Abstract Background Metabolic streamlining as a consequence of parasitism has resulted in the loss of lipid biosynthetic genes in nematodes. Angiostrongylus cantonensis , a zoonotic neurotropic parasite that causes eosinophilic meningitis in mammals, completes a complex migration through the rat brain before maturing in the pulmonary arteries. Polyunsaturated fatty acids (PUFAs) and their bioactive metabolites (oxylipins) are known to modulate nematode survival; however, their abundance and endogenous biosynthetic capacity in A. cantonensis remain elusive. Methods We integrated comparative genomics, stage-specific transcriptomics, and lipidomics to reconstruct the expression patterns of the biosynthetic enzymes in A. cantonensis and characterize their dynamic PUFA and oxylipin profiles during the neuro-pulmonary transition from brain-residing fourth-stage (L4) to lung-migrating L5 larvae. Results Genomic and transcriptomic analyses revealed a streamlined biosynthetic repertoire in A. cantonensis . The worm lacks Δ6 desaturase and canonical cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) enzymes, and expresses only residual levels of ptges2 and lta4h , which are markedly lower than those in free-living Caenorhabditis elegans across developmental stages. Using liquid chromatography-tandem mass spectrometry, L4–L5 larvae residing in the rat brain maintained stable PUFA and oxylipin profiles. In contrast, L5 larvae migrating to the lungs accumulated n -6 PUFAs and anti-inflammatory hydroxy eicosatetraenoic acids, epoxy eicosatrienoic acids and hydroxy docosahexaenoic acids, concurrent with reduced levels of pro-inflammatory prostaglandins and 5-oxo-eicosatetraenoic acid. Conclusions These stage- and tissue-specific lipidomic shifts correlate with distinct host microenvironments encountered during migration. These findings provide a foundation for understanding the evolutionary adaptation of lipid metabolism in parasitic nematodes.
Tang et al. (Tue,) studied this question.