2. Academic Validation
  3. 2'-Fucosyllactose restores the intestinal mucosal barrier in ulcerative colitis by inhibiting STAT3 palmitoylation and phosphorylation

2'-Fucosyllactose restores the intestinal mucosal barrier in ulcerative colitis by inhibiting STAT3 palmitoylation and phosphorylation

  • Clin Nutr. 2024 Feb;43(2):380-394. doi: 10.1016/j.clnu.2023.12.011.
Jinting Li 1,  Yuping Wei 1,  Chuan Liu 1,  Xingzhou Guo 1,  Zhengru Liu 2,  Luyun Zhang 1,  Shenglan Bao 1,  Xiaohan Wu 3,  Xiaoli Wang 4,  Jixiang Zhang 5,  Weiguo Dong 6
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China; Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, Hubei Province, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
  • 2 Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, Hubei Province, China; Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
  • 3 Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, Hubei Province, China; Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, China.
  • 4 Department of Plastic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
  • 5 Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China. Electronic address: [email protected].
  • 6 Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China. Electronic address: [email protected].
PMID: 38150914 DOI: 10.1016/j.clnu.2023.12.011
Abstract

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 quantitative 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 responses. 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.

Keywords

2'-fucosyllactose; Human milk oligosaccharides; Inflammation; STAT3; Ulcerative colitis.

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