Meta-analysis: Lactobacillus rhamnosus GG for abdominal pain-related functional gastrointestinal disorders in childhood

Background A lack of reliable treatments for abdominal pain‐related functional gastrointestinal disorders prompts interest in new therapies. Aim To evaluate systematically the effect of Lactobacillus rhamnosus GG (LGG) for treating abdominal pain‐related functional gastrointestinal disorders in children. Methods MEDLINE, EMBASE, CINAHL, the Cochrane Library, trial registries and proceedings of major meetings were searched for randomised controlled trials (RCTs) evaluating LGG supplementation in children with abdominal pain‐related functional gastrointestinal disorders based on the Rome II or Rome III criteria. Risk of bias was assessed for generation of the allocation sequence, allocation concealment, blinding and follow‐up. Results Compared with placebo, LGG supplementation was associated with a significantly higher rate of treatment responders (defined as no pain or a decrease in pain intensity) in the overall population with abdominal pain‐related functional gastrointestinal disorders (three RCTs, n = 290; risk ratio, RR 1.31, 95% CI 1.08–1.59, number needed to treat, NNT 7, 95% CI 4–22) and in the irritable bowel syndrome (IBS) subgroup (three RCTs, n = 167; RR 1.70, 95% CI 1.27–2.27, NNT 4, 95% CI 3–8). However, no difference was found in the rate of treatment responders between children with functional abdominal pain or functional dyspepsia who received placebo or LGG. The intensity of pain was significantly reduced in the overall study population and in the IBS subgroup. The frequency of pain was significantly reduced in the IBS subgroup only. Conclusion The use of Lactobacillus rhamnosus GG moderately increases treatment success in children with abdominal pain‐related functional gastrointestinal disorders, particularly among children with IBS.     

Treatment of pain symptoms in irritable bowel syndrome patients

Irritable bowel syndrome represents a common gastrointestinal disorder that significantly impacts patients' lives. It is defined by Rome II criteria and characterized by abdominal pain and bloating associated with changes in bowel habit. Visceral hypersensitivity is currently considered a biological marker for the disease. Current therapeutic treatments include the use of fiber supplements, antidiarrheal agents, laxatives, antispasmodics, tricyclic antidepressants and serotonergic agents. Through a proper understanding of the diagnostic criteria, pathophysiology and treatment options, this disorder can be treated effectively in many patients.     

Immune-mediated food reactions in irritable bowel syndrome

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by recurrent abdominal pain and an altered defecation pattern. Depending on the criteria used, it affects between 5 and 10% of the general population and has a serious impact on quality of life. Most patients with IBS show an induction or exacerbation of their symptoms, particularly abdominal pain, after eating certain foods. This raises the question of the role played by food in IBS pathophysiology. In this review, we describe the multiple risk factors of IBS, and we give an overview of the role of food as a trigger of IBS, distinguishing between immune and non-immune reactions to food. We finally highlight recent findings identifying an immune-mediated mechanism underlying food-induced abdominal pain in IBS.     

Effect of asimadoline, a kappa opioid agonist, on pain induced by colonic distension in patients with irritable bowel syndrome

