| Summary: | <i>Blastocystis hominis</i> is an intestinal protozoan that is often neglected, despite causing abdominal pain and diarrhea. Previous research has demonstrated that lipids can be synthesized by <i>B. hominis</i> or can accumulate in growth medium, but their function and mechanisms in the pathogenesis of <i>Blastocystis</i> remain unclear. Our study found that lipid-rich <i>Blastocystis</i> ST7-B can increase inflammation and disrupt Caco-2 cells more than the same parasite without the lipovenoes supplement. Additionally, the cysteine protease of <i>Blastocystis</i>, a virulence factor, is upregulated and has higher activity in lipid-rich <i>Blastocystis</i>. In order to better understand the effects of lipids on <i>Blastocystis</i> pathogenesis, we treated lipid-lowering pravastatin during <i>Blastocystis</i> ST7-B culturing with a lipovenoes supplement, which decreased the lipid levels of the <i>Blastocystis</i> and reduced the <i>Blastocystis</i>-induced inflammation and cell disruption of Caco-2 cells. We also analyzed the fatty acid composition and possible synthesis pathway in <i>Blastocystis</i> ST7-B, finding significantly higher ratios of arachidonic acid, oleic acid, and palmitic acid than in the other lipid components in lipid-rich <i>Blastocystis</i> ST7-B. These results suggest that lipids play a significant role in the pathogenesis of <i>Blastocystis</i> and provide important information on the molecular mechanisms of and potential treatments for <i>Blastocystis</i> infection.
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