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.     

Putative inflammatory and immunological mechanisms in functional bowel disorders.

The observations that irritable bowel syndrome (IBS) may be precipitated by an acute enteric infection, or occurs commonly in patients in remission from inflammatory bowel disease (IBD) has prompted consideration of inflammation as a putative basis for symptom generation in IBS. In this regard, IBS may follow a pattern of pathogenesis that is similar to asthma--which was once considered a psychosomatic disease. This review examines the basic scientific evidence of a functional interface between the immune and sensory-motor systems of the gut and discusses how this may be relevant to a subgroup of IBS patients. In addition, review will examine the implications of this for the diagnosis and treatment of IBS.     

Probiotics in functional bowel disorders

Functional bowel disorders (FBDs) are the most common gastrointestinal (GI) disorders seen by gastroenterologists and primary care physicians. The disorders affect patients functioning and quality of life (QOL) and are associated with significant healthcare burden. The current theory regarding the development of FBDs suggests brain-gut axis dysfunctions associated abnormal GI motility and sensation. Recent data suggest that alterations in the intestinal microbiota may have a role in the pathogenesis of FBDs; or at least have the potential to affect intestinal functions that are thought to be relevant to the development of functional GI symptoms. This has led to growing interest of healthcare providers and patients in targeting the intestinal microbiota for the treatment of FBDs. In this article we discuss the potential role probiotic interventions in the treatment of FBDs. We review the evidence from pre-clinical and clinical studies and discuss the current recommendations for the use of probiotics for FBDs in clinical practice.     

肠易激综合征内脏高敏感性机制的研究进展

肠易激综合征(irritable bowel syndrome,IBS)是一种以腹部不适和排便习惯改变为特征的胃肠功能性疾病.其发病机制复杂,尚未被人类充分认识,可能与包括心理因素、胃肠道异常运动与分泌、内脏高敏感性在内的中枢和外周因素有关.但有的因子既能够调节胃肠道的运动,又能够调节内脏的敏感性,使IBS患者的胃肠道对应激及食物的敏感性增强.目前认为内脏敏感性增高是其特征性的病理生理基础,但IBS内脏高敏感性确切的神经生物学机制尚不清楚,脑-肠轴上有多种机制单独或共同作用形成内脏感觉的异常.本文综述近年来有关IBS患者肠道神经丛、脊髓及中枢神经系统存在结构或功能的异常.     

Placebo response in functional bowel disorders

The placebo response in functional bowel disorders is incompletely understood, and is usually either mystified or down-played; a rational approach to the understanding of the placebo response, however, can be deduced from the scientific literature. We present 3 theories that may explain most of the placebo response in medical and psychological interventions. a) Regression to the Mean (RTM): This refers to "errors" in measuring the outcome of therapies that are due to small samples sizes, global assessment variables, spontaneous variability of symptoms, and other methodological reasons. b) Pavlovian Conditioning (PC): Here the placebo response occurs as the consequence of successful association of diagnostic and therapeutic procedures in the past (illness history) of the individual that resulted in symptom improvement. Stimuli in the context of a treatment can thus gain therapeutic potency (become conditioned stimuli), e. g., the procedure of an injection or the colour of a drug. c) Signal Detection theory (SDT): Manipulation of expectations and cognitions of the patient by suggestions and verbal instructions of the health-care system will change the willingness of the patient to perceive symptoms as improved/worsened, specifically if this happens under "noisy" circumstances, e. g., with high spontaneous variability of symptoms. All three models are illustrated with examples from the medical and psychological treatments or experiments, including recent findings of cortical correlates of the placebo response in functional brain imaging investigations. Potential biological mechanisms for the placebo response are discussed, including he possibility of the genetic predisposition to be a placebo responder.     

