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New techniques in the tissue diagnosis of gastrointestinal neuromuscular diseases

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World Journal of Gastroenterology 2009年第2期15卷 192-197页

作者： Charles H Knowles Joanne E Martin neurogastroenterology Group Centres for Academic Surgery and Pathology Institute of Cellular and Molecular Science Barts and the London Queen Mary's School of Medicine and Dentistry Whitechapel London United Kingdom

Gastrointestinal neuromuscular diseases are a clinically heterogeneous group of disorders of children and adults in which symptoms are presumed or proven to arise as a result of neuromuscular (including interstitial cell of Cajal) dysfunction. Common to most of these diseases are symptoms of impaired motor activity which manifest as slowed or obstructed transit with or without evidence of transient or persistent radiological visceral dilatation. A variety of histopathological techniques and allied investigations are being increasingly applied to tissue biopsies from such patients. This review outlines some of the more recent advances in this fi eld, particularly in the most contentious area of small bowel disease manifesting as intestinal pseudo-obstruction.

关键词：肠疾病肠神经疾病间隙细胞内脏疼痛

Intestinal epithelium, intraepithelial lymphocytes and the gut microbiota-Key players in the pathogenesis of celiac disease

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World Journal of Gastroenterology 2017年第42期23卷 7505-7518页

作者： Bozena Cukrowska Agnieszka Sowińska Joanna Beata Bierla Elzbieta Czarnowska Anna Rybak Urszula Grzybowska-Chlebowczyk Department of Pathology The Children's Memorial Health Institute Department of Gastroenterology Division of Neurogastroenterology and MotilityGreat Ormond Street Hospital Department of Pediatrics School of MedicineMedical University of Silesia

Celiac disease(CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Before activating the immune system, gluten peptides are transferred by the epithelial barrier to the mucosal lamina propria, where they are deamidated by intestinal tissue transglutaminase 2. As a result, they strongly bind to human leucocyte antigens(HLAs), especially HLA-DQ2 and HLA-DQ8, expressed on antigen-presenting cells. This induces an inflammatory response, which results in small bowel enteropathy. Although gluten is the main external trigger activating both innate and adaptive(specific) immunity, its presence in the intestinal lumen does not fully explain CD pathogenesis. It has been hypothesized that an early disruption of the gut barrier in genetically susceptible individuals, which would result in an increased intestinal permeability, could precede the onset of gluten-induced immune events. The intestinal barrier is a complex functional structure, whose functioning is dependent on intestinal microbiotahomeostasis, epithelial layer integrity, and the gutassociated lymphoid tissue with its intraepithelial lymphocytes(IELs). The aim of this paper was to review the current literature and summarize the role of the gut microbiota, epithelial cells and their intercellular junctions, and IELs in CD development.

关键词： Celiac disease Intestinal microbiota Epithelium Intraepithelial lymphocytes Intestinal barrier

Non-alcoholic fatty liver disease in irritable bowel syndrome:More than a coincidence?

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World Journal of Hepatology 2021年第12期13卷 1816-1827页

作者： Huw Purssell Peter J Whorwell Varinder S Athwal Dipesh H Vasant Hepatology Manchester University NHS Foundation TrustManchester M239LTUnited Kingdom Division of Diabetes Endocrinology and GastroenterologyUniversity of ManchesterManchester M239LTUnited Kingdom neurogastroenterology unit Wythenshawe HospitalManchester University NHS Foundation TrustManchester M239LTUnited Kingdom neurogastroenterology unit Department of GastroenterologyManchester University NHS Foundation TrustWythenshawe HospitalManchester M239LTUnited Kingdom

Irritable bowel syndrome(IBS)and non-alcoholic fatty liver disease(NAFLD)are amongst the most common gastrointestinal and liver conditions encountered in primary and secondary ***,there has been interest in the apparent coincidence of NAFLD in patients with IBS mainly driven by improved understanding of their shared risk factors and *** this paper we summarize the shared risk factors which include;overlapping nutritional and dietary factors as well as shared putative mechanisms of *** include changes in the gut microbiome,gut permeability,immunity,small bowel bacterial overgrowth and bile acid *** paper describes how these shared risk factors and etiological factors may have practical clinical implications for these highly prevalent *** also highlights some of the limitations of current epidemiological data relating to estimates of the overlapping prevalence of the two conditions which have resulted in inconsistent results and,therefore the need for further *** recognition and management of the overlap could potentially have impacts on treatment outcomes,compliance and morbidity of both *** with known IBS who have abnormal liver function tests or significant risk factors for NAFLD should be investigated appropriately for this ***,IBS should be considered in patients with NAFLD and symptoms of abdominal pain associated with defecation,an altered bowel habit and bloating.

