Higher plasma vitamin D is associated with reduced risk of Clostridium difficile infection in patients with inflammatory bowel diseases

Background Patients with inflammatory bowel diseases (IBD) have an increased risk of clostridium difficile infection (CDI). Cathelicidins are anti-microbial peptides that attenuate colitis and inhibit the effect of clostridial toxins. Plasma calcifediol [25(OH)D] stimulates production of cathelicidins. Aim To examine the association between plasma 25(OH)D and CDI in patients with IBD. Methods From a multi-institutional IBD cohort, we identified patients with at least one measured plasma 25(OH)D. Our primary outcome was development of CDI. Multivariate logistic regression models adjusting for potential confounders were used to identify independent effect of plasma 25(OH)D on risk of CDI. Results We studied 3188 IBD patients of whom 35 patients developed CDI. Patients with CDI-IBD were older and had greater co-morbidity. The mean plasma 25(OH)D level was significantly lower in patients who developed CDI (20.4ng/mL) compared to non-CDI-IBD patients (27.1ng/mL) (P=0.002). On multivariate analysis, each 1ng/mL increase in plasma 25(OH)D was associated with a 4% reduction in risk of CDI (OR 0.96, 95% CI 0.93-0.99, P=0.046). Compared to individuals with vitamin D >20ng/mL, patients with levels <20ng/mL were more likely to develop CDI (OR 2.27, 95% CI 1.16-4.44). The mean plasma 25(OH)D in patients with CDI who subsequently died was significantly lower (12.8 +/- 8.1ng/mL) compared to those who were alive at the end of follow-up (24.3 +/- 13.2ng/mL) (P=0.01). Conclusions Higher plasma calcifediol [25(OH)D] is associated with reduced risk of C. difficile infection in patients with IBD. Further studies of therapeutic supplementation of vitamin D in patients with inflammatory bowel disease and C. difficile infection may be warranted.