Review of current diagnostic methods and advances in Helicobacter pylori diagnostics in the era of next generation sequencing

Abstract

Helicobacter pylori (H. pylori) infection is highly prevalent in the human population and may lead to severe gastrointestinal pathology including gastric and duodenal ulcers, mucosa associated tissue lymphoma and gastric adenocarcinoma. In recent years, an alarming increase in antimicrobial resistance and subsequently failing empiric H. pylori eradication therapies have been noted worldwide, also in many European countries. Therefore, rapid and accurate determination of H. pylori’s antibiotic susceptibility prior to the administration of eradication regimens becomes ever more important. Traditionally, detection of H. pylori and its antimicrobial resistance is done by culture and phenotypic drug susceptibility testing that are cumbersome with a long turn-around-time. Recent advances in diagnostics provide new tools, like real-time polymerase chain reaction (PCR) and line probe assays, to diagnose H. pylori infection and antimicrobial resistance to certain antibiotics, directly from clinical specimens. Moreover, high-throughput whole genome sequencing technologies allow the rapid analysis of the pathogen’s genome, thereby allowing identification of resistance mutations and associated antibiotic resistance. In the first part of this review, we will give an overview on currently available diagnostic methods for detection of H. pylori and its drug resistance and their implementation in H. pylori management. The second part of the review focusses on the use of next generation sequencing technology in H. pylori research. To this end, we conducted a literature search for original research articles in English using the terms “Helicobacter”, “transcriptomic”, “transcriptome”, “next generation sequencing” and “whole genome sequencing”. This review is aimed to bridge the gap between current diagnostic practice (histology, rapid urease test, H. pylori culture, PCR and line probe assays) and new sequencing technologies and their potential implementation in diagnostic laboratory settings in order to complement the currently recommended H. pylori management guidelines and subsequently improve public health.

Keywords: Helicobacter pylori, Advances in diagnostics, Next generation sequencing, Whole genome sequencing, Clinical management

Core tip: With worldwide increasing antibiotic resistance in Helicobacter pylori (H. pylori), drug resistance phenotypes should be determined prior to the administration of antibiotic eradication regimens. Our literature search yielded studies that focused on the prediction of drug resistance phenotypes in H. pylori based on the presence of certain point mutations in the bacterium’s genome using next generation sequencing (NGS) technology. Thus, NGS technology may enable the implementation of rapid and accurate genotypic drug susceptibility testing prior to the administration of antimicrobial therapy. This may increase H. pylori eradication rates and ultimately improve patient management.