Artificial intelligence applications in inflammatory bowel disease: Emerging technologies and future directions

Antimicrobial peptides and the gut microbiome in inflammatory bowel disease

Summary: Background: Vitamin D deficiency is highly prevalent among patients with IBD, however, data on its association with clinical outcomes are conflicting.Aim: To perform a systematic review and meta‐analysis to explore the association of low vitamin D status with clinical outcomes in patients with IBD.Methods: We searched PubMed, Embase, Scopus and Web of Science from inception to February 2018 for observational studies evaluating the association of low 25(OH)D status on IBD disease activity, mucosal inflammation, clinical relapse and quality of life. Odds ratios (ORs) were pooled and analysed using a random effects model.Results: Twenty‐seven studies were eligible for inclusion comprising 8316 IBD patients (3115 ulcerative colitis, 5201 Crohn's disease). Among IBD patients, low 25(OH)D status was associated with increased odds of disease activity (OR 1.53, 95% CI 1.32‐1.77, I² = 0%), mucosal inflammation (OR 1.25, 95% CI 1.06‐1.47, I² = 0%), low quality of life (QOL) scores (OR 1.30, 95% CI 1.06‐1.60, I² = 0%) and future clinical relapse (OR 1.23, 95% CI 1.03‐1.47, I² = 0%). In subgroup analysis, low vitamin D status was associated with Crohn's disease activity (OR 1.66, 95% CI 1.36‐2.03, I² = 0%), mucosal inflammation (OR 1.39, 95% CI 1.03‐1.85, I² = 0%), clinical relapse (OR 1.35, 95% CI 1.14‐1.59, I² = 0%), and low QOL scores (OR 1.25, 95% CI 1.04‐1.50, I² = 0%) and ulcerative colitis disease activity (OR 1.47, 95% CI 1.03‐2.09, I² = 0%) and clinical relapse (OR 1.20, 95% 1.01‐1.43, I² = 0%).Conclusions: Low 25(OH)D status is a biomarker for disease activity and predictor of poor clinical outcomes in IBD patients.

The aim of this review is to explore the protective role of vitamin D on the gastrointestinal tract, summarize the epidemiology of vitamin D deficiency in inflammatory bowel disease (IBD), and highlight recent studies examining the impact of low vitamin D and vitamin D supplementation on IBD clinical outcomes. Vitamin D protects the gut barrier by regulating tight junction proteins and inhibiting intestinal apoptosis. Vitamin D enhances innate immunity by inducing antimicrobial peptides and regulates adaptive immunity by promoting anti-inflammatory T cells and cytokines. Vitamin D may also alter the gut microbiota. The prevalence of vitamin D deficiency in IBD is 30–40%. Predictors of vitamin D deficiency in IBD include non-white ethnicity, IBD-related surgery, BMI more than 30, female sex, and pregnancy. Low vitamin D is associated with increased disease activity, inflammation, and clinical relapse. The effect of vitamin D supplementation on IBD clinical outcomes is inconclusive. Vitamin D plays a protective role on gut health. Vitamin D deficiency in IBD is prevalent and associated with poor outcomes. The benefits of vitamin D supplementation in IBD is unclear. Measuring novel vitamin D metabolites and vitamin D absorption in IBD patients may help guide future studies.

Leukocyte trafficking to the gastrointestinal tract is recognized to play a role in the pathogenesis of inflammatory bowel disease (IBD). Integrins are expressed on immune cells and interact with cell adhesion molecules (CAM) to mediate leukocyte trafficking. Blockade of the gut-tropic integrin α 4β 7 and its subunits has been exploited as a therapeutic target in IBD. Natalizumab (anti-α 4) is approved for moderate to severe Crohn’s disease (CD), but its use is limited due to potential risk of progressive multifocal leukoencephalopathy. Vedolizumab (anti-α 4β 7) is approved for the treatment of ulcerative colitis (UC) and CD. It is the most widely used anti-integrin therapy in IBD and has been shown to be effective in both induction and maintenance therapy, with a favorable safety profile. Several models incorporating clinical, genetic, immune, gut microbial, and vitamin D markers to predict response to vedolizumab in IBD have been developed. Etrolizumab (anti-β 7) blocks leukocyte trafficking via α 4β 7 and cell adhesion via αEβ 7 integrins. Large phase 3 clinical trials evaluating efficacy of etrolizumab in the induction and maintenance of patients with IBD are underway. Other investigational anti-integrin therapies include abrilumab (anti-α 4β 7 IgG2), PN-943 (orally administered and gut-restricted α 4β 7 antagonist peptide), AJM300 (orally active small molecule inhibitor of α 4), and ontamalimab (anti-MAdCAM-1 IgG).