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Background <p>Metabolic streamlining as a consequence of parasitism has resulted in the loss of lipid biosynthetic genes in nematodes. <i>Angiostrongylus cantonensis</i>, 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 <i>A. cantonensis</i> remain elusive.</p> Methods <p>We integrated comparative genomics, stage-specific transcriptomics, and lipidomics to reconstruct the expression patterns of the biosynthetic enzymes in <i>A. cantonensis</i> and characterize their dynamic PUFA and oxylipin profiles during the neuro-pulmonary transition from brain-residing fourth-stage (L4) to lung-migrating L5 larvae.</p> Results <p>Genomic and transcriptomic analyses revealed a streamlined biosynthetic repertoire in <i>A. cantonensis</i>. The worm lacks Δ6 desaturase and canonical cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) enzymes, and expresses only residual levels of <i>ptges2</i> and <i>lta4h</i>, which are markedly lower than those in free-living <i>Caenorhabditis elegans</i> 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 <i>n</i>-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.</p> Conclusions <p>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.</p> Graphical Abstract <p></p>

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Polyunsaturated fatty acid and oxylipin profiles of Angiostrongylus cantonensis during cerebral-to-pulmonary migration illuminate parasite and host microenvironmental lipid signatures

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月2日

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  • Zhengxu Tang,
  • Jiaying Lai,
  • Yashan Song,
  • Song Li,
  • Lihua Xiao,
  • Yaoyu Feng,
  • Dongjuan Yuan

摘要

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.

Graphical Abstract