P912 Increased Primary Bile Acids with Ileocolonic Resection Impact Ileal Inflammation and Gut Microbiota in Inflammatory Bowel Disease
Bibliographic record
Abstract
Abstract Background A majority of Crohn’s disease (CD) patients require surgery. Ileitis recurs after most ileocolectomies and is a critical determinant for outcomes. The impact of ileocolectomy-induced bile acid (BA) perturbations on intestinal microbiota and inflammation are unknown. We characterized relationships between ileocolectomy, stool BA, microbiota, and intestinal inflammation in inflammatory bowel disease (IBD). Methods Validated IBD clinical and endoscopic assessments were prospectively collected. Matched primary and secondary BA concentrations measured in stool using Agilent Quadrupole Time of Flight Liquid chromatography-mass spectrometry were compared based on ileocolectomy and ileitis status. Primary BA thresholds for ileitis were evaluated using area under the receiver operating characteristic curve analyses. In CD, endoscopic remission was defined as SES-CD <3 or Rutgeerts 1. In UC, ER was defined as UC-ESS ≤ 1. Metagenomic sequencing profiled microbial composition and function. Relationships between ileocolectomy, BA and microbiota were assessed. Results In 166 patients, elevated primary and secondary BA existed with ileocolectomy. With ileitis, only primary BA (795 nMol/g vs 398 nMol/g, p=0.009) were higher compared to without ileitis. The optimal primary BA threshold (≥228nMol/g) identified ileitis on multivariable analysis (OR=2.3, p=0.04). Similar primary (471 nMol/g vs. 606 nMol/g, p=0.8) and secondary (382 nMol/g vs. 242 nMol/g, p=0.2) BA concentrations existed with and without colonic inflammation. Microbial diversity (Shannon index, p=0.0006), Faecalibacterium prausnitzii and O-acetylhomoserine aminocarboxypropyltransferase (MetY, p=0.0002) were decreased with elevated primary BA. Amongst ileocolectomy patients, only those with elevated primary BA had diversity (p=0.01), F.prausnitzii and MetY (p=0.04) reductions. Those with both ileocolectomy and intermediate (p=0.002) or high (≥228nMol/g, p=9.1e-11) ) primary BA had reduced F.prausnitzii compared to without ileocolectomy (Figure 1). Those with ileocolectomy and low (<29.2nMol/g) primary BA had similar F.prausnitzii as those without ileocolectomy (P=0.13). MetY was reduced with ileitis (p=0.02). Conclusion Elevated primary bile acids were associated with ileitis, and reduced microbial diversity, F.prausnitzii abundance, and enzymatic expression of MetY (acetate and L-methionine producing enzyme expressed by F.prausnitzii) and were the only factor associated with these findings after ileocolectomy.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".