Comparative Analysis of Host Metabolic Alterations in Murine Malaria Models with Uncomplicated or Severe Malaria

Malaria
varies in severity, with complications ranging from uncomplicated
to severe malaria. Severe malaria could be attributed to peripheral
hyperparasitemia or cerebral malaria. The metabolic interactions between
the host and Plasmodium species are yet to be understood
during these infections of varied pathology and severity. An untargeted
metabolomics approach utilizing the liquid chromatography–mass
spectrometry platform has been used to identify the affected host
metabolic pathways and associated metabolites in the serum of murine
malaria models with uncomplicated malaria, hyperparasitemia, and experimental
cerebral malaria. We report that mice with malaria share similar metabolic
attributes like higher levels of bile acids, bile pigments, and steroid
hormones that have been reported for human malaria infections. Moreover,
in severe malaria, upregulated levels of metabolites like phenylalanine,
histidine, valine, pipecolate, ornithine, and pantothenate, with decreased
levels of arginine and hippurate, were observed. Metabolites of sphingolipid
metabolism were upregulated in experimental cerebral malaria. Higher
levels of 20-hydroxy-leukotriene B4 and epoxyoctadecamonoenoic
acids were found in uncomplicated malaria, with lower levels observed
for experimental cerebral malaria. Our study provides insights into
host biology during different pathological stages of malaria disease
and would be useful for the selection of animal models for evaluating
diagnostic and therapeutic interventions against malaria. The raw
data files are available via MetaboLights with the identifier MTBLS4387.