β-Glucan and Inulin Estimated Intake Are Associated With Reduced Risk of Crohn's Disease, Improved Gut Barrier and Systemic Inflammation Markers, and Multi-Omic Signatures in a High-Risk Cohort.

Abstract

The cause of Crohn's disease (CD) remains unclear; however, evidence suggests fiber intake may play a role. We aimed to investigate the association between intake of total fiber and select fermentable fiber subtypes and future risk of CD in an at-risk population. The Genetic, Environmental, Microbial Project prospectively followed asymptomatic first-degree relatives of individuals with CD. Habitual intake of total fiber and select fiber subtypes was estimated from baseline food frequency questionnaires and biologic samples were collected. Incident CD was confirmed during follow-up. Cox proportional hazards models estimated hazard ratios (HRs) for CD. Associations between fiber subtype intake and urinary fractional excretion of lactulose-mannitol ratio, C-reactive protein, gut microbiota (16S ribosomal RNA sequencing), and serum proteomics (Olink) were evaluated using multivariable regression models. During a median follow-up of 8.5 years of 3314 first-degree relatives, 94 developed CD. Higher β-glucan (HR, 0.70; 95% confidence interval, 0.54-0.92) and inulin (HR, 0.68; 95% confidence interval, 0.49-0.96) intake were associated with lower CD risk. Associations were strongest in those with higher baseline relative abundance of Erysipelotrichaceae UCG-003, but weaker with higher Colidextribacter. Higher β-glucan and inulin intake were associated with lower lactulose-mannitol ratio, lower abundance of pathobionts (Ruminococcus torques and Lachnoclostridium), and lower concentrations of inflammation- and barrier-related proteins, including C-reactive protein, triggering receptor expressed on myeloid cells-1, oncostatin M, and matrix metalloproteinase 9. Higher estimated β-glucan and inulin intake was associated with preserved gut barrier function, lower systemic inflammatory markers, and lower CD risk, which was modified by the microbial context. These findings support microbiome-informed dietary strategies and intervention trials for CD prevention.