BACKGROUND: Visceral hypersensitivity plays a major role in irritable bowel syndrome pathophysiology. Opioid kappa receptors on afferent nerves may modulate it and be the target for new irritable bowel syndrome treatments. AIM: This study evaluated the effect of the kappa opioid agonist asimadoline on perception of colonic distension and colonic compliance in irritable bowel syndrome patients. METHOD: Twenty irritable bowel syndrome female patients (Rome II criteria; 40 +/- 13 years) and hypersensitivity to colonic distension (Pain threshold < or = 32 mmHg) were included in a randomized double-blind cross-over trial comparing the effect of a single oral dose of asimadoline 0.5 mg or placebo on sensory thresholds (defined as a constant and sustained sensation) elicited by left colon phasic distension (5 mmHg steps, 5 min) up to a sensation of abdominal pain. Colonic compliance was compared by the slope of the pressure-volume curves. RESULTS: On asimadoline, pain threshold (mean +/- s.d.) (29.8 +/- 7.2 mmHg) was higher than on placebo (26.3 +/- 7.8 mmHg), difference not statistically significant (P = 0.1756, ANOVA). Area under curve of pain intensity rated at each distension step was significantly lower on asimadoline (89.3 +/- 33.9, ANOVA) than on placebo (108.1 +/- 29.7) (P = 0.0411). Thresholds of perception of nonpainful distensions were not altered on asimadoline, as compared with placebo. Colonic compliance was not different on placebo and asimadoline. CONCLUSION: Asimadoline decreases overall perception of pain over a wide range of pressure distension of the colon in irritable bowel syndrome patients, without altering its compliance. These data suggest that further studies should explore the potential benefit of asimadoline in treatment of pain in irritable bowel syndrome patients.     

Review article: abdominal bloating and distension in functional gastrointestinal disorders--epidemiology and exploration of possible mechanisms

Background A sensation of abdominal bloating, sometimes accompanied by an increase in girth (distension), is one of the most common and most intrusive features of functional bowel disorders. Aim To conduct a systematic, evidence‐based review of the epidemiology and pathophysiology of abdominal bloating and its relationship to distension. Methods The terms bloating, distension, functional bowel, irritable bowel syndrome, constipation and diarrhoea were searched on MEDLINE up to 2006. References from selected articles and relevant abstracts were also included. Results Approximately 50% of irritable bowel syndrome patients with bloating also experience an increase in abdominal girth and this is more pronounced with constipation than diarrhoea. Bloating appears to be more frequently associated with visceral hypersensitivity, whereas distension is more often related to hyposensitivity and delayed transit. Although there is little evidence for excessive gas as a cause of bloating, gas infusion studies suggest that handling of gas may be impaired in irritable bowel syndrome and there may also be abnormal relaxation of the anterior abdominal musculature in these patients. Conclusions There is unlikely to be a single cause for bloating and distension, which probably have different, but overlapping, pathophysiological mechanisms. Relieving constipation might help distension, but the treatment of bloating may need more complex approaches involving sensory modulation.     

The effect of fluoxetine in patients with pain and constipation-predominant irritable bowel syndrome: a double-blind randomized-controlled study

BACKGROUND: Irritable bowel syndrome has been treated with selective serotonin reuptake inhibitors but there is not enough evidence from controlled trials to prove their effectiveness. AIM: To compare the effects of fluoxetine and placebo in the treatment of pain and constipation-predominant irritable bowel syndrome in a double-blind randomized-controlled trial. METHODS: Forty-four cases meeting Rome II criteria for irritable bowel syndrome with predominance of pain and constipation were included in this study. Organic causes were ruled out by detailed history, physical examination, laboratory tests and colonoscopy. Participants were then randomly assigned to receive either fluoxetine or placebo for 12 weeks. Symptoms addressed by the Rome II criteria were recorded during treatment and 4 weeks after termination of treatment. RESULTS: Fluoxetine was significantly more effective than placebo in decreasing abdominal discomfort, relieving feeling and sense of bloating, increasing frequency of bowel movements and decreasing consistency of stool. Mean number of symptoms per patient decreased from 4.6 to 0.7 in the fluoxetine group vs. 4.5 to 2.9 in controls (P < 0.001). CONCLUSIONS: Fluoxetine is an effective and well-tolerated short-term treatment for pain and constipation-predominant irritable bowel syndrome.     

