Association of Helicobacter pylori Positivity With Risk of Disease and Mortality

Abstract

Introduction: Helicobacter pylori colonizes the human stomach. Infection causes chronic gastritis and increases the risk of gastroduodenal ulcer and gastric cancer. Its chronic colonization in the stomach triggers aberrant epithelial and inflammatory signals that are also associated with systemic alterations.

Methods: Using a PheWAS analysis in more than 8,000 participants in the community-based UK Biobank, we explored the association of H. pylori positivity with gastric and extragastric disease and mortality in a European country.

Results: Along with well-established gastric diseases, we dominantly found overrepresented cardiovascular, respiratory, and metabolic disorders. Using multivariate analysis, the overall mortality of H. pylori -positive participants was not altered, while the respiratory and Coronovirus 2019-associated mortality increased. Lipidomic analysis for H. pylori -positive participants revealed a dyslipidemic profile with reduced high-density lipoprotein cholesterol and omega-3 fatty acids, which may represent a causative link between infection, systemic inflammation, and disease.

Discussion: Our study of H. pylori positivity demonstrates that it plays an organ- and disease entity-specific role in the development of human disease and highlights the importance of further research into the systemic effects of H. pylori infection.

Figure 1.

Manhattan plot of sex, age, body mass index, ethnic background, and socioeconomic status (Townsend deprivation index) adjusted −log10 (P values) for all selected PheCodes comparing their occurrence in Helicobacter pylori–positive individuals with controls. Highlighted are associations with P values <0.05 (corrected for multiple testing by false discovery rate to the threshold [dotted line] 0.0038). Upward/downward pointing triangular markers refer to PheCodes, that are overrepresented or underrepresented, respectively, in H. pylori–positive individuals compared with controls. CHF, congestive heart failure; NOS, not otherwise specified.

Figure 2.

The 27 most overrepresented/underrepresented PheCodes in individuals with Helicobacter pylori, adjusted for age, sex, BMI, ethnic background, and socioeconomic status. ORs are given as log (OR) and 95% confidence intervals. Only PheCodes that remained significant after adjustment for multiple testing are displayed and have thereby a P value of ≤0.0038. BMI, body mass index; CI, confidence interval; NOS, not otherwise specified; OR, odds ratio.

Figure 3.

Circle plot for lipidomic analysis for Helicobacter pylori–positive UKB participants compared with controls. Lipidomic parameters were measured through NMR spectroscopy. Hazard ratios (with 95% confidence intervals) are presented per 1-SD higher metabolic biomarker on the natural log scale, stratified by age, sex, body mass index, and Townsend deprivation index. *P < 0.05. Original code by Diego J Aguilar-Ramirez. DHA, docosahexaenoic acid; FAs, fatty acids; FAw3, omega-3 fatty acids; FAw6, omega-6 fatty acids; HDL-D, high-density lipoprotein particle diameter; LA, linoleic acid; LDL, low-density lipoproteins; LDL-D, low-density lipoprotein particle diameter; LP, lipoprotein; MUFA, monounsaturated fatty acids; NMR, nuclear magnetic resonance; PUFA, polyunsaturated fatty acids; SFA, saturated fatty acids; VLDL-D, very low-density lipoprotein particle diameter.