Zhao Bing, Ye Juan, Zhao Wenjing, Liu Xinyu, Lan Hongli, Sun Jinbing, Chen Jiao, Cai Xueting, Wei Qingyun, Zhou Qian, Zhang Zhengwei, Wu Yuze, Yang Yang, Cao Peng
State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, China.
Jiangsu Provincial Medical Innovation Center, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Research (Wash D C). 2024 Nov 7;7:0524. doi: 10.34133/research.0524. eCollection 2024.
Dietary factors play a crucial role in irritable bowel syndrome (IBS) pathogenesis. Therefore, the dietary contraindications for patients with IBS require further supplementation. Recent investigations have revealed that ginger consumption may pose a risk of aggravating the symptoms and incidence of IBS; however, the specific mechanism remains unknown. In this study, we developed experimental IBS and intestinal organoid differentiation screening models to elucidate the mechanisms underlying the ginger-mediated exacerbation of IBS symptoms. Subsequently, we used a knockout approach combined with click chemistry as well as virus infection to identify the toxic components of ginger and the target mechanism. Our results showed that a daily intake of 90 to 300 mg/kg ginger (equivalent to a human daily dose of 0.6 to 2 g per person) may pose a risk of exacerbating IBS symptoms. Furthermore, a component derived from 6-gingerol (ginger's main ingredient) through in vivo gastric acid and heat processing inhibited the formation of the eIF3 transcription initiation complex by covalently binding to the Cys site of eIF3A, a key factor regulating intestinal crypt stem cell differentiation, further reducing the goblet cell number and related mucus layer thickness and increasing lipopolysaccharide infiltration and low-grade inflammation in the ileum crypts, thereby exacerbating the symptoms of IBS in mice. Our study suggests that dietary ginger aggravates IBS and provides safety evaluation methods for the proper use of foods in specific populations.
饮食因素在肠易激综合征（IBS）的发病机制中起着关键作用。因此，IBS患者的饮食禁忌需要进一步补充。最近的研究表明，食用生姜可能会加重IBS的症状和发病率；然而，具体机制尚不清楚。在本研究中，我们建立了实验性IBS和肠道类器官分化筛选模型，以阐明生姜介导的IBS症状加重的潜在机制。随后，我们采用基因敲除方法结合点击化学以及病毒感染来鉴定生姜的毒性成分和靶标机制。我们的结果表明，每天摄入90至300mg/kg生姜（相当于人类每人每天0.6至2g的剂量）可能会有加重IBS症状的风险。此外，一种由6-姜酚（生姜的主要成分）经体内胃酸和热处理衍生而来的成分，通过与eIF3A的半胱氨酸位点共价结合，抑制eIF3转录起始复合物的形成，eIF3A是调节肠道隐窝干细胞分化的关键因子，进而减少杯状细胞数量和相关黏液层厚度，并增加回肠隐窝中脂多糖的浸润和低度炎症，从而加重小鼠IBS的症状。我们的研究表明，食用生姜会加重IBS，并为特定人群合理使用食物提供了安全性评估方法。
