Intestinal metabolite homocysteine participates in the regulation of irritable bowel syndrome
10.16352/j.issn.1001-6325.2025.07.0858
- VernacularTitle:肠道代谢物同型半胱氨酸参与调节肠易激综合征
- Author:
Shaochong LU
1
;
Haozhen YE
;
Songyuan HOU
;
Yesheng ZHOU
;
Si LIU
;
Shengtao ZHU
Author Information
1. 首都医科大学附属北京友谊医院 消化科 消化健康全国重点实验室 国家消化系统疾病临床医学研究中心胃肠早癌药械研发北京市重点实验室,北京 100050
- Keywords:
irritable bowel syndrome;
homocysteine;
intestinal barrier function;
visceral hypersensitivity;
tight junction protein
- From:
Basic & Clinical Medicine
2025;45(7):858-865
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of homocysteine(Hcy)in the pathogenesis of irritable bowel syn-drome(IBS)and its effects on intestinal motility,visceral hypersensitivity,and barrier function.Methods Clinical cohorts and animal models were combined for this study.Clinically,fifteen IBS patients meeting Rome Ⅲcriteria and 15 control individuals were enrolled to detect fecal Hcy levels and their correlation with symptoms.As for animal experiments,water avoidance stress(WAS)and 2,4,6-trinitrobenzene sulfonic acid(TNBS)chemical induction were utilized to establish IBS rat and mouse models,combined with a high-methionine diet(HMD)to simulate hyperhomocysteinemia.IBS symptoms were evaluated through fecal water content,carmine red intestinal transit time,and visceral hypersensitivity scores.Immune-fluorescence and Western blot were used to detect intes-tinal epithelial tight junction proteins.Serum and fecal Hcy concentrations were measured to assess Hcy levels.Statistical analyses included t-tests and One-way Anova.Results Fecal Hcy level in IBS patients were signifi-cantly higher than those in the healthy control group which demonstrated a positive correlation with defecation fre-quency(P＜0.01).In animal models,the combination of TNBS administration and a high-methionine diet markedly elevated serum and fecal Hcy levels in mice,while synergistically exacerbated intestinal motility disor-ders and visceral hypersensitivity.In vitro experiments showed that Hcy treatment down-regulates the expression of tight junction proteins in human colon cancer cell line(Caco-2).Conclusions Hcy plays an important role in the pathogenesis of IBS by impairing intestinal barrier function and enhancing visceral hypersensitivity,and it may serve as a potential new target for the treatment of IBS.
