The impact of interethnic lipidomic variation in falciparum malaria

Background: Shifts in dietary patterns during lifestyle transitions are integral components of the dynamic interactions between humans and their environments. Investigating the link between dietary diversity, the composition of the human lipidome and infection is key to understanding the interplay between diet and susceptibility to pathogens. Methods: Here we address this question by performing a comparative study of two ethnic groups with divergent dietary patterns: Fulani, who are nomad pastoralists with a dairy-centric diet, and Mossi, who are farmers with a plant-based diet. We generate 196 paired global lipidomes (927 lipid molecules) from both groups before and during natural Plasmodium falciparum infection. Results: Our analysis revealed 211 significantly differentially abundant lipid molecules between the two ethnic groups in both infection states. We show that ethnicity has a greater impact on the lipidome of these children than do P. falciparum infection and report inter-ethnic differences that impact pathogenesis. We highlight elevated levels of pentadecanoic acid (C15:0)-containing phospholipids in Fulani and experimentally demonstrate the suppressive effects of lysophosphatidylcholine LysoPC (15:0) on P. falciparum gametocyte production. Conclusion: These findings link the Fulani's dairy-centric diet and lower P. falciparum gametocyte densities reported in this group and underscore the intricate links between dietary lipids and the host response to infection.