Intestinal metabolite homocysteine participates in the regulation of irritable bowel syndrome

Objective To investigate the role of homocysteine (Hcy) in the pathogenesis of irritable bowel syndrome (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 pati...

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Main Author: LU Shaochong, YE Haozhen, HOU Songyuan, ZHOU Yesheng, LIU Si, ZHU Shengtao
Format: Article
Language:zho
Published: Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College. 2025-07-01
Series:Jichu yixue yu linchuang
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Online Access:https://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2025-45-7-858.pdf
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author LU Shaochong, YE Haozhen, HOU Songyuan, ZHOU Yesheng, LIU Si, ZHU Shengtao
author_facet LU Shaochong, YE Haozhen, HOU Songyuan, ZHOU Yesheng, LIU Si, ZHU Shengtao
author_sort LU Shaochong, YE Haozhen, HOU Songyuan, ZHOU Yesheng, LIU Si, ZHU Shengtao
collection DOAJ
description Objective To investigate the role of homocysteine (Hcy) in the pathogenesis of irritable bowel syndrome (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 Ⅲ criteria 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 intestinal 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 significantly higher than those in the healthy control group which demonstrated a positive correlation with defecation frequency(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 disorders 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.
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publisher Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.
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spelling doaj-art-1ad2202914eb4bf2abe1baa0e5810c2f2025-08-20T03:29:57ZzhoInstitute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.Jichu yixue yu linchuang1001-63252025-07-0145785886510.16352/j.issn.1001-6325.2025.07.0858Intestinal metabolite homocysteine participates in the regulation of irritable bowel syndromeLU Shaochong, YE Haozhen, HOU Songyuan, ZHOU Yesheng, LIU Si, ZHU Shengtao0Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University; State Key Laboratory of Digestive Health; National Clinical Research Center for Digestive Diseases; Beijing Key Laboratory of Early Gastrointestinal Cancer Medicine and Medical Devices, Beijing 100050, ChinaObjective To investigate the role of homocysteine (Hcy) in the pathogenesis of irritable bowel syndrome (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 Ⅲ criteria 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 intestinal 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 significantly higher than those in the healthy control group which demonstrated a positive correlation with defecation frequency(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 disorders 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.https://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2025-45-7-858.pdfirritable bowel syndrome|homocysteine|intestinal barrier function|visceral hypersensitivity|tight junction protein
spellingShingle LU Shaochong, YE Haozhen, HOU Songyuan, ZHOU Yesheng, LIU Si, ZHU Shengtao
Intestinal metabolite homocysteine participates in the regulation of irritable bowel syndrome
Jichu yixue yu linchuang
irritable bowel syndrome|homocysteine|intestinal barrier function|visceral hypersensitivity|tight junction protein
title Intestinal metabolite homocysteine participates in the regulation of irritable bowel syndrome
title_full Intestinal metabolite homocysteine participates in the regulation of irritable bowel syndrome
title_fullStr Intestinal metabolite homocysteine participates in the regulation of irritable bowel syndrome
title_full_unstemmed Intestinal metabolite homocysteine participates in the regulation of irritable bowel syndrome
title_short Intestinal metabolite homocysteine participates in the regulation of irritable bowel syndrome
title_sort intestinal metabolite homocysteine participates in the regulation of irritable bowel syndrome
topic irritable bowel syndrome|homocysteine|intestinal barrier function|visceral hypersensitivity|tight junction protein
url https://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2025-45-7-858.pdf
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