The Impact of Prenatal and Infant Undernutrition on Early Life Immunity

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About this Research Topic

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Background

Undernutrition is estimated to contribute to nearly 50% of global annual deaths in children under 5 years. Undernutrition can have an acute, chronic, or acute-on-chronic presentation and refers to children who are underweight for their age or length, too short for their age (stunted), sub-optimally breastfed, or deficient in key macro - or micronutrients. Well-established epidemiological associations between undernutrition, infection, and an increased risk of death among young children, suggest that undernutrition dysregulates protective host responses to infectious challenges. Although limited, longitudinal data suggest that current regimes for nutritional rehabilitation are alone not sufficient to correct immunologic derangements associated with undernutrition. This indicates that undernutrition during early childhood may have a lasting negative impact on overall trajectories of health, growth and development. Moreover, maternal nutritional status, quantity and quality of breastmilk, the maternal vaginal and gastrointestinal microbiota, and maternal antimicrobial use may also have distinct long-term effects on infant and child immunity and health.

The mechanisms linking undernutrition to vulnerability to infectious pathogens in young children are not understood. There is some evidence that reduced gut barrier function leading to nutrient loss, chronic bacterial translocation, intestinal dysbiosis, derangements to cellular metabolism, altered regulation of inflammatory adipocytokines and immune activation may contribute to dysregulated immunity during early childhood. Importantly, although the impact of maternal obesity on infant immunity and long-term health has been an active area of study, less is understood on how maternal undernutrition during pregnancy alters subsequent infant immune development and function. Understanding the distinct mechanisms whereby maternal and infant undernutrition dysregulate immunity during early life is essential to the design of interventions that improve survival, growth and neurodevelopmental outcomes among highly vulnerable young children in low- and middle-income settings.

This Research Topic will provide novel insights into how maternal and infant undernutrition impact immunity within the first 5 years of childhood. Infant immunity will be considered broadly, including innate immune responses, antigen-specific T cell and B cell responses (including regulatory T cells), and biomarkers of innate and adaptive immune activation and exhaustion. Undernutrition may include wasting, oedematous malnutrition and stunting, as well as specific micronutrient defects and the effects of suboptimal breastfeeding. Studies focused on human cohorts, as well as those employing validated animal models that focus on specific mechanistic pathways, are welcome.

We invite the submission of Original Research, Review, and Commentary articles covering, but not limited to, the follow sub-topics:

1. Impact of undernutrition during pregnancy and/or early life on acute and longitudinal childhood immune responses
2. Undernutrition and its impact on the infant gut microbiota, inflammation and early childhood immune responses
3. Impact of maternal undernutrition on vaginal and gut microbiomes, and subsequent associations with infant gut microbiome and early childhood immune responses
4. Epigenetic changes associated with maternal or infant undernutrition, and associated aberrations in early childhood immune responses
5. Impact of undernutrition on infant cellular metabolism and associated early childhood immune responses
6. The influence of suboptimal breastfeeding, breastmilk quantity and quality, on infant immune development
7. Animal models examining impact of undernutrition on host gut microbiome, epigenome, cellular metabolism, and subsequent responses to infectious challenge

Keywords: infant, nutritional status, immunity, microbiota, maternal nutritional physiological phenomena, milk human

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