Children of Helicobacter pylori-infected dyspeptic mothers are predisposed to H. pylori acquisition with subsequent iron deficiency and growth retardation

BACKGROUND: We tested whether Helicobacter pylori-infected dyspeptic mothers had a higher rate of H. pylori infection in their children, and whether such H. pylori-infected children were predisposed to iron deficiency or growth retardation. MATERIALS AND METHODS: A total of 163 children from 106 dyspeptic mothers (58 with and 48 without H. pylori infection) were enrolled to evaluate body weight, height, hemoglobin, serum ferritin, and H. pylori infection using the 13C-urea breath test. A questionnaire was used to evaluate demographic factors of each child. RESULTS: The rate of H. pylori infection in children with H. pylori-infected dyspeptic mothers was higher than that of children with noninfected mothers (20.5% vs. 5.3%; p<.01, OR: 4.6, 95% CI: 1.5-14.2). The rate of H. pylori infection in children elevated as the number of their H. pylori-infected siblings increased (p<.01). For children below 10 years of age, H. pylori infection was closely related to low serum ferritin and body weight growth (p<.05). CONCLUSION: The children of H. pylori-infected dyspeptic mothers had an increased risk for such infection. The risk further increased once their siblings were infected. H. pylori infection in pre-adolescent children may determine iron deficiency and growth retardation.     

The effect of Helicobacter pylori infection and dietary iron deficiency on host iron homeostasis: a study in mice

BACKGROUND: Helicobacter pylori, which requires iron to survive, may cause host iron deficiency by directly competing with the host for available iron or by impairing iron uptake as a consequence of atrophy-associated gastric hypochlorhydria. The aim of this study was to examine the effect of H. pylori infection and dietary iron deficiency on host iron homeostasis in a mouse model. MATERIALS AND METHODS: H. pylori SS1-infected and uninfected C57BL/6 mice, fed either a normal diet or an iron-deficient diet, were assessed for iron status and infection-associated gastritis over a 30-week period. RESULTS: After 10 weeks, serum ferritin values were higher in H. pylori-infected mice than in uninfected controls, irrespective of dietary iron intake (p = .04). The infection-related increase in body iron stores persisted in the iron-replete mice but diminished over time in mice with restricted dietary iron intake (p < .0001). At 30 weeks serum ferritin levels were lower in these animals (p = .063). No significant difference in bacterial numbers was detected at the 30-week time point (p > .05) and the histological changes observed were consistently associated with infection (p < .01) and not with the iron status of the mice (p = .771). CONCLUSIONS: Infection with H. pylori did not cause iron deficiency in iron-replete mice. However, diminished iron stores in mice as a result of limited dietary iron intake were further lowered by concurrent infection, thus indicating that H. pylori competes successfully with the host for available iron.     

326例儿童缺铁性贫血与感染幽门螺杆菌关系探究

目的分析幽门螺杆菌(H.pylori)对儿童缺铁性贫血(IDA)的影响,探讨H.pylori感染与儿童IDA的相关性,提高儿童IDA诊治率。方法应用~(13)C-呼气试验和胶体金法检测326例IDA患儿及211例健康儿童H.pylori感染情况,并对其结果进行统计学分析。结果 326例IDA患儿中H.pylori检测阳性217例(阳性率为66.56%),健康组儿童H.pylori检测阳性47例(阳性率为22.27%),两组比较差异有统计学意义(X~2=100.54,P0.01)。2-6岁组分别与7-9岁组及10-12岁组H.pylori阳性率比较差异均有统计学意义(X~2=8.61、21.46,P0.05),7-9岁组较10-12组H.pylori阳性率比较差异无统计学意义(X~2=2.62,P0.05)。其中女患儿H.pylori阳性率为78.06%(121/155),男患儿H.pylori阳性率为56.14%(96/171),两者比较差异有统计学意义(X~2=17.55,P0.01),且不同年龄组男女阳性率比较差异均有统计学意义。217例H.pylori感染的IDA患儿以轻度贫血为主,占95.85%(208/217)。结论H.pylori感染与儿童IDA之间存在相关性。     

Helicobacter felis infection causes an acute iron deficiency in nonpregnant and pregnant mice

