Effects of chronic Helicobacter pylori strain PMSS1 infection on whole brain and gastric iron homeostasis in male INS-GAS mice

Melissa I. Stair, Caroline Bodi Winn, Monika A. Burns, Hilda Holcombe, Stephen C. Artim, Zhongming Ge, Zeli Shen, Timothy C. Wang, Sureshkumar Muthupalani, Olga Franco-Mahecho, Kathleen Ennis, Michael K. Georgieff, James G. Fox

Research output: Contribution to journalArticlepeer-review


Iron deficiency, the most common micronutrient deficiency in humans, is associated with long-term deficits in cognition and memory if left untreated. Infection with the gastric pathogen Helicobacter pylori has been linked to iron deficiency anemia (IDA). The H. pylori virulence factor cytotoxin-associated gene A (cagA) is proposed to be especially pertinent in iron deficiency. Male INS-GAS/FVB mice were infected with the CagA+ strain pre-murine Sydney strain 1 (PMSS1) for 12–13 or 27–29 weeks to investigate the role of chronic H. pylori infection in iron deficiency and neurological sequelae. Mice at both timepoints demonstrated significantly elevated gastric histopathology scores and inflammatory cytokines compared to sham-dosed controls. However, only mice at 27–29 weeks post infection had changes in hematological parameters, with significantly decreased erythrocyte count, hematocrit, serum hemoglobin, and increased serum total iron binding capacity. Gastric transcription of iron-regulatory genes Hamp and Bmp4 were significantly downregulated at both timepoints. In the brain, iron-dependent myelingergic and synaptic markers were significantly downregulated at 27–29 weeks. These results indicated that long-term infection of the CagA + PMSS1 strain of H. pylori in this study caused anemia, altered gastric iron homeostasis, and neurological changes similar to those reported in other rodent H. pylori CagA strain infection models.

Original languageEnglish (US)
Article number105045
JournalMicrobes and Infection
Issue number3
StatePublished - Mar 1 2023

Bibliographical note

Funding Information:
We thank Parisa Zarringhalam and Elaine Robbins for technical assistance. Research reported in this publication was supported by Office of The Director of the National Institutes of Health under award number T3200010978 , R01CA093405 , P01CA028842-23 , and R35CA21088 , and National Institute of Environmental Health Sciences under award P30ES0022109 .

Publisher Copyright:
© 2022 Institut Pasteur


  • Helicobacter pylori
  • INS-GAS mouse
  • Iron deficiency anemia
  • Pre-murine Sydney strain 1

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


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