A11 IMMUNOGLOBULIN G AS A NOVEL SELECTIVE MARKER FOR THE IDENTIFICATION OF INTESTINAL PATHOBIONTS IN PAEDIATRIC INFLAMMATORY BOWEL DISEASES
Bibliographic record
Abstract
Several studies support a role for gut microorganisms in the development of the common and severely debilitating chronic inflammatory bowel diseases (IBD), Crohn disease (CD) and ulcerative colitis (UC). To date, most studies have examined only samples from stool or inflamed areas, limiting the ability to differentiate between cause and effect. Our recent work examined the uninflamed terminal ileum (TI) in pediatric UC, and showed changes in diversity and composition of bacteria, suggesting that microbes proximal to diseased areas may drive inflammation distally. As immunoglobulin (Ig)G is increased in IBD and has been shown to bind more selectively to pathogens than its counterpart, IgA, we hypothesized that IgG is formed in response to invasive microbes, and could be used to identify specific taxa involved in IBD pathogenesis. To test this, we isolated IgG-bound intestinal bacteria, identified by 16S rDNA sequencing, and tested their virulence in vitro. TI luminal washes were collected during endoscopy of pediatric IBD patients and non-IBD controls. IgG bound (IgG+) and unbound (IgG-) bacteria were separated and collected using FACS and DNA was extracted for 16S rDNA sequencing (Ilumina MiSeq platform). Virulence of specific IgG-bound bacteria was tested in-vitro via gentamycin protection assay, microscopy and qPCR for markers of immune response. Species diversity and microbial composition were reduced in UC compared to non-IBD. Furthermore, the ratio of IgG+/IgG- bacteria increased in CD and UC patients by 2 and 1.5 fold, respectively. Although total abundance of Burkholderia cepacia, was comparable in IBD and non-IBD, there was a 2.5 and 4.1 fold increase in the ratio of IgG+/IgG- binding to B. cepacia in remission/mild or moderate/severe UC, respectively, compared to non-IBD. B. cepacia was previously identified in the ileum of IBD cohorts however, it is not typically recognized as an intestinal pathogen. B. cepacia displays pro-inflammatory effects and invasive potential in an in-vitro model, supporting its pathobiont potential and further supporting the use of IgG as a marker of pathobionts in IBD. We have demonstrated the ability of IgG-binding to selectively identify previously unrecognized mucosa-associated pathobionts, validated in-vitro. Elucidating the role of specific bacterial species in UC pathogenesis will underpin new strategies to improve our ability to direct therapies to those patients most likely to respond. CCCCCFA
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".