关键词： Irritable bowel syndrome Non-alcoholic fatty liver disease Metabolic syndrome Obesity Prevalence Pathophysiology

Fecal microbiota transplantation for irritable bowel syndrome:An intervention for the 21st century

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World Journal of Gastroenterology 2021年第22期27卷 2921-2943页

作者： Magdy El-Salhy Tanisa Patcharatrakul Sutep Gonlachanvit Department of Medicine Stord Helse Fonna Hospital and University of BergenStord 5416Norway Department of Medicine King Chulalongkorn Memorial Hospital and Center of Excellence in Neurogastroenterology and MotilityChulalongkorn UniversityBangkok 10330Thailand

Irritable bowel syndrome(IBS)affects about 12%of the global *** IBS does not develop into a serious disease or increase mortality,it results in a considerable reduction in the quality of *** etiology of IBS is not known,but the intestinal microbiota appears to play a pivotal role in its *** is no effective treatment for IBS,and so the applied treatments clinically focus on symptom *** microbiota transplantation(FMT),an old Chinese treatment,has been applied to IBS patients in seven randomized controlled trials(RCTs).Positive effects on IBS symptoms in various degrees were obtained in four of these RCTs,while there was no effect in the remaining *** the seven RCTs there were marked differences in the selection processes for the donor and treated patients,the transplant dose,the route of administration,and the methods used to measure how the patients responded to *** present frontier discusses these differences and proposes:(1)criteria for selecting an effective donor(superdonor);(2)selection criteria for patients that are suitable for FMT;(3)the optimal FMT dose;and(4)the route of transplant *** appears to be safe,with only mild,self-limiting side effects of abdominal pain,cramping,tenderness,diarrhea,and *** it is early to speculate about the mechanisms underlying the effects of FMT,the available data suggest that changes in the intestinal bacteria accompanied by changes in fermentation patterns and fermentation products(specifically short-chain fatty acids)play an important role in improving the IBS symptoms seen after *** appears to be a promising treatment for IBS,but further studies are needed before it can be applied in everyday clinical practice.

关键词： Butyric acid Enteroendocrine cells Etiology Microbiota Short-chain fatty acids Superdonor Therapy

New technologies to investigate the brain-gut axis

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World Journal of Gastroenterology 2009年第2期15卷 182-191页

作者： Abhishek Sharma Dina Lelic Christina Brock Peter Paine Qasim Aziz Department of Gastrointestinal Science University of Manchester Manchester M13 9PL United Kingdom Neurogastro-enterology Group Wingate Institute of Neurogastroenterology Barts and the London School of Medicine and Dentistry London E1 2AJ United Kingdom Mech-Sense Department of Gastroenterology Aalborg Hospital Boulevarden 13 DK-9000 Aalborg Denmark

Functional gastrointestinal disorders are commonly encountered in clinical practice, and pain is their commonest presenting symptom. In addition, patients with these disorders often demonstrate a heightened sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity that is likely to be important in their pathophysiology. Knowledge of how the brain processes sensory information from visceral structures is still in its infancy. However, our understanding has been propelled by technological imaging advances such as functional Magnetic Resonance Imaging, Positron Emission To-mography, Magnetoencephalography, and Electroen-cephalography (EEG). Numerous human studies have non-invasively demonstrated the complexity involved in functional pain processing, and highlighted a number of subcortical and cortical regions involved. This review will focus on the neurophysiological pathways (primary afferents, spinal and supraspinal transmission), brain- imaging techniques and the influence of endogenous and psychological processes in healthy controls and patients suffering from functional gastrointestinal dis- orders. Special attention will be paid to the newer EEG source analysis techniques. Understanding the pheno- typic differences that determine an individual's response to injurious stimuli could be the key to understanding why some patients develop pain and hyperalgesia in response to inflammation/injury while others do not. For future studies, an integrated approach is required incorporating an individual's psychological, autonomic, neuroendocrine, neurophysiological, and genetic prof ile to def ine phenotypic traits that may be at greater risk of developing sensitised states in response to gut in? am- mation or injury.

