The Use of Peppermint Oil in Gastroenterology.

BACKGROUND: For decades, mint has been used worldwide for its relieving effects against gastrointestinal disturbances. Peppermint is a perennial herb common in Europe and North America. The active ingredient of peppermint oil is menthol and has various gastroenterological and non-gastroenterological uses, especially in the context of functional gastrointestinal disorders (FGIDs). METHODS: We conducted a literature search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials, and case series using the following keywords and acronyms and their associations: peppermint oil, gastro-intestinal motility, irritable bowel syndrome, functional dyspepsia, gastrointestinal sensitivity and gastrointestinal endoscopy. RESULTS: Peppermint oil and its constituents exert smooth muscle relaxant and anti-spasmodic effects on the lower esophageal sphincter, stomach, duodenum, and large bowel. Moreover, peppermint oil can modulate visceral and central nervous system sensitivity. Taken together, these effects suggest using peppermint oil both for improved endoscopic performance and for treating functional dyspepsia and irritable bowel syndrome. Importantly, peppermint oil has an attractive safety profile compared to classical pharmacological treatments, especially in FGIDs. CONCLUSION: Peppermint oil is a safe herbal medicine therapy for application in gastroenterology, with promising scientific perspectives and rapidly expanding use in clinical practice.

Targeting the endocannabinoid system for the treatment of abdominal pain in irritable bowel syndrome.

The management of visceral pain in patients with disorders of gut-brain interaction, notably irritable bowel syndrome, presents a considerable clinical challenge, with few available treatment options. Patients are increasingly using cannabis and cannabinoids to control abdominal pain. Cannabis acts on receptors of the endocannabinoid system, an endogenous system of lipid mediators that regulates gastrointestinal function and pain processing pathways in health and disease. The endocannabinoid system represents a logical molecular therapeutic target for the treatment of pain in irritable bowel syndrome. Here, we review the physiological and pathophysiological functions of the endocannabinoid system with a focus on the peripheral and central regulation of gastrointestinal function and visceral nociception. We address the use of cannabinoids in pain management, comparing them to other treatment modalities, including opioids and neuromodulators. Finally, we discuss emerging therapeutic candidates targeting the endocannabinoid system for the treatment of pain in irritable bowel syndrome.

Predictors of Symptom-Specific Treatment Response to Dietary Interventions in Irritable Bowel Syndrome.

(1) Background: Predictors of dietary treatment response in irritable bowel syndrome (IBS) remain understudied. We aimed to investigate predictors of symptom improvement during the low FODMAP and the traditional IBS diet for four weeks. (2) Methods: Baseline measures included faecal Dysbiosis Index, food diaries with daily energy and FODMAP intake, non-gastrointestinal (GI) somatic symptoms, GI-specific anxiety, and psychological distress. Outcomes were bloating, constipation, diarrhea, and pain symptom scores treated as continuous variables in linear mixed models. (3) Results: We included 33 and 34 patients on the low FODMAP and traditional IBS diet, respectively. Less severe dysbiosis and higher energy intake predicted better pain response to both diets. Less severe dysbiosis also predicted better constipation response to both diets. More severe psychological distress predicted worse bloating response to both diets. For the different outcomes, several differential predictors were identified, indicating that baseline factors could predict better improvement in one treatment arm, but worse improvement in the other treatment arm. (4) Conclusions: Psychological, nutritional, and microbial factors predict symptom improvement when following the low FODMAP and traditional IBS diet. Findings may help individualize dietary treatment in IBS.

Effect of slow, deep breathing on visceral pain perception and its underlying psychophysiological mechanisms.

BACKGROUND: Studies using somatic pain models have shown the hypoalgesic effects of slow, deep breathing. We evaluated the effect of slow, deep breathing on visceral pain and explored putative mediating mechanisms including autonomic and emotional responses. METHODS: Fifty-seven healthy volunteers (36 females, mean age = 22.0 years) performed controlled, deep breathing at a slow frequency (6 breaths per minute), controlled breathing at a normal frequency (14 breaths per minute; active control), and uncontrolled breathing (no-treatment control) in randomized order. Moderate painful stimuli were given during each condition by delivering electrical stimulation in the distal esophagus. Participants rated pain intensity after each stimulation. Heart rate variability and self-reported arousal were measured during each condition. KEY RESULTS: Compared to uncontrolled breathing, pain intensity was lower during slow, deep breathing (Cohen's d = 0.40) and normal controlled breathing (d = 0.47), but not different between slow, deep breathing and normal controlled breathing. Arousal was lower (d = 0.53, 0.55) and heart rate variability was higher (d = 0.70, 0.86) during slow, deep breathing compared to the two control conditions. The effect of slow, deep breathing on pain was not mediated by alterations in heart rate variability or arousal but was moderated by pain catastrophizing. CONCLUSIONS AND INFERENCES: Slow, deep breathing can reduce visceral pain intensity. However, the effect is not specific to the slow breathing frequency and is not mediated by autonomic or emotional responses, suggesting other underlying mechanisms (notably distraction). Whether a long-term practice of slow, deep breathing can influence (clinical) visceral pain warrants to be investigated.