Clinical trial: multispecies probiotic supplementation alleviates the symptoms of irritable bowel syndrome and stabilizes intestinal microbiota

Background Irritable bowel syndrome is the most common diagnosis in gastroenterology. Trials suggest certain probiotics to be beneficial. Aim To investigate the effects of multispecies probiotic supplementation (Lactobacillus rhamnosus GG, L. rhamnosus Lc705, Propionibacterium freudenreichii ssp. shermanii JS and Bifidobacterium animalis ssp. lactis Bb12) on abdominal symptoms, quality of life, intestinal microbiota and inflammatory markers in irritable bowel syndrome. Methods Eighty‐six irritable bowel syndrome patients (Rome II criteria) participated in this randomized, placebo‐controlled 5‐month intervention. Patients were randomized to receive daily either multispecies probiotic supplementation or placebo. Irritable bowel syndrome symptoms, quality of life, microarray‐based intestinal microbiota stability (n = 20), serum cytokines and sensitive C‐reactive protein were monitored. Results The composite irritable bowel syndrome score had at 5 months decreased 14 points (95% CI: ?19 to ?9) from baseline with the multispecies probiotic vs. three points (95% CI: ?8 to 1) with placebo (P = 0.0083). Especially, distension and abdominal pain were affected. A stabilization of the microbiota was observed, as the microbiota similarity index increased with the probiotic supplementation (1.9 ± 3.1), while it decreased with placebo (?2.9 ± 1.7). No differences were seen in C‐reactive protein. Conclusions This multispecies probiotic seems to be an effective and safe option to alleviate symptoms of irritable bowel syndrome, and to stabilize the intestinal microbiota.     

Atypical antipsychotics as a possible treatment option for irritable bowel syndrome

Introduction: Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder (FGID) that is characterised by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits. Although the pathophysiology of IBS is not fully understood, it is believed that psychiatric comorbidities are highly common in such patients. A variety of psychotropic medications are widely used in the treatment of IBS, particularly older antidepressants such as tricyclic antidepressants (TCAs).

Areas covered: With the advent of newer antidepressant classes with better safety and tolerability compared with TCAs, such as serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), clinicians now have more advanced treatment options for treating IBS. Additionally, some atypical antipsychotics (AAs) have recently received approval for treatment of major depressive disorder (MDD). Some AAs may have potentials based on their pharmacodynamic profile and proven benefit for mood symptoms, pain, anxiety and sleep disturbances. This article describes the potential rationale, clinical data and practical aspects involved in the use of AAs for patients with IBS.

Expert opinion: Atypical antipsychotics (AAs) may have a role in the treatment of irritable bowel syndrome (IBS) based on the currently available findings, although there is no clear evidence, and a number of clinical issues to be addressed in the use of AAs for the treatment of IBS.     

Visceral analgesics: drugs with a great potential in functional disorders?

Irritable bowel syndrome remains an incompletely understood, common syndrome with significant unmet medical needs. In IBS patients, abdominal pain is a primary factor related to quality of life impairment, symptom severity and health care utilization, and chronic visceral hyperalgesia has been identified as an important aspect of IBS pathophysiology. However, the development of therapies aimed at reducing this hyperalgesia (visceral analgesics) has been only partially successful despite preclinical evidence supporting the potential usefulness of several preclinical compounds aimed at peripheral as well as central targets.     

Review article: gender-related differences in functional gastrointestinal disorders

Many functional gastrointestinal disorders and other chronic visceral pain disorders such as interstitial cystitis and chronic pelvic pain are more common in women than in men. In irritable bowel syndrome (IBS) there is a 2 : 1 female to male ratio in prevalence of symptoms in community samples. Female irritable bowel syndrome patients are more likely to be constipated, complain of abdominal distension and of certain extracolonic symptoms.
While animal studies have clearly demonstrated gender-related differences in pain perception and antinociceptive mechanisms, unequivocal evidence for gender-related differences in human pain perception or modulation has only been provided recently. Gender-related differences may be related to constant differences in the physiology of pain perception, such as structural or functional differences in the visceral afferent pathways involved in pain transmission or modulation, and/or they may be related to fluctuations in female sex hormones.
Preliminary evidence suggests that female irritable bowel syndrome patients show specific perceptual alterations in regards to rectosigmoid balloon distension and that they show differences in regional brain activation measured by positron emission tomography. This preliminary evidence suggests that gender-related differences in symptoms and in the perceptual responses to visceral stimuli exist in IBS patients and can be detected using specific stimulation paradigms and neuroimaging techniques.     

