Skip to main content

Advertisement

Log in

Changes in the severity of gastric mucosal inflammation associated with Helicobacter pylori in humans coinfected with  intestinal helminths

  • Original Article
  • Published:
Indian Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Though a few studies in animal models suggest that intestinal helminths (IH) favorably affect evolution of gastritis associated with Helicobacter pylori (H. pylori) the studies supporting this concept in humans are only a few and are based on serological data.

Methods

To evaluate the possible influence of IH on the human gastric mucosa, three groups of Venezuelan adults with gastropathy (endoscopically diagnosed) were studied: H. pylori−/IH− (n = 17), H. pylori+/IH− (n = 18), and H. pylori+/IH+ (n = 11). Histological analysis (hematoxylin-eosin) and immunohistochemical staining (peroxidase) for cytokines interleukin-1beta (IL-1β), tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), and interleukin 4 (IL-4) were undertaken in gastric antral biopsies.

Results

Expression of the four cytokines was detected in all individuals in varying degrees, but proinflammatory cytokines were expressed in a higher degree in the H. pylori+/IH− group, mainly IL-1β (Th1-dominant immune response), associated with a higher degree of both histological inflammation and gastric cancer risk index (GCRI), as compared to the H. pylori−/IH− group. In contrast, an increased expression of IL-4 and a reduced expression of proinflammatory cytokines (Th2-dominant response), plus the tendency to a lower degree of mononuclear infiltration, mucosal atrophy in gastric corpus, and GCRI, were evidenced in the coinfected group.

Conclusions

The findings of the present study is perhaps the first histological evidence of a possible modulatory effect of IH on the gastric mucosal inflammatory response due to H. pylori infection in humans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Atherton JC, Blaser MJ. Coadaptation of Helicobacter pylori and humans: ancient history, modern implications. J Clin Invest. 2009;119:2475–87.

    Article  CAS  Google Scholar 

  2. Oluwasola AO. Genetic determinants and clinico-pathological outcomes of Helicobacter pylori infection. Ann Ib Postgrad Med. 2014;12:22–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Fox JG, Beck P, Dangler CA, et al. Concurrent enteric helminth infection modulates inflammation and gastric immune responses and reduces Helicobacter-induced gastric atrophy. Nat Med. 2000;6:536–42.

    Article  CAS  Google Scholar 

  4. Wroblewski LE, Peek RM, Wilson KT. Helicobacter pylori and gastric cancer: factors that modulate disease risk. Microbiol Rev. 2010;23:713–39.

    Article  CAS  Google Scholar 

  5. Rogers AB. Gastric Helicobacter spp. in animal models: pathogenesis and modulation by extragastric coinfections. Methods Mol Biol. 2012;921:175–88.

    Article  CAS  Google Scholar 

  6. Whary MT, Muthupalani S, Ge Z, et al. Helminth co-infection in Helicobacter pylori infected INS-GAS mice attenuates gastric premalignant lesions of epithelial dysplasia and glandular atrophy and preserves colonization resistance of the stomach to lower bowel microbiota. Microbes Infect. 2014;16:345–55.

    Article  CAS  Google Scholar 

  7. Martin HR, Shakya KP, Muthupalani S, et al. Brugia filariasis differentially modulates persistent Helicobacter pylori gastritis in the gerbil model. Microbes Infect. 2010;12:748–58.

    Article  CAS  Google Scholar 

  8. Whary MT, Sundina N, Bravo LE, et al. Intestinal helminthiasis in Colombian children promotes a Th2 response to Helicobacter pylori: possible implications for gastric carcinogenesis. Cancer Epidemiol Biomark Prev. 2005;14:1464–9.

    Article  CAS  Google Scholar 

  9. Ek C, Whary MT, Ihrig M, Bravo LE, Correa P, Fox JG. Serologic evidence that Ascaris and Toxoplasma infections impact inflammatory responses to Helicobacter pylori in Colombians. Helicobacter. 2012;17:107–15.

  10. Arismendi-Morillo G, Hernández I, Mengual E, Fuenmayor A, Romero G, Lizarzábal M. Comparison of three methods based on endoscopic gastric biopsies for diagnosis of Helicobacter pylori active infection in a clinical setting. Arq Gastroenterol. 2011;48:190–4.

  11. Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The Updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996;20:1161–81.

    Article  CAS  Google Scholar 

  12. Meining A, Bayerdörffer E, Müller P, et al. Gastric carcinoma risk index in patients infected with Helicobacter pylori. Virchows Arch. 1998;432:311–4.

    Article  CAS  Google Scholar 

  13. Serrano C, Diaz MI, Valdivia A, et al. Relationship between Helicobacter pylori virulence factors and regulatory cytokines as predictors of clinical outcome. Microbes Infect. 2007;9:428–34.

    Article  CAS  Google Scholar 

  14. Dhakhwa R, Acharya IL, Shrestha HG, Joshi DM, Lama S, Lakhey M. Histopathologic study of chronic antral gastritis. J Nepal Health Res Counc. 2012;10:57–60.

  15. Zhang C, Yamada N, Wu YL,  Wen M, Matsuhisa T, Matsukura N. Comparison of Helicobacter pylori infection and gastric mucosal histological features of gastric ulcer patients with chronic gastritis patients. World J Gastroenterol. 2005;11:976–81.

  16. Lamarque D, Tran Van Nhieu J, Breban M. What are the gastric modifications induced by acute and chronic Helicobacter pylori infection? Gastroenterol Clin Biol. 2003;27:391–400.

    CAS  PubMed  Google Scholar 

  17. Vega-Ramos B, Rodríguez-Moguel L. Helicobacter pylori. Its relationships and morphological controversies. Rev Gastroenterol Mex. 2000;65  4 Suppl 2:34–40.

