人芽囊原蟲(Blastocystis hominis)是一種寄生於人類消化道中的寄生性原蟲。近年來有文獻指出它的感染與消化道疾病，亦或是與大腸直腸癌有關。但是，人芽囊原蟲的致病機轉目前並不清楚。在本研究中我們首先將人芽囊原蟲與腸道細胞HT-29進行共培養，之後再利用微陣列分析的方式，我們總共找到10個基因表達量有明顯變化，其中CRABP2則是表達量上升最多的，而PCNA則是表達量下降最多的，透過與其他蛋白質作用關係分析，我們發現在人芽囊原蟲感染後會藉由調控維甲酸 (retinoic acid) 代謝路徑上的基因表現，進而導致腸道表皮細胞受到傷害。另一方面我們發現人芽囊原蟲在脂質豐富的環境中，對於細胞造成更明顯的傷害，不論是在細胞的脫落現象以及發炎指標基因IL-8的表現都有明顯的增加。此外Pravastatin其主要作用來降低脂肪，我們發現Pravastatin會降低人芽囊原蟲內部脂質的累積，與目前常用的治療藥物metronidazole合併使用可以增加治療的效果，並且Pravastatin可以降低人芽囊原蟲對細胞的傷害，Caco-2細胞中IL-8及CRABP2也有下降的趨勢，因此我們根據以上的結果，認為人芽囊原蟲的脂質累積與生合成是對其致病性是一個重要的因素。

Blastocystis hominis is one of the neglected intestinal protozoans. The molecular mechanisms of Blastocystis infection induced pathogenic effects remain unclear. In previous studies, lipid accumulation of Blastocystis was observed, the function of which is not well known. Here, we investigated the relationship between lipids and the pathogenesis of B. hominis. In addition, we also evaluated the effect of Pravastatin, a lipid-lowering statin drug, on B. hominis pathogenesis. During lipid accumulation, triglyceride and free fatty acid levels are significantly increased by Blastocystis ST-7 in the lipid rich environment as measured by lipid stain and TLC analysis. To gain insights into the lipid biogenesis of B. hominis, we utilized RNA-seq to quantify the gene expression of Blastocystis ST-7. RNA-seq data revealed that 4,287 of the 6,020 CDS are annotated, and we also reconstructed the fatty acid synthesis pathway of Blastocystis ST-7. The GPDH and G6PD involved in glycerol and free fatty acid synthesis were upregulated by Blastocystis ST-7 in the lipid rich environment. The cysteine protease of Blastocystis ST-7 was upregulated in the lipid rich environment and elicited a significant increase in cell inflammation and disruption in Caco2 cells. We also observed Blastocystis infection induced CRABP2 upregulation in HT-29 and Caco2 cells. Furthermore, Pravastatin decreased Blastocystis ST-7-induced inflammation and disruption of Caco2 cells. Our results showed that an important role of the lipid in the Blastocystis pathogenesis process. In addition, Pravastatin prevented Blastocystis-induced cell inflammation and disruption, suggesting a potential therapeutic in Blastocystis infection.

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