AUTHOR=Cui Yurong , Li Jinxin , Zhao Bing , Liu Junying 

TITLE=Helicobacter pylori infection and inflammatory bowel disease: a 2-sample Mendelian randomization study

JOURNAL=Frontiers in Microbiology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1384285

DOI=10.3389/fmicb.2024.1384285

ISSN=1664-302X

ABSTRACT=<sec><title>Introduction</title><p>Observational studies have discovered a contradictory phenomenon between <italic>Helicobacter pylori (H. pylori)</italic> infection and inflammatory bowel disease (IBD). The study aimed to confirm the causal association between <italic>H. pylori</italic> and IBD, including ulcerative colitis (UC) and Crohn's disease (CD).</p></sec><sec><title>Methods</title><p>We conducted a Mendelian randomization (MR) study with two sample Genome-Wide Association Studies (GWAS) to determine whether there is a causal relationship between <italic>H. pylori</italic> infection and IBD, as well as the possible pathogenic factors that may be involved. The reliability of the main MR assumptions was examined through a series of sensitivity analyses.</p></sec><sec><title>Results</title><p>Two genetic variants (SNPs) previously identified were employed as instrumental variables (IVs) for <italic>H. pylori</italic> infection. GWAS data for IBD, UC, and CD were obtained from the recent DF10 release10 of the FinnGen study. Our findings indicated a significant association between <italic>H. pylori</italic> seropositivity and an increased risk of IBD and UC (IBD: OR: 1.16, 95% CI, 1.03–1.31, <italic>P</italic> &lt; 0.05; UC: OR: 1.22, 95% CI, 1.08–1.37, <italic>P</italic> &lt; 0.001) while no causal relationship with CD (<italic>P</italic> &gt; 0.05). Analysis of the main virulence pathogenic factors revealed a causal relationship between cytotoxin-associated protein A (CagA) and IBD and UC (IBD: OR: 1. 06, 95% CI, 1.001–1.11, <italic>P</italic> &lt; 0.05; UC: OR: 1.07, 95% CI, 1.004–1.14, <italic>P</italic> &lt; 0.05), while no correlation was found for vacuolar cytotoxin A (VacA) (<italic>P</italic> &gt; 0.05). After applying the False Discovery Rate (FDR) correction, the causal relationship between CagA and the risk of IBD or UC was no longer statistically significant.</p></sec><sec><title>Conclusion</title><p>This study suggests a potential causal relationship between H. pylori infection and IBD, particularly UC. The effect may be more pronounced in individuals with previous <italic>H. pylori</italic> infections.</p></sec>