Molecular Nutrition, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Evans
authors.forename: Junqiang
authors.initials: J
authors.lastname: Tian
authors.forename: Li H
authors.initials: LH
authors.lastname: Gu
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Ziegler
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D019587:Dietary Supplements; D004195:Disease Models, Animal; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D007583:Jejunum / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D008297:Male; D009963:Orotic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012778:Short Bowel Syndrome / Q000178:diet therapy*; D014498:Uracil / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D014498:Uracil; D009963:Orotic Acid