Small Intestinal Co‐Perfusion of Alanyl‐Glutamine and Free Glutamine with fMLP Bacterial Peptide Resulted in a Diminished Inflammatory Response in Parenterally and Sow‐Fed Neonatal Piglets
Bibliographic record
Abstract
Small peptide absorption in the intestine is mediated by the transporter PepT1, which is also capable of transporting bacterial peptides such as formyl‐methionyl‐leucyl‐phenylalanine (fMLP). Previously, we demonstrated that fMLP induced mucosal inflammation during an intestinal perfusion experiment. Co‐perfusion of fMLP with the dipeptide cysteinyl‐glycine ameliorated the response as indicated by reduced myeloperoxidase activity and lower TNF‐α concentration in mucosal tissue. The objective of this study was to assess the interactions of alanyl‐glutamine or free alanine and glutamine with fMLP in a similar intestinal perfusion experiment; however, this time we employed a single‐pass perfusion model as opposed to re‐circulating the perfusion buffers to ensure constant exposure to fMLP. Piglets (10 d old) were assigned to either a total parenteral nutrition diet (TPN, 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 10 cm segments of intestine were isolated and left in situ, beginning at 50 cm proximal to the ileocecal valve; the isolated segments were each separated by 30 cm. The segments were perfused with one of the following: 1) 10 μM fMLP, 2) 5 mM alanyl‐glutamine, 3) 5 mM of each alanine + glutamine, 4) 5 mM alanyl‐glutamine + 10 μM fMLP, or 5) 5 mM of each alanine + glutamine + 10 μM fMLP. All perfusion solutions also contained 3 H‐fMLP to measure uptake and were perfused continuously for 3 h at a rate of 1 mL/min. 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 3 H‐fMLP disappearance from the perfusion buffers indicated that approximately 25% of fMLP was taken up by the intestine, regardless of treatments. Interestingly, we hypothesized that the single‐pass model should facilitate a greater inflammatory response to fMLP compared to the recirculating model from our previous work. Studies with glutamine supplementation in a number of models have demonstrated an immunomodulatory role in the small intestine, in part by enhancing mucosal integrity via tight junctions, or by mediating the cytokine cascade. Evidence of fMLP uptake without changes in TNF‐α concentration or myeloperoxidase 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. Support or Funding Information Canadian Institutes of Health Research, Research & Development Corporation of Newfoundland and Labrador
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".