A38 EXPLORING HOW BOWEL PREPARATION CAN AFFECT INFLAMMATORY BOWEL DISEASE VIA THE GUT MICROBIOTA
Bibliographic record
Abstract
Abstract Background Inflammatory bowel disease (IBD) is a debilitating disorder that targets the gastrointestinal (GI) tract. Although its causes remain unknown, recent studies have identified changes to the gut microbiota associated with IBD. While most gut bacteria are essential for GI health, pathobionts are bacteria that are prevalent in IBD patients and that can act as pathogens and induce inflammation. IBD patients undergo routine endoscopies which require the administration of laxative-based bowel prep to clear out the luminal contents of the GI for the endoscope. It has been found that after bowel prep some IBD patients experience inflammatory flareups. IBD patients may experience adverse reactions following bowel prep, including increased inflammation, emergency room visits, and medication adjustments. Importantly, bowel prep perturbs the gut microbiota, depleting beneficial microorganisms, while allowing pathobiont strains to thrive, which could be the cause for worsened symptoms post-bowel prep in some patients. Aims We hypothesize that the altered intestinal microenvironment during bowel prep causes commensal bacteria depletion and favours osmotolerant pathogenic species that lead to increased inflammation in two systems: 1) in a model disease-causing microorganism, Salmonella enterica 2) in an IBD microbiota. Methods To investigate pathogen expansion after bowel prep a Salmonella mouse model was established. Microbiota changes were determined by 16S rRNA sequencing and spot plating. Changes to the gut environment and the mechanism for pathogen colonization were characterized using Salmonella mutants and confocal imaging. To identify changes to the IBD microbiota, a humanized mouse model was established, and microbiota changes were investigated as done in the Salmonella model. IBD-associated pathobiont growth was also characterized in in vitro conditions that were identified in our in vivo model. Results We have demonstrated that bowel prep increases GI osmolality and leads to increased Salmonella colonization in the gut and systemic organs following bowel prep unlike mice treated with vehicle, supporting our hypothesis. We then explored the effects of bowel prep in a humanized mouse model of IBD, which showed increased translocation of bacteria from the gut to internal organs post-prep. Additionally, IBD-associated pathobionts were able to grow much greater than commensal strains highlighting that IBD pathobionts can persist in the gut after bowel prep. Conclusions Our study highlights that bowel prep disrupts the gut microbiota and the intestinal environment allowing for pathogen colonization and bacterial translocation. Therefore, bacterial translocation could provide mechanistic insight for inflammatory flareups following bowel prep. Ultimately, our research underscores the importance of the gut environment in facilitating pathobiont exacerbation of IBD. Funding Agencies 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 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".