5-羟色胺信号系统在炎症性肠病发病机制中的地位

炎症性肠病(IBD)患者较易出现功能性肠道症状,这些症状往往与肠道活动性炎症关系不大,却与肠功能紊乱有关,说明IBD的发病在某些方面与肠易激综合征(IBS)相似。5-羟色胺(5-HT)信号系统异常可致胃肠动力、分泌功能异常和内脏高敏感性,与多种功能性胃肠病密切相关。而IBD的发病机制中亦存在功能性因素,提示IBD与IBS可能存在某些分子水平的联系,有必要对5-HT信号系统在IBD发病机制中的作用进行研究。     

Neuroimmune mechanisms in functional bowel disorders

The enteric nervous system regulates diverse functions including gastrointestinal motility and nociception. The sensory neurons detect mechanical and chemical stimuli while motor neurons control peristalsis and secretion. In addition to this extensive neuronal network, the gut also houses a highly specialised immune system which plays an important role in the induction and maintenance of tolerance to food and other luminal antigens and in the protection of the epithelial barrier against pathogenic invasion. It is now increasingly recognised that the gastrointestinal immune system and the enteric nervous system closely interact. This review will focus on two common functional gastrointestinal disorders in which neuroimmune interaction is involved in the pathophysiology: i.e. postoperative ileus and irritable bowel syndrome. Postoperative ileus arises after almost every abdominal surgical procedure. Handling of the bowel results in local inflammation and activation of inhibitory neuronal pathways resulting in a generalised impairment of gastrointestinal motor function or ileus. On the other hand, postinfectious irritable bowel syndrome (PI-IBS) occurs in 10 to 30% of patients who suffer from infectious gastroenteritis. PI -IBS patients develop abnormal gastrointestinal sensitivity, motility and secretion which contribute to abdominal pain and discomfort, bloating and abnormal bowel function (diarrhoea and/or constipation). Biopsy studies revealed persistent low-grade inflammation and altered immunological function which may lead to abnormal pain perception and motor activity within the gastrointestinal tract.     

Symptom overlap and comorbidity of irritable bowel syndrome with other conditions

Irritable bowel syndrome (IBS) is one of several highly prevalent, multi-symptom gastrointestinal motility disorders that have a wide clinical spectrum and are associated with symptoms of gastrointestinal dysmotility and visceral hypersensitivity. Symptom overlap and comorbidity between IBS and other gastrointestinal motility disorders (eg, chronic constipation, functional dyspepsia, gastroesophageal reflux disease), with gastrointestinal disorders that are not related to motility (eg, celiac disease, lactose intolerance), and with somatic conditions (eg, fibromyalgia, chronic fatigue syndrome), are frequent. The clinical associations and pathophysiologic links between IBS and these disorders continue to be explored. This review discusses overlapping symptoms and comorbidity of IBS with select gastrointestinal and non-gastrointestinal disorders and attempts to identify commonalities among these conditions.     

Clinical use of manometry for the diagnosis of intestinal motor abnormalities

Digestive symptoms suggestive of intestinal motor disorders, such as abdominal pain and distension, fullness, vomiting, constipation and diarrhoea, are very common and non-specific, and may be clinical manifestations of both organic and functional diseases. Both radiology and endoscopy are important in the diagnosis of structural gastrointestinal lesions that can affect motility and offer indirect signs of impaired gastrointestinal functions, but the diagnosis of gut motility disorders currently relies on the manometric assessment of contractile activities. Small bowel manometry helps to identify normal motility features and consequently to identify abnormal motor patterns. Small bowel manometry can help to differentiate mechanical obstruction from pseudo-obstruction and neurogenic from myogenic motor disorders. Manometry is an invasive technique which is not well accepted by patients and requires specific skills from investigators. Also, manometric assessment is limited to referral centres with a specific interest in the field of digestive functions, in general, and motility, in particular. Only patients who remain undiagnosed after extensive traditional work-up and fail repeated courses with medical therapy should be referred for the manometric test. Understanding the underlying pathophysiologic mechanisms of abnormal motility and developing new therapies are the goals of the current research in this fascinating field of medicine.     

