A. Annaházi, T. Berger, I. Demir, F. Zeller, M. Müller, Markus Anneser, A. Skerra, K. Michel, M. Schemann
Serotonin (5‐HT) is an important mediator in the gastrointestinal tract, acting on different neuronal 5‐HT receptors. The ionotropic 5‐HT3 receptor mediates immediate but transient spike discharge in human enteric neurons. We studied the role of the metabotropic 5‐HT1P, 5‐HT4, and 5‐HT7 receptors to activate human submucous neurons.
{"title":"Metabotropic 5‐HT receptor‐mediated effects in the human submucous plexus","authors":"A. Annaházi, T. Berger, I. Demir, F. Zeller, M. Müller, Markus Anneser, A. Skerra, K. Michel, M. Schemann","doi":"10.1111/nmo.14380","DOIUrl":"https://doi.org/10.1111/nmo.14380","url":null,"abstract":"Serotonin (5‐HT) is an important mediator in the gastrointestinal tract, acting on different neuronal 5‐HT receptors. The ionotropic 5‐HT3 receptor mediates immediate but transient spike discharge in human enteric neurons. We studied the role of the metabotropic 5‐HT1P, 5‐HT4, and 5‐HT7 receptors to activate human submucous neurons.","PeriodicalId":19104,"journal":{"name":"Neurogastroenterology & Motility","volume":"105 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86628849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The central pathophysiological mechanisms underlying irritable bowel syndrome (IBS), a female‐predominant gastrointestinal disorder characterized by abdominal pain and abnormal bowel habits, remain poorly understood. IBS patients often report that chronic stress exacerbates their symptoms. Brain imaging studies have revealed that the amygdala, a stress‐responsive brain region, of IBS patients is overactive when compared to healthy controls. Previously, we demonstrated that downregulation of the glucocorticoid receptor (GR) in the central nucleus of the amygdala (CeA) underlies stress‐induced visceral hypersensitivity in female rats. In the current study, we aimed to evaluate in the CeA of female rats whether chronic water avoidance stress (WAS) alters DNA methylation of the GR exon 17 promoter region, a region homologous to the human GR promoter. As histone deacetylase (HDAC) inhibitors are able to change DNA methylation, we also evaluated whether administration of the HDAC inhibitor trichostatin A (TSA) directly into the CeA prevented WAS‐induced increases in DNA methylation of the GR exon 17 promoter. We found that WAS increased overall and specific CpG methylation of the GR promoter in the CeA of female rats, which persisted for up to 28 days. Administration of the TSA directly into the CeA prevented these stress‐induced changes of DNA methylation at the GR promoter. Our results suggest that, in females, changes in DNA methylation are involved in the regulation of GR expression in the CeA. These changes in DNA methylation may contribute to the central mechanisms responsible for stress‐induced visceral hypersensitivity.
肠易激综合征(IBS)是一种以腹痛和排便习惯异常为特征的女性为主的胃肠道疾病,其核心病理生理机制尚不清楚。肠易激综合征患者经常报告说,慢性压力加剧了他们的症状。脑成像研究显示,与健康对照组相比,IBS患者的杏仁核(应激反应脑区)过度活跃。在此之前,我们证明了雌性大鼠应激诱导的内脏超敏反应是杏仁核中央核糖皮质激素受体(GR)下调的基础。在本研究中,我们旨在评估雌性大鼠的CeA慢性水回避应激(WAS)是否会改变GR外显子17启动子区域的DNA甲基化,该区域与人类GR启动子同源。由于组蛋白去乙酰化酶(HDAC)抑制剂能够改变DNA甲基化,我们还评估了将HDAC抑制剂trichostatin A (TSA)直接注入CeA是否能阻止WAS诱导的GR外显子17启动子DNA甲基化的增加。我们发现WAS增加了雌性大鼠CeA中GR启动子的总体和特异性CpG甲基化,这种甲基化持续长达28天。将TSA直接注入CeA可防止应激诱导的GR启动子DNA甲基化变化。我们的研究结果表明,在雌性中,DNA甲基化的变化参与了CeA中GR表达的调节。这些DNA甲基化的变化可能有助于应激诱导的内脏超敏反应的核心机制。