内脏高敏感与功能性胃肠病

功能性胃肠病(functional gastrointestinal disorders,FGIDs)是指一组以慢性或反复发作的消化道症状就诊,但无明确胃肠黏膜结构改变或生化异常可查的症候群。心理、社会因素可加重FGIDs患者症状,患者可同时伴有躯体症状[1]。其发病机制目前尚不明确,最初该类疾病被认为是胃肠神经官能症,大量的流行病学资料表明,尽管精神压力与患者症状发作有关,但主要还是决定于患者的就医行为。此后,FGIDs发病机制的研究又集中在胃肠动力改变方面,肠易激综合征患者(IBS)、功能性消化不良患者(FD)、非心源性胸痛患者(NCCP)均发现了各种胃肠动力异…     

Efficient diagnosis of suspected functional bowel disorders

Functional bowel disorders (FBDs) are common disorders that are characterized by various combinations of abdominal pain and/or discomfort, bloating and changes in bowel habits. At present, diagnosing FBDs often incurs considerable health-care costs, partly because unnecessary investigations are performed. Patients are currently diagnosed as having an FBD on the basis of a combination of typical symptoms, normal physical examination and the absence of alarm features indicative of an organic gastrointestinal disease. Basic laboratory investigations, such as a complete blood count, measurement of the erythrocyte sedimentation rate and serological tests for celiac disease, are useful in the initial evaluation. No further investigations are needed for most patients who have typical symptoms and no alarm symptoms. The most important alarm symptoms include signs of gastrointestinal bleeding, symptom onset above 50 years of age, a family history of colorectal cancer, documented weight loss and nocturnal symptoms. The presence of alarm symptoms obviously does not exclude an FBD, but further investigation is needed before confirmation of the diagnosis. For patients with predominant and severe diarrhea, a more thorough diagnostic work-up should normally be considered, including colonoscopy with colonic biopsies and a test for bile-acid malabsorption.     

Role of visceral sensitivity in the pathophysiology of irritable bowel syndrome

Visceral hypersensitivity has been recognised as a characteristic of patients with irritable bowel syndrome (IBS). It may be involved in the pathogenesis of abdominal pain/discomfort, and seems to result from the sensitisation of nerve afferent pathways originating from the gastrointestinal tract. From a clinical point of view, hypersensitivity, although frequent, is not a constant finding among patients with IBS and cannot therefore be considered as a diagnostic marker of the condition. The advances made in understanding visceral hypersensitivity in patients with IBS are reviewed: the factors that influence abdominal distension are defined and different therapeutic perspectives are examined.     

A cost analysis of functional bowel disorders in Iran

Background and aims The objective of this work is to evaluate the health care utilization and cost of different types of functional bowel disorder (FBD) in a population of Iranian patients and compare the costs in consulters and non-consulters. Materials and methods A consecutive sample of 1,023 patients in an outpatient gastroenterology clinic in central Tehran were interviewed, using two questionnaires based on the Rome II criteria, from December 2004 to May 2005 to detect FBD patients and to determine the frequency of health resource utilization (physician visit, hospitalization, laboratory tests, imaging studies, and drugs) and productivity loss (days off work or with low functionality) due to FBD symptoms in the past 12 months. Societal perspective was used and cost per person per year was estimated in purchasing power parity dollars (PPP$). Results The direct costs (for consulters, non-consulters; data presented in this order) were: irritable bowel syndrome (IBS; $92.04, $1.04), unspecified functional bowel disorder (FBD; $100.94, $0.39), functional constipation ($57.23, $1.04), and functional abdominal bloating ($71.35, $0.63). Indirect costs (for consulters, non-consulters) were: IBS ($811.85, $669.09), unspecified FBD ($705.85, $263.47), functional constipation ($587.48, $97.49), and functional abdominal bloating ($147.88, $38.60). Total yearly costs of IBS and functional constipation for urban adult population of Iran were roughly estimated at 2.94 billion PPP$ and 89.2 million PPP$, respectively. Conclusions As proven in developed countries, FBD and especially IBS seem to put a heavy burden on the economy of a developing country like Iran. Further population-based studies are needed for more precise estimations.     