Efficacy and safety of spore-forming probiotics in the treatment of functional dyspepsia: a pilot randomised, double-blind, placebo-controlled trial.

BACKGROUND: Current treatments for functional dyspepsia have limited efficacy or present safety issues. We aimed to assess spore-forming probiotics in functional dyspepsia as monotherapy or add-on therapy to long-term treatment with proton-pump inhibitors. METHODS: In this single-centre, randomised, double-blind, placebo-controlled pilot trial that took place at University Hospitals Leuven (Leuven, Belgium), adult patients (≥18 years) with functional dyspepsia (as defined by Rome IV criteria, on proton-pump inhibitors or off proton-pump inhibitors) were randomly assigned (1:1) via computer-generated blocked lists, stratified by proton-pump inhibitor status, to receive 8 weeks of treatment with probiotics (Bacillus coagulans MY01 and Bacillus subtilis MY02, 2·5 × 109 colony-forming units per capsule) or placebo consumed twice per day, followed by an open-label extension phase of 8 weeks. Individuals with a history of abdominal surgery, diabetes, coeliac or inflammatory bowel disease, active psychiatric conditions, and use of immunosuppressant drugs, antibiotics, or probiotics in the past 3 months were excluded. All patients and on-site study personnel were masked to treatment allocation in the first 8 weeks. Symptoms, immune activation, and faecal microbiota were assessed and recorded. The primary endpoint was a decrease of at least 0·7 in the postprandial distress syndrome (PDS) score of the Leuven Postprandial Distress Scale in patients with a baseline PDS score of 1 or greater (at least mild symptoms), assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT04030780. FINDINGS: Between June 3, 2019, and March 11, 2020, of 93 individuals assessed for eligibility, we included 68 patients with functional dyspepsia (51 [75%] women, mean age 40·1 years [SD 14·4], 34 [50%] on proton-pump inhibitors). We randomly assigned 32 participants to probiotics and 36 to placebo. The proportion of clinical responders was higher with probiotics (12 [48%] of 25) than placebo (six [20%] of 30; relative risk 1·95 [95% CI 1·07-4·11]; p=0·028). The number of patients with adverse events was similar with probiotics (five [16%] of 32) and placebo (12 [33%] of 36). Two serious adverse events occurring during the open-label phase (appendicitis and syncope in two separate patients) were assessed as unlikely to be related to the study product. INTERPRETATION: In this exploratory study, B coagulans MY01 and B subtilis MY02 were efficacious and safe in the treatment of functional dyspepsia. Participants had potentially beneficial immune and microbial changes, which could provide insights into possible underlying mechanisms as future predictors or treatment targets. FUNDING: MY HEALTH.

Herbal medicines in functional dyspepsia-Untapped opportunities not without risks.

BACKGROUND: Contemporary treatments for functional dyspepsia have limitations. Herbal medicine has been suggested as adjunctive treatment. With growing scientific recognition and public interests, an in-depth review of this is timely. AIMS/PURPOSE: To evaluate the therapeutic potential and problems that may be associated with the adoption of herbal medicines in functional dyspepsia. METHODS: We reviewed the treatment landscape of functional dyspepsia and assessed the scientific community's interest in herbal medicine. Preclinical pharmacological and clinical trial data were reviewed for several herbal medicines available in the market. Challenges associated with adoption of herbal medicine in mainstream medicine were critically evaluated. RESULTS: We found that herbal medicines frequently comprise a combination of herbs with multiple reported pharmacological effects on gastrointestinal motility and secretory functions, as well as cytoprotective and psychotropic properties. We identified a number of commercially available herbal products that have undergone rigorous clinical trials, involving large numbers of well-defined subjects, reporting both efficacy and safety for functional dyspepsia. Persisting concerns include lack of rigorous assessments for majority of products, toxicity, consistency of ingredients, dose standardizations, and quality control. We provide a quality framework for its evaluation. CONCLUSIONS: We commend herbal medicine as a viable future option in managing functional dyspepsia. An attractive appeal of herbal medicine is the prospect to simultaneously target multiple pathophysiological mechanisms. Wider adoption and acceptance of herbal medicines in treatment algorithms of functional dyspepsia will require the application of the scientific rigor expected of chemical therapies, to all stages of their development and evaluation.

