title: Alanyl-glutamine restores maternal deprivation-induced TLR4 levels in a rat neonatal model.
abstract: OBJECTIVE
  Increased intestinal permeability of Irritable bowel syndrome (IBS) patients has been recently associated with a decreased level of glutamine synthetase. Neonatal maternal deprivation (NMD) is considered as an IBS-like model. The aim of our study was to investigate whether early nutritional intervention with glutamine may attenuate the deleterious impact of early life stress on gut barrier function in NMD.
  
  
  METHODS
  124 rat pups were separated from their dam 3 h daily during postnatal days 2-14, or left undisturbed (NS). Separated rats received by gavage either with alanyl-glutamine (GLN), an isonitrogenous amino acid mix (AA, control) or an equal amount of drinking water (H(2)O). Production of cytokines was measured by multiplex, expression of COX-2, PPARγ, tight junction proteins and TLR4 by western blot. Intestinal permeability was studied by Lactulose/Mannitol test.
  
  
  RESULTS
  Treatment of pups with GLN or AA abolished the decrease in body weight observed in NMD. Treatment with GLN decreased in the colon (i) TLR4 expression at D20, (ii) IL-2 and -10 productions at D60 (iii) protein expression of occludin at D20 compared to AA. GLN also decreased colon expression of COX2 and PPARγ at D60 compared to NS. Colon production of IFNγ is significantly reduced by GLN compared to H(2)O. No significant change in intestinal permeability was observed.
  
  
  CONCLUSIONS
  These results showed that an early nutritional intervention with alanyl-glutamine specifically abolished the up-regulation of TLR4 expression in NMD. Glutamine may be evaluated as a potential treatment for IBS patients.
authors.affiliation: Appareil Digestif Environnement Nutrition (ADEN EA 4311), University of Rouen, I.F.R. 23, Institute of Biomedical Research, 22, boulevard Gambetta, 76183 Rouen cedex, France.
authors.forename: Khaly
authors.initials: K
authors.lastname: Mbodji
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Torre
authors.forename: Verena
authors.initials: V
authors.lastname: Haas
authors.forename: Pierre
authors.initials: P
authors.lastname: Déchelotte
authors.forename: Rachel
authors.initials: R
authors.lastname: Marion-Letellier
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003106:Colon / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019587:Dietary Supplements; D004151:Dipeptides / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D043183:Irritable Bowel Syndrome / Q000178:diet therapy* / Q000378:metabolism*; D008426:Maternal Deprivation; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D062793:Occludin; D047495:PPAR gamma / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D004151:Dipeptides; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D047495:PPAR gamma; D012333:RNA, Messenger; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; C054122:alanylglutamine