P853 Immunoglobulin G selectively binds pathobionts in the terminal ileum of paediatric IBD patients
Bibliographic record
Abstract
Gut microorganisms have been associated with the development of Crohn disease (CD) and ulcerative colitis (UC) in a number of studies to date; however, most studies focused on identifying microbial changes have examined only samples from stool or inflamed areas of the intestine, limiting the ability to differentiate between cause and effect. Therefore, we focused on bacteria from non-inflamed areas and sought to develop a method to specifically identify pathobionts. Our hypothesis was that immunoglobulin (Ig)G, an antibody naturally formed in response to invasive microbes, can be used as a novel marker of pathobionts in IBD patients. Building on our recent work that demonstrated altered composition and diversity of bacteria from the uninflamed terminal ileum (TI) in paediatric UC patients, we focused on microbes proximal to diseased areas as we believe they may drive inflammation distally. Intestinal washes were collected during endoscopy from the TI of paediatric IBD patients and non-IBD controls. Using fluorescence-activated cell sorting (FACS) we separated IgG-bound (IgG+) from unbound (IgG-) bacteria, extracted their DNA, and analysed composition by 16S and metagenomic sequencing using the Illumina MiSeq platform. We then confirmed virulence of specific IgG-bound bacteria in-vitro. FACS was efficient in separating IgG+ from IgG- bacteria; the method was validated by Image Cytometry. Greater numbers of IgG-bound microbes were observed in CD (2-fold) and UC (1.5-fold) patients, compared with non-IBD. Interestingly, while there was relatively little difference in species abundance between IBD and non-IBD patients, IgG binding favoured specific Bacteroidetes, Firmicutes, and Proteobacteria in CD, and specific Bacteroidetes and Proteobacteria in UC. Many of these changes were more prominent in moderate/severe disease than in cases that were mild/in remission. When examined in-vitro, selective IgG+ species displayed pro-inflammatory effects and invasive potential, supporting their pathobiont potential. Using FACS to isolate IgG-bound bacteria collected from luminal washes in children with IBD we selectively identified previously unrecognised mucosa-associated microbes with apparent pathobiont qualities, associated with IBD. Further characterizing the role of specific bacterial species bound by IgG may provide insight into IBD pathogenesis and could assist in directing therapies to those patients most likely to respond, including by use of microbe-altering treatments.
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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 | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| 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 | 0.000 |
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".