Review article: new receptor targets for medical therapy in irritable bowel syndrome

Background  Despite setbacks to the approval of new medications for the treatment of irritable bowel syndrome, interim guidelines on endpoints for irritable bowel syndrome (IBS) trials have enhanced interest as new targets for medical therapy are proposed based on novel mechanisms or chemical entities.
Aims  To review the approved lubiprostone, two targets that are not meeting expectations (tachykinins and corticotrophin-releasing hormone), the efficacy and safety of new 5-HT₄ agonists, intestinal secretagogues (chloride channel activators, and guanylate cyclase-C agonists), bile acid modulation, anti-inflammatory agents and visceral analgesics.
Methods  Review of selected articles based on PubMed search and clinically relevant information on mechanism of action, safety, pharmacodynamics and efficacy.
Results  The spectrum of peripheral targets of medical therapy addresses chiefly the bowel dysfunction of IBS and these effects are associated with pain relief. The pivotal mechanisms responsible for the abdominal pain or visceral sensation in IBS are unknown. The new 5-HT₄ agonists are more specific than older agents and show cardiovascular safety to date. Secretory agents have high specificity, low bioavailability and high efficacy. The potential risks of agents 'borrowed' from other indications (such as hyperlipidaemia, inflammatory bowel disease or somatic pain) deserve further study.
Conclusions  There is reason for optimism in medical treatment of IBS with a spectrum of agents to treat bowel dysfunction. However, visceral analgesic treatments are still suboptimal.     

Stability of irritable bowel syndrome using a Rome II-based classification

BACKGROUND: As there is no biological marker for irritable bowel syndrome, a diagnosis is made using symptom-based criteria. AIM: To evaluate the stability of self-reported symptoms consistent with Rome II-based irritable bowel syndrome classification. METHODS: Irritable bowel syndrome subjects identified in a 2001 population-based study by modified Rome II criteria were re-contacted 2 years later. Data were collected via a web-based questionnaire. RESULTS: Of the 697 subjects, 30% remained in the same irritable bowel syndrome subtype in both surveys, 18.4% changed irritable bowel syndrome subtype and 52% no longer met the irritable bowel syndrome criteria at follow-up. Subjects continuing to meet the irritable bowel syndrome criteria were more likely to have been initially classified in the alternating irritable bowel syndrome subtype and had more psychological impairment and lower irritable bowel syndrome-related quality of life than subjects not fulfilling the irritable bowel syndrome criteria at follow-up. Lack of pain caused more subjects to fall out of the irritable bowel syndrome criteria than the absence of non-painful bowel symptoms. However, the majority of subjects that did not fulfill the pain component of the irritable bowel syndrome criteria continued to report abdominal pain of at least moderate severity. CONCLUSION: In a US population-based follow-up study using modified Rome II criteria, we found irritable bowel syndrome is episodic in nature and current classification is limited in capturing fluctuation of disease over time.     

肠易激综合征腹痛的发生机制和治疗

目的探讨肠易激综合征腹痛的发生机制及治疗方法。方法选取2011年5月～2012年5月在本院治疗的103例肠易激综合征腹痛患者为研究对象,全部患者给予综合对症治疗,观察其腹痛时间、腹痛次数、腹痛频率和腹痛程度改变情况。结果治疗后,肠易激综合征腹痛患者的腹痛时间明显缩短,腹痛次数减少,腹痛频率降低,腹痛程度明显减轻。结论造成肠易激综合征腹痛的原因有多种,临床对神经系统和胃肠系统作全方位的检查,根据病因对症治疗,可有效缓解其临床症状。     

Drug treatment of the irritable bowel syndrome.

