RESUMO
Hepcidin regulates iron metabolism. Its synthesis increases in infection and decreases in iron deficiency. The aim of this study was to evaluate the relationship between H. pylori infection and iron deficiency by levels of hepcidin in children. A total of 350 school-age children participated in this cross-sectional study. Determinations of serum ferritin, hemoglobin, hepcidin, C-reactive protein, and α-1-acid-glycoprotein were done. Active H. pylori infection was performed with a 13C-urea breath test. In schoolchildren without H. pylori infection, hepcidin was lower in those with iron deficiency compared to children with normal iron status (5.5 ng/mL vs. 8.2 ng/mL, p = 0.017); while in schoolchildren with H. pylori infection the levels of hepcidin tended to be higher, regardless of the iron nutritional status. Using multivariate analysis, the association between H. pylori infection and iron deficiency was different by hepcidin levels. The association between H. pylori and iron deficiency was not significant for lower values of hepcidin (Odds Ratio = 0.17; 95% Confidence Interval [CI] 0.02-1.44), while the same association was significant for higher values of hepcidin (OR = 2.84; CI 95% 1.32-6.09). This joint effect is reflected in the adjusted probabilities for iron deficiency: Individuals with H. pylori infection and higher levels of hepcidin had a probability of 0.24 (CI 95% 0.14-0.34) for iron deficiency, and this probability was 0.24 (CI 95% 0.14-0.33) in children without H. pylori infection and lower levels of hepcidin. In children with H. pylori infection and iron deficiency, the hepcidin synthesis is upregulated. The stimulus to the synthesis of hepcidin due to H. pylori infection is greater than the iron deficiency stimulus.
Assuntos
Anemia Ferropriva/sangue , Infecções por Helicobacter/sangue , Helicobacter pylori , Hepcidinas/sangue , Deficiências de Ferro , Adolescente , Anemia Ferropriva/microbiologia , Testes Respiratórios , Proteína C-Reativa/análise , Criança , Estudos Transversais , Feminino , Ferritinas/sangue , Infecções por Helicobacter/complicações , Hemoglobinas/análise , Humanos , Ferro/sangue , Masculino , Estado Nutricional , Razão de Chances , Orosomucoide/análiseRESUMO
Background: Anemia is a term that describes low hemoglobin concentrations and can result from micronutrient deficiencies, infection, or low birth weight. Early-life anemia, particularly iron-deficiency anemia (IDA) is associated with several negative metabolic, developmental, and cognitive outcomes, some of which persist into adulthood. Objective: The aim of this study was to investigate alterations in systemic metabolism and fecal microbial diversity and functionality associated with anemia and IDA in male and female infants from Iquitos, Peru. Design: Cross-sectional stool and serum samples were collected from 95 infants (53 boys and 42 girls) at 12 mo of age. The fecal microbiome was assessed by using 16S ribosomal RNA gene sequencing, and the fecal and serum metabolomes were quantified using 1H-nuclear magnetic resonance. Results: The prevalence of anemia was 64%, with a greater proportion of anemia in male infants attributed to iron deficiency. Metabolically, anemia was associated with decreased concentrations of tricarboxylic acid cycle metabolites in both sexes (males: succinate, P = 0.031; females: fumarate, P = 0.028). In addition, anemic male infants exhibited significantly lower serum concentrations of several amino acids compared with nonanemic male infants. Although no specific structural or functional differences in the microbiota were observed with anemia in general, likely due the heterogeneity of its etiology, IDA affected the microbiome both structurally and functionally. Specifically, the abundance of butyrate-producing bacteria was lower in IDA subjects of both sexes than in nonanemic, non-iron-deficient subjects of the same sex (females: Butyricicoccus, P = 0.041; males: Coprococcus, P = 0.010; Roseburia, P = 0.027). IDA male infants had higher concentrations of 4-hydroxyphenyllactate (P < 0.001) and putrescine (P = 0.042) than those without IDA, whereas IDA female infants exhibited higher concentrations of leucine (P = 0.011) and valine (P = 0.003). Conclusions: Sexually dimorphic differences associated with anemia and IDA are suggestive of greater mitochondrial dysfunction and oxidative stress in male infants compared with female infants, and alterations in microbial structure and function may further contribute. Differences in metabolic pathways associated with anemia and IDA in each sex point to potential mechanisms for the associated lasting cognitive deficits. This trial is registered at clinicaltrials.gov as NCT03377777.
