Integrated lipidomic and transcriptomic profiling of the host response in human malaria

BACKGROUND: Identifying the mechanisms of host-parasite interactions in vivo in malaria is essential for the development of antimalarial strategies tailored to clinically and physiologically relevant contexts. RESULTS: We analyzed 396 paired global serum lipidomes from pediatric patients sampled before and during blood-stage malaria infection in Burkina Faso, spanning three ethnic groups (Gouin, Mossi, and Fulani). Consistent infection-induced remodeling of the host lipidome was identified across populations, including depletion of 47 host-derived lipid species that correlated with parasitemia. Notably, we observed that Plasmodium falciparum selectively scavenges linoleic acid-containing phospholipids to support its proliferation and validated this with parasite culture assays. This integrative multi-omics analysis combining lipidomic profiles with host-parasite transcriptomes further identified a Plasmodium falciparum transcriptional program associated with lipid turnover in vivo. CONCLUSIONS: These results provide a high-resolution profile of lipidomic perturbations in malarial children and demonstrate how integrated clinical phenotyping, cross-ethnic population sampling, and multi-omics can reveal key host-parasite interactions and clinically relevant metabolic changes within the human host.