Helicobacter pylori Infection and Iron-Deficiency Anemia: Mechanisms, Clinical Evidence, and Therapeutic Implications: English

Alza Hamonangan Pasaribu; Wirandi  dalimunthe

doi:10.70471/xgj0b579

Authors

Alza Hamonangan Pasaribu Universitas Sumatera Utara Author
Wirandi dalimunthe Author

DOI:

https://doi.org/10.70471/xgj0b579

Keywords:

Helicobacter pylori, iron deficiency, iron-deficiency anemia, eradication therapy, narrative review

Abstract

Iron-deficiency anemia (IDA) is common, but its persistence cannot always be explained by diet, physiological demand, blood loss, or recognized malabsorption. Helicobacter pylori infection has therefore been investigated as a potentially modifiable contributor to disturbed iron homeostasis. To critically synthesize recent evidence on the association between H. pylori infection and iron deficiency (ID)/IDA, the biological mechanisms involved, and the implications for testing and eradication. A structured narrative search of PubMed, Google Scholar, ScienceDirect, Frontiers, and publisher websites was updated through 18 June 2026. Six core human studies with direct iron or hematological outcomes were comparatively appraised, while systematic reviews, mechanistic literature, and international guidelines were used for contextual interpretation. The evidence is population-dependent rather than uniformly consistent. In non-elderly adults, infection was associated with ID (adjusted odds ratio [OR] 3.03) but not clearly with anemia or IDA. A large sex-stratified study reported an association with ID/IDA in women. Pediatric meta-analyses found increased odds of ID (OR 1.52) and IDA (OR 1.83), although one analysis found no significant association with anemia as a broad endpoint and reported substantial heterogeneity. A longitudinal birth cohort suggested a strong association between CagA-positive strains and IDA, whereas a seven-patient adolescent case series documented sustained hematological improvement after successful eradication. The most plausible pathways are impaired gastric iron handling and inflammation-mediated hepcidin upregulation; bacterial iron acquisition and microscopic blood loss remain biologically credible but less directly quantified. H. pylori should be regarded as a possible contributor, not a universal cause, of IDA. Testing is most defensible in unexplained or iron-refractory IDA after common causes have been evaluated. Pediatric testing should follow endoscopy-based guideline indications rather than routine non-invasive screening.

Downloads

Download data is not yet available.

References

Annibale, B., Marignani, M., Monarca, B., Antonelli, G., Marcheggiano, A., Martino, G., Mandelli, F., Caprilli, R., & Delle Fave, G. (1999). Reversal of iron deficiency anemia after Helicobacter pylori eradication in patients with asymptomatic gastritis. Annals of Internal Medicine, 131(9), 668-672. DOI: https://doi.org/10.7326/0003-4819-131-9-199911020-00006

Gravina, A. G., Priadko, K., Ciamarra, P., Granata, L., Facchiano, A., Miranda, A., Dallio, M., Federico, A., & Romano, M. (2020). Extra-gastric manifestations of Helicobacter pylori infection. Journal of Clinical Medicine, 9(12), 3887. https://doi.org/10.3390/jcm9123887 DOI: https://doi.org/10.3390/jcm9123887

Homan, M., Jones, N. L., Bontems, P., Carroll, M. W., Czinn, S. J., Gold, B. D., Goodman, K., Harris, P. R., Jerris, R., Kalach, N., Kori, M., Megraud, F., Rowland, M., & Tavares, M. (2024). Updated joint ESPGHAN/NASPGHAN guidelines for management of Helicobacter pylori infection in children and adolescents (2023). Journal of Pediatric Gastroenterology and Nutrition, 79(3), 758-785. https://doi.org/10.1002/jpn3.12314 DOI: https://doi.org/10.1002/jpn3.12314

Hudak, L., Jaraisy, A., Haj, S., & Muhsen, K. (2017). An updated systematic review and meta-analysis on the association between Helicobacter pylori infection and iron deficiency anemia. Helicobacter, 22(1), e12330. https://doi.org/10.1111/hel.12330 DOI: https://doi.org/10.1111/hel.12330

Kato, S., Gold, B. D., & Kato, A. (2022). Helicobacter pylori-associated iron deficiency anemia in childhood and adolescence: Pathogenesis and clinical management strategy. Journal of Clinical Medicine, 11(24), 7351. https://doi.org/10.3390/jcm11247351 DOI: https://doi.org/10.3390/jcm11247351

Kato, S., Gold, B. D., & Kato, A. (2022). The resolution of severe iron-deficiency anemia after successful eradication of Helicobacter pylori in teenagers. JPGN Reports, 3(3), e238. https://doi.org/10.1097/PG9.0000000000000238 DOI: https://doi.org/10.1097/PG9.0000000000000238