{"title":"Chronic stress increases DNA methylation of the GR promoter in the central nucleus of the amygdala of female rats","authors":"T. Louwies, B. Greenwood-Van Meerveld","doi":"10.1111/nmo.14377","DOIUrl":"https://doi.org/10.1111/nmo.14377","url":null,"abstract":"The central pathophysiological mechanisms underlying irritable bowel syndrome (IBS), a female‐predominant gastrointestinal disorder characterized by abdominal pain and abnormal bowel habits, remain poorly understood. IBS patients often report that chronic stress exacerbates their symptoms. Brain imaging studies have revealed that the amygdala, a stress‐responsive brain region, of IBS patients is overactive when compared to healthy controls. Previously, we demonstrated that downregulation of the glucocorticoid receptor (GR) in the central nucleus of the amygdala (CeA) underlies stress‐induced visceral hypersensitivity in female rats. In the current study, we aimed to evaluate in the CeA of female rats whether chronic water avoidance stress (WAS) alters DNA methylation of the GR exon 17 promoter region, a region homologous to the human GR promoter. As histone deacetylase (HDAC) inhibitors are able to change DNA methylation, we also evaluated whether administration of the HDAC inhibitor trichostatin A (TSA) directly into the CeA prevented WAS‐induced increases in DNA methylation of the GR exon 17 promoter. We found that WAS increased overall and specific CpG methylation of the GR promoter in the CeA of female rats, which persisted for up to 28 days. Administration of the TSA directly into the CeA prevented these stress‐induced changes of DNA methylation at the GR promoter. Our results suggest that, in females, changes in DNA methylation are involved in the regulation of GR expression in the CeA. These changes in DNA methylation may contribute to the central mechanisms responsible for stress‐induced visceral hypersensitivity.","PeriodicalId":19104,"journal":{"name":"Neurogastroenterology & Motility","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84935585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huiling Chen, Xiaoli Li, Li-yun Gao, Dekui Zhang, Tiyun Han
Although intestinal smooth muscle cells (ISMCs) play an important role in the remodeling of the intestinal structure, considerably less is known about the molecular mechanisms that mediate the development and growth of ISMCs. A possible reason for this lag is the lack of cell lines that recapitulate ISMCs in vivo.
{"title":"Construction and identification of an immortalized rat intestinal smooth muscle cell line","authors":"Huiling Chen, Xiaoli Li, Li-yun Gao, Dekui Zhang, Tiyun Han","doi":"10.1111/nmo.14359","DOIUrl":"https://doi.org/10.1111/nmo.14359","url":null,"abstract":"Although intestinal smooth muscle cells (ISMCs) play an important role in the remodeling of the intestinal structure, considerably less is known about the molecular mechanisms that mediate the development and growth of ISMCs. A possible reason for this lag is the lack of cell lines that recapitulate ISMCs in vivo.","PeriodicalId":19104,"journal":{"name":"Neurogastroenterology & Motility","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77721826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruth E. Rabago, Alejandro Bonilla, Ernesto Escamilla-Diego, M. D. F. Higuera de la Tijera, M. Schmulson
There is no translation for bloating in Spanish, and distension is very technical.
西班牙语中没有关于腹胀的翻译,腹胀是非常专业的。
{"title":"Pictograms are more effective than verbal descriptors in Spanish for bloating and distension","authors":"Ruth E. Rabago, Alejandro Bonilla, Ernesto Escamilla-Diego, M. D. F. Higuera de la Tijera, M. Schmulson","doi":"10.1111/nmo.14364","DOIUrl":"https://doi.org/10.1111/nmo.14364","url":null,"abstract":"There is no translation for bloating in Spanish, and distension is very technical.","PeriodicalId":19104,"journal":{"name":"Neurogastroenterology & Motility","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87026217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinyi Huang, T. Oshima, Y. Akiba, Takanori Yoshimoto, Junji Chen, M. Taki, T. Tomita, H. Fukui, J. Kaunitz, H. Miwa
Low‐grade duodenal inflammation has recently been identified in patients with functional dyspepsia (FD). Chemosensory tuft cells were reported to be associated with gastrointestinal diseases. We therefore assessed duodenal tuft cell density and microinflammation in patients with FD to determine whether these measures could serve as useful biomarkers, and also correlated tuft cell density and microinflammation in FD patients.
