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2.
JAMA Pediatr ; 177(3): 223-224, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36689240

RESUMO

This Viewpoint discusses food insecurity and the importance of choline-fortified food aid products.


Assuntos
Colina , Estado Nutricional , Humanos , Criança , Alimentos Fortificados , Abastecimento de Alimentos
3.
EBioMedicine ; 75: 103791, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35030356

RESUMO

BACKGROUND: Kwashiorkor is a childhood syndrome of edematous malnutrition. Its precise nutritional precipitants remain uncertain despite nine decades of study. Remarkably, kwashiorkor's disturbances resemble the effects of experimental diets that are deficient in one-carbon nutrients. This similarity suggests that kwashiorkor may represent a nutritionally mediated syndrome of acute one-carbon metabolism dysfunction. Here we report findings from a cross-sectional exploration of serum one-carbon metabolites in Malawian children. METHODS: Blood was collected from children aged 12-60 months before nutritional rehabilitation: kwashiorkor (N = 94), marasmic-kwashiorkor (N = 43) marasmus (N = 118), moderate acute malnutrition (N = 56) and controls (N = 46). Serum concentrations of 16 one-carbon metabolites were quantified using LC/MS techniques, and then compared across participant groups. FINDINGS: Twelve of 16 measured one-carbon metabolites differed significantly between participant groups. Measured outputs of one-carbon metabolism, asymmetric dimethylarginine (ADMA) and cysteine, were lower in marasmic-kwashiorkor (median µmol/L (± SD): 0·549 (± 0·217) P = 0·00045 & 90 (± 40) P < 0·0001, respectively) and kwashiorkor (0·557 (± 0·195) P < 0·0001 & 115 (± 50) P < 0·0001), relative to marasmus (0·698 (± 0·212) & 153 (± 42)). ADMA and cysteine were well correlated with methionine in both kwashiorkor and marasmic-kwashiorkor. INTERPRETATION: Kwashiorkor and marasmic-kwashiorkor were distinguished by evidence of one-carbon metabolism dysfunction. Correlative observations suggest that methionine deficiency drives this dysfunction, which is implicated in the syndrome's pathogenesis. The hypothesis that kwashiorkor can be prevented by fortifying low quality diets with methionine, along with nutrients that support efficient methionine use, such as choline, requires further investigation. FUNDING: The Hickey Family Foundation, the American College of Gastroenterology, the NICHD, and the USDA/ARS.


Assuntos
Kwashiorkor , Desnutrição , Desnutrição Proteico-Calórica , Carbono , Criança , Pré-Escolar , Estudos Transversais , Humanos , Lactente , Kwashiorkor/etiologia , Kwashiorkor/metabolismo , Desnutrição Proteico-Calórica/metabolismo
4.
Nat Commun ; 10(1): 5791, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31857576

RESUMO

Edematous severe acute childhood malnutrition (edematous SAM or ESAM), which includes kwashiorkor, presents with more overt multi-organ dysfunction than non-edematous SAM (NESAM). Reduced concentrations and methyl-flux of methionine in 1-carbon metabolism have been reported in acute, but not recovered, ESAM, suggesting downstream DNA methylation changes could be relevant to differences in SAM pathogenesis. Here, we assess genome-wide DNA methylation in buccal cells of 309 SAM children using the 450 K microarray. Relative to NESAM, ESAM is characterized by multiple significantly hypomethylated loci, which is not observed among SAM-recovered adults. Gene expression and methylation show both positive and negative correlation, suggesting a complex transcriptional response to SAM. Hypomethylated loci link to disorders of nutrition and metabolism, including fatty liver and diabetes, and appear to be influenced by genetic variation. Our epigenetic findings provide a potential molecular link to reported aberrant 1-carbon metabolism in ESAM and support consideration of methyl-group supplementation in ESAM.