The pathophysiology of irritable bowel syndrome: inflammation and motor disorder]

Irritable bowel syndrome (IBS) is one of the most common disorders and a heterogeneous condition in view of symptoms and underlying mechanisms. Though underlying causes of pathophysiologic changes remain unclear, low grade mucosal inflammation and abnormal intestinal motility are accepted mechanisms which alter gut function and generate symptoms of IBS. First, before 1980s, abnormal colonic and rectal motor functions were regarded as the main pathophysiology of IBS, but only 25-75% of IBS patients have apparent motor abnormalities which differ from the motor functions in normal controls. So, various gastrointestinal motility tests were not indicated for the diagnosis of IBS. The high-amplitude propagating contractions of colon in IBS patients may be related to the visceral pain perception. Second, the low grade mucosal inflammation may be involved in the pathophysiology of visceral hypersensitivity. Post infectious IBS (PI-IBS) occupied 6-17% of the total IBS and some previous prospective studies reported that 7-33% of acute bacterial enteritis patients developed IBS after 6-12 months of infection. The relative risk of IBS in the gastroenteritis cohort was 11.9 and the strongest risk factor is the duration of diarrhea. After enteritis event, the increased number of immunocytes, mast cells and large amount of lymphocytes infiltration were revealed in mucosa and enteric nervous system of the gut. Beside the inflammatory cells, enterochromaffin cells, cytokines and inducible nitric oxide may be related to the pathophysiologic mechanism of PI-IBS. Lastly, the abnormalities in the gastrointestinal autonomic nervous system can induce constipation or motor disorders, but further research should elucidate it.     

Microbial-gut interactions in health and disease. Irritable bowel syndrome

The intestinal microbiota interacts with several aspects of gastrointestinal function that may affect the expression or progression of disease. For example, a role for bacterial metabolism of bile acids and food has been linked to colorectal cancer development. Studies have also shown a potential role of the intestinal microbiota in the modulation of inflammation in the intestine and joints. Normal gut physiology is molded by the interaction between the intestinal microbiota and the host's gastrointestinal tissues, including motility, absorption and secretion, and intestinal permeability. Early studies in axenic mice demonstrated gross morphological abnormalities and gut motor dysfunction related to the absence of a normal microflora, raising the possibility that shifts in commensal bacterial populations could play a role in the development of altered motility states including functional disorders of the gut. This chapter concentrates on the experimental evidence for a role of intestinal microbiota and the potential therapeutic value of probiotics in functional diseases such as irritable bowel syndrome.     

Physical activity and the gastrointestinal tract

Physical exercise is probably both beneficial and harmful for the gastrointestinal tract, depending partly on the training intensity. On the one hand, gastrointestinal symptoms such as heartburn, chest pain, nausea, vomiting, abdominal cramps, side ache and diarrhoea are common during heavy exercise. On the other hand, physical activity seems to protect from colon cancer, cholelithiasis and diverticular disease. Constipation has been shown to be related to inactivity. Despite this, no overwhelming evidence exists for a positive effect of physical exercise as a treatment option for chronic constipation. The reasons behind these somewhat discrepant effects are not understood fully. Altered gastrointestinal blood flow, effects on gastrointestinal motor function, neuroendocrine changes and mechanical effects are probably involved. Conflicting results exist regarding the effects of physical activity on gastrointestinal motility. Modern technologies now make motility studies in various parts of the gastrointestinal tract possible. More studies are needed to understand better the effects of physical exercise on the gastrointestinal tract. In particular, the relationship between the training intensity and duration and positive and negative alterations in gastrointestinal physiology needs to be addressed further.     

What do patients with irritable bowel syndrome dream about? A comparison with inflammatory bowel disease

BACKGROUND: It is a common experience for people to dream of events about which they are either anxious or concerned. We therefore hypothesised that the dreams of patients with irritable bowel syndrome may reflect their worries about their problem especially as hospital out-patients with this disorder tend to exhibit some anxiety. In addition, dreaming about, for instance bowels, in patients with irritable bowel syndrome in excess of that observed in other gastrointestinal disorders may be of importance. AIM: To establish whether patients with irritable bowel syndrome dream about bowel-related issues more than controls or patients with inflammatory bowel disease. PATIENTS AND METHODS: A total of 57 patients with irritable bowel syndrome and 57 patients with inflammatory bowel disease were compared with 60 healthy controls. All subjects completed a structured questionnaire concerning sleeping habits and dream characteristics as well as an assessment of anxiety and depression. RESULTS: There were no differences in the sleeping habits between any of the groups. However, significantly more patients with irritable bowel syndrome and inflammatory bowel disease dreamt about their bowels (22% inflammatory bowel disease patients, 18% irritable bowel syndrome patients vs 3% of controls, p < 0.05 inflammatory bowel disease and irritable bowel syndrome vs controls) and soiling themselves (16% of inflammatory bowel disease patients, 14% of irritable bowel syndrome patients vs 2% of controls; p < 0.05 inflammatory bowel disease and irritable bowel syndrome vs controls) than controls. CONCLUSION: Chronic gastrointestinal disorders, of both a functional and organic nature, may influence the nature of dreams. In those patients who dream about their symptoms, it would be interesting to know whether this affects the course of their disease, either positively or negatively, in any way.     