Lee, J. Y., Kim, S. E., Park, S. J., Park, M. I., Moon, W., Kim, J. H., & Jung, K. (2022). Helicobacter pylori infection and iron deficiency in non-elderly adults participating in a health check-up program. Korean Journal of Internal Medicine, 37(2), 304-312. https://doi.org/10.3904/kjim.2020.433 DOI: https://doi.org/10.3904/kjim.2020.433

Li, Y., Choi, H., Leung, K., Jiang, F., Graham, D. Y., & Leung, W. K. (2023). Global prevalence of Helicobacter pylori infection between 1980 and 2022: A systematic review and meta-analysis. The Lancet Gastroenterology & Hepatology, 8(6), 553-564. https://doi.org/10.1016/S2468-1253(23)00070-5 DOI: https://doi.org/10.1016/S2468-1253(23)00070-5

Lopez, A., Cacoub, P., Macdougall, I. C., & Peyrin-Biroulet, L. (2016). Iron deficiency anaemia. The Lancet, 387(10021), 907-916. https://doi.org/10.1016/S0140-6736(15)60865-0 DOI: https://doi.org/10.1016/S0140-6736(15)60865-0

Malfertheiner, P., Megraud, F., Rokkas, T., Gisbert, J. P., Liou, J. M., Schulz, C., Gasbarrini, A., Hunt, R. H., Leja, M., O'Morain, C., Rugge, M., Suerbaum, S., Tilg, H., Sugano, K., & El-Omar, E. M. (2022). Management of Helicobacter pylori infection: The Maastricht VI/Florence consensus report. Gut, 71(9), 1724-1762. https://doi.org/10.1136/gutjnl-2022-327745 DOI: https://doi.org/10.1136/gutjnl-2022-327745

Motupalli, S. K., & Oroszi, T. L. (2024). The nexus between Helicobacter pylori infection and anemia: A systematic review. Frontiers in Hematology, 3, 1423494. https://doi.org/10.3389/frhem.2024.1423494 DOI: https://doi.org/10.3389/frhem.2024.1423494

Navidifar, T., Meftah, E., Baghsheikhi, H., Kazemzadeh, K., Karimi, H., & Rezaei, N. (2025). Dual role of hepcidin in response to pathogens. Microbial Pathogenesis, 203, 107496. https://doi.org/10.1016/j.micpath.2025.107496 DOI: https://doi.org/10.1016/j.micpath.2025.107496

Pu, S., Zhuang, Z., Liu, N., Luo, Q., & Zhang, D. (2025). Research progress on the relationship between Helicobacter pylori infection and iron deficiency anemia. Frontiers in Microbiology, 16, 1552630. https://doi.org/10.3389/fmicb.2025.1552630 DOI: https://doi.org/10.3389/fmicb.2025.1552630

Queiroz, D. M. M., Braga, L. L. C., Rocha, G. A., Batista, S. A., Rocha, A. M. C., Saito, M., Checkley, W., Gilman, R. H., & Crabtree, J. E. (2024). Infection by Helicobacter pylori cytotoxin-A-associated antigen-positive strains is associated with iron deficiency anemia in a longitudinal birth cohort in Brazil. Haematologica, 109(12), 4112-4115. https://doi.org/10.3324/haematol.2024.285446 DOI: https://doi.org/10.3324/haematol.2024.285446

Saha, A., Hammond, C. E., Beeson, C., Peek, R. M., Jr., & Smolka, A. J. (2010). Helicobacter pylori represses proton pump expression and inhibits acid secretion in human gastric mucosa. Gut, 59(7), 874-881. DOI: https://doi.org/10.1136/gut.2009.194795

Tan, S., Noto, J. M., Romero-Gallo, J., Peek, R. M., Jr., & Amieva, M. R. (2011). Helicobacter pylori perturbs iron trafficking in the epithelium to grow on the cell surface. PLoS Pathogens, 7(5), e1002050. https://doi.org/10.1371/journal.ppat.1002050 DOI: https://doi.org/10.1371/journal.ppat.1002050

Walle, M., Tesfaye, A., Agidew, M. M., Semaw, M., & Mekuria, S. (2025). The association of Helicobacter pylori infection with the risk of anemia in children: A systematic review and meta-analysis. BMC Infectious Diseases, 25, 23. https://doi.org/10.1186/s12879-024-10427-8 DOI: https://doi.org/10.1186/s12879-024-10427-8

Wang, Z.-T., Tan, W.-T., Meng, M.-M., Su, H., Li, Q., Guo, C.-M., Wang, J., & Liu, H. (2024). The correlation between Helicobacter pylori infection and iron deficiency anemia in women. European Review for Medical and Pharmacological Sciences, 28(4), 1541-1553. https://doi.org/10.26355/eurrev_202402_35483

Wang, Z., Tan, W., & Xiao, F. (2025). Impact of Helicobacter pylori infection on iron deficiency anemia in children: A systematic review and meta-analysis with early intervention implications. Frontiers in Microbiology, 16, 1541011. https://doi.org/10.3389/fmicb.2025.1541011 DOI: https://doi.org/10.3389/fmicb.2025.1541011