Assuntos
Metilação de DNA , Epigenoma/genética , Desnutrição Aguda Grave/genética , Adolescente , Adulto , Estudos de Casos e Controles , Pré-Escolar , Ilhas de CpG/genética , Epigenômica/métodos , Feminino , Perfilação da Expressão Gênica , Humanos , Lactente , Jamaica/epidemiologia , Malaui/epidemiologia , Masculino , Mucosa Bucal , Estudos Prospectivos , Estudos Retrospectivos , Desnutrição Aguda Grave/mortalidade , Sobreviventes , Adulto Jovem
5.
Nutrients ; 10(5)2018 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-29786674

RESUMO

Hepatic steatosis is a hallmark feature of kwashiorkor malnutrition. However, the pathogenesis of hepatic steatosis in kwashiorkor is uncertain. Our objective was to develop a mouse model of childhood undernutrition in order to test the hypothesis that feeding a maize vegetable diet (MVD), like that consumed by children at risk for kwashiorkor, will cause hepatic steatosis which is prevented by supplementation with choline. A MVD was developed with locally sourced organic ingredients, and fed to weanling mice (n = 9) for 6 or 13 days. An additional group of mice (n = 4) were fed a choline supplemented MVD. Weight, body composition, and liver changes were compared to control mice (n = 10) at the beginning and end of the study. The MVD resulted in reduced weight gain and hepatic steatosis. Choline supplementation prevented hepatic steatosis and was associated with increased hepatic concentrations of the methyl donor betaine. Our findings show that (1) feeding a MVD to weanling mice rapidly induces hepatic steatosis, which is a hallmark disturbance of kwashiorkor; and that (2) hepatic steatosis associated with feeding a MVD is prevented by choline supplementation. These findings support the concept that insufficient choline intake may contribute to the pathogenesis of hepatic steatosis in kwashiorkor.


Assuntos
Colina/administração & dosagem , Suplementos Nutricionais , Fígado Gorduroso/prevenção & controle , Kwashiorkor/dietoterapia , Fígado/patologia , Zea mays , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Colina/metabolismo , Modelos Animais de Doenças , Ingestão de Alimentos , Metabolismo Energético/genética , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Feminino , Regulação da Expressão Gênica , Kwashiorkor/genética , Kwashiorkor/metabolismo , Kwashiorkor/patologia , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Masculino , Camundongos , Estado Nutricional , Fatores de Tempo , Transcrição Gênica , Aumento de Peso
6.
Microbiome ; 3: 37, 2015 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-26334878

RESUMO

BACKGROUND: Resistant starch (RS) decreases intestinal inflammation in some settings. We tested the hypothesis that gut inflammation will be reduced with dietary supplementation with RS in rural Malawian children. Eighteen stunted 3-5-year-old children were supplemented with 8.5 g/day of RS type 2 for 4 weeks. The fecal samples were analyzed for the microbiota, the microbiome, short chain fatty acids, metabolome, and proteins indicative of inflammation before and after the intervention. Subjects served as their own controls. RESULTS: The consumption of RS changed the composition of the microbiota; at the phylum level Actinobacteria increased, while Firmicutes decreased. Among the most prevalent genera, Lactobacillus was increased and Roseburia, Blautia, and Lachnospiracea incertae sedis were decreased. The Shannon H index at the genus level decreased from 2.02 on the habitual diet and 1.76 after the introduction of RS (P < 0.01). Fecal acetate concentration decreased, and fecal propionate concentration increased after RS administration (-5.2 and 2.0 µmol/g, respectively). Fecal calprotectin increased from 29 ± 69 to 89 ± 49 µg/g (P = 0.003) after RS was given. The lipopolysaccharide biosynthesis pathway was upregulated. CONCLUSIONS: Our findings do not support the hypothesis that RS reduces gut inflammation in rural Malawian children.


Assuntos
Carboidratos da Dieta , Gastroenterite/metabolismo , Gastroenterite/microbiologia , Microbiota , População Rural , Amido , Fatores Etários , Biomarcadores , Criança , Fezes/microbiologia , Feminino , Gastroenterite/epidemiologia , Gastroenterite/genética , Humanos , Malaui/epidemiologia , Masculino , Metagenoma , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Ribossômico 16S/genética
7.
J Trace Elem Med Biol ; 30: 43-48, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25744509