The effect of rikkunshito on gastrointestinal symptoms and gastric motor function: The first study in a Belgian functional dyspepsia population.

BACKGROUND: Rikkunshito, a traditional Kampo medicine, has shown efficacy to treat functional dyspepsia (FD) in controlled trials in Japan. Its putative benefit for European patients and mechanism of action has not been established. METHODS: This study examined the effect of rikkunshito on gastric motility and GI symptom perception in FD-PDS patients in a randomized, placebo-controlled, cross-over study. After a 2-week run-in period, patients received rikkunshito or matching placebo (2.5 g t.i.d.) for 4 weeks, separated by a 4-week washout period. Symptoms were assessed by the Leuven Postprandial Distress Scale (LPDS) diary throughout the study. At baseline and after both treatment arms, intragastric pressure (IGP) was measured to evaluate gastric accommodation and gastric motility. Simultaneously, GI symptoms were scored on a 100 mm visual analogue scale. Validated symptom questionnaires (PAGI-SYM, VSI, DSS, and PHQ) were completed each study visit. KEY RESULTS: Twenty-three patients completed the study (33 ± 14 years, 22.7 ± 3.22 kg/m2 ). Intragastric pressure was numerically, but not significantly, lower after rikkunshito compared with baseline and placebo (P = .14). No differences were found in gastric accommodation, nutrient volume tolerance, and symptoms assessed during IGP measurements. Early satiation and postprandial fullness (daily diary) decreased after rikkunshito compared with baseline (P < .041 for both). Placebo also improved most other symptoms assessed. No significant changes in VSI scores occurred. No adverse reactions occurred. CONCLUSIONS: Rikkunshito did not alter gastric motility. Treatment with rikkunshito improved upper GI symptoms in FD patients but similarly high placebo effects were observed using the LPDS diary, PAGI-SYM, SF-NDI, and DSS scores. Rikkunshito was safe and well-tolerated.

Herbal medicine in the treatment of functional gastrointestinal disorders: A systematic review with meta-analysis.

BACKGROUND AND AIMS: The efficacy of herbal medicines (HMs) for functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS), functional dyspepsia (FD) and functional constipation (FC) is controversial. A systematic review with meta-analysis was conducted to determine their effectiveness for FGIDs. METHODS: We searched the following electronic databases till July 2019 with English language restriction: The Cochrane Library, EMBASE and PUBMED. Randomized double-blind controlled trials of HMs compared with placebo or conventional pharmacological drugs for adult FGIDs patients were included. RESULTS: In total, 49 trials involving 7396 participants with FGIDs were included. The risk of bias was low in 9, unclear in 36, and high in 4 trials. More than 33 different herbal formulae were tested. HMs demonstrated statistically significant benefits for symptom improvement compared with placebo in 46 trials (RR = 1.67, 95% CI 1.48-1.88). When compared with conventional pharmacological therapy in 5 trials, HMs were found to be non-inferior (RR = 1.10, 95% CI 1.03-1.18). The number of trials with regards to FD, IBS and FC were 19, 23 and 7 respectively. Subgroup analysis found that HMs were better than placebo in alleviating symptoms for FD (RR = 1.50, 95% CI 1.32-1.69), IBS (RR = 1.62, 95% CI 1.32-1.97) and FC (RR = 3.83, 95% CI 2.26-6.50). HMs tended to have more patients with adverse events than placebo, but similar to conventional pharmacological drugs. CONCLUSIONS: Our findings provide a positive signal for HMs as a potentially well-tolerated and effective treatment for FGIDs, deserving further examination in high-quality trials.

Irritable bowel syndrome: diagnosis and management.

