Helicobacter pylori sabA gene is associated with iron deficiency anemia in childhood and adolescence

Abstract

BackgroundGastric Helicobacter pylori colonization leads to iron deficiency anemia (IDA), especially in children and adolescents. However the pathogenesis is poorly understood.ObjectiveWe sought to identify specific H. pylori genes involved in IDA development, by comparing bacterial genome-wide expression profiling in patients affected or not.MethodsH. pylori were isolated from four children with IDA and four from matched controls without IDA. Based on these isolates, cDNA microarrays under iron-replete or depleted conditions were systematically performed to compare gene expression profiles at the whole genome level. Real-time reverse-transcription (RT-) PCR and protein assays were performed for further assessing the profile differentiation of the identified H. pylori IDA-associated genes.ResultsWe identified 29 and 11 genes with significantly higher or lower expression in the IDA isolates compared to non-IDA isolates, respectively. Especially notable were higher expression of sabA gene encoding sialic acid-binding adhesin in the IDA isolates, which was confirmed by real-time RT-PCR study. Moreover, iron-depletion in vitro led to up-regulation of fecA1 and frpB1 genes and down-regulation of pfr, as predicted. Known iron-regulated genes such as fur, pfr, fecA, and feoB did not significantly differ between both groups. The IDA isolates had significantly higher expression of vacuolating cytotoxin gene vacA than non-IDA isolates, consistent with the results of VacA protein assays. There were no significant differences in bacterial growth value between IDA and non-IDA isolates.ConclusionsIt is likely that H. pylori carrying high expression of sabA causes IDA, especially in children and adolescents who have increased daily iron demand. In addition, it is possible that several host-interactive genes, including vacA, may play a synergistic role for sabA in IDA development.

Prevalence of <i>Helicobacter pylori cag</i>A and <i>sab</i>A Genotypes in Patients with Gastric Disease

“…Although we did not find any significant results for the sabA gene, it is still recognized as a virulence marker for its ability to promote intense recruitment of neutrophils and establishment of a persistent colonization [28] [29].…”

Helicobacter pyloriand some aspects of gut microbiota in children

“…Kato et al 11 15 and 20% (36/180) vs 60% (108/180), respectively. 16 In addition, the latter study also demonstrated significantly higher serum IL-10 levels in nonatopic subjects.…”

“…Kato et al tried to identify specific H. pylori genes involved in IDA development, by comparing bacterial genome‐wide expression profiling in H. pylori isolates from patients with and without IDA. Isolates from IDA patients had a higher expression of the sab A gene (that encodes sialic acid binding adhesin) and the vacuolating cytotoxin gene vac A.…”

Helicobacter pylori and extragastric diseases

“…While El‐Said et al did not report a significant effect of H. pylori on IDA in patients with hemodialysis, Katu et al showed how genetic characteristics of H. pylori may influence the occurrence of IDA in children and adolescents. In fact, they reported a higher expression of sialic acid‐binding ( sab ) gene and vacuolating cytotoxin gene A ( vac A) in patients with IDA compared to healthy subjects . Maruyama et al clearly demonstrated how H. pylori eradication is able to decrease weight loss and prevent subclinical IDA in older subjects …”

“…In fact, they reported a higher expression of sialic acid-binding (sab) gene and vacuolating cytotoxin gene A (vacA) in patients with IDA compared to healthy subjects. 33…”