title: Impact of caloric intake on parenteral nutrition-associated intestinal morphology and mucosal barrier function.
abstract: BACKGROUND
  Parenteral nutrition (PN) is known to induce villus atrophy, epithelial cell (EC) apoptosis, and increase mucosal permeability. The study hypothesized that increasing amounts of energy delivery to mice would result in the best outcome, with the least effects on the mucosa.
  
  
  METHODS
  Mice were randomized to enteral controls (saline infusion with ad libitum enteral food) or to 1 of 3 PN groups (with no enteral nutrition): full (100% of daily average energy intake for the mouse), reduced (75% of energy intake) or very low (50% of energy intake). Mice received PN for 7 days. Mucosal morphology, EC apoptosis, and bacterial translocation were assessed.
  
  
  RESULTS
  Villus height decreased significantly with decreasing levels of caloric intake and was significantly lower in all PN groups compared with controls. Body weight loss was significantly greater in PN groups vs controls and was greatest in mice with the lowest caloric delivery. A consistent trend toward a higher EC apoptotic index with decreasing caloric intake was observed, and apoptosis in all PN groups exceeded controls (2-fold). All PN groups demonstrated greater bacterial translocation than controls.
  
  
  CONCLUSIONS
  PN induces intestinal EC apoptosis and villus and crypt atrophy, even at 100% of predicted energy needs, and such changes increased with greater reduction of energy intake. This study supports a concept that lack of enteral nutrition, rather than absolute caloric levels, is responsible for many of the adverse effects of PN. The study also allows the investigators to better optimize a mouse model of PN delivery.
authors.affiliation: Department of Surgery, Section of Pediatric Surgery, University of Michigan, Mott Children's Hospital, Ann Arbor, Michigan 48109, USA.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Sun
authors.forename: Ariel U
authors.initials: AU
authors.lastname: Spencer
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.forename: Emir Q
authors.initials: EQ
authors.lastname: Haxhija
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Teitelbaum
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018988:Bacterial Translocation / Q000187:drug effects*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002149:Energy Intake / Q000502:physiology*; D004750:Enteral Nutrition; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010288:Parenteral Nutrition / Q000009:adverse effects*; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms; D015430:Weight Gain