Increasing Small Intestinal Permeability Worsens Colitis in the IL-10−/− Mouse and Prevents the Induction of Oral Tolerance to Ovalbumin
Bibliographic record
Abstract
BACKGROUND: Increased intestinal permeability is found in noninflamed portions of the gut of inflammatory bowel disease patients and in their first-degree relatives, suggesting that it is not a consequence of inflammation. Additionally, increased small intestinal permeability precedes colonic disease in animal models of inflammatory bowel disease. However, it is not known how small intestinal permeability modulates disease in the colon. The aim of this study was to determine if increasing small intestinal permeability modulates colonic inflammation in interleukin (IL)-10 mice and if an increase in permeability is sufficient to prevent oral tolerance to a dietary antigen. METHODS: IL-10 mice were treated with the zonula occludens toxin pathway agonist AT-1002 for 8 weeks, and colitis severity was measured at 12 weeks of age. Wild-type mice were also treated with AT-1002 and fed ovalbumin (OVA) to determine the local and systemic immune response to this antigen under increased small intestinal permeability conditions. RESULTS: IL-10 mice treated with AT-1002 showed exacerbated colitis at 12 weeks of age. AT-1002 also induced a significant OVA-specific humoral response compared with mice that received OVA alone. In addition, the intestinal production of IL-10 and TGF-β in response to oral OVA was prevented when OVA was given with AT-1002. CONCLUSIONS: Increasing small intestinal permeability worsens colitis in IL-10 mice, and it prevents the development of oral tolerance to OVA in wild-type mice. This study suggests that small intestinal permeability is not merely a consequence of inflammation but a condition that leads to two of the main pathological features of inflammatory bowel disease.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".