Dysregulated Glycerophospholipid Metabolism and ChAT Overexpression in Wrap-Restraint Stress-Induced IBS Mice: A Multi-Omics Approach to Gut-Brain Axis Disruption and Potential Therapeutic Targets

Author:

Zhang Fan1,Zhou Yanlin2,Li Fuhao1,Sun Shaopeng1,Guo Lingnan1,Xu Maosheng2,Lv Bin2

Affiliation:

1. The First School of Clinical Medicine of Zhejiang Chinese Medical University

2. The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)

Abstract

Abstract Background: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that affects a significant portion of the global population. Despite extensive research in recent years, the pathophysiology of IBS remains poorly understood, and there is currently no definitive cure for the condition. However, recent advances in high-throughput technologies such as genomics, transcriptomics, proteomics, and metabolomics have allowed for exploration of IBS at the multi-omics level. These approaches enable us to examine IBS from multiple perspectives and identify potential biomarkers and therapeutic targets for the condition. Methods:This study employed a comprehensive multi-omics investigation on the IBS model induced by “wrap-restraint stress”, revealing significant abnormalities in systemic glycerophospholipid metabolism within the gut-brain axis. Results:Metabolomics analysis demonstrated decreased phosphatidylcholine (PC) content and increased lysophosphatidylcholine (lyso-PC) levels in multiple tissues of IBS mice. Concurrently, transcriptomic analysis indicated increased transcription of Choline acetyltransferase (ChAT), a crucial enzyme involved in the acetylcholine synthesis pathway. To explore potential therapies, we administered α-NETA, a ChAT inhibitor, to IBS mice in subsequent experiments. Remarkably, α-NETA treatment improved various IBS-like symptoms, including increased body weight, decreased visceral sensitivity, reduced fecal water content, and alleviated anxiety-like behaviors. Additionally, α-NETA administration significantly elevated PC levels in multiple tissues while reducing the levels of Cytosolic phospholipase A2 (cPLA2), an enzyme responsible for PC degradation into lyso-PC. Conclusions: Our findings suggest that elevated levels of acetylcholine induced by ChAT overexpression and enhanced activity induce gut-brain axis disturbances and a variety of IBS-like symptoms in mice. This study highlights the therapeutic potential of targeting glycerophospholipid metabolism and ChAT as a promising approach for managing IBS.

Publisher

Research Square Platform LLC

Reference51 articles.

1. Irritable bowel syndrome;Ford AC;Lancet,2020

2. ACG Clinical Guideline: Management of Irritable Bowel Syndrome;Lacy BE;AM J GASTROENTEROL,2021

3. Sperber AD, Bangdiwala SI, Drossman DA, Ghoshal UC, Simren M, Tack J, Whitehead WE, Dumitrascu DL, Fang X, Fukudo S et al. Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study. GASTROENTEROLOGY 2021, 160(1):99–114.

4. Anxiety and Depression in Irritable Bowel Syndrome;Banerjee A;INDIAN J PSYCHOL MED,2017

5. Systematic review with meta-analysis: the prevalence of anxiety and depression in patients with irritable bowel syndrome;Zamani M;ALIMENT PHARM THER,2019

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3