肠易激综合征重叠症的研究进展

肠易激综合征(IBS)是一种常见的以反复发作的腹痛或腹部不适伴排便频率或粪便性状改变为特征的功能性肠病,可单独发生,亦可与其他疾病并存。IBS除可与胃肠道疾病如胃食管反流病(GERD)、功能性消化不良(FD)、炎症性肠病(IBD)、显微镜肠炎(MC)、乳糜泻等重叠外,还可与非胃肠道疾病如焦虑症、哮喘等重叠。本文从流行病学和病理生理学角度对IBS重叠症作一综述。     

Neuropathy in the brain-in-the-gut

* The enteric nervous system has sensory neurons, interneurons and motor neurons and functions as a brain-in-the-gut. * Smooth muscles of the digestive tract are autogenic in the absence of neural control. * Enteric inhibitory motor neurons control excitability of the autogenic musculature. * The neuropathic form of chronic intestinal pseudo-obstruction is a form of disinhibitory motor disease linked with neuropathic degeneration in the enteric nervous system. * Patients with inflammatory degenerative neuropathy may progress from irritable bowel syndrome (IBS)-like symptoms to chronic pseudo-obstruction. * Detection of anti-enteric neuronal antibodies may be a useful diagnostic test for early stages of inflammatory degenerative neuropathy in patients with symptoms of a functional gastrointestinal disorder. Awareness is increasing that autoimmune attack targeted to neuronal elements of the enteric nervous system may underlie irritable bowel-like symptoms that progress to chronic pseudo-obstruction. The inflammatory neuropathy disrupts the integrative functions of the brain-in-the-gut, including reduction in the population of inhibitory motor neurons to the musculature. Extreme loss of inhibitory motor neurons is manifest as disinhibitory motor disease characterized by achalasia in smooth muscle sphincters and hyperactive, disorganized contractile behaviour of intestinal circular muscle which results in pseudo-obstruction. Detection of anti-enteric neuronal antibodies in the serum of patients with early symptoms of a functional gastrointestinal motility disorder may prove to be a useful diagnostic test for inflammatory enteric neuropathy.     

Fecal calprotectin use in inflammatory bowel disease and beyond: A mini-review

Given the number of inflammatory disorders affecting the gastrointestinal tract directly and indirectly, coupled with the considerable overlap with functional disorders, it is evident that more useful noninvasive diagnostic tests are required to aid with diagnosis. If these tests can also have some utility for individual patient follow-up in terms of disease activity and response to treatment, as well as providing forewarning of disease relapse, it would be extremely useful information for the clinician. One recently described test that may fulfill several of these attributes is based on leakage of a mononuclear cell cytoplasmic protein, calprotectin, along the intestinal tract, which can then be quantified in feces. This has been used to distinguish patients exhibiting symptoms of irritable bowel syndrome from patients with inflammatory bowel disease, with a measure of success greater than with currently used techniques. The present article summarizes the experience with this test used in inflammatory bowel disease, as well as a variety of gastrointestinal disorders.     

Inflammatory bowel disease imaging: current practice and future directions

The purpose of this paper is to evaluate the role of imaging in inflammatory bowel disease(IBD), including detection of extraluminal complications and extraintestinal manifestations of IBD, assessment of disease activity and treatment response, and discrimination of inflammatory from fibrotic strictures. IBD is a chronic idiopathic disease affecting the gastrointestinal tract that is comprised of two separate, but related intestinal disorders; Crohn's disease and ulcerative colitis. The paper discusses, in detail the pros and cons of the different IBD imaging modalities that need to be considered in order to optimize the imaging and clinical evaluation of patients with IBD. Historically, IBD evaluation of the bowel has included imaging to assess the portions of the small bowel that are inaccessible to optical endoscopic visualization. This traditionally was performed using barium fluoroscopic techniques; however, cross-sectional imaging techniques(computed tomography and magnetic resonance imaging) are being increasingly utilized for IBD evaluation because they can simultaneously assess mural and extramural IBD manifestations. Recent advances in imaging technology, that continue to improve the ability of imaging to noninvasively follow disease activity and treatment response, are also discussed. This review article summarizes the current imaging approach in inflammatory bowel disease as well as the role of emerging imaging modalities.     

