A267 IDENTIFYING ENTEROBACTERIACEAE VIRULENCE GENES ASSOCIATED WITH ACTIVE DISEASE IN ULCERATIVE COLITIS PATIENTS USING CULTURE-DEPENDENT AND -INDEPENDENT APPROACHES
Bibliographic record
Abstract
Abstract Background The prevalence of inflammatory bowel disease (IBD) in Canada is among the highest in the world and is estimated to affect 1 in 100 Canadians by 2030. Ulcerative colitis (UC) is a type of IBD characterized by mucosal inflammation of the large intestine. UC is believed to arise through a complex interplay of the host immune responses and changes in the gut microbiota in a genetically susceptible individual. Therapies targeting the gut microbiota, such as antibiotics and fecal microbiota transplantation (FMT), have been effective in treating UC, suggesting infectious triggers should be explored. Purpose Some data suggests the development of UC can be driven by pathogenic bacteria of the family Enterobacteriaceae, which can carry virulence genes important for colonizing the gut (e.g. fimH) and disrupting the intestinal epithelium (e.g. hylA). However, many studies have focused on a single species (e.g. Escherichia coli) and thereby underestimate the importance of these virulence genes that are shared across the Enterobacteriaceae family. I aim to investigate whether specific virulence genes contribute to disease activity in some patients with UC and to show that these virulence genes are carried by strains of many Enterobacteriaceae species. Method UC patient stool samples were collected throughout enrolment in randomized control trials of FMT for adult UC and microbiome studies in early-onset pediatric UC. The stool samples were cultured on MacConkey agar to enrich for Enterobacteriaceae. Samples from before and after treatment were sent for targetted cultured-enriched metagenomic sequencing and strains were isolated from baseline samples only for whole genome sequencing. The taxonomy of each genome and taxonomic composition of each metagenome were annotated along with virulence genes and antimicrobial resistance genes. Phenotypic assays of cultured isolates were used to capture diversity and virulence activity. Result(s) Approximately 7500 colonies from UC patient stool samples were isolated and phenotyped. Based on the initial screens, 130 isolates were selected to comprise our Enterobacteriaceae strain collection. Across all patient samples, we detected 19 different species of the Enterobacteriaceae family across six genera from the genomic and metagenomic data. We identified virulence genes found across multiple species from the Enterobacteriaceae family within genomes and metagenomes, and by performing phenotypic assays of the cultured isolates. Conclusion(s) Further exploration of the distribution of these virulence genes in UC patients during active disease or remission and healthy controls can provide insight into the pathogenesis of UC. Identifying infectious agents in even a subset of UC patients will allow for more targeted diagnosis and treatment approaches. Disclosure of Interest None Declared
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| 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) | 0.002 | 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".