Amin Talebi Bezmin Abadi
Fatemeh Haji Abbas Tabrizi
Ashraf Mohabbati Mobarez
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands, Utercht, Netherlands.
Department of Internal Medicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Biology, Kharazmi University, Karaj, Tehran, Islamic Republic of Iran.
Department of Bacteriology, School of Medical Sciences, Tarbiat Modares University, Tehran, Islamic Republic of Iran
We read with great interest the recent publication by Ramis IB et al, who investigated Helicobacter pylorivirulence factors in Brazilian dyspeptic patients1. It has been firmly shown that no reliable diagnostic biomarkers exist to predict a specific disease outcome after primary colonization of H. pylori, although this has become an interesting area of research on this important microorganism worldwide. Many studies had been conducted to test/validate proper disease-related biomarkers of H. pylori. Recent findings based on sequencing and proteomic technologies have suggested new determinants as virulence factors that are disease-specific for H. pylori2,3. Ramis IB et al found that cagA/cagE/babA2/vacAm1s1/iceA1 was a significant biomarker among only 15% (4/26) of their entire investigated population1. Indeed, the conclusion in this study is based on a very small number of H. pylori strains (57 isolates), which cannot serve as a proper sample size from which to draw a comprehensive conclusion. Furthermore, the presence of a gene alone is not sufficient to suggest that it is a virulence factor. Gene expression analysis or proteomic tests are needed to identify true biomarkers of H. pylori that are associated with certain gastroduodenal diseases. Undeniably, additional in vitro and in vivo studies are necessary to elucidate the relationship between the H. pylori cagE gene and pathologic findings. It may be advisable to design a prospective study with different samples from other originating populations, and larger groups will be required to enhance the preliminary hypothesis stated in the current study. Moreover, it has been broadly recognized that gastroduodenal diseases are quite complicated outcomes of a variety of parameters, including environmental factors and host genetics. Additional in-depth studies are required to define a true biomarker for Helicobacter pylori-associated gastroduodenal disorders. Another controversial issue in the field of H. pylori biomarker and disease research is whether physicians can use this type of data in clinical trials. While characterizing accurate H. pylori biomarkers associated with certain diseases seems difficult, new, full-genome sequencing studies may answer unsolved related issues in the near future.
1. Ramis IB, Vianna JS, Silva Junior LV, Groll AV, Silva PEA. cagE as a biomarker of the pathogenicity of Helicobacter pylori. Rev Soc Bras Med Trop 2013;46:185-189. [ Links ]
2. Abadi AT, Taghvaei T, Wolfram L, Kusters JG. Infection with Helicobacter pylori strains lacking dupA is associated with an increased risk of gastric ulcer and gastric cancer development. J Med Microbiol 2012;61:23-30. [ Links ]
3. Abadi ATB, Rafiei A, Ajami A, Hosseini V, Taghvaei T, Jones KR, et al. Helicobacter pylori homB, but Not cagA, Is Associated with Gastric Cancer in Iran. J Clin Microbiol 2011; 49:3191-3197. [ Links ]
In our paper, we concluded that cagE could be a risk biomarker for gastric lesions and may contribute to a better evaluation of the pathogenic potential of Helicobacter pylori and, in particular, the diversity of factors involved in the relationship between gastric diseases and H. pylori colonization/infection. Thus, we have been studying new biomarkers for H. pylori, patient susceptibility, and environmental factors. Our results suggest only that cagE, like cagA, vacA, iceA, or babA2, could be related to the virulence of H. pylori.
Our hypothesis, in agreement with Dr. Abadi et al and others, is that a combination of patient and microorganismal genetics and environmental conditions determine the actual risk of gastric diseases related to H. pylori colonization/infection.
With respect to sequencing, transcriptome, and proteomic studies, sequencing of the genomes of the main strains circulating in each region is necessary because of the high genetic diversity found in both the host and the microorganism. Indeed, studies on gene expression should also consider different aspects of the regulation of these genes, such as the identification of the inducers?
Obviously, this is a complex issue, and more highly refined studies are required to confirm or reject some hypotheses. Finally, it is important to highlight that recent studies have shown that H. pyloricolonization/infection should be eradicated with caution because some diseases, such as gastro-esophageal reflux and allergy, may be related to H. pylori eradication. Our study is not the final word but rather contributes to progress in the knowledge obtained from the search for a putative biomarker of microorganism pathogenicity and the inferred relationship with gastric disease.