  18. Lopes AI, Quiding-Jarbrink M, Palha A, et al. Cytokine expression in pediatric Helicobacter pylori infection. Clin Diagn Lab Immunol. 2005;12:994–1002.

    Article  CAS  Google Scholar 

  19. Strömberg E, Edebo A, Svennerholm AM, Lindholm C. Decreased epithelial cytokine responses in the duodenal mucosa of Helicobacter pylori-infected duodenal ulcer patients. Clin Diagn Lab Immunol. 2003;10:116–24.

    Article  Google Scholar 

  20. Lindholm C, Quiding-Järbrink M, Lönroth H, Hamlet A, Svennerholm AM. Local cytokine response in Helicobacter pylori-infected subjets. Infect Immun. 1998;66:5964–71.

  21. D’Elios MM, Manghetti M, De Carli M, et al. T helper 1 effector cells specific for Helicobacter pylori in the gastric antrum of patients with peptic ulcer disease. J Immunol. 1997;158:962–7.

    Google Scholar 

  22. Bamford KB, Fan X, Crowe SE, et al. Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype. Gastroenterology. 1998;114:482–92.

    Article  CAS  Google Scholar 

  23. D’Elios MM, Amedei A, Benagiano M, Azzurri A, Del Prete G. Helicobacter pylori, T cells and cytokines: the ‘dangerous liaisons’. FEMS Immunol Med Microbiol. 2005;44:113–9.

  24. Amedei A, Cappon A, Codolo G, et al. The neutrophil-activating protein of Helicobacter pylori promotes Th1 immune responses. J Clin Invest. 2006;116:1092–101.

    Article  CAS  Google Scholar 

  25. Pellicanò A, Imeneo M, Leone I,  Larussa T, Luzza F. Enhanced activation of cyclooxygenase-2 downregulates Th1 signaling pathway in Helicobacter pylori-infected human gastric mucosa. Helicobacter. 2007;12:193–9.

  26. Bimczok D, Clements RH, Waites KB, et al. Human primary gastric dendritic cells induce a Th1 response to H. pylori. Mucosal Immunol. 2010;3:260–9.

    Article  CAS  Google Scholar 

  27. Uehara A, Okumura T, Sekiya C, Okamura K, Takasugi Y, Namiki M. Interleukin-1 inhibits the secretion of gastric acid in rats: possible involvement of prostaglandin. Biochem Biophys Res Commun. 1989;162:1578–84.

  28. Datta De D, Bhattacharjya S, Maitra M, et al. IL1β induced Smad 7 negatively regulates gastrin expression. PLoS One. 2011;6:e14775.

    Article  CAS  Google Scholar 

  29. Nutman TB. Looking beyond the induction of Th2 responses to explain immunomodulation by helminthes. Parasite Immunol. 2015;37:304–13.

    Article  CAS  Google Scholar 

  30. Maizels RM, Smits HH, McSorley HJ. Modulation of host immunity by helminths: the expanding repertoire of parasite effector molecules. Immunity. 2018;49:801–18.

    Article  CAS  Google Scholar 

  31. Eichenberger RM, Ryan S, Jones L, et al. Hookworm secreted extracellular vesicles interact with host cells and prevent inducible colitis in mice. Front Immunol. 2018;9:850.

  32. Whary MT, Fox JG. Th1-mediated pathology in mouse models of human disease is ameliorated by concurrent Th2 responses to parasite antigens. Curr Top Med Chem. 2004;4:531–8.

    Article  CAS  Google Scholar 

  33. Moreau E, Chauvin A. Immunity against helminths: interactions with the host and the intercurrent infections. J Biomed Biotechnol. 2010;428593.

Download references

Acknowledgments

The authors thank doctors Jesús Mosquera, Hector Pons, and Yasmir Quiroz for the counseling for quantitation of cytokines. The authors also thank Gladys Colina, Nivia Abreu, and Neyla Molero de Bohórquez for the technical collaboration.

Funding

This work was partially supported by the Scientific and Humanistic Development Council of the Universidad del Zulia, Venezuela (Subvention No. CC-0660-10).

Author information

Authors and Affiliations

Authors

Contributions

Alisbeth Fuenmayor Boscán: study concept and protocol design; collecting data; analysis of data; preparing the initial draft of the manuscript; obtained funding.

Ileana Hernández-Rincón: study concept and protocol design; critical revision of the manuscript for intellectual content; study supervision.

Gabriel Arismendi-Morillo, Edgardo Mengual, Zulbey Rivero, Gisela Romero, and Maribel Lizarzábal: technical, administrative and material support.

Melchor Álvarez-Mon: study concept and protocol design; critical revision of the manuscript for intellectual content.

Corresponding author

Correspondence to Alisbeth Fuenmayor-Boscán.

Ethics declarations

Conflict of interest

AF-B, IH-R, GA-M, EM, ZR, GR, ML, and MA-M declare that they have no conflict of interest.

Ethics statement

The study was performed conforming to the Helsinki declaration of 1975, as revised in 2000 and 2008 concerning human and animal rights, and the authors followed the policy concerning informed consent as shown on Springer.com.

Disclaimer

The authors are solely responsible for the data and the contents of the paper. In no way, the Honorary Editor-in-Chief, Editorial Board Members, or the printer/publishers are responsible for the results/findings and content of this article.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fuenmayor-Boscán, A., Hernández-Rincón, I., Arismendi-Morillo, G. et al. Changes in the severity of gastric mucosal inflammation associated with Helicobacter pylori in humans coinfected with  intestinal helminths. Indian J Gastroenterol 39, 186–195 (2020). https://doi.org/10.1007/s12664-020-01023-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12664-020-01023-0

Keywords

Navigation