ABSTRACT
BACKGROUND & AIMS: Biomarkers that integrate genetic and environmental factors and predict outcome in complex immune diseases such as inflammatory bowel disease (IBD; including Crohn's disease [CD] and ulcerative colitis [UC]) are needed. We showed that morphologic patterns of ileal Paneth cells (Paneth cell phenotype [PCP]; a surrogate for PC function) is one such cellular biomarker for CD. Given the shared features between CD and UC, we hypothesized that PCP is also associated with molecular/genetic features and outcome in UC. Because PC density is highest in the ileum, we further hypothesized that PCP predicts outcome in UC subjects who underwent total colectomy and ileal pouch-anal anastomosis (IPAA). METHODS: Uninflamed ileal resection margins from UC subjects with colectomy and IPAA were used for PCP and transcriptomic analyses. PCP was defined using defensin 5 immunofluorescence. Genotyping was performed using Immunochip. UC transcriptomic and genotype associations of PCP were incorporated with data from CD subjects to identify common IBD-related pathways and genes that regulate PCP. RESULTS: The prevalence of abnormal ileal PCP was 27%, comparable to that seen in CD. Combined analysis of UC and CD subjects showed that abnormal PCP was associated with transcriptomic pathways of secretory granule maturation and polymorphisms in innate immunity genes. Abnormal ileal PCP at the time of colectomy was also associated with pouch complications including de novo CD in the pouch and time to first episode of pouchitis. CONCLUSIONS: Ileal PCP is biologically and clinically relevant in UC and can be used as a biomarker in IBD.
ABSTRACT
Epidemiological trends have led to a growing consensus that diet plays a central role in the etiopathogenesis of inflammatory bowel diseases (IBD). A Western diet high in ultra-processed foods has been associated with an increased prevalence of IBD worldwide. Much attention has focused on components of the Western diet, including the high fat content, lack of fiber, added sugars, and use of additives, such as carrageenan and other emulsifiers. Less attention has been paid to the impact of high salt intake, an integral component of ultra-processed foods, which has increased dramatically in the US diet over the past 50 years. We review a growing body of literature linking the rise in dietary salt intake with the epidemiology of IBD, increased consumption of salt as a component of ultra-processed foods, high salt intake and imbalances in immune homeostasis, the effects of a high-salt diet on other inflammatory disorders, salt's impact on animal colitis models, salt as an underrecognized component in diet modification-induced remission of IBD, and directions for future investigation.
Recent studies have shown that high dietary salt intake is proinflammatory and contributes to chronic inflammatory conditions. Combined with investigations demonstrating low-salt exclusive enteral nutrition induced Crohn's remission, salt intake is likely a contributory factor to inflammatory bowel diseases' pathogenesis and severity.
