Multiomic profiling of iron-deficient infant monkeys reveals alterations in neurologically important biochemicals in serum and cerebrospinal fluid before the onset of anemia

Brian J. Sandri, Jonathan Kim, Gabriele R. Lubach, Eric F. Lock, Candace Guerrero, Lee Ann Higgins, Todd W. Markowski, Pamela J. Kling, Michael K. Georgieff, Christopher L. Coe, Raghavendra B. Rao

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The effects of iron deficiency (ID) during infancy extend beyond the hematologic compartment and include short- and long-term adverse effects on many tissues including the brain. However, sensitive biomarkers of iron-dependent brain health are lacking in humans. To determine whether serum and cerebrospinal fluid (CSF) biomarkers of ID-induced metabolic dysfunction are concordant in the pre/early anemic stage of ID before anemia in a nonhuman primate model of infantile iron deficiency anemia (IDA). ID (n = 7), rhesus infants at 4 mo (pre-anemic period) and 6 mo of age (anemic) were examined. Hematological, metabolomic, and proteomic profiles were generated via HPLC/MS at both time points to discriminate serum biomarkers of ID-induced brain metabolic dysfunction. We identified 227 metabolites and 205 proteins in serum. Abnormalities indicating altered liver function, lipid dysregulation, and increased acute phase reactants were present in ID. In CSF, we measured 210 metabolites and 1,560 proteins with changes in ID infants indicative of metabolomic and proteomic differences indexing disrupted synaptogenesis. Systemic and CSF proteomic and metabolomic changes were present and concurrent in the pre-anemic and anemic periods. Multiomic serum and CSF profiling uncovered pathways disrupted by ID in both the pre-anemic and anemic stages of infantile IDA, including evidence for hepatic dysfunction and activation of acute phase response. Parallel changes observed in serum and CSF potentially provide measurable serum biomarkers of ID that reflect at-risk brain processes prior to progression to clinical anemia.

Original languageEnglish (US)
Pages (from-to)R486-R500
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume322
Issue number6
DOIs
StatePublished - 2022

Bibliographical note

Funding Information:
This work was supported by National Institute of General Medical Sciences Grant R01GM130622 and National Institutes of Health Grants NIHR01HD089989, NIHR01HD080201, NIHR01HD057064, and NIHR01HD39386.

Publisher Copyright:
Copyright © 2022 the American Physiological Society.

Keywords

  • cerebrospinal fluid
  • iron deficiency anemia
  • metabolomics
  • neurological function
  • proteomics

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