P708 Ileal involvement defined by Montreal classification in Crohn’s disease is associated with a distinct microbial composition in ileal and colonic mucosa
Bibliographic record
Abstract
Abstract Background The Montreal classification of inflammatory bowel disease (IBD) recognizes distinct subgroups based on location of disease, age at onset and behaviour for Crohn’s disease (CD) and extent in ulcerative colitis (UC). CD with ileal involvement is in part genetically determined and tends to progress to surgery and to be more refractory to medical therapy compared to colonic disease location. We investigated the association of different aspects of the Montreal classification with the ileal and colonic mucosa-associated microbiota. Methods Healthy control (HC) and IBD patients underwent colonoscopy with biopsy samples taken from terminal ileum, ascending and sigmoid colon. Mucosal 16s rRNA gene profiling was analysed and an amplicon sequence variant table was generated and normalized. Patients with prior intestinal resection, IBD-unclassified and recent antibiotic exposure were excluded. Endoscopic activity was defined as a segmental Mayo endoscopic subscore > 0 in UC and a simple endoscopic score > 2 in CD. Blood samples were drawn for genotyping and a weighted genetic risk score (GRS) was built based on 169 IBD risk variants. Pooled ileal and colonic samples were analysed for taxonomic differential abundance (DA) among the variables of the Montreal classification using a linear mixed-effects model (MaAsLin2) with age, sex, biopsy site, endoscopic activity and GRS as covariates. P-values were corrected for false discovery rate (FDR) and < 5% was considered significant. Results A total of 546 biopsy samples from 201 IBD patients and 48 HC were analysed. The characteristics of the cohort and Montreal classification are depicted in the Table. At colonoscopy 168 samples (31.4%) showed endoscopic activity. The multivariate analysis revealed that the genera Agathobacter and Faecalibacterium, as well as the family Ruminococacceae and the order Oscillospirales were significantly reduced in CD with ileal involvement (L1+L3) when compared to either isolated colonic CD (L2), UC (any extent) and HC independent of age, sex, endoscopic activity, biopsy site, and GRS (Figure). Samples from UC and isolated colonic CD patients did not show differences in their microbial profile irrespective of biopsy site. No differences in DA were observed in subgroups based on age at onset and disease behaviour in CD or extent in UC. GRS was not associated with microbial composition. Conclusion These data suggest that CD with ileal involvement (Montreal L1+L3) is a major determinant of the tissue-associated microbial composition in both ileal and colonic mucosa irrespective of variables such as endoscopic activity and GRS. The reduction of several beneficial microbes in CD with ileal involvement might partially explain the more progressive phenotype in such patients.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.001 |
| Research integrity | 0.001 | 0.000 |
| 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".