A297 GOBLET CELLS AND INTESTINAL TREFOIL FACTOR PLAY CRITICAL ROLES IN INNATE PROTECTION AGAINST CLOSTRIDIUM DIFFICILT COLITIS AND MEDIATE RECOVERY FOLLOWING CDIF COLITIS.
Bibliographic record
Abstract
Cdif colitis is a leading cause of morbidity and mortality in many populations including elderly hospitalized, those with inflammatory bowel disease, and the immunosuppressed. Although depletion of the density and diversity of the intestinal microbiome is clearly the main underlying mechanistic risk factor, little is known of the innate mechanisms involved in protection against Cdif and those involved in recovery following Cdif colitis. One of the hallmarks of Cdif colitis are pseudomembranes (composed of mucus, fibrin and debris). Altered mucus secretion (MUC2) has been described in pts with Cdif colitis. The hypothesis of the present study was to assess the role of goblet cells, mucins and associated growth factors (ITF, secreted by goblets cells) in mediating protection against Cdif induced injury/inflammation and recovery following Cdif colitis. Colitis was induced in C57Bl6 mice either via intrarectal administration of Cdif toxin (A&B) or in the Cdif oral gavage infection model. Human tissue models included; in vitro (CaCO2, IECs) & ex vivo studies (fresh human colonic biopsies exposed to toxin A/B). Cdif injury/inflammation was assessed via histology, MPO, cytokine release, permeability, LDH release, apoptosis markers. ITF, MUC2, KGF and goblet cells were assessed via WB, PCR, AB/PAS + immunostaining. Cdif toxin and infection significantly depleted goblet cells, the protective growth factor ITF and MUC2 in mouse and human tissues. Recovery from Cdif colitis was associated with increased ITF expression, MUC2 and goblet cell number. MUC2 -/- mice were more susceptible to Cdif colitis vs wt mice (increased MPO, histological scores). ITF -/- mice had similar levels of acute Cdif colitis but had marked impairment in recovery from colitis at 24 and 48h post toxin exposure. We then assessed the role of keratinocyte growth factor (KGF) which is upstream of ITF and induces ITF expression. KGF -/- mice had decreased ITF and increased toxin induced goblet cell depletion and markedly impaired recovery from Cdif colitis. Exogenous KGF (i.p.) enhanced recovery from Cdif colitis in wt and KGF-/- mice but not in ITF-/- mice. In our human tissue models ITF or KGF exposure reduced Cdif toxin induced injury (barrier function, LDH release, apoptosis and cytokine release). Goblet cells, MUC2 and growth factors ITF and KGF are important in the innate protection against Cdif colitis and are critical in the recovery from Cdif colitis. These findings mat lead to new approached in the management of patients with Cdif coltis. CIHR
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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) | 0.000 | 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) | 0.002 | 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".