A111 ANALYSIS OF GUT MICROBIOME OF HEALTHY INDIVIDUALS THAT GO ON TO DEVELOP CELIAC DISEASE
Bibliographic record
Abstract
Celiac disease (CeD) is characterized by inflammation of the small intestine due to an intolerance to the gliadin fraction of gluten. Studies have identified a strong genetic component with disease. Several genetic variants have been located within genes of the HLA region, in fact, 85–95% of CeD subjects carry at least one variant of the HLA-DQ2 and/or HLA-DQ8 allele.However, carriers of these variant do not necessarilydevelop the disease. Indeed, although about 40% of the general population are thought to carry the HLA risk allele, only 2–5 % of healthy carriers will develop CeD over time. Recent findings suggest that the microbiota is a contributing factor toward the onset of CeD, however no preexiting celiac microbial signature has been identified. In this study, we assess the pre-disease fecal microbiome composition of CeD patients. As part of the ongoing GEM Project, we identified 15 subjects who self reported developing CeD. The diagnosis of CeD was supported by the presence of at least one genetic variant associated with CeD. Genotyping was performed using the HumanCoreEXOME chip and imputed to the 1KG genome imputation panel. Seven subjects had bacterial 16S rDNA from stool sequenced using MiSeq Illumina platform after amplification of the V4 hypervariable region. Closed reference operational taxonomic unit picking was performed against GreenGenes database (v 13_8) using QIIME (v1.9) pipeline.Four controls matched for Age, gender, and DQ2.2, DQ2.5, DQ4, and DQ8 allele. The relative abundanceof 230 taxa were compared using a conditional logistic regression. Covariates of the model included total number of reads per sample. Relative abundance of the genus Coprococcus and of an unknown genus of the Peptostreptococcacae family were higher in the CeD individuals (p <0.05). Alpha diversity, as assessed by the Shannon index was similar between the two groups. These findings suggest an increase in Coprococcus and of an unknown genus of the Peptostreptococcacae family in prediseasesamples of CeD patients, although the p values did not survive correction for multiple testing. The potential implication of these difference remain to be confirmed but suggest the possibility of a microbiome driven initiation of disease. Submitted on behalf of behalf of the CCC IBD GEM Project research team. CCC, CIHR
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".