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

Abstract

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.

Iron Deficiency-Induced Changes in the Hippocampus, Corpus Striatum, and Monoamines Levels That Lead to Anxiety, Depression, Sleep Disorders, and Psychotic Disorders

“…Another mechanism of how iron deficiency can affect behavior is through hippocampal gene expression, as was shown in a study by Burns et al [47]. They studied Helicobacter pylori infection's effect on the hippocampal gene expression.…”

The Associations of Dietary Iron Intake and the Transferrin Receptor (TFRC) rs9846149 Polymorphism with the Risk of Gastric Cancer: A Case–Control Study Conducted in Korea

“…This finding is in agreement with previously reported results [ 31 , 32 ]. In addition, an animal model showed that low dietary iron may result in iron deficiency anemia, enhanced H. pylori virulency and increased GC risk [ 20 ]. Moreover, another study indicated that body iron status was inversely associated with risk of GC [ 33 ].…”

“…To our knowledge, the interaction effect between dietary iron and the TFRC gene on GC risk modification has not been investigated in epidemiological studies. Moreover, despite the strong biological mechanisms, observational studies failed to obtain consistent findings regarding the relationship of dietary iron with the risk of GC [ 4 , 9 , 19 , 20 , 21 , 22 ]. Importantly, the majority of studies have focused on heme iron rather than nonheme iron [ 9 , 22 , 23 , 24 ].…”

Evaluation of Helicobacter pylori Infection, Neutrophil–Lymphocyte Ratio and Platelet–Lymphocyte Ratio in Dyspeptic Patients

“…In our study, H. pylori-positive patients had lower folic acid, iron and ferritin levels than the negative ones (Table 1). Several pathways are blamed for decreased iron stores in the H. pylori-positive patients, including chronic gastritis with achlorhydria, reduced ascorbic acid secretion in the gastric mucosa, iron uptake by the bacterium, and bleeding ulcers related to H. pylori [31]. However, the studies that assess the effect of H. pylori eradication therapy on the improvement of iron deficiency are controversial [32].…”