A18 EARLY LIFE EXPOSURE TO PARENTAL CROHN'S DISEASE IS ASSOCIATED WITH GUT MICROBIAL COMPOSITION AND FUNCTION, GUT PERMEABILITY AND INCREASED RISK OF FUTURE CROHN'S DISEASE
Bibliographic record
Abstract
Abstract Background Previous studies show that offspring of persons with Crohn’s disease (CD) have a 7-fold higher risk of incident CD than the general population. Newborns of women with CD (vs healthy women) have altered stool microbiome composition and elevated fecal calprotectin (FCP). The perinatal period (pregnancy and first year postpartum) is critical for the development of the gut microbiome and immune system. Aims We investigated whether perinatal exposure to parental CD (compared to exposure later in life) has an impact on offspring’s gut barrier function, microbiome composition, and risk of future CD. Methods We assessed 1252 healthy offspring of persons with CD who were recruited in the CCC-GEM Project. We classified offspring into "perinatally exposed (pregnancy and first year postpartum)" vs "exposed later in life" to parental CD diagnosis. We measured baseline FCP and urinary fractional excretion ratio of lactulose to mannitol (marker of intestinal permeability, LMR). Fecal microbiome composition was determined by 16S rRNA gene sequencing. Microbiome function was imputed by PICRUSt2 (q value defined as false discovery rate-adjusted p<0.05). Multivariable regression and Cox proportional-hazards analyses were used to assess if peri-natal exposure to parental CD is associated with LMR, FCP, altered microbial composition, and future CD onset. Results Offspring exposed to a CD parent perinatally had a 4.7-fold higher risk (aHR 95%CI 1.3-17.5) of developing CD compared to those exposed to a parent who developed CD later in life (11/586 vs 3/666). LMR was significantly higher in the offspring exposed to parental CD perinatally (p=0.003), while no significant difference was observed for FCP at recruitment (p=0.94). Five bacterial taxa were significantly increased in the perinatally exposed group (q<0.05). The microbial functions such as glycine amidinotransferase, serine protein kinase and cyanophycin synthase were significantly increased in the perinatally exposed group (q<0.05). Conclusions Offspring exposed to parental CD perinatally had a higher risk of developing CD than those exposed to parental CD later in life. Early life exposure to parental CD was associated with higher baseline LMR, altered bacterial taxa and functional capacities. Environmental exposure during the perinatal period may determine the offspring’s risk of developing CD. Funding Agencies CAG, CCC, CIHRCanada Research Chair
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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".