Irritable bowel syndrome (IBS) is defined as a functional bowel disorder in which abdominal pain is associated with defecation or a change in bowel habit, and with features of disordered defecation and distension. The irritable bowel syndrome occurs in 10 to 20% of people worldwide and is very commonly encountered in clinical practice. This has encouraged the pharmaceutical industry to search for effective drug therapy. So far, a universally effective agent has not been found, and since this is a chronic, benign disorder, beginning in youth, long term drug use should be avoided. Nevertheless, if a specific IBS symptom, such as constipation or abdominal pain dominates, a specific drug may be helpful. However, tests and treatment should be minimised or even avoided in order to do no harm. A largely nonpharmaceutical approach to IBS should be taken. This approach employs drugs sparingly and then only targeted at specific and resistant symptoms.     

Irritable bowel syndrome: recent and novel therapeutic approaches

Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder affecting up to 3-15% of the general population in Western countries. It is characterised by unexplained abdominal pain, discomfort and bloating in association with altered bowel habits. The pathophysiology of IBS is considered to be multifactorial, involving disturbances of the brain-gut-axis: IBS has been associated with abnormal gastrointestinal motor functions, visceral hypersensitivity, psychosocial factors, autonomic dysfunction and mucosal inflammation. Traditional IBS therapy is mainly symptom oriented and often unsatisfactory. Hence, there is a need for new treatment strategies. Increasing knowledge of brain-gut physiology, mechanisms, and neurotransmitters and receptors involved in gastrointestinal motor and sensory function have led to the development of several new therapeutic approaches. This article provides a systematic overview of recently approved or novel medications that show promise for the treatment of IBS; classification is based on the physiological systems targeted by the medication. The article includes agents acting on the serotonin receptor or serotonin transporter system, novel selective anticholinergics, alpha-adrenergic agonists, opioid agents, cholecystokinin antagonists, neurokinin antagonists, somatostatin receptor agonists, neurotrophin-3, corticotropin releasing factor antagonists, chloride channel activators, guanylate cyclase-c agonists, melatonin and atypical benzodiazepines. Finally, the role of probiotics and antibacterials in the treatment of IBS is summarised.     

Review article: current and emerging therapies for functional dyspepsia

Functional dyspepsia represents a heterogeneous group of gastrointestinal disorders marked by the presence of upper abdominal pain or discomfort. Although its precise definition has evolved over the last several decades, this disorder remains shrouded in controversy. The symptoms of functional dyspepsia may overlap with those of other functional bowel disorders including irritable bowel syndrome and non-erosive reflux disease. There may be coexistent psychological distress or disease complicating its presentation and response to therapy. Given the prevalence and chronicity of functional dyspepsia, it remains a great burden to society. Suspected physiological mechanisms underlying functional dyspepsia include altered motility, altered visceral sensation, inflammation, nervous system dysregulation and psychological distress. Yet the exact pathophysiological mechanisms that cause symptoms in an individual patient remain difficult to delineate. Numerous treatment modalities have been employed including dietary modifications, pharmacological agents directed at various targets within the gastrointestinal tract and central nervous system, psychological therapies and more recently, complementary and alternative treatments. Unfortunately, to date, all of these therapies have yielded only marginal results. A variety of emerging therapies are being developed for functional dyspepsia. Most of these therapies are intended to normalize pain perception and gastrointestinal motor and reflex function in this group of patients.     

