Objective To conduct a comprehensive global systematic review and meta-analysis on the association between Helicobacter pylori infection and IBD. As bacterial antigen cross-reactivity has been postulated to be involved in this association, published data on enterohepatic Helicobacter spp (EHS) and Campylobacter spp and IBD was also analysed.

Design Electronic databases were searched up to July 2015 for all case-control studies on H. pylori infection/EHS/Campylobacter spp and IBD. Pooled ORs (P-OR) and 95% CIs were obtained using the random effects model. Heterogeneity, sensitivity and stratified analyses were performed.

Results Analyses comprising patients with Crohn's disease (CD), UC and IBD unclassified (IBDU), showed a consistent negative association between gastric H. pylori infection and IBD (P-OR: 0.43, p value <1e-10). This association appears to be stronger in patients with CD (P-OR: 0.38, p value <1e-10) and IBDU (P-OR: 0.43, p value=0.008) than UC (P-OR: 0.53, p value <1e-10). Stratification by age, ethnicity and medications showed significant results. In contrast to gastric H. pylori, non H. pylori-EHS (P-OR: 2.62, p value=0.001) and Campylobacter spp, in particular C. concisus (P-OR: 3.76, p value=0.006) and C. showae (P-OR: 2.39, p value=0.027), increase IBD risk.

Conclusions H. pylori infection is negatively associated with IBD regardless of ethnicity, age, H. pylori detection methods and previous use of aminosalicylates and corticosteroids. Antibiotics influenced the magnitude of this association. Closely related bacteria including EHS and Campylobacter spp increase the risk of IBD. These results infer that H. pylori might exert an immunomodulatory effect in IBD.