Dataset Information

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

ABSTRACT:

Background

The current literature suggests a protective benefit of Helicobacter pylori (H. pylori) infection against inflammatory bowel disease (IBD). Here we assessed whether this effect varied by IBD subtype-Crohn's disease (CD) or ulcerative colitis (UC)-and geographic region: East Asia, Europe (non-Mediterranean) or Mediterranean region.

Methods

A database search was performed up to July 2019 inclusive for all studies that compared H. pylori infection in IBD patients vs. non-IBD controls. The relative risk (RR) was used to quantify the association between IBD and H. pylori, and the effects were combined across studies using a mixed-effects meta-regression model, which included IBD subtype and geographic region as categorical moderator variables.

Results

Our meta-regression model exhibited moderate heterogeneity (I²=48.74%). Pooled RR depended on both region (P=0.02) and subtype (P<0.001). Pooled RRs were <1 for all subtype and region combinations, indicative of a protective effect of H. pylori against IBD. The pooled RR was 28% (9%, 50%; P=0.001) greater for UC vs. CD and 43% (4%, 96%; P=0.02) greater for Mediterranean countries vs. East Asia. The pooled RR was 18% (-13%, 60%; P=0.48) greater for Europe vs. East Asia and 21% (-13%, 68%; P=0.42) greater for Mediterranean vs. Europe, though these differences were not statistically significant.

Conclusions

The protective effect of H. pylori on IBD varied by both subtype (more protection against CD vs. UC) and region (East Asia more protected than Mediterranean regions). Variation due to these effects could provide insight into IBD etiology.

SUBMITTER: Imawana RA

PROVIDER: S-EPMC7406810 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: The genome of Helicobacter pylori, an oncogenic bacterium in the human stomach, rapidly evolves and shows wide geographical divergence. The high incidence of stomach cancer in East Asia might be related to bacterial genotype. We used newly developed comparative methods to follow the evolution of East Asian H. pylori genomes using 20 complete genome sequences from Japanese, Korean, Amerind, European, and West African strains. RESULTS: A phylogenetic tree of concatenated well-defined core genes supported divergence of the East Asian lineage (hspEAsia; Japanese and Korean) from the European lineage ancestor, and then from the Amerind lineage ancestor. Phylogenetic profiling revealed a large difference in the repertoire of outer membrane proteins (including oipA, hopMN, babABC, sabAB and vacA-2) through gene loss, gain, and mutation. All known functions associated with molybdenum, a rare element essential to nearly all organisms that catalyzes two-electron-transfer oxidation-reduction reactions, appeared to be inactivated. Two pathways linking acetyl~CoA and acetate appeared intact in some Japanese strains. Phylogenetic analysis revealed greater divergence between the East Asian (hspEAsia) and the European (hpEurope) genomes in proteins in host interaction, specifically virulence factors (tip?), outer membrane proteins, and lipopolysaccharide synthesis (human Lewis antigen mimicry) enzymes. Divergence was also seen in proteins in electron transfer and translation fidelity (miaA, tilS), a DNA recombinase/exonuclease that recognizes genome identity (addA), and DNA/RNA hybrid nucleases (rnhAB). Positively selected amino acid changes between hspEAsia and hpEurope were mapped to products of cagA, vacA, homC (outer membrane protein), sotB (sugar transport), and a translation fidelity factor (miaA). Large divergence was seen in genes related to antibiotics: frxA (metronidazole resistance), def (peptide deformylase, drug target), and ftsA (actin-like, drug target). CONCLUSIONS: These results demonstrate dramatic genome evolution within a species, especially in likely host interaction genes. The East Asian strains appear to differ greatly from the European strains in electron transfer and redox reactions. These findings also suggest a model of adaptive evolution through proteome diversification and selection through modulation of translational fidelity. The results define H. pylori East Asian lineages and provide essential information for understanding their pathogenesis and designing drugs and therapies that target them.