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders (FGIDs) encountered in clinical practice. In the absence of an accurate biomarker for the disorder, IBS is mainly diagnosed based symptomology using the Rome criteria. Due to the heterogeneity of the disorder, finding the correct treatment option is often challenging. In general, lifestyle and dietary changes, including the low-FODMAP of gluten-free diet, are the first-in-line treatment for all patients. Issues with dietary changes are the strict elimination of multiple food products and hence difficult compliance to the diet. When lifestyle changes do not lead to adequate symptom relief, patients should be treated according to their predominant bowel habits and most prominent symptoms. Laxatives or prokinetics and antidiarrheals are used to treat constipation and diarrhea respectively, but have little effect on abdominal pain. To treat gastro-intestinal (GI) symptoms, antispasmodics can be attributed. Low doses of neuromodulators can help gain control over GI and central symptoms, but are also prone to more severe side effects, restricting their widespread use. Refractory IBS symptoms can be treated with probiotics, antibiotics, histamine-receptor antagonists or alternative therapy, including psychotherapy, hypnotherapy, acupuncture or phytomedicines. However, for many of these options, scientific evidence is sparse and high-quality research is often lacking, leading to inconclusive results. In general, all of the available treatment options only provide symptom relief for a subset of patients. This review provides a full overview of the diagnostic process and currently available treatment options for IBS.

Efficacy and Safety of Peppermint Oil in a Randomized, Double-Blind Trial of Patients With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Peppermint oil is frequently used to treat irritable bowel syndrome (IBS), despite a lack of evidence for efficacy from high-quality controlled trials. We studied the efficacy and safety of small-intestinal-release peppermint oil in patients with IBS and explored the effects of targeted ileocolonic-release peppermint oil. METHODS: We performed a double-blind trial of 190 patients with IBS (according to Rome IV criteria) at 4 hospitals in The Netherlands from August 2016 through March 2018; 189 patients were included in the intent-to-treat analysis (mean age, 34.0 years; 77.8% female; 57.7% in primary care), and 178 completed the study. Patients were randomly assigned to groups given 182 mg small-intestinal-release peppermint oil, 182 mg ileocolonic-release peppermint oil, or placebo for 8 weeks. The primary endpoint was abdominal pain response, as defined by the US Food and Drug Administration: at least a 30% decrease in the weekly average of worst daily abdominal pain compared with baseline in at least 4 weeks. The co-primary endpoint was overall relief of IBS symptoms, as defined by the European Medicines Agency. Secondary endpoints included abdominal pain, discomfort, symptom severity, and adverse events. RESULTS: Abdominal pain response did not differ significantly between the peppermint oil and placebo groups: 29 of 62 patients in the small-intestinal-release peppermint oil group had a response (46.8%, P = .170 vs placebo), 26 of 63 patients in the ileocolonic-release peppermint oil group had a response (41.3%, P = .385 vs placebo), and 22 of 64 patients in the placebo group had a response (34.4%). We did not find differences among the groups in overall relief (9.7%, P = .317 and 1.6%, P = .351 vs 4.7% for placebo). The small intestinal peppermint oil did, however, produce greater improvements than placebo in secondary outcomes of abdominal pain (P = .016), discomfort (P = .020), and IBS severity (P = .020). Adverse events, although mild, were more common in both peppermint oil groups (P < .005). CONCLUSIONS: In a randomized trial of patients with IBS, we found that neither small-intestinal-release nor ileocolonic-release peppermint oil (8 weeks) produced statistically significant reductions in abdominal pain response or overall symptom relief, when using US Food and Drug Administration/European Medicines Agency recommended endpoints. The small-intestinal-release peppermint oil did, however, significantly reduce abdominal pain, discomfort, and IBS severity. These findings do not support further development of ileocolonic-release peppermint oil for treatment of IBS. Clinicaltrials.gov, Number: NCT02716285.

Drugs under development for the treatment of functional dyspepsia and related disorders.

Introduction: Functional dyspepsia (FD), defined as the presence of chronic functional symptoms originating from the gastroduodenal, is one of the most common functional gastrointestinal disorders. FD is subdivided into postprandial distress syndrome (PDS), with meal-related symptoms such as postprandial fullness and early satiation, and epigastric pain syndrome (EPS), with meal-unrelated symptoms such as epigastric pain or burning. Therapeutic options for FD are very limited, probably reflecting the complex pathophysiology which comprises disorders of gastric sensorimotor function as well as low-grade duodenal inflammation.Areas covered: This review summarizes recent and ongoing drug development for FD as identifiedExpert opinion: Proton pump inhibitors (PPIs) are the traditional first-line therapy while potassiumcompetitive acid blockers are being studied. Ongoing drug development focuses on gastric motility with prokinetics (dopamine-2 antagonists and 5-HT4 agonists) and fundus relaxant therapies (acotiamide, azapirones), and on sensitivity with peripherally (guanylate cyclase and cannabinoid agonists) and centrally acting neuromodulators. Drugs under development for gastroparesis may be efficacious in PDS. There are emerging data with pro-and antibiotics and with phytotherapeutic agents. Duodenal low-grade inflammation is a newly emerging target which may respond also to PPIs, histamine and leukotriene receptor blockers.

