P572 Half of children with acute severe colitis have predominant single faecal bacterial species, mostly Escherichia coli: Microbiome results from the PRASCO trial
Bibliographic record
Abstract
Acute severe ulcerative colitis (ASC) is one of the few medical emergencies of gastroenterology. We previously reported the clinical results of the PRASCO randomised controlled trial in which oral antibiotics (AB) improved disease activity after 5 days of treatment in children with ASC. This suggests that the microbiome is implicated in the aetiology and progression of ASC. We thus aimed to explore the microbiome of children enrolled in the PRASCO trial. In the PRASCO trial, 26 children with ASC were randomised: 11 received IV corticosteroids (IVCS) and 15 received four oral AB's (amoxycillin, doxycillin/ciprofloxacin, metronidazole, vancomycin) in addition to IVCS. Stool samples were collected at regular intervals during admission. Metagenomic sequencing was performed using Illumina Nextera XT library preparation kit on a HiSeq platform. After filtering low quality and human reads using the KneadData pipeline, species-level taxonomic abundances were inferred for all samples using MetaPhlAn2. At baseline before treatment, 14/26 (54%) children harboured more than 30% of a single species: 9 (35%) with Escherichia coli, 2 (7.7%) Haemophilus species, and 1 (3.8%) each with Klebsiella pneumoniae, Barnesiella intestinihominis or Parabacteroides sp. (none with Fusobacterium varium). interestingly, of the 15 children in the AB arm, 11 (73%) had a transient relative bloom of >50% Enterobacteriaceae (mainly E. coli) after treatment, compared with only 3/11 in the IVCS only arm (p = 0.02). Despite this, disease activity at Day 5 was lower in the AB arm and time to remission was shorter (p = 0.049). When analysing all samples, several species of Lachnospiraceae family and Clostridium bartlettii were significantly and positively associated with remission. C. bartletti and R. torques (previously observed to be depleted in IBD and known butyrate producers) were lower in children with more severe disease. This is the first report of microbiome pattern in ASC, showing provocative results. Over half of children with ASC have gut microbiomes highly enriched (>30%) at baseline with a specific species, mostly Enterobacteriaceae. This association may suggest that some ASC episodes are triggered by yet unknown enteric infections. While our antibiotic cocktail transiently exacerbated this enrichment it reduced disease activity, possibly due to niche availability after treatment, which can subsequently be filled by butyrate-producing microbes. In addition, the enrichment is relative to other species; it is possible that the absolute count was much lower in the AB group. Dysregulation of butyrate production may be associated with ASC in children. This study was supported by grants from: IOIBD, Helmsley Charitable Trust and Janssen
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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 | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.010 | 0.002 |
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".