MMPI assessment of patients with functional bowel disorders

This prospective study was undertaken to assess personality differences among patients with chronic pelvic floor disorders. Sixty patients (43 females and 17 males) of a mean age of 58 (range, 33–87) years with fecal incontinence (n=19), constipation (n=30), or levator spasm (n=11) had a mean duration of symptoms of 35 (range, 2–50) years. The Minnesota Multiphasic Personality Inventory (MMPI) was utilized for psychologic assessment for all patients prior to treatment. Mean scores for scales 1 (hypochondriasis), 2 (depression), and 3 (hysteria) were significantly elevated for the levator spasm group (71, 75, and 73, respectively). A similar pattern was seen for the constipation group, where the mean scores for scales 1 and 2 were significantly elevated (70 and 74, respectively) with a moderate elevation on scale 3 (68). The hypochondriasis (1), depression (2), and hysteria (3) scales are referred to as the neurotic triad, and profile patterns such as these indicate that these subjects may manifest their psychologic distress as physical symptoms. By contrast, the fecal incontinence patients were within the normal range on all scales. The information from these MMPI profiles can be used to understand the personality and emotional composition of these patients to assist in their evaluation and treatment.     

Sleep disturbances in clinic patients with functional bowel disorders

OBJECTIVE: Sleep deprivation can lower visceral perception thresholds and nonregenerative sleep has been implicated as an etiological factor in chronic hyperalgesia syndromes. The aims of our study were to quantify the self-reported prevalence and type of sleep disturbances in patients with different functional bowel disorders (FBD) and to determine if this prevalence is related to involvement of the upper or lower gastrointestinal (GI) tract, perceived disease severity, or psychological comorbidity. METHODS: We enrolled 505 new FBD patients from an academic referral center specializing in functional GI disorders and 247 community based healthy controls. All patients and controls were prospectively evaluated by validated bowel symptom and sleep questionnaires. A psychological profile was obtained by SCL-90R. RESULTS: We found that 68% of functional dyspepsia (FD), 71.2% of irritable bowel syndrome (IBS)+FD, 50.2% of IBS, and 55.1% of the normal subjects reported having sleep disturbances. Waking up repeatedly during the night and waking up in the morning feeling tired or not rested were the most commonly reported sleep patterns; 57.2% of the patients reported that their abdominal ache awakened them from sleep during the night. Self-reported sleep disturbance was directly related to the perceived intensity of GI symptoms. Self-reported sleep disturbances were equally common in both male (57%) and female (58.4%) FBD patients. There was no significant difference between the mean anxiety and depression scores between patients with and without sleep dysfunction. CONCLUSIONS: FD patients, but not IBS patients, reported sleep disturbances more frequently than healthy control subjects. Abdominal pain or discomfort that awaken FBD patients from sleep during the night were common, and thus a poor discriminating factor between organic and functional disorders.     

Placebo responses and placebo effects in functional bowel disorders

The nature and determinants of the placebo response are widely unknown, as are the underlying psychological and biological mechanisms. Placebo response rates in functional bowel disorders (functional dyspepsia, irritable bowel syndrome) trials are similar to those in nonintestinal pain conditions and are comparable with other organic gastrointestinal diseases (duodenal ulcer, inflammatory bowel diseases). In this narrative review, different methodologies (meta-analyses, reanalyses, and experimental setups) are discussed that have been applied to the study of the placebo response in functional dyspepsia and the irritable bowel syndrome.     

Depression and functional bowel disorders in gastrointestinal outpatients.

Although depression has been linked with both the irritable bowel syndrome and non-organic abdominal pain, which are common in gastrointestinal outpatients, the prevalence of depression in most surveys of outpatient practice has been low. Use of the Beck Depression Inventory to screen new referrals to a general medical and gastrointestinal clinic and to a minor surgical clinic showed that 50 of 100 medical patients were rated as having some degree of depression, compared with 14 of 75 (19%) of the surgical patients in whom abdominal pain and bowel dysfunction were rare (X2 = 9.6, p less than 0.01). In the medical clinic no organic disorder was detected in 64% of the depressed patients, the majority of whom presented with abdominal pain or irritable bowel syndrome. Depression was significantly commoner in this group of patients than in those with other conditions, (X2 = 6.63, p = 0.01). That depression is common in gastrointestinal outpatients is not always appreciated and its symptoms should be sought in all patients with bowel dysfunction and chronic abdominal pain.