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  2. Vitamin B12 ameliorates gut epithelial injury via modulating the HIF-1 pathway and gut microbiota

Vitamin B12 ameliorates gut epithelial injury via modulating the HIF-1 pathway and gut microbiota

  • Cell Mol Life Sci. 2024 Sep 11;81(1):397. doi: 10.1007/s00018-024-05435-5.
Chenxi Feng # 1 Jinhua Yan # 2 Ting Luo # 2 Hong Zhang 3 Hu Zhang 3 Yu Yuan 1 Yi Chen 4 Haiyang Chen 5 6
Affiliations

Affiliations

  • 1 Division of Gastrointestinal Surgery, Laboratory of Stem Cell and Anti-Aging Research, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
  • 2 Center of Gerontology and Geriatrics, Laboratory of Stem Cell and Anti-Aging Research, National Clinical Research Center for Geriatrics and Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
  • 3 Department of Gastroenterology and Hepatology and Laboratory of Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
  • 4 Division of Gastrointestinal Surgery, Laboratory of Stem Cell and Anti-Aging Research, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. toddychan@163.com.
  • 5 Division of Gastrointestinal Surgery, Laboratory of Stem Cell and Anti-Aging Research, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. chenhy82@scu.edu.cn.
  • 6 Center of Gerontology and Geriatrics, Laboratory of Stem Cell and Anti-Aging Research, National Clinical Research Center for Geriatrics and Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. chenhy82@scu.edu.cn.
  • # Contributed equally.
Abstract

Inflammatory bowel diseases (IBDs) are immune chronic diseases characterized by recurrent episodes, resulting in continuous intestinal barrier damage and intestinal microbiota dysbiosis. Safe strategies aimed at stabilizing and reducing IBDs recurrence have been vigorously pursued. Here, we constructed a recurrent intestinal injury Drosophila model and found that vitamin B12 (VB12), an essential co-factor for organism physiological functions, could effectively protect the intestine and reduce dextran sulfate sodium-induced intestinal barrier disruption. VB12 also alleviated microbial dysbiosis in the Drosophila model and inhibited the growth of gram-negative bacteria. We demonstrated that VB12 could mitigate intestinal damage by activating the hypoxia-inducible factor-1 signaling pathway in injured conditions, which was achieved by regulating the intestinal oxidation. In addition, we also validated the protective effect of VB12 in a murine acute colitis model. In summary, we offer new insights and implications for the potential supportive role of VB12 in the management of recurrent IBDs flare-ups.

Keywords

Gut microbiota; Gut regeneration; Hypoxia-inducible factor-1; Intestinal inflammation diseases; Vitamin B12.

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