The Effect of <i>Helicobacter pylori</i> Infection and Dietary Iron Deficiency on Host Iron Homeostasis: A Study in Mice

Keenan, Jacqueline I.; Peterson, Richard A.; Fraser, Robin; Frampton, C.; Walmsley, T A; Allardyce, Randall A.; Roake, Justin

doi:10.1111/j.1083-4389.2004.00278.x

Cited by 20 publications

(20 citation statements)

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“…In a previous study that evaluated the effect of low dietary iron (8ppm Fe) in both male and female C57BL/6 mice after 30 weeks of H . pylori infection, mice on the low iron diet had lower serum iron, transferrin saturation, and hemoglobin than uninfected controls on low iron diet [51]. The results of the current study corroborated many of these findings, and extended analysis to a chronic timepoint of 12 months postinfection.…”

Section: Discussionsupporting

confidence: 81%

Helicobacter pylori infection and low dietary iron alter behavior, induce iron deficiency anemia, and modulate hippocampal gene expression in female C57BL/6 mice

Burns¹,

Amaya²,

Bodi³

et al. 2017

PLoS ONE

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Helicobacter pylori (H.pylori), a bacterial pathogen, is a causative agent of gastritis and peptic ulcer disease and is a strong risk factor for development of gastric cancer. Environmental conditions, such as poor dietary iron resulting in iron deficiency anemia (IDA), enhance H.pylori virulence and increases risk for gastric cancer. IDA affects billions of people worldwide, and there is considerable overlap between regions of high IDA and high H.pylori prevalence. The primary aims of our study were to evaluate the effect of H.pylori infection on behavior, iron metabolism, red blood cell indices, and behavioral outcomes following comorbid H. pylori infection and dietary iron deficiency in a mouse model. C57BL/6 female mice (n = 40) were used; half were placed on a moderately iron deficient (ID) diet immediately post-weaning, and the other half were maintained on an iron replete (IR) diet. Half were dosed with H.pylori SS1 at 5 weeks of age, and the remaining mice were sham-dosed. There were 4 study groups: a control group (-Hp, IR diet) as well as 3 experimental groups (-Hp, ID diet; +Hp, IR diet; +Hp,ID diet). All mice were tested in an open field apparatus at 8 weeks postinfection. Independent of dietary iron status, H.pylori -infected mice performed fewer exploratory behaviors in the open field chamber than uninfected mice (p<0.001). Hippocampal gene expression of myelination markers and dopamine receptor 1 was significantly downregulated in mice on an ID diet (both p<0.05), independent of infection status. At 12 months postinfection, hematocrit (Hct) and hemoglobin (Hgb) concentration were significantly lower in +Hp, ID diet mice compared to all other study groups. H.pylori infection caused IDA in mice maintained on a marginal iron diet. The mouse model developed in this study is a useful model to study the neurologic, behavioral, and hematologic impact of the common human co-morbidity of H. pylori infection and IDA.

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Section: Discussionsupporting

confidence: 81%

Helicobacter pylori infection and low dietary iron alter behavior, induce iron deficiency anemia, and modulate hippocampal gene expression in female C57BL/6 mice

Burns¹,

Amaya²,

Bodi³

et al. 2017

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…H. pylori could cause iron deficiency indirectly by suppressing gastric acid secretion, thereby reducing solubilization and uptake of dietary iron. There is also evidence obtained with a mouse infection model suggesting that H. pylori successfully competes for dietary iron when the diet is iron poor (20). Furthermore, a recent study showed that clinical isolates of H. pylori from patients with iron-deficiency anemia have higher rates of inorganic iron uptake than strains from patients with non-irondeficiency anemia (39).…”

mentioning

confidence: 99%

Unique Host Iron Utilization Mechanisms of Helicobacter pylori Revealed with Iron-Deficient Chemically Defined Media

