Abstract/Summary

Iron deficiency (ID) is the most prevalent micronutrient deficiency worldwide and is defined by systemic haemoglobin (Hb) levels between 95- and 110 g/L in human infants. If left untreated, ID can progress to iron deficiency anaemia (IDA) when Hb levels are reduced further to <95 g/L. Infants and young children are at particular risk, especially in low- and middle-income countries (LMICs), where IDA can ultimately result in stunted growth, which has life-long health implications. Oral iron supplementation is the most common strategy used worldwide to prevent and treat ID/IDA. However, this has been associated with detrimental side effects including diarrhoea and increased risk of infectious diseases, although there is limited mechanistic understanding in this area. Piglets are valuable models for human infants since they share many physiological characteristics with humans. In addition, their precocial nature permits early separation from maternal interference so their environment and nutrition can be tightly controlled. Furthermore, if left untreated with iron, piglets will reliably develop IDA in the first weeks of life. The aim of this PhD was to explore the effects of IDA, and different forms of iron supplementation on growth and metabolism in human infants using a neonatal piglet model. Twenty-four 1d old piglets were litter-matched into 4 treatment groups (n=6 each). Treatments were goup 1, control (no iron); group 2, intramuscular iron (IM, 200mg Fe); group 3, oral iron (150mg/Kg of iron sulphate); group 4, oral and IM iron. Weight gain was measured twice a week and sequential blood parameters were analysed using a portable haem meter and standard veterinary diagnostic laboratory methods. Host systemic metabolites, microbial-derived short chain fatty acids (SCFAs) and lipid profiles were assessed using liquid chromatography - mass spectrometry (LC-MS), while gut microbiota composition was analysed using 16S Illumina sequencing techniques. The results demonstrated that all types of iron treatments prevented anaemia by sustaining sufficient concentrations of Hb and other iron-dependent blood parameters, and by maintaining host-derived metabolite concentrations. However, oral iron supplementation was associated with significant reductions in weight gain (~ 0.5Kg, p<0.05) and abundances of Lachnospiraceae (p<0.05) in piglets compared to their IM iron treated siblings, and significant reductions in lactobacilli (p<0.05) were observed in all iron treated piglets compared to IDA siblings. In terms of systemic lipids, IDA was associated with reductions in sphingo- (p<0.05) and a range of phospholipids (p<0.05), which are important for growth and development. Taken together, these results demonstrate that both IDA and iron supplementation have significant impacts on piglet growth and metabolism both directly and via shifts in gut microbiota populations and metabolic outputs. This could have important consequences for oral iron supplementation recommendations, especially in small-for-age infants in LMICs and is especially relevant for iron-replete infant fed iron-rich formula milk.