Characterising the short- and long-term biomolecular consequences of early life malnutrition and its impact on health and development

Abstract

Childhood undernutrition remains a prevalent global health issue. Many nutritional and lifestyle interventions targeting this have demonstrated limited or variable effectiveness. Understanding the biochemical perturbations, alongside the intra- and inter-person variability associated with such derangements will help to explain these shortfalls and identify novel future interventions. This thesis employed integrated metabolomic and multivariate statistical approaches to characterise the broad biochemical derangements induced by various forms of undernutrition and how these are modulated by interventions, individual-specific factors, and the environment. This was achieved by leveraging samples and data from three human studies performed in Tanzania, Malawi, and Bangladesh. In the Tanzanian cohort, persistent birth-season-dependent variation was observed in developmentally relevant metabolites up to 18 months of life, which in turn associated with cognitive outcomes, reported food insecurity, and environmental factors. A season-dependent response was also observed in the responsiveness to a nutritional intervention targeting stunting. In the Malawian cohort, long-term metabolic derangements were observed in adolescent SAM survivors who experienced rapid post-undernutrition recovery growth in childhood. Such metabolic differences characterised altered muscle function, energy, and lipid metabolism. However, no metabolic differences were observed between the SAM survivors and matched controls. Finally, in the Bangladeshi cohort, a distinct urinary metabolome was observed based on the presence of a micronutrient deficiency, namely nutritional rickets. This thesis highlights the importance of considering the infant and environment as a whole when addressing issues related to undernutrition. By demonstrating the impact of individual variability and environmental influences on metabolic outcomes, this thesis calls for personalised treatments in the future to address the diverse needs of undernourished populations globally.

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Identifiers

ORCID for Elizabeth Ann Wimborne: orcid.org/0000-0001-8471-4489

ORCID for Caroline Childs: orcid.org/0000-0001-6832-224X

ORCID for Jonathan Swann: orcid.org/0000-0002-6485-4529

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