消化门诊肠易激综合征患者肠外症状分析

目的了解肠易激综合征(IBS)患者临床症状表现,尤其是肠外症状,提高IBS诊断率。方法对2010年12月至2011年7月郑州大学第一附属医院消化内科门诊就诊并按照罗马Ⅲ标准诊断为IBS的患者进行问卷调查。共调查866例,收回问卷847份作为统计病例。结果 IBS是一种复杂的身心疾病,除表现在胃肠功能紊乱,腹痛、腹部不适,排便性状、频率改变外,还表现有咽部不适及异物感,口干、口苦、口臭、无味觉,功能性消化不良,无饥饿感,腰背及肌肉酸、痛、纤维肌痛综合征等全身不明原因的疼痛,手心、脚心灼热等功能性低热,肢体凉、畏寒,失眠、头痛,心烦,慢性疲劳综合征,体重减轻,尿道不适,性交困难等肠外表现等。结论 IBS患者多反复就诊于综合医院的各个科室,部分临床医生对IBS复杂的临床症状尤其是肠道外症状认识少,鉴别困难,使IBS诊断率低,治疗效果差。     

Diagnosis and treatment of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common medical disorder characterized by symptoms of abdominal pain and bowel dysfunction. It is associated with significant disability and health care costs. A practical approach to diagnosis is the symptom-based Rome criteria. Management of patients has been helped by recent findings relating to the epidemiology, pathophysiology and psychosocial contributions of the disorder. Dysregulation of intestinal motor, sensory and central nervous system function is currently believed to be the basis for IBS symptoms. Symptoms are due to both abnormal intestinal motility and enhanced visceral sensitivity. Psychosocial factors are not a cause but can affect the illness experience and clinical outcome. Finally, treatment involves an effective physician-patient relationship and an integrated pharmacologic and behavioral approach that is determined by the needs of the patient, the type and severity of the symptoms and the degree of disability.     

Effect of a laxative with and without tegaserod in adolescents with constipation predominant irritable bowel syndrome

AIM: To determine the effect of a laxative alone and in combination with tegaserod in alleviating pain and improving stool frequency in adolescents with constipation predominant irritable bowel syndrome. PATIENTS: Forty-eight postpubertal adolescents of both sexes with constipation predominant irritable bowel syndrome, as defined by Rome II criteria, were randomly allocated to Group A (n = 27) for treatment with a laxative (polyethylene glycol 3350 oral solution) only or Group B (n = 21) for combination therapy with the laxative and tegaserod. Symptoms of abdominal pain (scale 0-10) and frequency of bowel movements were recorded daily in the pre-treatment phase and the post-treatment phase after a 7-day 'washout' period. Patients served as their own controls. RESULTS: Treatment with the laxative alone (Group A) resulted in significant increase in frequency of bowel movements (P < 0.05), but not significant improvement in pain (P > 0.05). Treatment with the combination of the laxative and tegaserod (Group B) led to significant increase in the frequency of bowel movements and also significant reduction in pain (P < 0.05). CONCLUSIONS: The laxative alone improved stooling but not pain in adolescents with constipation predominant irritable bowel syndrome. Addition of tegaserod resulted in alleviation of pain as well.     

Antinociceptive potency of enkephalins and enkephalinase inhibitors in the mouse model of colorectal distension—proof‐of‐concept

Irritable bowel syndrome (IBS) is a chronic disease characterized by abdominal pain and changes in bowel habits. Patients with IBS comprise a significant portion of attendants at the outpatient clinics. Targeting intestinal opioid receptors was found successful in alleviating pain and diarrhea—two major symptoms of IBS. In this study, we aimed to evaluate a novel potential pharmacological option: the use of enkephalinase inhibitors in therapy of visceral pain occurring in the course of IBS. We thus assessed the antinociceptive efficacy of enkephalins: Leu‐enkephalin and Met‐enkephalin, and enkephalinase inhibitors: opiorphin and sialorphin in the mouse model of visceral pain induced by colorectal distension. Leu‐enkephalin, Met‐enkephalin, and sialorphin, but not opiorphin, at the dose of 1 mg/kg injected subcutaneously potently decreased the visceromotor response to colon distension as compared to control. To conclude, enkephalinase inhibitors are worth being considered as potential therapeutics in patients with chronic abdominal pain and/or changed bowel habits, that is, suffering from IBS.