Antibiotics augment the impact of iron deficiency on metabolism in a piglet model

Abstract

Infancy and childhood represent a high-risk period for developing iron deficiency (ID) and is a period of increased susceptibility to infectious disease. Antibiotic use is high in children from low-, middle-, and high-income countries, and thus we sought to determine the impact of antibiotics in the context of ID. In this study, a piglet model was used to assess the impact of ID and antibiotics on systemic metabolism. ID was induced by withholding a ferrous sulfate injection after birth to piglets in the ID group and providing an iron deficient diet upon weaning on postnatal day (PD) 25. Antibiotics (gentamicin and spectinomycin) were administered on PD34-36 to a set of control (Con*+Abx) and ID piglets (ID+Abx) after weaning. Blood was analyzed on PD30 (before antibiotic administration) and PD43 (7 days after antibiotic administration). All ID piglets exhibited growth faltering and had lower hemoglobin and hematocrit compared to control (Con) and Con*+Abx throughout. The metabolome of ID piglets at weaning and sacrifice exhibited elevated markers of oxidative stress, ketosis, and ureagenesis compared to Con. The impact of antibiotics on Con*+Abx piglets did not result in significant changes to the serum metabolome 7-days after treatment; however, the impact of antibiotics on ID+Abx piglets resulted in the same metabolic changes observed in ID piglets, but with a greater magnitude when compared to Con. These results suggest that antibiotic administration in the context of ID exacerbates the negative metabolic impacts of ID and may have long lasting impacts on development.

Keywords: Antibiotics; Growth; Infant; Iron deficiency; Metabolism; Metabolomics.