Background & aims: 2'-Fucosyllactose (2'-FL), the primary constituent of human milk oligosaccharides, has been identified as a potential regulator of inflammation in inflammatory bowel disease. Despite this recognition, the specific mechanisms through which 2'-FL alleviates ulcerative colitis (UC) remain ambiguous. This study seeks to investigate the potential anti-inflammatory properties of 2'-FL concerning intestinal inflammation and uncover the associated mechanisms.Methods: C57BL/6J mice were orally administered a daily dose of 500 mg/kg 2'-FL for 11 consecutive days, followed by the induction of colitis using 3 % (wt/vol) dextran sulfate sodium (DSS) for the final 6 days. Subsequently, a comprehensive range of techniques, including an Acyl-biotin exchange assay, fluorescein-isothiocyanate-labeled dextran assay, histopathology, ELISA, quantitative real-time PCR, Western blot, immunofluorescence staining, immunohistochemistry staining, Alcian blue-periodic acid schiff staining, TdT-mediated dUTP nick end labeling, transmission electron microscopy, iTRAQ quanti-tative proteomics, bioinformatics analysis, and the generation of signal transducer and activator of transcription 3 (STAT3) knockout mice, were employed to explore the relevant molecular mechanisms.Results: Administration of 2'-FL significantly ameliorated DSS-induced colitis in mice and enhanced the integrity of the intestinal mucosal barrier. 2'-FL downregulated the phosphorylation of STAT3 and inhibited STAT3-related signaling pathways in colon tissues, which, in turn, reduced inflammatory re-sponses. Interestingly, knockdown of STAT3 attenuated the protective effects of 2'-FL, highlighting that 2'-FL-mediated inflammatory attenuation is dependent on STAT3 expression. Additionally, 2'-FL could influence STAT3 activation by modulating the palmitoylation and depalmitoylation of STAT3.Conclusions: 2'-FL promotes the recovery of the intestinal mucosal barrier and suppresses inflammation in ulcerative colitis by inhibiting the palmitoylation and phosphorylation of STAT3.(c) 2023 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
基金：
National Natural Science Foundation of China [82370538, 82000521, 82170549, 82102797]
第一作者机构：[1]Wuhan Univ, Renmin Hosp, Dept Gastroenterol, Wuhan, Hubei, Peoples R China[2]Key Lab Hubei Prov Digest Syst Dis, Wuhan, Hubei, Peoples R China[3]Wuhan Univ, Renmin Hosp, Cent Lab, Wuhan, Hubei, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Wuhan Univ, Renmin Hosp, Dept Gastroenterol, Wuhan, Hubei, Peoples R China[7]Wuhan Univ, Renmin Hosp, Dept Gastroenterol, 238 Jiefang Rd, Wuhan 430060, Hubei, Peoples R China
推荐引用方式(GB/T 7714)：
Li Jinting,Wei Yuping,Liu Chuan,et al.2'-Fucosyllactose restores the intestinal mucosal barrier in ulcerative colitis by inhibiting STAT3 palmitoylation and phosphorylation[J].CLINICAL NUTRITION.2024,43(2):380-394.doi:10.1016/j.clnu.2023.12.011.
APA：
Li, Jinting,Wei, Yuping,Liu, Chuan,Liu, Zhengru,Zhang, Luyun...&Dong, Weiguo.(2024).2'-Fucosyllactose restores the intestinal mucosal barrier in ulcerative colitis by inhibiting STAT3 palmitoylation and phosphorylation.CLINICAL NUTRITION,43,(2)
MLA：
Li, Jinting,et al."2'-Fucosyllactose restores the intestinal mucosal barrier in ulcerative colitis by inhibiting STAT3 palmitoylation and phosphorylation".CLINICAL NUTRITION 43..2(2024):380-394
医学