A systematic review and meta-analysis for association of Helicobacter pylori colonization and celiac disease

Abstract

Background and objectives: Based on some previous observational studies, there is a theory that suggests a potential relationship between Helicobacter pylori (H. pylori) colonization and celiac disease (CeD); however, the type of this relationship is still controversial. Therefore, we aimed to conduct a systematic review and meta-analysis to explore all related primary studies to find any possible association between CeD and human H. pylori colonization.

Data sources: Studies were systematically searched and collected from four databases and different types of gray literature to cover all available evidence. After screening, the quality and risk of bias assessment of the selected articles were evaluated.

Synthesis methods: Meta-analysis calculated pooled odds ratio (OR) on the extracted data. Furthermore, heterogeneity, sensitivity, subgroups, and publication bias analyses were assessed.

Results: Twenty-six studies were included in this systematic review, with a total of 6001 cases and 135512 control people. The results of meta-analysis on 26 studies showed a significant and negative association between H. pylori colonization and CeD (pooled OR = 0.56; 95% CI = 0.45-0.70; P < 0.001), with no publication bias (P = 0.825). The L'Abbé plots also showed a trend of having more H. pylori colonization in the control group. Among subgroups, ORs were notably different only when the data were stratified by continents or risk of bias; however, subgroup analysis could not determine the source of heterogeneity.

Conclusions: According to the meta-analysis, this negative association might imply a mild protective role of H. pylori against celiac disease. Although this negative association is not strong, it is statistically significant and should be further considered. Further investigations in both molecular and clinic fields with proper methodology and more detailed information are needed to discover more evidence and underlying mechanisms to clear the interactive aspects of H. pylori colonization in CeD patients.

Systematic review registration number (prospero): CRD42020167730 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=167730.

Fig 1. Flow diagram of literature search, screening, and selection of studies for review and meta-analysis.

Fig 2. The Forest plot of the meta-analysis on the association of the Helicobacter pylori and celiac disease.

The random-effects model was used to calculate pooled ORs with 95% CI. CI, Confidence interval; OR, Odds ratio.

Fig 3

(A) The drapery plot shows p-value functions for the included studies as well as pooled estimates and the two-sided confidence intervals for all possible alpha levels (confidence interval function). Each number represents a study. The red-bolded line (in the online version; bold line in the printed version) indicates the range of pooled odds ratio (OR) in each alpha level. (B) The Funnel chart shows no significant publication bias, as all studies are in a symmetric scheme. (C) The Baujat plot shows the effect of each study on the heterogeneity and overall influence of the results. As can be seen in the graph, the study of Narang et al. contributes more than the other studies to the overall heterogeneity. Each circle represents a study. (D) The L’Abbé plot shows more positive results for H. pylori colonization in the control group. The diagonal (x = y) oblique line represents the odds ratio (OR) equal to one. The dashed line indicates the OR of the studies. The size of each circle indicates the assigned random weight of each study. As the picture shows, most studies show an OR of less than one.