结肠炎
偶氮甲烷
多不饱和脂肪酸
炎症性肠病
癌变
结直肠癌
医学
TLR4型
基因剔除小鼠
免疫学
癌症研究
内科学
受体
炎症
脂肪酸
生物
癌症
生物化学
疾病
作者
Weicang Wang,Yuxin Wang,Katherine Z. Sanidad,Yige Wang,Jianan Zhang,Wenqi Yang,Quancai Sun,Ipek Bayram,Renhua Song,Haixia Yang,David Johnson,Heather L. Sherman,Daeyoung Kim,Lisa M. Minter,Justin Wong,Melody Y. Zeng,Eric A. Decker,Guodong Zhang
出处
期刊:Journal of Crohn's and Colitis
[Oxford University Press]
日期:2024-09-14
标识
DOI:10.1093/ecco-jcc/jjae148
摘要
Abstract Background and Aims Human studies suggest that a high intake of polyunsaturated fatty acid (PUFA) is associated with an increased risk of inflammatory bowel disease (IBD). PUFA is highly prone to oxidation. To date, it is unclear whether unoxidized or oxidized PUFA is involved in the development of IBD. Here, we aim to compare the effects of unoxidized PUFA vs. oxidized PUFA on the development of IBD and associated colorectal cancer. Methods We evaluated the effects of unoxidized and oxidized PUFA on dextran sodium sulfate (DSS)- and IL-10 knockout-induced colitis, and azoxymethane (AOM)/DSS-induced colon tumorigenesis in mice. Additionally, we studied the roles of gut microbiota and Toll-like receptor 4 (TLR4) signaling involved. Results Administration of a diet containing oxidized PUFA, at human consumption-relevant levels, increases the severity of colitis and exacerbates the development of colitis-associated colon tumorigenesis in mice. Conversely, a diet rich in unoxidized PUFA doesn’t promote colitis. Furthermore, oxidized PUFA worsens colitis-associated intestinal barrier dysfunction and leads to increased bacterial translocation, and it fails to promote colitis in Toll-like receptor 4 (TLR4) knockout mice. Finally, oxidized PUFA alters the diversity and composition of gut microbiota, and it fails to promote colitis in mice lacking the microbiota. Conclusions These results support that oxidized PUFA promotes the development of colitis and associated tumorigenesis in mouse models via TLR4- and gut microbiota-dependent mechanisms. Our findings highlight the potential need to update regulation policies and industrial standards for oxidized PUFA levels in food.
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