BACKGROUND: The role of Helicobacter pylori infection in iron deficiency during pregnancy is limited. The aim of the present study was to assess the relationship between Helicobacter infection and levels of iron stores in pregnant mice. MATERIALS AND METHODS: Female C57BL/6 mice were either inoculated with 10(8) H. pylori, Helicobacter felis or water. In the nonpregnant study, 15 mice from each group were sacrificed after 4 and 20 weeks of infection. In the pregnancy study, after 6 weeks of infection all female mice were mated and approximately 2 weeks after mating, half of the pregnant mice (n = 9/group) from each group were sacrificed. The remaining mice were allowed to give birth, and approximately 4 weeks after birth, mice were asphyxiated with CO2, followed by heart puncture, and killed by cervical dislocation. Serum ferritin and iron were determined with a micro-particle enzyme immunoassay method and by a timed-endpoint method. RESULTS: Serum iron levels in mice infected with H. felis were significantly (p < .05) lowered compared to control (24%) and H. pylori (27%)-infected mice at 4 weeks of infection. Serum iron in the control, H. pylori and H. felis groups were significantly (p < .05) elevated at 20 weeks by 39, 26 and 77%, respectively, compared to 4 weeks of infection. H. felis-infected mice had a significantly (p < .05) decreased serum ferritin level during pregnancy (61%) compared to H. pylori-infected mice. CONCLUSION: These results suggest that H. felis but not H. pylori infection causes an acute iron deficiency in normal and pregnant mice.     

Micronutrients (Other than iron) and Helicobacter pylori infection: a systematic review

Background: Many micronutrients depend on a healthy stomach for absorption. Helicobacter pylori chronic gastritis may alter gastric physiology affecting homeostasis of vitamins and minerals. Objectives: Systematic review to assess whether H. pylori infection is associated with reduced micronutrient levels (other than iron) in the plasma or gastric juice and whether low micronutrient levels are modified by eradication treatment. Method: Medline was searched for relevant publications from inception to June 2010. Studies describing micronutrient levels in H. pylori‐infected and not‐infected adults and/or the effect of eradication treatment on micronutrient levels were included. Findings: Fifty‐two publications were selected: 46 investigated the association between H. pylori infection and reduced micronutrient levels and 14 the effect of eradication treatment on micronutrient levels. Sixty‐four studies investigated vitamins (23 ascorbic acid, four ß‐carotene, 21 cobalamin, 11 folate, and five α‐tocopherol) and 10 addressed minerals (one calcium, one copper, one magnesium, one phosphorus, three selenium, and three zinc). Pooled standardized mean differences in micronutrient levels showed positive associations with H. pylori infection for ascorbic acid (gastric juice, ?1.087) and cobalamin (?0.744), and a positive effect of eradication treatment, which increased ascorbic acid in the gastric juice (?1.408) and serum cobalamin (?1.910). No significant association between infection and low folate levels was observed. Meta‐analyses for other micronutrients were not performed owing to insufficient data. Conclusions: Meta‐analyses indicate that H. pylori infection is associated with reduced levels of ascorbic acid and cobalamin, supported by the positive effect of eradication treatment. For other micronutrients, further studies are needed.     

The Expression of Iron-repressible Outer Membrane Proteins in Helicobacter pylori and Its Association with Iron Deficiency Anemia

Background: Helicobacter pylori infection is known to be a cause of iron deficiency anemia (IDA) that is unresponsive to iron supplements. H. pylori bind iron to a specific receptor by iron-repressible outer membrane proteins (IROMPs) under conditions of restricted iron.
Materials and Methods: We compared the expression of IROMPs from strains of H. pylori under both iron-restricted and iron-supplemented conditions to determine the difference between strains with and without IDA. One standard strain, two clinical strains, and three IDA strains were cultured; and then the IROMPs were extracted under iron-restricted and iron-supplemented conditions. We used SDS-PAGE to compare the expression of the IROMPs from each strain.
Results:  IROMPs were found in IDA strains under iron-restricted conditions and their molecular sizes were estimated to be 56, 48, 41, and 37 kDa. In the iron-repleted media, the IROMPs were no longer present.
Conclusion: In the iron-depleted state, specific H. pylori strains associated with IDA demonstrated an advantage in iron acquisition due to a higher expression of IROMPs. Our results can explain in part why some patients with H. pylori infection are more prone to develop clinical IDA under restricted iron conditions in the host.     

