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 g...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 gingermediated 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 O.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 elF3 transcription initiation complex by covalently binding to the Cys^(58)site of elF3A,a key factor regulating intestinal crypt stem celldifferentiation,further reducing the goblet cellnumber 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.展开更多
基金supported by the National Natural Science Foundation of China(grant numbers 82125037,8197-3498,82104508,and 81774283)Science Foundation for Distinguished Young Scholars of Jiangsu Province(BK20231528)+5 种基金the National Key Research and Development Program of China(2023YFC2308200)Key R&D Program of Jiangsu Province(grant number BE2022815)Jiangsu Provincial Medical Innovation Center(grant number CXZX202225)Young Elite Scientists Sponsorship Program of the China Association for Science and Technology(grant number 2021-QNRC2-B17)333 high-level talents project of Jiangsu Province for Y.Y.(BRA202202)Suzhou GuSu Medical Talent Project(GSWS2022100).
文摘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 gingermediated 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 O.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 elF3 transcription initiation complex by covalently binding to the Cys^(58)site of elF3A,a key factor regulating intestinal crypt stem celldifferentiation,further reducing the goblet cellnumber 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.
