Poster Session II - A235 FROM PLATE TO GUT: AGE-DEPENDENT EFFECTS OF DIETARY LIPIDS AND GUT MICROBIOTA ON CROHN’S DISEASE RISK

Abstract Background Previous studies suggest dietary lipids may influence Crohn’s disease (CD) risk. Our group previously identified gut microbial signatures predictive of CD onset. However, how dietary lipid–microbiota interactions may contribute to CD risk remains poorly understood, especially across age groups from childhood to early adulthood. Aims To investigate age-dependent associations between dietary lipids and CD risk. Methods We analyzed 2,342 first-degree relatives of CD patients from CCC-GEM (66 pre-CD, 2,276 controls). Participants completed food frequency questionnaires and provided stool samples at recruitment. Clustering analysis of 53 dietary lipids yielded 26 representative lipids. Stool microbiome was profiled by 16S rRNA sequencing; fecal calprotectin (FCP) measured by ELISA. Cox models assessed time-to-CD onset; age-stratified regression examined lipid-FCP associations across pediatric (<15), young adult (15-25), and adult (25-40) groups. Results We observed age-dependent associations between dietary lipids, inflammation, and CD risk. In the overall cohort, alpha-linolenic acid (ALA) (β = 177.15, p = 0.007) and behenic acid (β = 159.70, p = 0.005) associated with elevated FCP. Age-stratified analysis revealed these pro-inflammatory effects were pediatric-specific: ALA (β = 0.25, p = 0.035), behenic acid (β = 0.36, p = 0.025), and trans-palmitoleic acid (β = 0.98, p = 0.046) elevated FCP in children but not in young adults or older adults (all p > 0.05). Despite elevating inflammation in children, protective CD associations emerged exclusively in young adults (15-25): ALA (HR = 0.53, p < 0.001), behenic acid (HR = 0.75, p = 0.042), and tetracosenoic acid (HR = 0.77, p < 0.001), with no effects in pediatric or older adult groups. These associations remained significant after FCP adjustment (ALA HR = 0.61, p = 0.008; behenic acid HR = 0.72, p = 0.020; tetracosenoic acid HR = 0.81, p = 0.043). In the overall cohort, cholesterol associated with increased CD risk (HR = 1.37, p = 0.04). Trans-palmitoleic acid correlated with R. torques only in adults (ρ = 0.07-0.09, p < 0.01). Conclusions Our findings reveal age-specific lipid associations with CD risk, with inverse associations in young adults (15-25) but not pediatric (<15) or older adults (25-40). While ALA and behenic acid were associated with reduced CD risk in young adults independent of FCP, their pro-inflammatory effects in children without corresponding risk reduction suggest age-dependent mechanisms requiring validation in prospective cohorts. Funding Agencies CCC, CIHRHelmsley Charitable Trust, and International Organization for the Study of Inflammatory Bowel Diseases (IOIBD)