title: Parenteral nutrition increases susceptibility of ileum to invasion by E coli.
abstract: BACKGROUND
  Parenteral nutrition (PN), with the lack of enteral feeding, compromises mucosal immune function and increases the risk of infections. We developed an ex vivo intestinal segment culture (EVISC) model to study the ex vivo effects of PN on susceptibility of the ileum to invasion by extra-intestinal pathogenic Escherichia coli (ExPEC) and on ileal secretion of antimicrobial secretory phospholipase A2 (sPLA2) in response to the pathogen.
  
  
  METHODS
  Study 1: Using mouse (n = 7) ileal tissue, we examined the effects of ileal region (proximal versus distal) and varying ExPEC inoculum concentrations on ex vivo susceptibility to ExPEC invasion and sPLA2 secretion. Study 2: Ten mice were randomized to oral chow or intravenous PN feeding for 5 d (n = 5/group). Using the EVISC model, we compared the susceptibility of ileal tissue to invasion by ExPEC and sPLA2 secretion in response to the pathogen.
  
  
  RESULTS
  Study 1: The proximal ileum was more susceptible to invasion (P < 0.0001) and secreted lower amounts of sPLA2 (P = 0.0002) than the distal ileum. Study 2: Ileal tissue from PN-fed animals was more susceptible (approximately 4-fold, P = 0.018) to invasion than those from chow-fed animals. Ileal tissue from PN-fed animals secreted less sPLA2 (P < 0.02) than those from chow-fed animals.
  
  
  CONCLUSIONS
  The data illustrate EVISC as a reproducible model for studying host-pathogen interactions and the effects of diet on susceptibility to infections. Specifically, the findings support our hypothesis that PN with the lack of enteral feeding decreases mucosal responsiveness to pathogen exposure and provides a plausible mechanism by which PN is associated with increased risk of infectious complication.
authors.affiliation: Veterans Administration Research Services, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Pierre
authors.forename: Aaron F
authors.initials: AF
authors.lastname: Heneghan
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Meudt
authors.forename: Michael P
authors.initials: MP
authors.lastname: Shea
authors.forename: Christian G
authors.initials: CG
authors.lastname: Krueger
authors.forename: Jess D
authors.initials: JD
authors.lastname: Reed
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Kudsk
authors.forename: Dhanansayan
authors.initials: D
authors.lastname: Shanmuganayagam
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000209:etiology*; D004750:Enteral Nutrition; D004926:Escherichia coli / Q000302:isolation & purification / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000453:epidemiology*; D054884:Host-Pathogen Interactions; D007077:Ileal Diseases / Q000453:epidemiology* / Q000382:microbiology*; D007082:Ileum / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010288:Parenteral Nutrition / Q000009:adverse effects*; D054467:Phospholipases A2 / Q000378:metabolism; D012307:Risk Factors
chemical_list: D054467:Phospholipases A2
keywords: Enteroinvasion; Escherichia coli; Extra-intestinal pathogens; Ex vivo; Paneth cells; Parenteral nutrition; Polarized in vitro organ culture; Secretory phospholipase A2