Skip to main content Skip to main navigation menu Skip to site footer

Lower IFN-γ expression causes more severe gastric inflammation in BALB/c infected by Bali 03 Helicobacter pylori isolate that provided by low iron diet

  • I Made Suma Wirawan ,
  • Novitasari ,
  • I Gde Raka Widiana ,
  • I Nyoman Mantik Astawa ,
  • I Gusti Alit Artha ,
  • Zainul Muttaqin ,


Background: Helicobacter pylori (H. pylori) infection is associated with various gastrointestinal diseases including gastritis, peptic ulcers, gastric carcinoma, and gastric mucosa-associated lymphoid-tissue lymphoma (MALT) lymphoma. Several studies have shown that H. pylori plays a role in iron deficiency that is refractory to iron administration. This study aims to analyze whether the lower IFN-γ expression causes more severe gastric inflammation in BALB/c infected by Bali 03 H. pylori isolate that is provided by a low iron diet.

Methods: This research was an experimental study by inoculating the bacterial isolate H. pylori Bali 03 in two groups of BALB/c mice. The treatment group was given a low iron diet at a dose of <3 mg/kgBW of mice, while the control group was given a normal dose of iron diet at a dose of 40 mg/kgBW of mice. The cellular immune response of the two groups of BALB/c mice was measured by comparing the expression of IFN-γ, granzyme B, IFN-γ/IL-10 ratio to the degree of gastric inflammation.

Results: The results of the research were that the H. pylori Bali 03 isolate caused inflammation in 36 (100%) gastric of the mice. The degree of gastric inflammation of mice was more severe in the treatment group than in the control group, within 6 weeks precancerous lesions occurred, namely gastric gland atrophy and metaplasia in the treatment group, 1 (2.7%). There is a significant difference between the control group and the treatment group (p=0.019). There was a significant difference in IFN-γ expression between the treatment group and the control group (p=0.034).

Conclusion: Iron deficiency affects the degree of gastric inflammation through IFN-γ expression in BALB/c infected with H. pylori isolate Bali 03. Iron deficiency worsens the degree of gastric inflammation in BALB/c mice infected with H. pylori isolate Bali 03.



