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

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. 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. 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.