Gastric Helicobacter Infection Induces Iron Deficiency in the INS-GAS Mouse

Abstract

There is increasing evidence from clinical and population studies for a role of H. pylori infection in the aetiology of iron deficiency. Rodent models of Helicobacter infection are helpful for investigating any causal links and mechanisms of iron deficiency in the host. The aim of this study was to investigate the effects of gastric Helicobacter infection on iron deficiency and host iron metabolism/transport gene expression in hypergastrinemic INS-GAS mice. INS-GAS mice were infected with Helicobacter felis for 3, 6 and 9 months. At post mortem, blood was taken for assessment of iron status and gastric mucosa for pathology, immunohistology and analysis of gene expression. Chronic Helicobacter infection of INS- GAS mice resulted in decreased serum iron, transferrin saturation and hypoferritinemia and increased Total iron binding capacity (TIBC). Decreased serum iron concentrations were associated with a concomitant reduction in the number of parietal cells, strengthening the association between hypochlorhydria and gastric Helicobacter-induced iron deficiency. Infection with H. felis for nine months was associated with decreased gastric expression of iron metabolism regulators hepcidin, Bmp4 and Bmp6 but increased expression of Ferroportin 1, the iron efflux protein, iron absorption genes such as Divalent metal transporter 1, Transferrin receptor 1 and also Lcn2 a siderophore-binding protein. The INS-GAS mouse is therefore a useful model for studying Helicobacter-induced iron deficiency. Furthermore, the marked changes in expression of gastric iron transporters following Helicobacter infection may be relevant to the more rapid development of carcinogenesis in the Helicobacter infected INS-GAS model.

Hepcidin as a Major Component of Renal Antibacterial Defenses against Uropathogenic Escherichia coli

“…37 The authors attributed this effect to the reduced number of parietal cells that synthesize hepcidin. However, in our UTI model, renal epithelium remained intact up to 48 hours postinfection.…”

Helicobacter pyloriinfection does not promote hepatocellular cancer in a transgenic mouse model of hepatitis C virus pathogenesis

“…27,59 In addition, chronic H. felis infection induced iron deficiency in hypergastrinemic INS-GAS mice. 60 Whether H. pylori infection can decrease the risk of HCC in FL-N/35 mice fed a high iron diet requires additional studies.…”

Dietary Composition Influences Incidence of Helicobacter pylori-Induced Iron Deficiency Anemia and Gastric Ulceration

“…Previous studies in rodent models have reached inconsistent conclusions about the capacity of H. pylori to cause anemia (19)(20)(21)(22). The inconsistent conclusions might reflect the use of different H. pylori strains, differences in animal models, differences in diets, or differences in the time points selected for analysis.…”

“…Animal studies examining a potential link between H. pylori infection and anemia have also yielded conflicting results (19)(20)(21)(22). In one study, H. pylori-infected male INS-GAS mice (which overexpress gastrin) exhibited reductions in both hemoglobin and serum ferritin levels compared to uninfected animals; however, the mean corpuscular volume (MCV; a measure of the average size of erythrocytes) was elevated in the infected cohort (21), a finding that differs from the reduced MCV typically observed in patients with IDA.…”

“…In one study, H. pylori-infected male INS-GAS mice (which overexpress gastrin) exhibited reductions in both hemoglobin and serum ferritin levels compared to uninfected animals; however, the mean corpuscular volume (MCV; a measure of the average size of erythrocytes) was elevated in the infected cohort (21), a finding that differs from the reduced MCV typically observed in patients with IDA. Infection of INS-GAS mice with the related organism H. felis also resulted in anemia (19). A potential limitation of the mouse model for studying H. pylori-associated IDA is that H. pylori strains often undergo inactivating mutations in the cag pathogenicity island during the course of mouse stomach colonization (23,24).…”