Fut2, also known as fucosyltransferase 2, is an enzyme that adds fucose to proteins or lipids via α-1,2-fucosylation in the intestinal mucosa [1,2,3,4,5,6]. It plays a crucial role in various biological processes related to the gut, such as maintaining mucosal integrity, influencing the function of intestinal stem cells, and modulating the interaction between the host and gut microbiota. Genetic models, like knockout (KO) or conditional knockout (CKO) mouse models, have been instrumental in studying its functions [1,2,3,4,5,6].

Intestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice have shown that Fut2 deficiency leads to more severe intestinal inflammation, disrupted gut microbiota, and increased susceptibility to colitis and colorectal cancer (CRC) [3,4,5]. In CRC, Fut2 inhibits epithelial-mesenchymal transition (EMT), metastasis, and promotes apoptosis. It does this by increasing the fucosylation of proteins like LRP1, HYOU1, and LAMP1, and regulating related pathways [1,2,6]. In intestinal stem cells, Fut2-dependent fucosylation of HYOU1 protects against inflammatory injury by regulating the unfolded protein response [2].

In conclusion, Fut2 is essential for maintaining gut health and homeostasis. The use of Fut2 KO/CKO mouse models has revealed its significant role in intestinal inflammation, colitis, and CRC. Understanding Fut2's functions provides potential therapeutic targets for treating intestinal injury disorders and CRC [1,2,3,4,5,6].

References:

1. He, Lingnan, Guo, Zijun, Wang, Weijun, Tian, Shuxin, Lin, Rong. 2023. FUT2 inhibits the EMT and metastasis of colorectal cancer by increasing LRP1 fucosylation. In Cell communication and signaling : CCS, 21, 63. doi:10.1186/s12964-023-01060-0. https://pubmed.ncbi.nlm.nih.gov/36973740/

2. Wang, Zhe, Tan, Chen, Duan, Caihan, Han, Chaoqun, Hou, Xiaohua. 2023. FUT2-dependent fucosylation of HYOU1 protects intestinal stem cells against inflammatory injury by regulating unfolded protein response. In Redox biology, 60, 102618. doi:10.1016/j.redox.2023.102618. https://pubmed.ncbi.nlm.nih.gov/36724577/

3. Tang, Xuelian, Wang, Weijun, Hong, Gaichao, Lin, Rong, Hou, Xiaohua. 2021. Gut microbiota-mediated lysophosphatidylcholine generation promotes colitis in intestinal epithelium-specific Fut2 deficiency. In Journal of biomedical science, 28, 20. doi:10.1186/s12929-021-00711-z. https://pubmed.ncbi.nlm.nih.gov/33722220/

4. Hong, Gaichao, Zhao, Yajuan, Li, Qingyuan, Liu, Side. 2024. Fut2 deficiency aggravates chronic colitis through 2-oxindole-AHR mediated cGAS-STING pathway. In International immunopharmacology, 137, 112512. doi:10.1016/j.intimp.2024.112512. https://pubmed.ncbi.nlm.nih.gov/38897123/

5. Wang, Weijun, Tang, Xuelian, Duan, Caihan, Hou, Xiaohua, Lin, Rong. 2023. Intestinal epithelium-specific Fut2 deficiency promotes colorectal cancer through down-regulating fucosylation of MCAM. In Journal of translational medicine, 21, 82. doi:10.1186/s12967-023-03906-0. https://pubmed.ncbi.nlm.nih.gov/36739428/

6. Guo, Zijun, He, Lingnan, Wang, Weijun, Tian, Shuxin, Lin, Rong. 2025. FUT2-dependent fucosylation of LAMP1 promotes the apoptosis of colorectal cancer cells by regulating the autophagy-lysosomal pathway. In Cancer letters, 619, 217643. doi:10.1016/j.canlet.2025.217643. https://pubmed.ncbi.nlm.nih.gov/40112906/