Gastrointestinal motility and the brain‐gut axis

The role of the brain‐gut axis in gastrointestinal motility is discussed according to the specific organs of the gastrointestinal tract. Not only clinical studies but basic animal research are reviewed. Although the mechanism of functional gut disorders remains to be clarified, recent data suggest that there is evidence that the brain‐gut axis has significant effects on gastrointestinal motility. The major role of endoscopy in the diagnosis of functional gastrointestinal disorders is to exclude organic gastrointestinal disorders. In the esophagus, the lower esophageal sphincter and a gamma‐aminobutyric acid B mechanism are considered to play important roles in gastroesophageal reflux disease. In the stomach, corticotropin‐releasing factor, neuropeptide Y and other substances might be involved in the pathogenesis of non‐ulcer dyspepsia. In the small intestine, corticotropin‐releasing factor, gamma‐aminobutyric acid B and other substances are considered to modulate intestinal transit via central mechanisms. In the colon, it is known that psychiatric factors are related to the onset and clinical course of irritable bowel syndrome. Serotonin, corticotropin‐releasing factor, gamma‐aminobutyric acid, orphanin FQ and neuropeptide Y have been reported as putative neurotransmitters. More efforts in basic science studies and animal and human studies of physiology of the gastointestinal tract are still required. These efforts will elucidate further mechanisms to clarify the etiology of motility disorders and encourage the investigation of new therapies in this field.     

Applied principles of neurogastroenterology: physiology/motility sensation

Many of the symptoms prominent in the functional gastrointestinal disorders (FGIDs) are consistent with dysfunction of the sensory and/or motor apparatus of the digestive tract. Assessment of these phenomena in man can be undertaken by using a wide variety of invasive and noninvasive techniques, some well established and others requiring further validation. By using such techniques, alterations in both sensory and motor function have been reported in the FGIDs; various combinations of such dysfunction occur in different regions of the digestive tract in the FGIDs. Our understanding of the origins of this gut sensorimotor dysfunction is gradually increasing. Thus, inflammatory, immunologic, and other processes, as well as psychosocial factors such as stress, can alter the normal patterns of sensitivity and motility through alterations in local reflex activity or via altered neural processing along the brain-gut axis. In this context, a potential role of genetic factors, early-life influences, enteric flora, dietary components, and autonomic dysfunction also should be considered in the disease model. A firm relationship between sensorimotor dysfunction and the production of symptoms, however, has been difficult to show, and so the clinical relevance of the former requires continuing exploration. Based on the conceptual framework established to date, a number of recommendations for further progress can be made.     

Neurological disorders and inflammatory bowel diseases

Extraintestinal manifestations occur in about one-third of patients living with inflammatory bowel disease (IBD) and may precede the onset of gastrointestinal symptoms by many years. Neurologic disorders associated with IBD are not frequent, being reported in 3% of patients, but they often represent an important cause of morbidity and a relevant diagnostic issue. In addition, the increasing use of immunosuppressant and biological therapies for IBD may also play a pivotal role in the development of neurological disorders of different type and pathogenesis. Hence, we provide a complete and profound review of the main features of neurological complications associated with IBD, with particular reference to those related to drugs and with a specific focus on their clinical presentation and possible pathophysiological mechanisms.     

