Association Between Helicobacter pylori Exposure and Decreased Odds of Eosinophilic Esophagitis—A Systematic Review and Meta-analysis

Abstract

Background & Aims: Previous or current infection with Helicobacter pylori (exposure) has been reported to protect against eosinophilic esophagitis (EoE), perhaps due to H pylori -induced immunomodulation. However, findings vary. We performed a systematic review and meta-analysis of comparative studies to more clearly define the association between H pylori exposure and EoE. Methods: We searched 4 large databases to identify comparative clinical studies that included sufficient detail to determine the odds or risk of EoE (primary outcome) or esophageal eosinophilia (secondary outcome) among individuals exposed to H pylori (exposed) vs individuals who were tested and found to be unexposed. Estimates were pooled using a random-effects model. Meta-regression and sensitivity analyses were planned a priori. Studies were evaluated for quality, risk of bias, publication bias, and heterogeneity. Results: We analyzed 11 observational studies comprising data on 377,795 individuals worldwide. H pylori exposure vs non-exposure was associated with a 37% reduction in odds of EoE (odds ratio [OR], 0.63; 95% CI, 0.51–0.78) and a 38% reduction in odds of esophageal eosinophilia (OR, 0.62; 95% CI, 0.52–0.76). Fewer prospective studies found a significant association between H pylori exposure and EoE ( P =.06) than retrospective studies. Effect estimates were not affected by study location, whether the studies were performed in pediatric or adult populations, time period (before vs after 2007), or prevalence of H pylori in the study population. Conclusions: In a comprehensive meta-analysis, we found evidence for a significant association between H pylori exposure and reduced odds of EoE. Studies are needed to determine the mechanisms of this association.

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

“…As additional support, we demonstrated that individuals exposed to H pylori but who were CagA seronegative had similar odds of IBD, CD and UC as individuals without H pylori exposure. We further compiled a complementary synthesis of relevant experimental data, which provide a platform of support for biological plausibility of CagA as one critical mediator of the protective association observed clinically between H pylori exposure and odds of IBD, as well as very likely other immune‐mediated diseases …”

“…When present, host responses to H pylori strains expressing CagA are more robust in children, which is when H pylori exposure most often occurs . Indeed, these early H pylori associated immunomodulatory effects might also protect against immune‐mediated diseases other than IBD, such as asthma and allergy . One cross‐sectional analysis of 7663 adults from the Third National Health and Nutrition Examination Survey found that the inverse association between H pylori and asthma, allergic rhinitis and allergies was more pronounced amongst younger individuals and amongst those who were CagA seropositive …”

“…Helicobacter pylori is the most common chronic bacterial infection in the world and is estimated to infect approximately 4.4 billion people . Although considered the primary risk factor for gastric cancer, H pylori has co‐evolved with humans for over 100 000 years, and accumulating data support a potential protective role of H pylori against certain immune‐mediated diseases, including IBD . Certain H pylori strain‐specific virulence constituents, including cytotoxin‐associated gene A ( cagA ) and certain alleles of vacuolating cytotoxin ( vacA ), while associated with an increased risk of gastric cancer, might also mediate beneficial effects of H pylori through modulation of host immune defenses and other mechanisms.…”

Review: Extragastric diseases andHelicobacter pylori

“…In a systematic review with meta-analysis, including 11 studies and 377 795 patients, H pylori was found to be associated with a decreased risk of eosinophilic oesophagitis (OR 0.63; 95% CI, 0.51-0.78). 95 The relationship between allergy and H pylori was also investigated in preclinical models. Perinatal exposure to H pylori extract or to VacA was found to protect mice against allergic airway inflammation.…”

Review: Helicobacter pylori and non‐malignant upper gastrointestinal diseases

“…A decline in H pylori prevalence over the past decades corresponds temporally and geographically to an increased incidence of eosinophilic esophagitis (EoE) and other immune‐mediated diseases. A meta‐analysis by Shah et al included 11 observational studies incorporating over 350 000 individuals and found that H pylori infection is associated with a 37% reduced risk of EoE . Nine of these studies defined EoE as 15 or more eosinophils per high‐power field (eos/hpf) together with esophageal symptoms.…”