What question did this study set out to answer?

The research aims to investigate the relationship between dietary lipids and Crohn’s disease risk, focusing on fecal calprotectin and non-inflammatory pathways.

January 23, 2026

P0145Dietary alpha-linolenic acid contributes to reduced Crohn’s disease risk independent of fecal calprotectin

Key Points

The research aims to investigate the relationship between dietary lipids and Crohn’s disease risk, focusing on fecal calprotectin and non-inflammatory pathways.
Enrolled 5,013 first-degree relatives of Crohn's disease patients in the GEM Project.
Analyzed dietary intake using food frequency questionnaires and fecal calprotectin measurements.
Used Cox proportional hazards regression to evaluate associations between fatty acids and incident Crohn’s disease, adjusting for confounding factors.
Conducted mediation analysis to differentiate between inflammatory and non-inflammatory pathways for fatty acids.
Performed age-stratified analyses to examine the effects across different age groups.
74 of 2,450 evaluated individuals developed Crohn’s disease over an average follow-up of 9.8 years.
Alpha-linolenic acid was found to significantly reduce the risk of Crohn’s disease with an HR of 0.73, mainly through non-inflammatory pathways.
Age-stratified analysis revealed that the protective effect of alpha-linolenic acid was significant in adults aged 25 years and older (HR = 0.48).
Other fatty acids, such as oleic and palmitoleic acids, had varying levels of association with Crohn’s disease risk, with some primarily linked to inflammatory pathways.

Abstract

Abstract Background Dietary fatty acids may influence the development of Crohn’s disease (CD), but the underlying mechanisms are unclear (1). We examined: 1) the relationship between dietary lipids and CD risk in healthy first-degree relatives (FDR), focusing on Fecal Calprotectin (FCP) and non-FCP-dependent pathways, and 2) whether age modifies these associations. Methods The GEM Project enrolled and prospectively followed 5,013 FDR of CD patients. We analyzed 2,450 participants with baseline dietary assessment via food frequency questionnaire (representing dietary pattern in the past year) and FCP measurement. Dietary lipid intake was estimated using a database derived from Canadian nutrient file (CNF) and validated by serum metabolomic profiling (Metabolon®). FCP was measured by BÜHLMANN fCAL® ELISA. Cox proportional hazards regression evaluated associations between fatty acids and incident CD, adjusting for age, sex, and total energy intake. Formal mediation analysis decomposed effects into FCP-mediated (inflammatory pathway) versus FCP-independent (non-inflammatory) components. Age-stratified analyses tested effect modification across pediatric (15y), young adult (15-25y), and adult (≥25y) groups. Results Baseline FCP demonstrated a dose-response relationship with incident CD (p-trend 0.001), validating its role as an inflammatory pathway marker. 74 of 2450 FDR developed incident CD during follow-up (median 9.8 years, IQR 6.1-13.1 years). Multiple fatty acids contributed to CD risk with variable degrees of FCP mediation. Alpha-linolenic acid (ALA) was inversely associated with risk (HR = 0.73, 95% CI: 0.58–0.93, p = 0.01), with predominantly FCP-independent effects (80% non-FCP-mediated, 20% FCP-mediated), suggesting non-inflammatory mechanisms. In contrast, oleic acid (HR = 0.84, 95% CI: 0.69-1.02, p = 0.13) operated primarily through FCP-mediated pathways (74% inflammatory). Palmitoleic acid (HR = 1.13, 95% CI: 0.92-1.39, p = 0.24) and cholesterol (HR = 1.29, 95% CI: 1.01-1.63, p = 0.08) showed positive associations with varying FCP mediation (100% and 38%, respectively). Age-stratified analysis demonstrated significant effect modification for ALA, with inversely association with risk observed exclusively in adults ≥25 years (HR = 0.48, 95% CI: 0.26-0.88, p = 0.017), but not in pediatric or young adult groups. Conclusion Dietary fatty acids modulate CD risk through mechanisms with varying degrees of involvement in the inflammatory pathway. ALA’s predominantly non-inflammatory protective effects (80% FCP-independent) were most effective in adults ≥25y, suggesting both pathway-specific and age-specific opportunities for dietary prevention strategies. Reference: 1. Ananthakrishnan AN, Khalili H, Konijeti GG, Higuchi LM, de Silva P, Fuchs CS, Willett WC, Richter JM, Chan AT. Long-term intake of dietary fat and risk of ulcerative colitis and Crohn’s disease. Gut. 2014 May;63(5):776-84. doi: 10.1136/gutjnl-2013-305304. Epub 2013 Jul 4. PMID: 23828881; PMCID: PMC3915038. Conflict of interest: Dr. Guevara Agudelo, Fredy Alexander: No conflict of interest Jeong, Sean: No conflict of interest Khorasaniha, Reihane: No conflict of interest Waslyk, Alyssa: No conflict of interest Griffiths, Anne: No conflict of interest Steinhart, Hillary: No conflict of interest Panaccione, Remo: No conflict of interest Armstrong, Heather: No conflict of interest Lee, Sun-Ho: No conflict of interest Croitoru, Kenneth: No conflict of interest Turpin, Williams: No conflict of interest

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