Letter: Disappearing Microbe, Emerging Disease? Nuancing the Protective Effects of Helicobacter pylori Against Eosinophilic Oesophagitis. Authors' Reply

We sincerely appreciate the constructive comments from Drs. Emanuele and Minoretti [1] on our meta-analysis of the potential protective role of Helicobacter pylori (H. pylori) infection against eosinophilic oesophagitis (EoE) [2], and are keen to address each point they raised.

The cagA protein has a well-known virulence effect in positive strains, and its enhancement of the Th1 response may play a role in reducing the Th2 response characteristic of EoE. Although a comparison of patients with H. pylori infection based on their cagA status would be of interest, we were unable to make this subgroup analysis due to the lack of availability of pertinent data in included studies.

We also acknowledge that the significant differences in the prevalence of H. pylori infection between Eastern and Western cohorts may be explained by region-specific confounders, which may be further depicted by regression models. However, we also highlight that the odds ratios in the two cohorts were almost equal (0.53 v. 0.52). This suggests that, regardless of the specific geographical prevalence of H. pylori infection, related mechanisms of protection are similar worldwide.

We agree with Drs. Emanuele and Minoretti that further evidence, arising from case–control studies nested within longitudinal birth cohorts and Mendelian randomisation studies, may clarify whether early H. pylori infection may be associated with a lower prevalence of EoE. However, we did not observe a significant odds reduction for EoE in paediatric patients infected with H. pylori. Possible explanations were the limited number of studies and the influence of genetic factors over environment [2]. However, this suggests that further evidence is needed to address the relationship between H. pylori and EoE in early life.

We are well aware that non-invasive biomarkers are an unmet need in EoE, and that its diagnosis and monitoring currently rely totally on upper endoscopy and histology. Several tests are emerging as potential candidates to monitor disease activity, but their application in clinical practice is still under validation [3-5]. In addition, omics technologies offer new insights into the genetic and immunologic mechanisms of EoE, but research is still nascent [6, 7].

Finally, incorporating the prevalence of H. pylori infection into ongoing EoE studies [8-10] would be of utmost interest because it could help clarify whether H. pylori plays a role in treatment response and whether it should be considered a factor in therapeutic decision-making.

We thank Drs. Emanuele and Minoretti for their careful analysis of our work and for their contribution to this important discussion.

Irene Spinelli: conceptualization, investigation, methodology, data curation, resources, project administration, validation, visualization, writing – original draft, writing – review and editing, formal analysis. Gianluca Ianiro: conceptualization, methodology, data curation, supervision, project administration, validation, visualization, writing – review and editing, investigation, formal analysis.

The authors' declarations of personal and financial interests are unchanged from those in the original article [2].

This article is linked to Spinelli et al papers. To view these articles, visit https://doi.org/10.1111/apt.70042 and https://doi.org/10.1111/apt.70075.