Shoff Shannon, Thomas Sydney, Ji Peng, Parenti Mariana, Slupsky Carolyn M
Department of Nutrition, UC Davis, One Shields Avenue, Davis, CA 95616, USA.
Department of Food Science and Technology, UC Davis, One Shields Avenue, Davis, CA 95616, USA.
Metabolites. 2025 Aug 14;15(8):549. doi: 10.3390/metabo15080549.
: Iron deficiency (ID) is a common nutritional deficiency in infancy and early childhood associated with increased risk of infection and increased likelihood of receiving antibiotic intervention. In the context of ID, antibiotics have been shown to exaggerate the growth impairments and negative impacts on metabolic health of ID itself. The objective of this research was to assess the tissue-level impact of antibiotics when provided during ID. : ID was induced in piglets by withholding an iron dextran shot shortly after birth, and iron deficiency was maintained after weaning by providing an iron-deficient diet starting on postnatal day (PD) 25. Half of the ID piglets received a 3-day antibiotic course (ID + Abx) consisting of spectinomycin and gentamicin from PD34-36. The kidney, liver, skeletal muscle, and hippocampal metabolomes, as well as activity of proteins in the mTOR signaling pathway, were assessed on PD43. : While ID had minimal impacts on the liver, kidney, and skeletal muscle metabolomes, ID + Abx impaired energy metabolism and increased ketosis and oxidative stress in peripheral tissues. Hippocampal metabolites involved in neurotransmitter synthesis pathways were affected by ID and ID + Abx to a greater extent. Additionally, the activities of several proteins in the mTOR pathway were upregulated in the hippocampi of ID + Abx piglets compared to both ID and control piglets. Abx provided to iron-sufficient piglets had minimal effects on tissue metabolomes and did not alter the activity of proteins in the mTOR pathway. : These results highlight that antibiotic treatment in ID alters metabolism in peripheral tissues and the developing hippocampus beyond those induced by ID alone. Considering that infants and children are develop rapidly, the combination of ID and antibiotics may have lasting impacts on neurodevelopment and cognition.
缺铁（ID）是婴幼儿期常见的营养缺乏症，与感染风险增加以及接受抗生素干预的可能性增加有关。在缺铁的情况下，抗生素已被证明会加剧缺铁本身对生长的损害以及对代谢健康的负面影响。本研究的目的是评估在缺铁期间使用抗生素对组织水平的影响。通过在仔猪出生后不久不给右旋糖酐铁注射来诱导缺铁，断奶后从出生后第25天（PD）开始提供缺铁饮食来维持缺铁状态。一半的缺铁仔猪从PD34至36接受为期3天的由壮观霉素和庆大霉素组成的抗生素疗程（ID + Abx）。在PD43评估肾脏、肝脏、骨骼肌和海马体的代谢组，以及mTOR信号通路中蛋白质的活性。虽然缺铁对肝脏、肾脏和骨骼肌代谢组的影响最小，但ID + Abx损害了能量代谢，增加了外周组织中的酮症和氧化应激。参与神经递质合成途径的海马体代谢物受缺铁和ID + Abx的影响更大。此外，与缺铁仔猪和对照仔猪相比，ID + Abx仔猪海马体中mTOR途径中几种蛋白质的活性上调。给铁充足的仔猪使用抗生素对组织代谢组的影响最小，并且没有改变mTOR途径中蛋白质的活性。这些结果表明，缺铁时使用抗生素会改变外周组织和发育中的海马体的代谢，其影响超出了单独缺铁所诱导的范围。考虑到婴幼儿发育迅速，缺铁和抗生素的联合使用可能会对神经发育和认知产生持久影响。
