Dietary Iron and Heme Iron Consumption, Genetic Susceptibility, and Risk of Crohnʼs Disease and Ulcerative Colitis

Abstract

Introduction Dietary iron and heme, likely through their effect on gut commensal bacteria and colonic barrier function, have been shown to modulate colonic inflammation in animal models of colitis. Nonetheless, the link between dietary total and heme iron and risk of Crohn’s disease (CD) and ulcerative colitis (UC) has not been previously explored. Methods We conducted a prospective cohort study of 165,331 U.S. women enrolled in the Nurses’ Health Study (NHS) and NHSII. Dietary information was collected using a validated food frequency questionnaire at baseline (1984) and updated every 2–4 years. Self-reported CD and UC diagnoses were confirmed through medical records review. We used Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CIs) while adjusting for potential confounders. In a case-control study nested within these cohorts, we evaluated the interaction between single nucleotide polymorphisms (SNPs) associated with genome-wide susceptibility to CD and UC and dietary total and heme iron intake on risk of CD and UC using logistic regression modeling. Results Through 2011, over 3,038,049 person-years of follow up, we documented 261 incident cases of CD and 321 incident cases of UC. Dietary heme iron was non-significantly associated with increased risk of UC (Ptrend = 0.12). This association appeared to be modified by the UC-susceptibility locus, rs1801274, a coding variant in the FcγRIIA gene (Pinteraction = 7.00E-05). In contrast, there was no association between dietary heme iron and risk of CD (Ptrend = 0.67). We also did not observe an association between total dietary intake of iron and risk of CD or UC (All Ptrend > 0.35). Conclusion In two large prospective cohort studies, dietary total and heme iron were not associated with risk of CD or UC. Our suggestive finding that the association between dietary heme iron intake and risk of UC may be modified by a coding variant in FcγRIIA gene warrants additional investigation.

The role of diet in the aetiopathogenesis of inflammatory bowel disease

“…Early work from the NHS and NHSII showed a low risk of Crohn’s disease among individuals who consume high amounts of fiber, particularly fiber from vegetables and fruits (Table 1) 40 . By contrast, a high n-3:n-6 fatty acids ratio was associated with a low risk of ulcerative colitis, whereas a high intake of red meat was associated with an increased risk of ulcerative colitis (Table 1) 41, 42 . Owing to the increasingly recognized role of specific nutrients and electrolytes such as heme, potassium and zinc in regulating the intestinal barrier and immune function 43–50 , over the past 5 years studies have focused on examining the relationship between quantity of nutrient consumption and risk of IBD.…”

“…Owing to the increasingly recognized role of specific nutrients and electrolytes such as heme, potassium and zinc in regulating the intestinal barrier and immune function 43–50 , over the past 5 years studies have focused on examining the relationship between quantity of nutrient consumption and risk of IBD. Preliminary data from these cohorts have shown an inverse association between dietary zinc and potassium intake and risk of Crohn’s disease, whereas dietary sodium, heme and iron intake were not associated with IBD risk (Table 1) 42, 51, 52 .…”

Dietary Inflammatory Potential and Risk of Crohn’s Disease and Ulcerative Colitis

“…48 However, contrary to our findings, epidemiologic studies have mostly demonstrated an association between red meat intake and UC. 49 In addition, patients with CD have an abnormal expression of carcinoembryonic antigen-related cell adhesion molecule 6, a receptor for adherent-invasive Escherichia coli, in the ileal epithelium. 50 Martinez-Medina et al 29 showed that a diet high in fat and sugar alters the composition of intestinal microbiota and host homeostasis (eg, increased intestinal permeability and TNF-a secretion) in carcinoembryonic antigen-related cell adhesion molecule 10 transgenic mice, leading to a higher ability of adherent-invasive E. coli to colonize the gut mucosa and induce inflammation.…”

Association between dietary iron and zinc intake and development of ulcerative colitis: A case–control study in Japan

“…In the USA, a prospective cohort study showed no significant association between dietary heme iron consumption and the risk of UC. The study concluded that dietary heme iron and the risk of UC may be modified by a variant in genetic susceptibility to UC …”