## 4 Discussion
In addition, PUFAs have shown to increase mitochondrial \(\beta\)-oxidation and ROS production, which might cause mitochondrial dysfunction [124]. Of note, lipid peroxidation-related mitochondrial dysfunction has been linked to several pathologies including non-alcoholic steatohepatitisitis, ischemic cardiac reperfusion, and IBD [125; 126; 127]. We observed downregulation of the cellular phagosomal pathway in PDiff Caco-2 cells for all treatment groups. Among downregulated genes were those that encode subunits of vacuolar-ATPase involved in organelle acidification, such as _ATP6V1D/V0B_. Intestinal epithelial cells are considered non-professional phagocytic cells and this effect of reduced phagosomal pathway could be attributed to the reduction of oxidative phosphorylation, particularly in 13-HPODE-treated cells, as phagocytosis is known to be an energy-dependent process [128; 129]. It has been demonstrated that modification of photoreceptor outer segments by lipid peroxidation products causes impairment of lysosomal degradation [130], suggesting the negative regulation of lysosomal/phagosomal degradation by LOOH adducts. Of note, impaired intestinal epithelial autophagy has been implicated in the pathology of IBD [131], and impaired intestinal epithelial phagosomal function may affect the ability of epithelial cells, the first line of defense in the gut, to clear the pathogens they encounter [128]. Thus, disruption of both oxidative phosphorylation and phagosomal pathway could propose a mechanism by which dietary LOOHs contribute to IBD and/or IBD-related carcinogenesis in intestinal crypt or tumor cells. On the other hand, PDiff Caco-2 cells showed an anti-inflammatory response to either treatment evidenced by downregulation of inflammatory chemokines, _CXCL1/L3_ and _CCL20_, and NOD-like receptor signaling. We demonstrated that upregulation of PPAR signaling by 13-HPODE might exert an anti-inflammatory response, which is consistent with a previous study reported the protective anti-inflammatory effect of PPAR against lipopolysaccharideamide [132]. Furthermore, PPAR ligands have shown to reduce expression of TNF\(\alpha\) as well as chemokine receptors and chemokines [133] including _CXCL1_[134]. Previous studies also reported anti-inflammatory properties of PUFAs [135, 136, 137] consisting with our results. H\({}_{2}\)O\({}_{2}\) is a source of oxidative stress that can be found in food preservatives, dental care products, and in some beverages consumed daily such as coffee and tea, and might predispose the intestinal epithelium to oxidative stress [138]. To evaluate whether H\({}_{2}\)O\({}_{2}\) has a similar impact of 13-HPODE on the transcriptomic profile of Caco-2 cells, we treated PDiff cells with 100 uM H\({}_{2}\)O\({}_{2}\). A previous study reported that PDiff Caco-2 cells maintained 95% viability when treated with 100 uM of H\({}_{2}\)O\({}_{2}\) and that cellular and DNA damage was observed at 150 uM H\({}_{2}\)O\({}_{2}\) or higher [58]. H\({}_{2}\)O\({}_{2}\) is normally detoxified by peroxisomal catalase and glutathione defense mechanism [115]. Similar to what we observed in 13-HPODE-treated cells, H\({}_{2}\)O\({}_{2}\)-treated cells showed upregulation of multiple pathways involved in detoxification such as peroxisome, cytochrome P450, and glutathione metabolism suggesting disrupted redox status in both treatment groups. We observed upregulation of _CAT_, _PEX6_, and _PEX11A_, as well as peroxisomal lipid metabolism genes including _IDHI_, _ABCD1_, and _CROT_ in H\({}_{2}\)O\({}_{2}\)-treated cells. It has been reported that H\({}_{2}\)O\({}_{2}\) may cause peroxisomal proliferation supporting the antioxidant role of peroxisome against ROS [74]. Upregulated genes also included alcohol dehydrogenases _ADH5/6_, and _UGTB2B4_ involved in metabolism of toxic compounds and xenobiotics.