et al. 2010

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Helicobacter pylori chronically infects the gastric mucosa, where it can be found free in mucus, attached to cells, and intracellularly. H. pylori requires iron for growth, but the sources of iron used in vivo are unclear. In previous studies, the inability to culture H. pylori without serum made it difficult to determine which host iron sources might be used by H. pylori. Using iron-deficient, chemically defined medium, we determined that H. pylori can bind and extract iron from hemoglobin, transferrin, and lactoferrin. H. pylori can use both bovine and human versions of both lactoferrin and transferrin, contrary to previous reports. Unlike other pathogens, H. pylori preferentially binds the iron-free forms of transferrin and lactoferrin, which limits its ability to extract iron from normal serum, which is not iron saturated. This novel strategy may have evolved to permit limited growth in host tissue during persistent colonization while excessive injury or iron depletion is prevented.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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

et al. 2016

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Epidemiologic studies have provided conflicting data regarding an association between Helicobacter pylori infection and iron deficiency anemia (IDA) in humans. Here, a Mongolian gerbil model was used to investigate a potential role of H. pylori infection, as well as a possible role of diet, in H. pylori-associated IDA. Mongolian gerbils (either H. pylori infected or uninfected) received a normal diet or one of three diets associated with increased H. pylori virulence: high-salt, low-iron, or a combination of a high-salt and low-iron diet. In an analysis of all infected animals compared to uninfected animals (independent of diet), H. pylori-infected gerbils had significantly lower hemoglobin values than their uninfected counterparts at 16 weeks postinfection (P < 0.0001). The mean corpuscular volume (MCV) and serum ferritin values were significantly lower in H. pylori-infected gerbils than in uninfected gerbils, consistent with IDA. Leukocytosis and thrombocytosis were also detected in infected gerbils, indicating the presence of a systemic inflammatory response. In comparison to uninfected gerbils, H. pylori-infected gerbils had a higher gastric pH, a higher incidence of gastric ulcers, and a higher incidence of fecal occult blood loss. Anemia was associated with the presence of gastric ulceration but not gastric cancer. Infected gerbils consuming diets with a high salt content developed gastric ulcers significantly more frequently than gerbils consuming a normal-salt diet, and the lowest hemoglobin levels were in infected gerbils consuming a high-salt/low-iron diet. These data indicate that H. pylori infection can cause IDA and that the composition of the diet influences the incidence and severity of H. pylori-induced IDA.A nemia affects up to 1.6 billion people worldwide, potentially resulting in fatigue, decreased productivity, increased susceptibility to infection, or death (1-5). A wide variety of infectious processes can be primary causes of anemia or can exacerbate anemia arising from noninfectious etiologies. For example, intestinal parasitic infections can cause chronic blood loss, leading to iron deficiency anemia (IDA; i.e., anemia due to iron deficiency) (3, 6). Anemia arises in patients with malaria because the parasites invade erythrocytes (2), and bacterial toxins can cause hemolysis (7). In addition, chronic infections, chronic immune activation, and cancer can cause a form of anemia known as "anemia of chronic disease" (8).Colonization of the human stomach with the gastric bacterium Helicobacter pylori is another potential cause of anemia. Anemia often occurs in the setting of symptomatic H. pylori-associated diseases (peptic ulcer disease or gastric cancer), but it has been suggested that H. pylori may also be a cause of IDA in asymptomatic persons with no evidence of peptic ulcer disease or gastric cancer (9). H. pylori has been linked to several other hematologic diseases, including pernicious anemia (vitamin B 12 deficiency arising through an autoimmune-mediated process) and idiopathic throm...

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The Effect of Helicobacter pylori Infection and Dietary Iron Deficiency on Host Iron Homeostasis: A Study in Mice

Cited by 20 publications

References 50 publications

Helicobacter pylori infection and low dietary iron alter behavior, induce iron deficiency anemia, and modulate hippocampal gene expression in female C57BL/6 mice

Helicobacter pylori infection and low dietary iron alter behavior, induce iron deficiency anemia, and modulate hippocampal gene expression in female C57BL/6 mice

Unique Host Iron Utilization Mechanisms of Helicobacter pylori Revealed with Iron-Deficient Chemically Defined Media

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

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