Small bowel epithelial gaps and intestinal permeability in Crohnʼs disease
Bibliographic record
Abstract
Crohn's disease is a chronic relapsing condition characterized by patchy inflammation anywhere along the alimentary tract from mouth to anus. It affects the mucosal barrier in genetically susceptible individuals with a defect in the innate immune response resulting in chronic activation of the adaptive immunity in the intestine. Loss of epithelial cells can be induced by pro-inflammatory cytokines or may be a primary defect and has been shown to precede inflammatory reactions in the intestinal wall. Therefore, epithelial cell shedding may promote chronic intestinal inflammation and epithelial ulceration under certain conditions. We hypothesize that epithelial cell shedding is increased in patients with Crohn's disease, and contribute to abnormal intestinal permeability. In this study, we quantified the epithelial gaps and epithelial cells seen on confocal endomicroscopy (CEM) imaging of patients with Crohn's disease compared to controls. Intestinal permeability was also measured in these patients. The study cohort of Crohn's disease patients undergoing routine colonoscopy were on maintenance therapy with immunosuppressives or oral 5-ASA compounds. The controls were patients undergoing screening colonoscopy for colon cancer without any gastrointestinal (GI) symptoms or history of chronic GI disorders. Both cohorts had small intestinal permeability determined with a lactulose/mannitol test. CEM was performed using the Cellvizio confocal Gastroflex miniprobes immediately after the intestinal permeability assay. Subjects were imaged with CEM by a single, blinded endoscopist following a standardized method. After intravenous administration of fluorescein to enhance imaging, serial confocal images of the terminal ileum were recorded in all patients at the same location;10 cm proximal to the ileocecal valve. An anti-spasmotic agent (glucagon) was used whenever necessary to reduce movement artifacts. The experimental cohort consisted of 6 controls (2 M; mean age = 58 ± 14 yrs) and 8 active and inactive Crohn's patients (5 M; mean age = 44 ± 15 yrs). Adequately imaged villi, defined as villi with 75% surface area visualized in the CEM images, were used for analysis. Gaps were ascertained in at least three different sequential images. Ten villi from each patient were manually counted for the number of epithelial cells and gaps. The gap density was defined as the number of gaps divided by the number of cells counted in the 10 adequately imaged villi (gap density = gaps/cells). The gap density (mean ± standard error) was 17.70 ± 5.64 gaps/1000 cells for controls and 117.30 ± 32.90 gaps/1000 cells for Crohn's disease patients (p= 0.001). Adherent bacteria were not observed in the epithelial gaps of controls, whereas they were seen in the gaps of 2 Crohn's disease patients. The lactulose/mannitol ratio was 0.014 ± 0.0027 for controls and 0.020 ± 0.0027 for Crohn's patients (p= 0.15). The epithelial gap density is significantly higher for patients with Crohn's disease compared to healthy non-IBD controls. This is associated with slightly increased permeability in these patients, however, increased patient numbers are needed to evaluate the strength of this relationship.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| 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".