{"title":"Duodenal cholinergic tuft cell number is increased in functional dyspepsia","authors":"Xinyi Huang, T. Oshima, Y. Akiba, Takanori Yoshimoto, Junji Chen, M. Taki, T. Tomita, H. Fukui, J. Kaunitz, H. Miwa","doi":"10.1111/nmo.14378","DOIUrl":"https://doi.org/10.1111/nmo.14378","url":null,"abstract":"Low‐grade duodenal inflammation has recently been identified in patients with functional dyspepsia (FD). Chemosensory tuft cells were reported to be associated with gastrointestinal diseases. We therefore assessed duodenal tuft cell density and microinflammation in patients with FD to determine whether these measures could serve as useful biomarkers, and also correlated tuft cell density and microinflammation in FD patients.","PeriodicalId":19104,"journal":{"name":"Neurogastroenterology & Motility","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75166642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Functional esophageal disorders (functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia) are the disorders of gut‐brain interactions (DGBI) and present with esophageal symptoms not associated with a structural, major motility or underlying inflammatory condition. Notably, many patients with the latter conditions may still experience esophageal symptoms beyond what could be attributed to their underlying disorders. Esophageal visceral hypersensitivity and hypervigilance are the two pathways which drive functional esophageal disorders and symptoms. These functional esophageal symptoms may be severe, leaving patients with impaired quality of life and inadequate treatment outcomes. Neuromodulators are the foundation of the pharmacologic approach of many of the functional esophageal disorders and symptoms, modulating both peripheral and central hyperalgesia. There is also emerging evidence for brain‐gut behavioral therapies (BGBT) such as gut‐directed hypnotherapy and cognitive behavior therapy for the treatment of a variety of DGBIs. In this issue of Neurogastroenterology and Motility, Hurtte et al. add to the literature on the effectiveness of BGBT in treating functional esophageal symptoms, showing multimodal therapy with pharmacologic and non‐pharmacologic approaches led to improvement in health‐related quality of life. In this review, we outline the mechanistic underpinnings of BGBT and review the existing evidence for BGBT for functional esophageal disorders and symptoms. We also highlight the future research directions and challenges for scaling these therapies.
{"title":"The Clinical value of brain‐gut behavioral therapies for functional esophageal disorders and symptoms","authors":"Yuying Luo, L. Keefer","doi":"10.1111/nmo.14373","DOIUrl":"https://doi.org/10.1111/nmo.14373","url":null,"abstract":"Functional esophageal disorders (functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia) are the disorders of gut‐brain interactions (DGBI) and present with esophageal symptoms not associated with a structural, major motility or underlying inflammatory condition. Notably, many patients with the latter conditions may still experience esophageal symptoms beyond what could be attributed to their underlying disorders. Esophageal visceral hypersensitivity and hypervigilance are the two pathways which drive functional esophageal disorders and symptoms. These functional esophageal symptoms may be severe, leaving patients with impaired quality of life and inadequate treatment outcomes. Neuromodulators are the foundation of the pharmacologic approach of many of the functional esophageal disorders and symptoms, modulating both peripheral and central hyperalgesia. There is also emerging evidence for brain‐gut behavioral therapies (BGBT) such as gut‐directed hypnotherapy and cognitive behavior therapy for the treatment of a variety of DGBIs. In this issue of Neurogastroenterology and Motility, Hurtte et al. add to the literature on the effectiveness of BGBT in treating functional esophageal symptoms, showing multimodal therapy with pharmacologic and non‐pharmacologic approaches led to improvement in health‐related quality of life. In this review, we outline the mechanistic underpinnings of BGBT and review the existing evidence for BGBT for functional esophageal disorders and symptoms. We also highlight the future research directions and challenges for scaling these therapies.","PeriodicalId":19104,"journal":{"name":"Neurogastroenterology & Motility","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89643969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. Carbone, A. Vandenberghe, L. Holvoet, H. Piessevaux, J. Arts, P. Caenepeel, D. Staessen, P. Vergauwe, P. Maldague, T. De Ronde, F. Wuestenberghs, V. Lamy, V. Lefebvre, P. Latour, T. Vanuytsel, Michael Jones, J. Tack
Itopride, a mixed D2 antagonist and cholinesterase inhibitor, has prokinetic effects on gastric motility. The Leuven Postprandial Distress Scale is a validated patient‐reported outcome instrument for functional dyspepsia (FD) postprandial distress syndrome (PDS). We aimed to use the LPDS to assess treatment outcome in PDS and PDS/EPS (epigastric pain syndrome).