Assuntos
Anemia Ferropriva/sangue , Anemia Ferropriva/microbiologia , Microbioma Gastrointestinal/fisiologia , Fatores Sexuais , Aminoácidos/sangue , Ciclo do Ácido Cítrico , Estudos Transversais , Fezes/química , Fezes/microbiologia , Feminino , Humanos , Lactente , Leucina/análise , Masculino , Metaboloma/fisiologia , Mitocôndrias/fisiologia , Estresse Oxidativo , Peru , Fenilpropionatos/análise , Putrescina/análise , Valina/análiseRESUMO
BACKGROUND: Iron therapy induces inflammation, which could decrease iron absorption. Increased exposure of iron in the gut could also alter microbiome file. Providing antioxidants such as vitamin E with iron therapy has been associated with reduced oxidative potential. OBJECTIVE: The aim of the present study was to test the efficacy of adding vitamin E to therapeutic iron therapy on iron repletion, inflammation markers, and gut microbiome in iron-deficient infants and toddlers. DESIGN: This was a randomized, double-blind, control trial in which infants and toddlers (Denver, CO metro area) who were at risk of iron deficiency were screened. Eligible participants were randomized to receive iron therapy (6 mgâ·âkgâ·âday) plus placebo (nâ=â22) or iron (6 mgâ·âkgâ·âday) and vitamin E (18 mg/day, nâ=â14) for 8 weeks. Iron and inflammation status, and gut microbiome (16S sequencing) were analyzed in all participants before and after the treatment. RESULTS: After 8 weeks of treatment, average serum ferritin level returned to normal for both ironâ+âplacebo and ironâ+âvitamin E groups at 33.3â±â20.2 and 33.5â±â21.5 µg/L, respectively. Serum vitamin E concentration increased in ironâ+âvitamin E group. No change over time was observed regarding serum interleukin-4, tumor necrosis factor-α, or fecal calprotectin. The relative abundance of the genus Roseburia (phylum Firmicutes), a butyrate producer, increased in the Feâ+âE group (Δ1.3%, Pâ<â0.01). Also at the genus level, the genus Escherichia decreased by 1.2% on average among all participants (effect of time Pâ=â0.01). CONCLUSIONS: Using a therapeutic iron dose of 6 mgâ·âkgâ·âday is effective in treating iron deficiency during an 8-week period, without inducing persistent inflammatory response. Changes of the gut microbiome raised the possibility that antioxidant therapy in conjunction with therapeutic iron supplementation could potentially improve microbial community profiles in the intestinal tract.
Assuntos
Anemia Ferropriva/tratamento farmacológico , Antioxidantes/uso terapêutico , Microbioma Gastrointestinal , Ferro/administração & dosagem , Vitamina E/administração & dosagem , Anemia Ferropriva/microbiologia , Pré-Escolar , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Ferritinas/sangue , Humanos , Lactente , Masculino , RNA Ribossômico 16S/genética , Vitamina E/sangueRESUMO
OBJECTIVE: Iron deficiency (ID) and iron deficiency anaemia (IDA) are global major public health problems, particularly in developing countries. Whilst an association between H. pylori infection and ID/IDA has been proposed in the literature, currently there is no consensus. We studied the effects of H. pylori infection on ID/IDA in a cohort of children undergoing upper gastrointestinal endoscopy for upper abdominal pain in two developing and one developed country. METHODS: In total 311 children (mean age 10.7±3.2 years) from Latin America--Belo Horizonte/Brazil (nâ=â125), Santiago/Chile (nâ=â105)--and London/UK (nâ=â81), were studied. Gastric and duodenal biopsies were obtained for evaluation of histology and H. pylori status and blood samples for parameters of ID/IDA. RESULTS: The prevalence of H. pylori infection was 27.7% being significantly higher (p<0.001) in Latin America (35%) than in UK (7%). Multiple linear regression models revealed H. pylori infection as a significant predictor of low ferritin and haemoglobin concentrations in children from Latin-America. A negative correlation was observed between MCV (râ=â-0.26; pâ=â0.01) and MCH (râ=â-0.27; pâ=â0.01) values and the degree of antral chronic inflammation, and between MCH and the degree of corpus chronic (râ=â-0.29, pâ=â0.008) and active (râ=â-0.27, pâ=â0.002) inflammation. CONCLUSIONS: This study demonstrates that H. pylori infection in children influences the serum ferritin and haemoglobin concentrations, markers of early depletion of iron stores and anaemia respectively.