RESUMO

OBJECTIVE: This study tested the hypothesis that Malawian children at risk for zinc deficiency will have reduced endogenous fecal zinc (EFZ) and increased net absorbed zinc (NAZ) following the addition of high amylose maize resistant starch (RS) to their diet. METHODS: This was a small controlled clinical trial to determine the effects of added dietary RS on zinc homeostasis among 17 stunted children, aged 3-5 years consuming a plant-based diet and at risk for perturbed zinc homeostasis. Dual zinc stable isotope studies were performed before and after 28 d of intervention with RS, so that each child served as their own control. The RS was incorporated into fried wheat flour dough and given under direct observation twice daily for 28 d. Changes in zinc homeostatic measures were compared using paired Student's t-tests and linear regression analysis. RESULTS: Children had a mean height-for-age Z-score of -3.3, and consumed animal source foods ≤twice per month. Their habitual diet contained a phytate:zinc molar ratio of 34:1. Children avidly consumed the RS without complaints. EFZ was 0.8±0.4mg/d (mean±SD) both before and after the intervention. Fractional absorption of zinc was 0.38±0.08 and 0.35±0.06 before and after the RS intervention respectively. NAZ was 1.1±0.5 and 0.6±0.7 before and after the RS intervention. This reduction of NAZ corresponded with diminished dietary zinc intake on the study day following intervention with RS. Regression analysis indicated no change in zinc absorption relative to dietary intake as a result of the RS intervention. CONCLUSION: Consumption of RS did not improve zinc homeostasis in rural African children without zinc deficiency. RS was well tolerated in this setting.


Assuntos
Homeostase/efeitos dos fármacos , População Rural , Amido/farmacologia , Zinco/metabolismo , Pré-Escolar , Fezes/química , Feminino , Alimentos , Humanos , Absorção Intestinal/efeitos dos fármacos , Malaui , Masculino , Análise de Regressão
8.
Inflamm Bowel Dis ; 19(3): 614-20, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23380935

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is more common in countries with improved hygiene, suggesting that environmental exposures may be associated with its development. The primary objective of this study was to examine the association between self-reported childhood helminth infection and the development of IBD in South Africa. METHODS: Unmatched case-control study. Logistic regression was used to model associations with IBD. RESULTS: There were 88 patients with Crohn's disease (CD), 63 with ulcerative colitis (UC), and 219 control subjects. Of the 151, 93 (61.6%) IBD subjects (35 of 63 [55.6%] had UC and 58 of 88 [65.9%] had CD) reported childhood helminth exposure compared with 200 of 219 (91.3%) non-IBD subjects (P < 0.001). Helminth infection (adjusted odds ratio [AOR] = 0.2; 95% confidence interval [CI], 0.1-0.4), shared housing (AOR = 0.1; 95% CI, 0.04-0.4), and raw beef consumption (AOR = 0.2; 95% CI, 0.1-0.6) were protective, whereas urban dwelling (AOR = 4.2; 95% CI, 2.0-8.8) and parental tertiary education (AOR = 18.2; 95% CI, 3.2-103.7) were associated with CD. Helminth infection (AOR = 0.2; 95% CI, 0.1-0.6), mixed race (AOR = 0.1; 95% CI, 0.03-0.5), smoking (AOR = 0.2; 95% CI, 0.07-0.5), shared housing (AOR = 0.1; 95% CI, 0.01-0.4), and raw beef consumption (AOR = 0.1; 95% CI 0.04-0.5) were protective against UC, whereas parental tertiary education (AOR = 12.7; 95% CI, 1.0-157.4) was associated with UC. CONCLUSION: This study demonstrates a protective association of childhood helminth infection against the development of IBD and supports the "hygiene hypothesis" that improved living conditions may increase the incidence of IBD. Our epidemiologic conclusions provide support that helminths may have immunomodulatory effects which provides protection against the development of IBD later in life.


Assuntos
Colite Ulcerativa/etiologia , Doença de Crohn/etiologia , Helmintíase , Hipótese da Higiene , Adulto , Estudos de Casos e Controles , Colite Ulcerativa/prevenção & controle , Doença de Crohn/prevenção & controle , Feminino , Helmintíase/complicações , Helmintíase/epidemiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Fatores de Risco , Autorrelato , Fatores Socioeconômicos , África do Sul/epidemiologia
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