关键词：胃肠无序脑中枢神经系统神经生理学

Brain changes in diabetes mellitus patients withgastrointestinal symptoms

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World Journal of Diabetes 2016年第2期7卷 14-26页

作者： Anne M Drewes Eirik Søfteland Georg Dimcevski Adam D Farmer Christina Brock Jens B Frøkjær Klaus Krogh Asbjørn M Drewes Department of Medicine Haukeland University Hospital5021 BergenNorway Centre for Digestive Diseases Blizard Institute of Cell and Molecular ScienceWingate Institute of NeurogastroenterologyBarts and the London School of Medicine and DentistryQueen Mary University of LondonLondon E1 2AJUnited Kingdom Department of Gastroenterology University Hospitals of North MidlandsStoke on TrentStraffordshire ST4 6QGUnited Kingdom Mech-Sense Department of Gastroenterology and Hepatology and Clinical InstituteAalborg University Hospital9100 AalborgDenmark Department of Radiology Aalborg University Hospital9100 AalborgDenmark neurogastroenterology unit Department of Hepatology and GastroenterologyAarhus University Hospital8000 AarhusDenmark

Diabetes mellitus is a common disease and its prevalence is increasing worldwide. In various studies up to 30%-70% of patients present dysfunction and complications related to the gut. To date several clinical studies have demonstrated that autonomic nervous system neuropathy and generalized neuropathy of the central nervous system(CNS) may play a major role. This systematic review provides an overview of the neurodegenerative changes that occur as a consequence of diabetes with a focus on the CNS changes and gastrointestinal(GI) dysfunction. Animal models where diabetes was induced experimentally support that the disease induces changes in CNS. Recent investigations with electroencephalography and functional brain imaging in patients with diabetes confirm these structural and functional brain changes. Encephalographic studies demonstrated that altered insular processing of sensory stimuli seems to be a key player in symptom generation. In fact one study indicated that the more GI symptoms the patients experienced, the deeper the insular electrical source was located. The electroencephalography was often used in combination with quantitative sensory testingmainly showing hyposensitivity to stimulation of GI organs. Imaging studies on patients with diabetes and GI symptoms mainly showed microstructural changes,especially in brain areas involved in visceral sensory processing. As the electrophysiological and imaging changes were associated with GI and autonomic symptoms they may represent a future therapeutic target for treating diabetics either pharmacologically or with neuromodulation.

关键词： Diabetes mellitus Gastrointestinal Electroencephalogram Magnetic resonance imaging Brain

以便秘和腹泻为主的肠易激综合征与5-羟色胺信号改变

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世界核心医学期刊文摘（胃肠病学分册） 2006年第6期2卷 32-33页

作者： Atkinson W. Lockhart S. Whorwell P. J. L.A. Houghton. 李宏宇(译) 郑世成(校) 不详 neurogastroenterology unit Academic Division of Medicine and Surgery Wythenshawe Hospital F Block Southmoor Road WythenshaweManchester M23 9LT United Kingdom