Assuntos
Dor Abdominal/sangue , Anemia Ferropriva/sangue , Ferritinas/metabolismo , Infecções por Helicobacter/sangue , Hemoglobinas/metabolismo , Ferro/sangue , Dor Abdominal/complicações , Dor Abdominal/microbiologia , Dor Abdominal/patologia , Adolescente , Anemia Ferropriva/complicações , Anemia Ferropriva/microbiologia , Anemia Ferropriva/patologia , Biópsia , Brasil/epidemiologia , Criança , Chile/epidemiologia , Duodenoscopia , Duodeno/metabolismo , Duodeno/microbiologia , Duodeno/patologia , Feminino , Mucosa Gástrica/metabolismo , Gastroscopia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/metabolismo , Humanos , Londres/epidemiologia , Masculino , Prevalência , Estômago/microbiologia , Estômago/patologiaRESUMO
Association between H. pylori infection, iron deficiency and iron deficiency anaemia has been described, but the mechanisms involved have not been established. We hypothesized that in H. pylori infected children increased gastric concentrations of IL-1ß and/or TNF-α, both potent inhibitors of gastric acid secretion that is essential for iron absorption, are predictors for low blood concentrations of ferritin and haemoglobin, markers of early depletion of iron stores and anaemia, respectively. We evaluated 125 children undergoing endoscopy to clarify the origin of gastrointestinal symptoms. Gastric specimens were obtained for H. pylori status and cytokine evaluation and blood samples for determination of iron deficiency/iron deficiency anaemia parameters and IL1 cluster and TNFA polymorphisms that are associated with increased cytokine secretions. Higher IL-1ß and TNF-α gastric concentrations were observed in H. pylori-positive (nâ=â47) than in -negative (nâ=â78) children. Multiple linear regression models revealed gastric IL-1ß, but not TNF-α, as a significant predictor of low ferritin and haemoglobin concentrations; results were reproduced in young children in whom IL1RN polymorphic genotypes associated with higher gastric IL-1ß expression and lower blood ferritin and haemoglobin concentrations. In conclusion, high gastric levels of IL-1ß can be the link between H. pylori infection and iron deficiency/iron deficiency anaemia in childhood.
Assuntos
Anemia Ferropriva/microbiologia , Mucosa Gástrica/metabolismo , Infecções por Helicobacter/metabolismo , Helicobacter pylori/isolamento & purificação , Interleucina-1beta/metabolismo , Ferro/metabolismo , Estômago/microbiologia , Adolescente , Anemia Ferropriva/genética , Anemia Ferropriva/metabolismo , Criança , Pré-Escolar , Endoscopia/métodos , Feminino , Ferritinas/genética , Ferritinas/metabolismo , Genótipo , Infecções por Helicobacter/sangue , Infecções por Helicobacter/genética , Infecções por Helicobacter/microbiologia , Humanos , Proteína Antagonista do Receptor de Interleucina 1/genética , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-1beta/genética , Ferro/sangue , Masculino , Polimorfismo Genético , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
AIM: The aim of the study was to evaluate the association between Helicobacter pylori infection and iron deficiency (ID) in adolescents attending a public school. PATIENTS AND METHODS: From March to June 2001, a cross-sectional study was conducted among adolescents (10-16 years) enrolled in a single public school in São Paulo, Brazil. Of 400 eligible students, 195 agreed to participate, but 1 was excluded due to sickle cell disease. A blood sample was collected from each subject to measure hemoglobin and ferritin. H pylori status was investigated with the C-urea breath test. All of the subjects with either anemia or ID were given iron therapy. RESULTS: H pylori prevalence was 40.7% (79/194), being higher in male subjects (45/90 vs 34/104, P = 0.014). There was no relation between infection and nutritional status. Abnormally low serum ferritin was observed in 12 subjects, half of whom were positive for H pylori (odds ratio [OR] 1.49, 95% confidence interval [CI] 0.38-5.81). The median serum ferritin was 33.6 ng/mL (interquartile range 23.9-50.9) in infected subjects and 35.1 ng/mL (interquartile range 23.7-53.9) in uninfected subjects. Anemia was detected in 2% (4/194) of the students, half of whom were infected (OR 1.47, 95% CI 0.1-20.6). The mean hemoglobin value in infected subjects was 13.83 g/dL ± 1.02 versus 14 g/dL ± 1.06 in uninfected subjects. CONCLUSIONS: The study was not able to find a relation between H pylori infection and ID or anemia.
