RESUMEN
BACKGROUND: Maternal dietary choline has a central role in foetal brain development and may be associated with later cognitive function. However, many countries are reporting lower than recommended intake of choline during pregnancy. METHODS: Dietary choline was estimated using food frequency questionnaires in pregnant women participating in population-derived birth cohort, the Barwon Infant Study (BIS). Dietary choline is reported as the sum of all choline-containing moieties. Serum total choline-containing compounds (choline-c), phosphatidylcholine and sphingomyelin were measured using nuclear magnetic resonance metabolomics in the third trimester. The main form of analysis was multivariable linear regression. RESULTS: The mean daily dietary choline during pregnancy was 372 (standard deviation (SD) 104) mg/day. A total of 236 women (23%) had adequate choline intake (440 mg/day) based on the Australian and New Zealand guidelines, and 27 women (2.6%) took supplemental choline ([Formula: see text] 50 mg/dose) daily during pregnancy. The mean serum choline-c in pregnant women was 3.27 (SD 0.44) mmol/l. Ingested choline and serum choline-c were not correlated (R2) = - 0.005, p = 0.880. Maternal age, maternal weight gain in pregnancy, and a pregnancy with more than one infant were associated with higher serum choline-c, whereas gestational diabetes and environmental tobacco smoke during preconception and pregnancy were associated with lower serum choline-c. Nutrients or dietary patterns were not associated with variation in serum choline-c. CONCLUSION: In this cohort, approximately one-quarter of women met daily choline recommendations during pregnancy. Future studies are needed to understand the potential impact of low dietary choline intake during pregnancy on infant cognition and metabolic intermediaries.
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Colina , Ingestión de Alimentos , Lactante , Humanos , Femenino , Embarazo , Australia , Dieta , Mujeres EmbarazadasRESUMEN
Environmental exposures during pregnancy that alter both the maternal gut microbiome and the infant's risk of allergic disease and asthma include a traditional farm environment and consumption of unpasteurized cow's milk, antibiotic use, dietary fiber, and psychosocial stress. Multiple mechanisms acting in concert may underpin these associations and prime the infant to acquire immune competence and homeostasis following exposure to the extrauterine environment. Cellular and metabolic products of the maternal gut microbiome can promote the expression of microbial pattern recognition receptors, as well as thymic and bone marrow hematopoiesis relevant to regulatory immunity. At birth, transmission of maternally derived bacteria likely leverages this in utero programming to accelerate postnatal transition from a TH2- to TH1- and TH17-dominant immune phenotype and maturation of regulatory immune mechanisms, which in turn reduce the child's risk of allergic disease and asthma. Although our understanding of these phenomena is rapidly evolving, the field is relatively nascent, and we are yet to translate existing knowledge into interventions that substantially reduce disease risk in humans. Here, we review evidence that the maternal gut microbiome impacts the offspring's risk of allergic disease and asthma, discuss challenges and future directions for the field, and propose the hypothesis that maternal carriage of Prevotella copri during pregnancy decreases the offspring's risk of allergic disease via production of succinate, which in turn promotes bone marrow myelopoiesis of dendritic cell precursors in the fetus.
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Microbioma Gastrointestinal , Hipersensibilidad/epidemiología , Animales , Suplementos Dietéticos , Femenino , Humanos , Recién Nacido , Embarazo , Probióticos , RiesgoRESUMEN
BACKGROUND: Fatty acids have been implicated in early life immune development. Food allergy provides a clear phenotype of early allergic disease. Fish oil and vitamin D have immune-modulating properties. We aimed to identify the metabolomic profile of (i) infant food allergy and (ii) factors linked to food allergy in past studies such as fish oil supplementation and serum 25OHD3 levels in early life. METHODS: NMR was used to quantify 73 metabolites in plasma of 1 year old infants from the Barwon Infant Study (n=485). Logistic regression models were used to examine associations between infant metabolome and food allergy in infants. Linear regression models were used to describe associations between maternal fish oil supplementation and 25OHD3 levels with infant metabolites. RESULTS: A higher linoleic acid: total fatty acid (FA) ratio and phenylalanine level were associated with higher odds of food allergy. Antenatal fish oil supplementation was positively associated with docosahexaenoic acid (DHA) and omega-3 related metabolite levels. Postnatal 25OHD3 levels at 1 year of age were positively associated with several FA measures and creatinine and inversely with the saturated FA: total FA ratio. Only the postnatal 25OHD3 patterns persisted after adjustment for multiple comparisons. CONCLUSIONS: Infants with food allergy had altered fatty acid profiles at one year. Fish oil supplementation in pregnancy was associated with higher DHA and omega-3 related metabolites at 1 year of age. Associations were modest and the most robustly altered metabolomic profiles were with postnatal 25OHD3 levels.
