Background Vitamin D plays a role in several immune-mediated diseases, but its association with inflammatory bowel disease (IBD) is unclear. We conducted a systematic review and meta-analysis to assess the association between IBD and vitamin D deficiency. Methods We searched electronic databases from inception to December 2014 for observational studies reporting the presence of vitamin D deficiency (defined as serum 25-hydroxycholecalciferol [25(OH)D] level of ≤20 ng/ml) in IBD patients and having a control group without IBD. Odds ratios (OR) were combined using a random effects model. Meta-regression was performed using latitude as a moderator. Study quality was assessed using the Newcastle-Ottawa scale. Results Out of 816 citations, 14 eligible studies were identified, comprising 1891 participants (938 IBD cases and 953 controls). Meta-analysis showed that patients with IBD had 64% higher odds of vitamin D deficiency when compared to controls (OR = 1.64; 95% CI: 1.30, 2.08; I2 = 7%; p < 0.0001). UC patients had more than double the odds of vitamin D deficiency when compared to normal controls (OR = 2.28; 1.18, 4.41; I2 = 41%; p=0.01). Latitude did not influence the association between IBD and vitamin D deficiency (p = 0.34). Generalizability of our results might be limited as we summarized unadjusted ORs, due to non-availability of adjusted ORs in individual studies. Conclusions IBD is significantly associated with having higher odds of vitamin D deficiency. Well-designed RCTs and longitudinal studies are needed to further clarify the role of vitamin D in IBD pathogenesis and its therapy.

Histology is fundamental to assess two-dimensional intestinal inflammation; however, inflammatory bowel diseases (IBDs) are often indistinguishable microscopically on the basis of mucosal biopsies. Here, we use stereomicroscopy (SM) to rapidly profile the entire intestinal topography and assess inflammation. We examine the mucosal surface of >700 mice (encompassing >16 strains and various IBD-models), create a profiling catalogue of 3D-stereomicroscopic abnormalities and demonstrate that mice with comparable histological scores display unique sub-clusters of 3D-structure-patterns of IBD pathology, which we call 3D-stereoenterotypes, and which are otherwise indiscernible histologically. We show that two ileal IBD-stereoenterotypes (‘cobblestones' versus ‘villous mini-aggregation') cluster separately within two distinct mouse lines of spontaneous ileitis, suggesting that host genetics drive unique and divergent inflammatory 3D-structural patterns in the gut. In humans, stereomicroscopy reveals ‘liquefaction' lesions and hierarchical fistulous complexes, enriched with clostridia/segmented filamentous bacteria, running under healthy mucosa in Crohn's disease. We suggest that stereomicroscopic (3D-SMAPgut) profiling can be easily implemented and enable the comprehensive study of inflammatory 3D structures, genetics and flora in IBD.

The meta-analysis results seem to support the effectiveness of SRP in the improvement of glycemic control in patients with CP and DM2; however, future studies are needed to confirm these results.