Lactoferrin and desferrioxamine are ineffective in the treatment of Helicobacter pylori infection and may enhance H. pylori growth and gastric inflammation in mice

Aims:  To evaluate the efficacy of bovine lactoferrin (BLf), recombinant human lactoferrin (rHLf) and desferrioxamine against Helicobacter pylori in vitro and in mice and also to determine whether BLf or rHLf alter gastric inflammation.
Methods and Results:  In vitro: Broth dilution susceptibility tests were performed using different concentrations of desferrioxamine, BLf and rHLf. Murine trials: In the prevention trial, C57BL/6 female mice were treated with BLf or rHLF, and then infected with the SS1 strain of H. pylori . In the treatment trial, mice were gavaged with either BLf, rHLf or desferrioxamine. In addition, gastric myeloperoxidase activity (MPO) was measured to assess gastric inflammation. Desferoxamine was found to have a direct bactericidal effect, while BLf and rHLf only partially suppressed H. pylori growth in vitro . However, in both prevention and treatment trials all three forms of treatment failed to reduce H. pylori load in mice. Gastric MPO activity and H. pylori load were noted to be higher with lactoferrin treatments.
Conclusions:  Our study does not support the use of BLf or rHLF in the treatment of human H. pylori infection. Interestingly, H. pylori growth and gastric inflammation appear to be enhanced by lactoferrin treatment.
Significance and Impact of the Study:  The mouse model is ideal for testing novel H. pylori eradicating agents.     

Increased serum copper and decreased serum zinc levels in children with iron deficiency anemia

In order to evaluate serum copper and zinc status in children with iron deficiency anemia (IDA), 60 children with IDA aged 1–14 yr and 64 healthy children as controls aged 1–14 yr were included the study. Serum copper levels were higher in children with IDA (189 ± 49 (Μg/dL) than those of controls (163 ± 37 Μg/dL) (p = 0.001). Serum zinc levels were lower in the patient group (109 ± 59 Μg/dL) than those of control subjects (135 ± 56 Μg/dL) (p = 0.017). In addition, there were statistically significant negative correlations between hematological parameters and serum copper levels in the patient group, but not in controls. No correlation between hematological parameters and serum zinc levels were found in both patient and control groups, except positive correlation between mean corpuscular volume (MCV) and serum zinc level in patients. It was concluded that at the time of managing children with IDA, zinc deficiency must be borne in mind and if necessary treatment should be initiated with zinc.     

Polymorphisms in cytokine genes and risk of Helicobacter pylori infection among Jamaican children

Background: Infection by Helicobacter pylori is often acquired during childhood. Recent studies suggest that inflammatory cytokines may play a role in susceptibility to, and disease phenotype caused by, H. pylori infection, but the association of host genetic variability with risk of H. pylori infection has not been studied in children. Methods: We investigated the relationship between the risk of H. pylori antibody positivity and cytokine gene polymorphisms among 199 two‐year‐old Jamaicans. H. pylori seropositivity was determined by a validated research enzyme‐linked immunosorbent assay. Real‐time Taqman® polymerase chain reaction was used to determine variants at 17 loci in 11 cytokine genes (IL1A, IL1B, IL2, TNF, TLR4, IL4, IL6, IL10, IL10RA, IL12A and IL13). We estimated the odds ratio and the 95% confidence interval for the association of genetic polymorphisms with H. pylori seropositivity, using logistic regression. Results: Forty (20.1%) of 199 children were seropositive. Children's H. pylori seropositivity correlated highly with maternal H. pylori seropositivity (OR = 7.98, 95% CI = 1.05–60.60, p = .02). Children carrying IL1A?889T had a lower risk of H. pylori positivity, compared to those carrying ?889C, with each T allele associated with 43% risk reduction (OR = 0.57, 95% CI = 0.33–0.99, p‐trend = .05). No other loci we examined were associated with the risk of H. pylori seropositivity. Conclusions: The IL1A?889 T allele, known to express a higher level of cytokine IL‐1α, is associated with a lower risk of H. pylori infection among Jamaican children. Our finding supports the hypothesis that an upregulation of pro‐inflammatory cytokines may protect against persistent H. pylori colonization.     

