title: Enteral nutrient deprivation in patients leads to a loss of intestinal epithelial barrier function.
abstract: OBJECTIVE
  To investigate the effect of nutrient withdrawal on human intestinal epithelial barrier function (EBF). We hypothesized that unfed mucosa results in decreased EBF. This was tested in a series of surgical small intestinal resection specimens.
  
  
  METHODS
  Small bowel specifically excluding inflamed tissue, was obtained from pediatric patients (aged 2 days to 19 years) undergoing intestinal resection. EBF was assessed in Ussing chambers for transepithelial resistance (TER) and passage of fluorescein isothiocyanate (FITC)-dextran (4 kD). Tight junction and adherence junction proteins were imaged with immunofluorescence staining. Expression of Toll-like receptors (TLR) and inflammatory cytokines were measured in loop ileostomy takedowns in a second group of patients.
  
  
  RESULTS
  Because TER increased with patient age (P < .01), results were stratified into infant versus teenage groups. Fed bowel had significantly greater TER versus unfed bowel (P < .05) in both age populations. Loss of EBF was also observed by an increase in FITC-dextran permeation in enteral nutrient-deprived segments (P < .05). Immunofluorescence staining showed marked declines in intensity of ZO-1, occludin, E-cadherin, and claudin-4 in unfed intestinal segments, as well as a loss of structural formation of tight junctions. Analysis of cytokine and TLR expression showed significant increases in tumor necrosis factor (TNF)-α and TLR4 in unfed segments of bowel compared with fed segments from the same individual.
  
  
  CONCLUSIONS
  EBF declined in unfed segments of human small bowel. This work represents the first direct examination of EBF from small bowel derived from nutrient-deprived humans and may explain the increased incidence of infectious complications seen in patients not receiving enteral feeds.
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Ralls
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.
authors.forename: Farokh R
authors.initials: FR
authors.lastname: Demehri
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.
authors.forename: Yongjia
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Woods Ignatoski
authors.affiliation: Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI. Electronic address: dttlbm@umich.edu.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Teitelbaum
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D004750:Enteral Nutrition; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007413:Intestinal Mucosa / Q000378:metabolism / Q000503:physiopathology*; D007421:Intestine, Small / Q000378:metabolism / Q000503:physiopathology*; D016014:Linear Models; D008297:Male; D010288:Parenteral Nutrition / Q000009:adverse effects*; D010539:Permeability; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019108:Tight Junctions / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D051193:Toll-Like Receptors