{"title":"A double‐blind randomized, multicenter, placebo‐controlled study of itopride in functional dyspepsia postprandial distress syndrome","authors":"F. Carbone, A. Vandenberghe, L. Holvoet, H. Piessevaux, J. Arts, P. Caenepeel, D. Staessen, P. Vergauwe, P. Maldague, T. De Ronde, F. Wuestenberghs, V. Lamy, V. Lefebvre, P. Latour, T. Vanuytsel, Michael Jones, J. Tack","doi":"10.1111/nmo.14337","DOIUrl":"https://doi.org/10.1111/nmo.14337","url":null,"abstract":"Itopride, a mixed D2 antagonist and cholinesterase inhibitor, has prokinetic effects on gastric motility. The Leuven Postprandial Distress Scale is a validated patient‐reported outcome instrument for functional dyspepsia (FD) postprandial distress syndrome (PDS). We aimed to use the LPDS to assess treatment outcome in PDS and PDS/EPS (epigastric pain syndrome).","PeriodicalId":19104,"journal":{"name":"Neurogastroenterology & Motility","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87095794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ting-ting Xu, Li Li, Lin Geng, Bingduo Zhou, Shengliang Zhu
Mental stress is an important risk factor for gastroesophageal reflux disease (GERD), which interacts with acid reflux and affects the efficacy of single acid suppression treatment. However, the specific mechanism remains elusive, and there is a lack of available models for further support.
{"title":"Peripheral and central pathophysiological changes in a new rat model of acid reflux combined with mental stress","authors":"Ting-ting Xu, Li Li, Lin Geng, Bingduo Zhou, Shengliang Zhu","doi":"10.1111/nmo.14360","DOIUrl":"https://doi.org/10.1111/nmo.14360","url":null,"abstract":"Mental stress is an important risk factor for gastroesophageal reflux disease (GERD), which interacts with acid reflux and affects the efficacy of single acid suppression treatment. However, the specific mechanism remains elusive, and there is a lack of available models for further support.","PeriodicalId":19104,"journal":{"name":"Neurogastroenterology & Motility","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81801884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Afrin N. Kamal, G. Triadafilopoulos, C. Gyawali, L. Nguyen, G. Sayuk, D. Azagury, R. Tatum, J. Clarke
{"title":"Model for multi‐disciplinary, multi‐institutional virtual learning: The Stanford Esophageal Virtual Collaborative Conference on benign esophageal diseases","authors":"Afrin N. Kamal, G. Triadafilopoulos, C. Gyawali, L. Nguyen, G. Sayuk, D. Azagury, R. Tatum, J. Clarke","doi":"10.1111/nmo.14369","DOIUrl":"https://doi.org/10.1111/nmo.14369","url":null,"abstract":"","PeriodicalId":19104,"journal":{"name":"Neurogastroenterology & Motility","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85683249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael P. Jones, Ayesha Shah, M. Walker, N. Koloski, G. Holtmann, N. Talley
Co‐occurring (overlapping) irritable bowel syndrome (IBS), functional dyspepsia (FD), and heartburn has been observed. However, whether it is a distinct entity has not been established, nor what clinical, demographic, lifestyle, and psychological traits are associated with it. This study sought to estimate the prevalence and temporal stability of this overlap and to identify features specific to it in order to gain some insights into the potential etiopathogenesis.
{"title":"Overlap of heartburn, functional dyspepsia, and irritable bowel syndrome in a population sample: Prevalence, temporal stability, and associated comorbidities","authors":"Michael P. Jones, Ayesha Shah, M. Walker, N. Koloski, G. Holtmann, N. Talley","doi":"10.1111/nmo.14349","DOIUrl":"https://doi.org/10.1111/nmo.14349","url":null,"abstract":"Co‐occurring (overlapping) irritable bowel syndrome (IBS), functional dyspepsia (FD), and heartburn has been observed. However, whether it is a distinct entity has not been established, nor what clinical, demographic, lifestyle, and psychological traits are associated with it. This study sought to estimate the prevalence and temporal stability of this overlap and to identify features specific to it in order to gain some insights into the potential etiopathogenesis.","PeriodicalId":19104,"journal":{"name":"Neurogastroenterology & Motility","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74976823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}