Assuntos
Anemia Ferropriva/epidemiologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/isolamento & purificação , Adolescente , Anemia Ferropriva/sangue , Anemia Ferropriva/microbiologia , Brasil/epidemiologia , Testes Respiratórios , Criança , Comorbidade , Estudos Transversais , Feminino , Ferritinas/sangue , Infecções por Helicobacter/sangue , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Razão de Chances , Prevalência , Distribuição por SexoRESUMO
OBJECTIVE: : Helicobacter pylori colonizes the gastric mucosa of about half of the world's population and it has been related to extragastrointestinal diseases. The present study sought to evaluate the association between H pylori infection and iron, zinc, and copper nutritional status in symptomatic children. PATIENTS AND METHODS: : A cross-sectional study was carried out in 395 children (4-16 years) with upper gastrointestinal symptoms, who were tested for H pylori infection by the C-urea breath test. Iron status was determined by hemoglobin, serum ferritin, and serum transferrin receptors. Copper and zinc serum concentrations were also evaluated. Epidemiological data, dietary assessment, and anthropometric indicators were analyzed as potential confounding factors. RESULTS: : Prevalence of H pylori infection was 24.3%. Anemia and iron deficiency (ID) were found in 12.0% and 14.3% of the H pylori-positive and 8.9% and 11.0% of the H pylori-negative children, respectively. There was no association between H pylori infection and anemia (odds ratio = 1.54 [95% confidence interval [CI] 0.73%-3.24%]) or ID (odds ratio = 1.35 [95% CI 0.67-2.70]). Crude beta coefficients showed that H pylori has no significant effect on hemoglobin, serum ferritin, serum transferrin receptors, copper, and zinc concentrations. However, adjusted results suggested that H pylori-infected children had an increase of 9.74 microg/dL (95% CI 2.12-17.37 microg/dL) in copper concentrations. CONCLUSIONS: : This study revealed that H pylori infection was not associated with iron deficiency, anemia, or zinc concentrations; however, a positive relation with copper status was found after adjusting for confounding factors. The contribution of H pylori infection to higher copper concentrations needs to be confirmed by additional studies.
Assuntos
Anemia Ferropriva/complicações , Cobre/sangue , Infecções por Helicobacter/complicações , Helicobacter pylori , Ferro/sangue , Estado Nutricional , Zinco/sangue , Adolescente , Anemia Ferropriva/microbiologia , Criança , Estudos Transversais , Feminino , Ferritinas/sangue , Infecções por Helicobacter/sangue , Infecções por Helicobacter/microbiologia , Hemoglobinas/metabolismo , Humanos , Masculino , Razão de Chances , Prevalência , Receptores da Transferrina/sangueRESUMO
OBJECTIVE: The objective was to investigate the role of Helicobacter pylori infection in iron-deficiency anemia (IDA) of pubescent athletes. STUDY DESIGN: Blood sampling and a questionnaire survey were performed on 440 regular high school students and 220 athletes of a physical education high school. Hemoglobin, serum iron, total iron-binding capacity, ferritin, and immunoglobulin G antibody to H. pylori were measured to compare the prevalence of IDA and H. pylori infection in the groups. Nutritional analysis and a questionnaire survey for socioeconomic status were undertaken to compare and control for other risk factors that might influence IDA and H. pylori infection in the groups. In those with IDA coexistent with H. pylori infection, we also determined whether IDA can be managed by H pylori eradication. RESULTS: The prevalence rates of IDA, H pylori infection, and H. pylori -associated IDA in female athletes were higher than in the control group. The relative risk of IDA was 2.9 (95% CI, 1.5 to 5.6) for those with H. pylori infection. Athletes who exhibited H. pylori -associated IDA showed significant increases in hemoglobin, iron, and ferritin levels after H. pylori eradication. The subjects in the control group who were treated orally with iron alone showed no significant changes. CONCLUSION: Adolescent female athletes may have development of H. pylori -associated IDA, which can be managed by H. pylori eradication.