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Immune Dysfunction as a Cause and Consequence of Malnutrition

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      Abstract

      Malnutrition, which encompasses under- and overnutrition, is responsible for an enormous morbidity and mortality burden globally. Malnutrition results from disordered nutrient assimilation but is also characterized by recurrent infections and chronic inflammation, implying an underlying immune defect. Defects emerge before birth via modifications in the immunoepigenome of malnourished parents, and these may contribute to intergenerational cycles of malnutrition. This review summarizes key recent studies from experimental animals, in vitro models, and human cohorts, and proposes that immune dysfunction is both a cause and a consequence of malnutrition. Focusing on childhood undernutrition, we highlight gaps in current understanding of immune dysfunction in malnutrition, with a view to therapeutically targeting immune pathways as a novel means to reduce morbidity and mortality.

      Trends

      Undernourished children principally die of common infections, and immune defects are consistently demonstrated in under- and overnutrition.

      Parental malnutrition leads to epigenetic modifications of infant immune and metabolic genes.

      Healthy gut development relies on sensing of dietary nutrients, commensal, and pathogenic microbes via immune receptors.

      Recurrent infections, chronic inflammation, and enteropathy compound clinical malnutrition by altering gut structure and function.

      Immune cell activation and systemic proinflammatory mediator levels are increased in malnutrition.

      Malnutrition impairs immune priming by DC and monocytes, and impairs effector memory T cell function.

      Immune dysfunction can directly drive pathological processes in malnutrition, including malabsorption, increased metabolic demand, dysregulation of the growth hormone and HPA axes, and greater susceptibility to infection.

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      Most cited references 96

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        Maternal and child malnutrition in low-income and middle-income countries encompasses both undernutrition and a growing problem with overweight and obesity. Low body-mass index, indicative of maternal undernutrition, has declined somewhat in the past two decades but continues to be prevalent in Asia and Africa. Prevalence of maternal overweight has had a steady increase since 1980 and exceeds that of underweight in all regions. Prevalence of stunting of linear growth of children younger than 5 years has decreased during the past two decades, but is higher in south Asia and sub-Saharan Africa than elsewhere and globally affected at least 165 million children in 2011; wasting affected at least 52 million children. Deficiencies of vitamin A and zinc result in deaths; deficiencies of iodine and iron, together with stunting, can contribute to children not reaching their developmental potential. Maternal undernutrition contributes to fetal growth restriction, which increases the risk of neonatal deaths and, for survivors, of stunting by 2 years of age. Suboptimum breastfeeding results in an increased risk for mortality in the first 2 years of life. We estimate that undernutrition in the aggregate--including fetal growth restriction, stunting, wasting, and deficiencies of vitamin A and zinc along with suboptimum breastfeeding--is a cause of 3·1 million child deaths annually or 45% of all child deaths in 2011. Maternal overweight and obesity result in increased maternal morbidity and infant mortality. Childhood overweight is becoming an increasingly important contributor to adult obesity, diabetes, and non-communicable diseases. The high present and future disease burden caused by malnutrition in women of reproductive age, pregnancy, and children in the first 2 years of life should lead to interventions focused on these groups. Copyright © 2013 Elsevier Ltd. All rights reserved.
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          Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns.

          Upon delivery, the neonate is exposed for the first time to a wide array of microbes from a variety of sources, including maternal bacteria. Although prior studies have suggested that delivery mode shapes the microbiota's establishment and, subsequently, its role in child health, most researchers have focused on specific bacterial taxa or on a single body habitat, the gut. Thus, the initiation stage of human microbiome development remains obscure. The goal of the present study was to obtain a community-wide perspective on the influence of delivery mode and body habitat on the neonate's first microbiota. We used multiplexed 16S rRNA gene pyrosequencing to characterize bacterial communities from mothers and their newborn babies, four born vaginally and six born via Cesarean section. Mothers' skin, oral mucosa, and vagina were sampled 1 h before delivery, and neonates' skin, oral mucosa, and nasopharyngeal aspirate were sampled <5 min, and meconium <24 h, after delivery. We found that in direct contrast to the highly differentiated communities of their mothers, neonates harbored bacterial communities that were undifferentiated across multiple body habitats, regardless of delivery mode. Our results also show that vaginally delivered infants acquired bacterial communities resembling their own mother's vaginal microbiota, dominated by Lactobacillus, Prevotella, or Sneathia spp., and C-section infants harbored bacterial communities similar to those found on the skin surface, dominated by Staphylococcus, Corynebacterium, and Propionibacterium spp. These findings establish an important baseline for studies tracking the human microbiome's successional development in different body habitats following different delivery modes, and their associated effects on infant health.
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            Author and article information

            Affiliations
            [1 ]Centre for Genomics and Child Health, Blizard Institute, Queen Mary University of London, London, UK
            [2 ]Kenya Medical Research Institute (KEMRI)–Wellcome Trust Collaborative Research Programme, Centre for Geographic Medicine Research, Kifili, Kenya
            [3 ]Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK
            [4 ]Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe
            Author notes
            [* ]Correspondence: c.bourke@ 123456qmul.ac.uk
            Contributors
            Journal
            Trends Immunol
            Trends Immunol
            Trends in Immunology
            Elsevier Science Ltd
            1471-4906
            1471-4981
            1 June 2016
            June 2016
            : 37
            : 6
            : 386-398
            27237815
            4889773
            S1471-4906(16)30006-0
            10.1016/j.it.2016.04.003
            © 2016 The Authors

            This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

            Categories
            Review
            Series: Lifetime Immunity

            Immunology

            metabolism, malnutrition, immunodeficiency, inflammation, infection, enteropathy

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