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Hipersensibilidad a los Alimentos/sangre , Ácido Linoleico/sangre , Fenilalanina/sangre , Adulto , Femenino , Aceites de Pescado/administración & dosificación , Hipersensibilidad a los Alimentos/prevención & control , Humanos , Lactante , Recién Nacido , Masculino , Metabolómica , Gemelos , Vitamina D/administración & dosificaciónRESUMEN
Maternal immune dysregulation seems to affect fetal or postnatal immune development. Preeclampsia is a pregnancy-associated disorder with an immune basis and is linked to atopic disorders in offspring. Here we show reduction of fetal thymic size, altered thymic architecture and reduced fetal thymic regulatory T (Treg) cell output in preeclamptic pregnancies, which persists up to 4 years of age in human offspring. In germ-free mice, fetal thymic CD4+ T cell and Treg cell development are compromised, but rescued by maternal supplementation with the intestinal bacterial metabolite short chain fatty acid (SCFA) acetate, which induces upregulation of the autoimmune regulator (AIRE), known to contribute to Treg cell generation. In our human cohorts, low maternal serum acetate is associated with subsequent preeclampsia, and correlates with serum acetate in the fetus. These findings suggest a potential role of acetate in the pathogenesis of preeclampsia and immune development in offspring.
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Acetatos/sangre , Feto/inmunología , Preeclampsia/inmunología , Efectos Tardíos de la Exposición Prenatal/inmunología , Linfocitos T Reguladores/inmunología , Acetatos/administración & dosificación , Acetatos/inmunología , Acetatos/metabolismo , Adulto , Animales , Animales Recién Nacidos , Estudios de Casos y Controles , Desarrollo Infantil , Preescolar , Suplementos Dietéticos , Femenino , Feto/citología , Feto/diagnóstico por imagen , Microbioma Gastrointestinal/inmunología , Vida Libre de Gérmenes/inmunología , Humanos , Tolerancia Inmunológica/inmunología , Lactante , Recién Nacido , Estudios Longitudinales , Intercambio Materno-Fetal/inmunología , Ratones , Tamaño de los Órganos/inmunología , Preeclampsia/sangre , Preeclampsia/diagnóstico , Embarazo , Efectos Tardíos de la Exposición Prenatal/patología , Efectos Tardíos de la Exposición Prenatal/prevención & control , Estudios Prospectivos , Timo/citología , Timo/diagnóstico por imagen , Timo/crecimiento & desarrollo , Timo/inmunología , Factores de Transcripción/inmunología , Factores de Transcripción/metabolismo , Ultrasonografía Prenatal , Adulto Joven , Proteína AIRERESUMEN
Studies from several countries have reported an association between latitudes further from the equator and proxy markers of food allergy prevalence. As latitudes further from the equator are associated with lower sun exposure and vitamin D status (VDS), it has been proposed that low VDS may be a risk factor for food allergy. A range of basic science evidence supports the biological plausibility of this hypothesis; and recent work has identified a cross sectional association between low VDS and challenge proven food allergy in infants. Overall, however, the evidence regarding the relationship between VDS and food allergy remains controversial and the limited longitudinal data are discouraging. In this review we consider the evidence for and against low VDS as a risk factor for food allergy and discuss the possibility that other factors (including genetic variables) may contribute to the inconsistent nature of the available observational evidence. We then discuss whether genetic and/or environmental factors may modify the potential influence of VDS on food allergy risk. Finally, we argue that given the rising burden of food allergy, the balance of available evidence regarding the potential relevance of VDS to this phenomenon, and the inherent limitations of the existing observational data, there is a compelling case for conducting randomised clinical trials of vitamin D supplementation for the prevention of food allergy during early life.
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Hipersensibilidad a los Alimentos/patología , Vitamina D/sangre , Sangre Fetal/metabolismo , Hipersensibilidad a los Alimentos/genética , Predisposición Genética a la Enfermedad , Genética , Humanos , Factores de RiesgoRESUMEN
We have utilized differential display polymerase chain reaction to investigate the gene expression of hematopoietic progenitor cells from adult bone marrow and umbilical cord blood. A differentially expressed gene was identified in CD34+ hematopoietic progenitor cells, with low expression in CD34- cells. We have obtained the full coding sequence of this gene which we designated human mammalian ependymin-related protein 1 (MERP1). Expression of MERP1 was found in a variety of normal human tissues, and is 4- and 10-fold higher in adult bone marrow and umbilical cord blood CD34+ cells, respectively, compared to CD34- cells. Additionally, MERP1 expression in a hematopoietic stem cell enriched population was down-regulated with proliferation and differentiation. Conceptual translation of the MERP1 open reading frame reveals significant homology to two families of glycoprotein calcium-dependant cell adhesion molecules: ependymins and protocadherins.