Alex Trevors - October 31

The use of alanyl-glutamine as a source of glutamine for the compromised GI tract in parenterally-fed neonatal piglets.

Gastrointestinal disorders in newborn infants commonly lead to the use of parenteral (IV) nutrition. Total parenteral nutrition (TPN), although necessary, causes the small intestine to atrophy and alters intestinal barrier function, increasing the risk of infection and inflammation. Glutamine is a vital fuel source for intestinal tissues, and imparts a protective effect in part by maintaining intestinal tight junction barriers. However, uptake of glutamine may be compromised in an atrophied gut. Amino acids may be transported more efficiently as dipeptides by the peptide transporter, PepT1, a proton dependent cotransporter responsible for the uptake of a large variety of di- and tri- peptides. Its expression appears to be maintained during intestinal atrophy. The objectives of this study were to investigate whether glutamine uptake was more efficient as alanyl-glutamine compared to free glutamine, and whether the presence of the dipeptide interfered with the uptake and pro-inflammatory activities of a peptide of bacterial origin (fMLP).

Piglets (10 d old) were assigned to either a TPN diet (n=6) for 4 full days to induce intestinal atrophy, or left to suckle on the sow (SF, n=6). Piglets subsequently underwent an intestinal perfusion procedure under anesthesia. Five segments of intestine were isolated, left in situ, and were perfused with one of the following: 1) fMLP, 2) alanyl-glutamine, 3) alanine and glutamine, 4) alanyl-glutamine and fMLP, or 5) alanine, glutamine, and fMLP. Myeloperoxidase activity in intestinal mucosa was higher in the TPN pigs compared to SF pigs (P<0.05), but was not affected by any of the treatments. Furthermore, there were no differences in mucosal TNF-α concentrations in response to fMLP perfusion or diet. Intestinal morphology also did not differ between methods of feeding or perfusion treatments. Measuring 3H-fMLP disappearance from the perfusion buffers indicated that approximately 25% of fMLP was taken up by the intestine, regardless of treatments. Evidence of fMLP uptake without changes in TNF-α concentration or MPO activity suggests that glutamine, delivered either enterally to the mucosa or absorbed and supplied via the systemic circulation, may provide protection against bacterial peptide-induced inflammation in the neonatal gut.



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