The Lipid Composition of the Exo-Metabolome from Haemonchus contortus

<b>Background/Objectives</b>: Metabolomic studies of different parasite-derived biomolecules, such as lipids, are needed to broaden the discovery of novel targets and overcome anthelmintic resistance. Lipids are involved in diverse functions in biological systems, including parasitic helminths, but little is known about their role in the biology of these organisms and their impact on host-parasite interactions. This study aimed to characterize the lipid profile secreted by <i>Haemonchus contortus</i>, the major parasitic nematodes of farm ruminants. <b>Methods</b>: <i>H. contortus</i> adult worms were recovered from infected sheep and cultured ex vivo. Parasite medium was collected at different time points and samples were subjected to an untargeted global lipidomic analysis. Lipids were extracted and subjected to Liquid Chromatography-Mass Spectrometry (LC-MS/MS). Annotated lipids were normalized and subjected to statistical analysis. Lipid clusters' fold change (FC) and individual lipid features were compared at different time points. Lipids were also analyzed by structural composition and saturation bonding. <b>Results</b>: A total of 1057 <i>H. contortus</i> lipid features were annotated, including glycerophospholipids, fatty acyls, sphingolipids, glycerolipids, and sterols. Most of these compounds were unsaturated lipids. We found significant FC differences in the lipid profile in a time-dependent manner. <b>Conclusions</b>: We predict that many lipids found in our study act as signaling molecules for nematodes' physiological functions, such as adaptation to nutrient changes, life span and mating, and as modulators on the host immune responses.