A17 ASSOCIATION BETWEEN HOST INFLAMMATION-RELATED PROTEOMICS AND GUT MICROBIOME IN HEALTHY FIRST-DEGREE RELATIVES OF CROHN’S DISEASE PATIENTS
Bibliographic record
Abstract
Abstract Background Crohn’s disease (CD) is a chronic inflammatory condition of the gastrointestinal tract. It has been suggested that the cause of CD is due to microbial and environmental factors that induce an imbalance of the immune system in genetically susceptible individuals. The Genetic Environmental Microbial (GEM) Project is a prospective study of asymptomatic first-degree relatives (FDR) of CD patients, recruited to understand the biological and environmental determinants of disease development. Aims Here, we aim to define the relationships between the host inflammation-related proteomics and gut microbiome composition in a cohort of 320 healthy CD FDRs at the time of recruitment. Methods We measured 92 inflammation-related serum proteins using the Olink® ’Inflammation’ proteomics panel. Stool microbial composition was determined by sequencing the V4 region of the 16S rRNA. To assess the relationship between serum protein levels and the relative abundance of microbial taxa, we used a zero-inflated two-part regression model corrected for multiple-comparisons (significant association at p< 2.75 × 10–4). Results We found fifteen serum proteins that were each significantly associated with the relative abundances of one to five genera or families, depending on the analyte. Of particular interest to CD, the relative abundance of both TNF-β and LIGHT (TNFSF14) were negatively associated with the relative abundance of bacteria in the Parabacteroides genus. Both TNF-β and LIGHT are members of the Tumor Necrosis Factor (TNF) family of cytokines with roles in mucosal healing, IgA production, and in control of innate lymphoid cells (ILCs). These processes have been hypothesized to have critical roles in CD pathology. Interestingly, prior work also demonstrates that Parabacteroides distasonis enhanced colitis in a mouse model and was isolated from a gut wall-cavitating microlesion in a patient with severe CD. Other inflammation-related proteins with significant taxa associations include IL-2, IL-33, OSM, 4E_BP1, IL-1α, ARTN, AXIN1, and CDCP1. Conclusions This study highlights the associations between inflammation associated proteomics and gut microbial taxa in asymptomatic FDRs of CD patients. The mechanisms explaining this association will require further analysis. Funding Agencies CCC The Leona M. and Harry B. Helmsley Charitable Trust
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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 | 0.002 |
| 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) | 0.003 | 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".