A118 EXPOSURE TO CROHN’S DISEASE-ASSOCIATED ADHERENT-INVASIVE E.COLI (AIEC) AT THE HEIGHT OF INFECTIOUS COLITIS IMPAIRS HOST-MEDIATED CLEARANCE OF AIEC
Bibliographic record
Abstract
Prior exposure to foodborne pathogens causing acute gastroenteritis can have long lasting consequences, including an increased risk of Crohn’s disease (CD). However, the underlying pathologic connection between the inciting event and CD, a chronic inflammatory condition, is not known. Adherent-invasive E. coli (AIEC) are enriched in the intestinal mucosa of CD patients though exactly how it contributes to this chronic illness is unclear. We recently demonstrated that AIEC-colonized mice exposed to acute infectious gastroenteritis drives the expansion of tissue-associated AIEC in regions of pronounced inflammation. Since AIEC are associated with inflamed regions of the gut, we hypothesized that host inflammation could be a susceptibility factor that promotes de novo AIEC colonization. We tested this in a conventional C57BL/6 mice that when exposed to AIEC develop a self-limited infection. C57BL/6 mice were infected with Citrobacter rodentium to initiate acute infectious colitis, or kept uninfected. Subsequently, C. rodentium-infected mice were exposed to AIEC at one of three distinct stages of colitis (peak Citrobacter load, peak inflammatory response, or during convalescence after Citrobacter clearance and mucosal restitution). Over the infectious period, bacterial load was measured in feces and tissues. Pathology was evaluated by ELISA and microscopically. We report that Citrobacter-colonized mice challenged with AIEC at either the peak of Citrobacter load or during the convalescence period resulted in clearance of AIEC within 2–3 weeks and without overt influence on overall pathology. Strikingly, Citrobacter-colonized mice infected with AIEC during peak period of colitis led to bacterial persistence and impaired clearance as mice remained AIEC-positive as late as day 59 after the acute infectious colitis resolved. In contrast, Citrobacter-naïve mice resolved the infection by day 19 and lacked the pronounced pathology observed in the co-infected group. Together, our data suggests that the period of peak inflammation following infectious colitis is a time when host succeptitibilty to AIEC is greatest, leading to protracted AIEC colonization and greater immunopathology. CAG, 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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".