<h3>Objective</h3> To conduct a comprehensive global systematic review and meta-analysis on the association between <i>Helicobacter pylori</i> infection and IBD. As bacterial antigen cross-reactivity has been postulated to be involved in this association, published data on enterohepatic <i>Helicobacter</i> spp (EHS) and <i>Campylobacter</i> spp and IBD was also analysed. <h3>Design</h3> Electronic databases were searched up to July 2015 for all case-control studies on <i>H. pylori</i> infection/EHS/<i>Campylobacter</i> spp and IBD. Pooled ORs (P-OR) and 95% CIs were obtained using the random effects model. Heterogeneity, sensitivity and stratified analyses were performed. <h3>Results</h3> Analyses comprising patients with Crohn9s disease (CD), UC and IBD unclassified (IBDU), showed a consistent negative association between gastric <i>H. pylori</i> 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 <i>H. pylori</i>, non <i>H. pylori</i>-EHS (P-OR: 2.62, p value=0.001) and <i>Campylobacter</i> spp, in particular <i>C. concisus</i> (P-OR: 3.76, p value=0.006) and <i>C. showae</i> (P-OR: 2.39, p value=0.027), increase IBD risk. <h3>Conclusions</h3> <i>H. pylori</i> infection is negatively associated with IBD regardless of ethnicity, age, <i>H. pylori</i> detection methods and previous use of aminosalicylates and corticosteroids. Antibiotics influenced the magnitude of this association. Closely related bacteria including EHS and <i>Campylobacter</i> spp increase the risk of IBD. These results infer that <i>H. pylori</i> might exert an immunomodulatory effect in IBD.