Intestinal epithelial barrier and neuromuscular compartment in health and disease

A number of digestive and extra-digestive disorders, including inflammatory bowel diseases, irritable bowel syndrome, intestinal infections, metabolic syndrome and neuropsychiatric disorders, share a set of clinical features at gastrointestinal level, such as infrequent bowel movements, abdominal distension, constipation and secretory dysfunctions. Several lines of evidence indicate that morphological and molecular changes in intestinal epithelial barrier and enteric neuromuscular compartment contribute to alterations of both bowel motor and secretory functions in digestive and extra-digestive diseases. The present review has been conceived to provide a comprehensive and critical overview of the available knowledge on the morphological and molecular changes occurring in intestinal epithelial barrier and enteric neuromuscular compartment in both digestive and extra-digestive diseases. In addition, our intent was to highlight whether these morphological and molecular alterations could represent a common path(or share some common features) driving the pathophysiology of bowel motor dysfunctions and related symptoms associated with digestive and extra-digestive disorders. This assessment might help to identify novel targets of potential usefulness to develop original pharmacological approaches for the therapeutic management of such disturbances.     

Structural brain lesions in inflammatory bowel disease

Central nervous system (CNS) complications or manifestations of inflammatory bowel disease deserve particular attention because symptomatic conditions can require early diagnosis and treatment, whereas unexplained manifestations might be linked with pathogenic mechanisms. This review focuses on both symptomatic and asymptomatic brain lesions detectable on imaging studies, as well as their frequency and potential mechanisms. A direct causal relationship between inflammatory bowel disease (IBD) and asymptomatic structural brain changes has not been demonstrated, but several possible explanations, including vasculitis, thromboembolism and malnutrition, have been proposed. IBD is associated with a tendency for thromboembolisms; therefore, cerebrovascular thromboembolism represents the most frequent and grave CNS complication. Vasculitis, demyelinating conditions and CNS infections are among the other CNS manifestations of the disease. Biological agents also represent a risk factor, particularly for demyelination. Identification of the nature and potential mechanisms of brain lesions detectable on imaging studies would shed further light on the disease process and could improve patient care through early diagnosis and treatment.     

Diagnostic value of faecal calprotectin in paediatric gastroenterology clinical practice

BACKGROUND: Faecal calprotectin (FC) is a new marker of intestinal inflammation. Data on FC in paediatric gastroenterology clinical practice are still scarce. AIMS: To assess FC values in different paediatric gastrointestinal diseases comparing them with those obtained in healthy children. PATIENTS: Two hundred and eighty-one children (age range 13-216 months) consecutively referred for gastrointestinal symptoms. Seventy-six healthy controls (age range 13-209 months). The exclusion criteria in healthy children were the following: any known underlying chronic disease or a history of abdominal pain, diarrhoea, acute respiratory tract infection, intake of non-steroidal anti-inflammatory drugs, gastric acidity inhibitors, antibiotics, drugs influencing gut motility, and menstrual or nasal bleeding in the last 3 weeks. METHODS: Stool samples stored, prepared and analyzed by an ELISA assay. RESULTS: In healthy children the median FC value was 28.0 microg/g (15-57 interquartile range) with a 95th percentile value of 95.3 microg/g. An increase in FC concentration was observed in all diseases characterized by gastrointestinal mucosa inflammation, and the active inflammatory bowel disease patients showed the higher FC values. All children affected by functional bowel disorders or by non-inflammatory diseases showed normal values. We calculated an optimized FC cut off value of 102.9266 microg/g (revealed by the receiver operating characteristic curve) to distinguish patients with active organic/inflammatory disorders from healthy subjects and from patients with functional bowel disorders. CONCLUSIONS: Calprotectin is a sensitive, but not disease specific, marker to easily detect inflammation throughout the whole gastrointestinal tract. It may help in identifying an organic disease characterized by intestinal mucosa inflammation and in the differential diagnosis of functional bowel disorders.     

Esophageal motility,heartburn, and gastroesophageal reflux: Variations in clinical presentation of esophageal dysphagia

Dysphagia is a potentially important symptom, often leading to the finding of an anatomical or motility disorder of the esophagus. Dysphagia and heartburn represent two of the most common symptoms associated with esophageal motility disorders. To explore the relationship of symptomatic esophageal dysphagia and heartburn and their association with primary esophageal motor disorders, we have performed a retrospective assessment of 1035 patient evaluations performed at our gastrointestinal laboratory. A clear statistical association of symptomatic dysphagia and heartburn was established; however, no pattern diagnostic of a specific motility disorder was discernible. A sizable fraction of our patient population with dysphagia demonstrated normal esophageal motility. A significant portion of dyspeptic patients exhibited both normal motility and acid exposure. The differences observed between the incidence of subjective symptoms and objective dysfunction may be explained in part by an altered or increased esophageal sensitivity of these patients.