  1. Öztekin M, Yılmaz B, Ağagündüz D, Capasso R. Overview of Helicobacter pylori Infection: Clinical Features, Treatment, and Nutritional Aspects. Diseases. 2021;9(4):66. doi:10.3390/diseases9040066.
  2. Kato S, Gold BD, Kato A. Helicobacter pylori-Associated Iron Deficiency Anemia in Childhood and Adolescence-Pathogenesis and Clinical Management Strategy. J Clin Med. 2022;11(24):7351. doi:10.3390/jcm11247351.
  3. Ansari S, Yamaoka Y. Helicobacter pylori Infection, Its Laboratory Diagnosis, and Antimicrobial Resistance: a Perspective of Clinical Relevance. Clin Microbiol Rev. 2022;35(3):e0025821. doi:10.1128/cmr.00258-21.
  4. Ding SZ, Du YQ, Lu H, et al. Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition). Gut. 2022;71(2):238-253. doi:10.1136/gutjnl-2021-325630.
  5. Wang L, Cao ZM, Zhang LL, et al. Helicobacter Pylori and Autoimmune Diseases: Involving Multiple Systems. Front Immunol. 2022;13:833424. doi:10.3389/fimmu.2022.833424.
  6. Ailloud F, Didelot X, Woltemate S, et al. Within-host evolution of Helicobacter pylori shaped by niche-specific adaptation, intragastric migrations and selective sweeps. Nat Commun. 2019;10(1):2273. doi:10.1038/s41467-019-10050-1.
  7. Baj J, Forma A, Sitarz M, et al. Helicobacter pylori Virulence Factors-Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment. Cells. 2020;10(1):27. doi:10.3390/cells10010027.
  8. Elbehiry A, Marzouk E, Aldubaib M, et al. Helicobacter pylori Infection: Current Status and Future Prospects on Diagnostic, Therapeutic and Control Challenges. Antibiotics (Basel). 2023;12(2):191. doi:10.3390/antibiotics12020191.
  9. Vital JS, Tanoeiro L, Lopes-Oliveira R, Vale FF. Biomarker Characterization and Prediction of Virulence and Antibiotic Resistance from Helicobacter pylori Next Generation Sequencing Data. Biomolecules. 2022;12(5):691. doi:10.3390/biom12050691.
  10. Ali A, AlHussaini KI. Helicobacter pylori: A Contemporary Perspective on Pathogenesis, Diagnosis and Treatment Strategies. Microorganisms. 2024;12(1):222. doi:10.3390/microorganisms12010222.
  11. Sharndama HC, Mba IE. Helicobacter pylori: an up-to-date overview on the virulence and pathogenesis mechanisms. Braz J Microbiol. 2022;53(1):33-50. doi:10.1007/s42770-021-00675-0.
  12. Pohl D, Keller PM, Bordier V, Wagner K. Review of current diagnostic methods and advances in Helicobacter pylori diagnostics in the era of next generation sequencing. World J Gastroenterol. 2019;25(32):4629-4660. doi:10.3748/wjg.v25.i32.4629
  13. Gonciarz W, Krupa A, Hinc K, et al. The effect of Helicobacter pylori infection and different H. pylori components on the proliferation and apoptosis of gastric epithelial cells and fibroblasts. PLoS One. 2019;14(8):e0220636. doi:10.1371/journal.pone.0220636.
  14. Ansari S, Yamaoka Y. Helicobacter pylori Virulence Factors Exploiting Gastric Colonization and its Pathogenicity. Toxins (Basel). 2019;11(11):677. Published 2019 Nov 19. doi:10.3390/toxins11110677.
  15. Gobert AP, Wilson KT. Induction and Regulation of the Innate Immune Response in Helicobacter pylori Infection. Cell Mol Gastroenterol Hepatol. 2022;13(5):1347-1363. doi:10.1016/j.jcmgh.2022.01.022.
  16. Saruuljavkhlan B, Alfaray RI, Oyuntsetseg K, et al. Study of Helicobacter pylori Isolated from a High-Gastric-Cancer-Risk Population: Unveiling the Comprehensive Analysis of Virulence-Associated Genes including Secretion Systems, and Genome-Wide Association Study. Cancers (Basel). 2023;15(18):4528. doi:10.3390/cancers15184528.
  17. Santos MLC, de Brito BB, da Silva FAF, et al. Helicobacter pylori infection: Beyond gastric manifestations. World J Gastroenterol. 2020;26(28):4076-4093. doi:10.3748/wjg.v26.i28.4076.
  18. Asiimwe D, Bangi I, Esanyu J, et al. Association Between Helicobacter pylori Infection and Anemia Among Adult Dyspeptic Patients Attending Kiryandongo General Hospital, Uganda. J Blood Med. 2023;14:57-66.. doi:10.2147/JBM.S392146.
  19. Martin-Nuñez GM, Cornejo-Pareja I, Clemente-Postigo M, Tinahones FJ. Gut Microbiota: The Missing Link Between Helicobacter pylori Infection and Metabolic Disorders?. Front Endocrinol (Lausanne). 2021;12:639856. doi:10.3389/fendo.2021.639856.
  20. Chen CC, Liou JM, Lee YC, Hong TC, El-Omar EM, Wu MS. The interplay between Helicobacter pylori and gastrointestinal microbiota. Gut Microbes. 2021;13(1):1-22. doi:10.1080/19490976.2021.1909459.
  21. Afsar MNA, Jhinu ZN, Bhuiyan MAI, Islam Z, Siddiqua TJ. Helicobacter pylori infection and micronutrient deficiency in pregnant women: a systematic review and meta-analysis. BMJ Open Gastroenterol. 2020;7(1):e000490. doi:10.1136/bmjgast-2020-000490.
  22. González MF, Díaz P, Sandoval-Bórquez A, Herrera D, Quest AFG. Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development. Int J Mol Sci. 2021;22(9):4823. doi:10.3390/ijms2209482.
  23. Al Mutawa OA, Izhari MA, Alharbi RA, et al. Helicobacter pylori (H. pylori) Infection-Associated Anemia in the Asir Region, Saudi Arabia. Diagnostics (Basel). 2023;13(14):2404. doi:10.3390/diagnostics13142404.
  24. Nabavi-Rad A, Azizi M, Jamshidizadeh S, et al. The Effects of Vitamins and Micronutrients on Helicobacter pylori Pathogenicity, Survival, and Eradication: A Crosstalk between Micronutrients and Immune System. J Immunol Res. 2022;2022:4713684. doi:10.1155/2022/4713684.
  25. Eyoum Bille BB, Kouitcheu Mabeku LB. Relationship between active Helicobacter pylori infection and anemia, iron deficiency, iron deficiency anemia: A cross-sectional study in a sub-Saharan setting. JGH Open. 2022;6(8):554-568. doi:10.1002/jgh3.12787.
  26. Mehata S, Parajuli KR, Pant ND, et al. Prevalence and correlates of Helicobacter pylori infection among under-five children, adolescent and non-pregnant women in Nepal: Further analysis of Nepal national micronutrient status survey 2016. PLoS Negl Trop Dis. 2021;15(6):e0009510. doi:10.1371/journal.pntd.0009510.
  27. Soares GAS, Moraes FAS, Ramos AFPL, et al. Dietary habits and Helicobacter pylori infection: is there an association?. Therap Adv Gastroenterol. 2023;16:17562848231160620. doi:10.1177/17562848231160620.

How to Cite

Wirawan, I. M. S., Novitasari, I Gde Raka Widiana, Astawa, I. N. M. ., Artha, I. G. A. ., & Muttaqin, Z. . (2024). Lower IFN-γ expression causes more severe gastric inflammation in BALB/c infected by Bali 03 Helicobacter pylori isolate that provided by low iron diet. Indonesia Journal of Biomedical Science, 18(1), 99–104.




Search Panel