Background &Aims: Evidence suggests that postprandial platelet-depleted plasma 5-hydroxytryptamine (5-HT) concentrations may be abnormal in irritable bowel syndrome (IBS). However, interpretation of the data has been hampered by the variable methodology and rather small numbers used in previous studies. Therefore, the aim of this study was to measure concentrations of platelet-depleted plasma 5-HT and its metabolite 5-HIAA under fasting and fed conditions in a large group of patients with diarrhea-predominant (d-) and constipation-predominant (c-) IBS, compared with controls. The ratio of plasma 5-HIAA:5-HT and platelet stores was also assessed. Methods: Twenty-nine c-IBS patients (aged, 19-53 years), 55 d-IBS patients (aged, 19-52 years), and 35 healthy volunteers (aged, 18-46 years) had platelet-depleted plasma 5-HT/5-HIAA concentrations measured using reverse-phase, high-performance liquid chromatography with fluorimetric detection before and after a standard meal. Results: d-IBS patients had raised platelet-depleted plasma 5-HT concentrations under fasting and fed conditions (P < .05). However, the postprandial relative to fasting concentration was similar to controls. In contrast, c-IBS patients failed to show an increase in platelet-depleted plasma 5-HT concentration with meal ingestion compared with controls (P < .01). c-IBS was associated with decreased 5-HIAA (P < .01) but normal 5-HIAA:5-HT ratio and d-IBS with normal 5-HIAA concentrations but reduced 5-HIAA:5-HT ratio (P < .005). c-IBS but not d-IBS patients had increased platelet 5-HT. Conclusions: These results support the concept that d-IBS is characterized by reduced 5-HT reuptake, whereas impaired release may be a feature of c-IBS. These results also provide a rational basis for current pharmacologic approaches involving modulation of different 5-HT receptors in c-and d-IBS.

关键词：肠易激综合征(IBS) 腹泻型IBS 5-羟色胺便秘型信号改变反相高效液相色谱法血小板血浆 IBS患者 5-羟吲哚乙酸

EndoFLIP技术在胃食管反流病中的应用进展

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中华胃食管反流病电子杂志 2016年第1期3卷 31-33页

作者：郭洁时昭红陈建德武汉市第一医院消化内科 430022 Johns Hopkins Center for neurogastroenterology Division of Gastroenterology and Hepatology

内镜下功能性腔道成像探针（Endolumenal Functional Lumen Imaging Probe,Endo FLIP）技术是一种是可测量人体内各种空腔器官、组织及腔道括约肌功能状态的革新性技术。其主要工作原理[1]是通过内镜技术将一个可以充入导电液体的袋状... 详细信息

内镜下功能性腔道成像探针（Endolumenal Functional Lumen Imaging Probe,Endo FLIP）技术是一种是可测量人体内各种空腔器官、组织及腔道括约肌功能状态的革新性技术。其主要工作原理[1]是通过内镜技术将一个可以充入导电液体的袋状电极置于所需要评估其功能状态的器官或组织处,袋内的16个阻抗测量电极会自动测量其所在位置的截面积,袋内的压力感受器会同时测量压力。

关键词： EndoFLIP 胃食管反流导电液体空腔器官括约肌功能测量压力革新性组织处需要评估自动测量

Caecal pH is a biomarker of excessive colonic fermentation

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World Journal of Gastroenterology 2014年第17期20卷 5000-5007页

作者： Adam D Farmer Sahar D Mohammed George E Dukes S Mark Scott Anthony R Hobson Centre for Digestive Diseases Blizard Institute of Cell and Molecular ScienceWingate Institute of NeurogastroenterologyBarts and the London School of Medicine and DentistryQueen Mary University of LondonLondon E1 2AJUnited Kingdom GlaxoSmithKline Research and Development Durham County NC 27709-3398United States Functional Gut Clinic London W1G 6NBUnited Kingdom

AIM:To ascertain whether caecal pH is different in patients with irritable bowel syndrome(IBS),whose primary symptoms are bloating and distension,to healthy ***:Motility and pH data were reviewed from16 patients with RomeⅢdefined IBS and 16 healthy controls,who had undergone a wireless motility capsule(WMC)study using a standardized *** measures were anchored around known anatomical landmarks as identified by compartmental pH ***-minute epochs were used to quantify antral,duodenal,ileal,caecal and distal colonic *** maximum and minimum pH was measured either side of the ileo-caecal ***:No differences were seen in motility parameters,compartmental transit times or maximal ileal pH between the two *** pH was significantly lower in patients compared to controls(5.12±0.05vs 6.16±0.15,P<0.0001).The ileal:caecalΔchange was greater in patients than controls(-2.63±0.08 vs-1.42±0.11,P<0.0001).There was a significant correlation between caecal pH and right colonic contractility(r=0.54,P=0.002).CONCLUSION:Patients with bloating and distension have a lower caecal pH compared to *** measurement of caecal pH using the WMC provides a quantifiable biomarker of fermentation potentially identifying those patients that may preferentially benefit from antibiotic or dietary interventions.

关键词： Caecal pH Caecoparesis Bloating Colonic microbiota