胃微生物菌群与幽门螺杆菌感染的胃贲门腺癌发病相关性分析

目的 研究胃微生物菌群与胃贲门腺癌发病的相关性。方法 选择2016年4月—2018年4月在本院就诊的胃贲门腺癌（GCA）患者109例。患者均经病理科组织病理确诊为GCA。对照组为健康人群100例,根据有无H. pylori检出将对照组和GCA组患者分为有H. pylori和无H. pylor,其中对照组有H. pylori检出19例,无H. pylori检出81例,GCA组有H. pylori检出53例,无H. pylori检出56例。用胃镜采集标本,胃镜采集镜下正常的贲门胃黏膜。样本取材后置于无菌冻存管放入液氮中保存,使用16S rRNA的方法进行胃黏膜微生物种类检测。结果 GCA组患者幽门螺杆菌（Helicobacter pylori）感染比例明显高于对照组,无论有无H. pylori感染的对照组人群中,丰度较高的菌属是不动杆菌（Acinetobacter）,罗斯氏菌（Rothhia）,嗜血杆菌（Haemophilus）,拟杆菌（Bacteroides）,链球菌（Streptococcus）,韦荣球菌（Veillonella）,普氏菌（Prevotella）。无H. pylori组内,GCA组样本中普氏菌（Prevotella）、瓦氏菌（Shewanella）、盐单胞菌（Halomonas）丰度明显高于对照组,有H. pylori组内,GCA组样本中普氏菌（Prevotella）、瓦氏菌（Shewanella）、盐单胞菌（Halomonas）、卟啉单胞菌（Porphyromonas）、梭杆菌（Fusobacterium）丰度明显高于对照组,不动杆菌（Acinetobacter）明显低于对照组。有H. pylori的GCA组样本中普氏菌（Prevotella）、瓦氏菌（Shewanella）、盐单胞菌（Halomonas）、卟啉单胞菌（Porphyromonas）、梭杆菌（Fusobacterium）丰度明显高于无H. pylori的GCA组,不动杆菌（Acinetobacter）明显低于无H. pylori的GCA组。结果还发现GCA与普氏菌（Prevotella）、瓦氏菌（Shewanella）、盐单胞菌（Halomonas）、卟啉单胞菌（Porphyromonas）、梭杆菌（Fusobacterium）正相关,与不动杆菌（Acinetobacter）负相关。结论 GCA患者胃内菌群数量和结果与健康人群存在明显差异,H. pylori可能影响胃内菌群结构在GCA发病中发挥作用。     

Prevalence of Helicobacter pylori among Alaskans: Factors associated with infection and comparison of urea breath test and anti‐Helicobacter pylori IgG antibodies

Background

Helicobacter pylori is one of the most common human infections in the world, and studies in Alaska Native people, as well as other Indigenous peoples, have shown a high prevalence of this gastric infection. This study was undertaken to determine the prevalence of H. pylori infection by urea breath test (UBT) and anti‐ H. pylori IgG among Alaskans living in four regions of the state and to identify factors associated with infection.

Methods

A convenience sample of persons > 6 months old living in five rural and one urban Alaskan community were recruited from 1996 to 1997. Participants were asked about factors possibly associated with infection. Sera were collected and tested for anti‐ H. pylori IgG antibodies; a UBT was administered to participants > 5 years old.

Results

We recruited 710 people of whom 571 (80%) were Alaska Native and 467 (66%) were from rural communities. Rural residents were more likely to be Alaska Native compared with urban residents (P < .001). Of the 710 people, 699 (98%) had a serum sample analyzed, and 634 (97%) persons > 5 years old had a UBT performed. H. pylori prevalence was 69% by UBT and 68% by anti‐ H. pylori IgG. Among those with a result for both tests, there was 94% concordance. Factors associated with H. pylori positivity were Alaska Native racial status, age ≥ 20 years, rural region of residence, living in a crowded home, and drinking water that was not piped or delivered.

Conclusions

Helicobacter pylori prevalence is high in Alaska, especially in Alaska Native persons and rural residents. Concordance between UBT and serology was also high in this group. Two socioeconomic factors, crowding and drinking water that was not piped or delivered, were found to be associated with H. pylori positivity.     

金山西部地区5~7岁儿童H.pylori感染调查及与胃蛋白酶原相关性分析

目的了解金山西部地区5~7岁健康儿童幽门螺杆菌(H.pylori)感染情况,并探讨其与胃蛋白酶原(PG)的相关性。方法选取2019年3-5月金山地区5~7岁健康儿童共464例,分析不同年龄及性别幼儿H.pylori感染、胃蛋白酶原Ⅰ(PGⅠ)、胃蛋白酶原Ⅱ(PGⅡ)水平以及PGⅠ/PGⅡ比值的差异,采用Spearman相关性分析H.pylori感染与PGⅠ、PGⅡ水平和PGⅠ/PGⅡ的相关性。结果5~7岁儿童H.pylori阳性率达11.96%,5岁组、6岁组、7岁组儿童H.pylori阳性率分别为10.07%、12.96%、13.73%,阳性率逐年升高。不同年龄和性别幼儿的PGⅠ、PGⅡ水平和PGⅠ/PGⅡ间差异有统计学意义(P<0.05)。H.pylori是否感染与PGⅠ/PGⅡ呈显著正相关,与PGⅠ/PGⅡ呈显著负相关(P<0.05)。结论本地区5~7岁儿童H.pylori感染率相对较低且有着自身的特点,而且H.pylori感染与血清PG水平的关系密切,未来应加强对幼儿H.pylori感染与血清PG 水平的监测及防治。     

