Systematic review with meta‐analysis: association between Helicobacter pylori CagA seropositivity and odds of inflammatory bowel disease

Abstract

Background: Accumulating data support a protective role of Helicobacter pylori against inflammatory bowel diseases (IBD), which might be mediated by strain-specific constituents, specifically cagA expression. Aim:To perform a systematic review and meta-analysis to more clearly define the association between CagA seropositivity and IBD. Methods:We identified comparative studies that included sufficient detail to determine the odds or risk of IBD, Crohn's disease (CD) or ulcerative colitis (UC) amongst individuals with vs without evidence of cagA expression (eg CagA seropositivity).Estimates were pooled using a random effects model. Results:Three clinical studies met inclusion criteria. cagA expression was represented by CagA seropositivity in all studies. Compared to CagA seronegativity overall, CagA seropositivity was associated with lower odds of IBD (OR 0.31, 95% CI 0.21-0.44) and CD (OR 0.25, 95% CI 0.17-0.38), and statistically nonsignificant lower odds for UC (OR 0.68, 95% CI 0.35-1.32). Similarly, compared to H pylori non-exposed individuals, H pylori exposed, CagA seropositive individuals had lower odds of IBD (OR 0.26, 95% CI 0.16-0.41) and CD (OR 0.23, 95% CI 0.15-0.35), but not UC (OR 0.66, 0.34-1.27).However, there was no significant difference in the odds of IBD, CD or UC between H pylori exposed, CagA seronegative and H pylori non-exposed individuals. Conclusion:We found evidence for a significant association between CagA seropositive H pylori exposure and reduced odds of IBD, particularly CD, but not for CagA seronegative H pylori exposure. Additional studies are needed to confirm these findings and define underlying mechanisms. S U PP O RTI N G I N FO R M ATI O NAdditional supporting information will be found online in the Supporting Information section at the end of the article.How to cite this article: Tepler A, Narula N, Peek RM Jr, et al. Systematic review with meta-analysis: association betweenHelicobacter pylori CagA seropositivity and odds of inflammatory bowel disease. Aliment Pharmacol Ther.

Review: Extragastric diseases andHelicobacter pylori

“…49 associated with an increased IBD risk. 50 These data support a likely protective effect of H pylori on IBD as reported by other meta-analyses, [51][52][53] possibly caused by the bacterium's ability to promote immune system maturation and prevent the onset of aberrant immune responses. Indeed, H pylori exerts immunomodulatory effects by increasing the number of regulatory T cells, which suppress excessive inflammatory T-cell responses through the secretion of IL-10 and TGF-β.…”

Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review)

“…By affecting immune and inflammatory responses [ 78 , 92 , 431 , 432 , 433 ]. HPI may protect against asthma and allergy (particularly in children), autoimmune disorders (systemic lupus erythematosus, rheumatoid arthritis [RA] and multiple sclerosis, coeliac disease), inflammatory bowel disease (especially Crohn’s disease), eosinophilic esophagitis, eczema, obesity [ 9 , 78 , 342 , 433 , 434 , 435 , 436 , 437 , 438 , 439 , 440 , 441 ] and tooth loss [ 442 ]. Negative associations between these diseases and HPI (beneficial effects) were observed mainly in patients colonized with cagA+ strains of H.p.…”

The relationship between inflammatory bowel disease and Helicobacter pylori across East Asian, European and Mediterranean countries: a meta-analysis

“…Previous meta-analyses have suggested that the beneficial effects of H. pylori on the risk of IBD are greater for eastern than for western populations [ 16 ]. A possible explanation is the greater relative abundance of the seropositive CagA H. pylori strain in East Asian compared to western populations [ 23 ]. It has been suggested that expression of CagA might increase the production of beta-defensins, thought to play a protective role in IBD pathogenesis [ 23 ].…”

“…A possible explanation is the greater relative abundance of the seropositive CagA H. pylori strain in East Asian compared to western populations [ 23 ]. It has been suggested that expression of CagA might increase the production of beta-defensins, thought to play a protective role in IBD pathogenesis [ 23 ]. Another possible theory is that during H. pylori infection, the response of the type 2 T helper cell 2 (Th2) cytokine is dependent on the presence of CagA strain [ 23 ].…”