Mucoid Helicobacter pylori isolates with fast growth under microaerobic and aerobic conditions

Background: Helicobacter pylori is microaerobic and turns into coccoid under aerobic conditions. In this study, two mucoid strains, A and D, were isolated from gastric biopsies which grew well on blood agar after 24‐hour incubation under aerobic as well as microaerobic conditions. The aim of this study was to identify these strains and compare their growth under aerobic and microaerobic conditions with that of control H. pylori. Materials and Methods: The two isolates A and D were identified as H. pylori according to microscopic morphology, urease, catalase and oxidase tests. Their growth under humidified aerobic and microaerobic conditions was compared with that of control H. pylori which grew only under microaerobic conditions. They were further identified by amplification of 16S rRNA, vacA alleles, cagA and ureAB genes by PCR. Their susceptibility to current antimicrobials was also examined. Results: The strains A and D produced mucoid colonies under aerobic and microaerobic conditions after 24‐hour, exhibiting the typical spiral morphology of H. pylori. The results of urease, catalase and oxidase tests were positive. Sequencing of amplified products showed 99–100% homology with those of the reference H. pylori strains in GenBank. Both strains exhibited resistance to the high concentrations of antimicrobials. Conclusions: This study reports the isolation of two mucoid strains of H. pylori with confluent growth under aerobic and microaerobic conditions. It appears that production of exopolysaccharide (EXP) could serve as a physical barrier to reduce oxygen diffusion into the bacterial cell and uptake of antibiotics. EXP protected the mucoid H. pylori isolates against stressful conditions, the result of which could be persistence of bacterial infection in the stomach.     

Helicobacter pylori interacts with heparin and heparin-dependent growth factors

Abstract The pathogenic bacterium Helicobacter pylori , which causes active, chronic type B gastritis and peptic ulcer disease, and increases the risk for development of gastric cancer, could tentatively interfere with growth factors and growth factor receptors of importance for the gastroduodenal mucosa, e.g. heparin-binding FGFs (fibroblast growth factors). H. pylori binds FGF with an extremely strong affinity (3.8 × 10⁻¹² M), and also heparan sulfate and heparin with higher affinity ( K _d 9 × 10⁻⁹ M) than FGFs bind to heparin (10⁻⁸–10⁻⁹ M). FGF receptors are also dependent on heparin for their activation. Heparan sulfate binding proteins (HSBP) are exposed on and shed from the surface of H. pylori , which often are localised close to the epithelial stem cells in the gastroduodenal glands. H. pylori could thus efficiently interfere with growth factors and growth factor receptors, tentatively resulting in disturbance of the delicate balance that control the renewal, maintenance and repair of the gastroduodenal mucosa. This mode of action has previously not been considered, but may constitute part of its pathogenic mechanism. Such a dynamic mode of action of H. pylori may explain the reason for that infected victims may either suffer from gastrointestinal symptoms or lack clinical evidence of disease or discomfort.     

Production of reactive oxygen species in peripheral blood is increased in individuals with Helicobacter pylori infection and decreased after its eradication

BACKGROUND: Helicobacter pylori infection has been reported to cause gastroduodenal ulcer, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Recent studies have suggested that H. pylori infection may also associate with other diseases, including hematologic and dermatologic disorders, and cardiovascular injury, by unknown mechanisms. METHODS: Production of reactive oxygen species (ROS) was determined in peripheral blood samples from 86 patients (34 H. pylori-negative and 52 H. pylori-positive subjects) using a highly sensitive chemiluminescence probe, L-012 (8-amino-5-chloro-7-phenylpyrido(3,4-d) pyridazine-1 and 4 (2H, 3H) dione). Eleven H. pylori-positive individuals were also analyzed their ROS production in peripheral blood after H. pylori eradication. RESULTS: ROS production was significantly higher in individuals with H. pylori infection than in those without infection. Enhanced production of ROS was decreased significantly after eradication of H. pylori. No correlation was found between the extent of ROS production and sex, age, smoking status, alcohol ingestion, use of medications, or serum level of C-reactive protein. CONCLUSION: These findings suggest that ROS production was enhanced in peripheral blood by H. pylori infection. Chemiluminescence analysis of blood samples using L-012 permits evaluation of systemic oxidative stress in patients with H. pylori infection.