Review article: treatment options for functional dyspepsia.

BACKGROUND: Functional dyspepsia, consisting of epigastric pain syndrome and postprandial distress syndrome, is a prevalent functional gastrointestinal disorder. To date, only limited treatment options are available and conflicting results in terms of efficacy have been reported. Consequently, nonpharmacological treatment options are increasingly being explored for functional dyspepsia. AIM: To provide an overview of current pharmacological and nonpharmacological treatment options for functional dyspepsia. METHODS: A literature search was conducted on Pubmed and other sources to identify relevant studies. RESULTS: Acid suppressive therapy reduced symptoms in 30%-70% of the patients, with higher benefit in epigastric pain syndrome and superior effectiveness for proton pump inhibitors compared to H2 -antagonists. Prokinetic agents, primarily used to treat postprandial distress syndrome, showed variable efficiency: 59%-81% responder rate for dopamine receptor antagonists, 32%-91% for serotonin-4-receptor agonists and 31%-80% for muscarinic receptor antagonists. H Pylori eradication, recommended in infected patients, was effective in 24%-82%. Refractory symptoms are addressed with neuromodulators. However, their efficacy in functional dyspepsia remains incompletely elucidated, available data showing symptom reduction in 27%-71% of the patients. Regarding herbal agents, peppermint oil reduced symptoms in 66%-91%, rikkunshito in 29%-34% and iberogast in 20%-95%. Lastly, acupuncture, cognitive behavioural therapy and hypnotherapy may help to provide symptom control, but research on their efficacy remains sparse. CONCLUSIONS: None of the available therapies is effective in the majority of patients without being associated with major side effects. Developing new treatment options is challenging due to the heterogeneity of functional dyspepsia, the lack of readily identified target mechanisms and the poor association between pathophysiological disturbances and symptoms.

Postprandial distress syndrome: stratification and management.

INTRODUCTION: Functional dyspepsia (FD), defined by the Rome consensus as the presence of functional symptoms originating from the gastroduodenum, is one of the most common functional gastrointestinal disorders. FD is subdivided into postprandial distress syndrome (PDS), with meal-related symptoms such as postprandial fullness and early satiation, and epigastric pain syndrome (EPS), with meal-unrelated symptoms such as epigastric pain or burning. We used a literature search for a narrative review on the current state of knowledge regarding PDS. Areas covered: Epidemiological studies support PDS as a separate entity and the biggest FD subgroup. The pathophysiology of PDS is heterogeneous, and disorders of gastric sensorimotor function as well as low grade duodenal inflammation have been implicated. Although prokinetic agents may provide the most pathophysiology-oriented treatment option, there is a paucity of suitable agents, and proton pump inhibitors are the traditional first-line therapy. Other options include agents that enhance gastric accommodation, such as acotiamide and 5-HT1A agonists, neuromodulators such as mirtazapine, and traditional medicine approaches. Expert commentary: PDS is highly prevalent, with probably heterogeneous underlying pathophysiology. Motility modifying agents and neuromodulators are the cornerstone of PDS therapy, but there is a need for high quality studies of new therapeutic approaches.

Functional dyspepsia.

Functional dyspepsia is one of the most prevalent functional gastrointestinal disorders. Functional dyspepsia comprises three subtypes with presumed different pathophysiology and aetiology: postprandial distress syndrome (PDS), epigastric pain syndrome (EPS) and a subtype with overlapping PDS and EPS features. Functional dyspepsia symptoms can be caused by disturbed gastric motility (for example, inadequate fundic accommodation or delayed gastric emptying), gastric sensation (for example, sensations associated with hypersensitivity to gas and bloating) or gastric and duodenal inflammation. A genetic predisposition is probable but less evident than in other functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). Psychiatric comorbidity and psychopathological state and trait characteristics could also play a part, although they are not specific to functional dyspepsia and are less pronounced than in IBS. Possible differential diagnoses include Helicobacter pylori infection and peptic ulceration. Pharmacological therapy is mostly based on the subtype of functional dyspepsia, such as prokinetic and fundus-relaxing drugs for PDS and acid-suppressive drugs for EPS, whereas centrally active neuromodulators and herbal drugs play a minor part. Psychotherapy is effective only in a small subset of patients, whereas quality of life can be severely affected in nearly all patients. Future therapies might include novel compounds that attempt to treat the underlying gastric and duodenal inflammation.

Startle responding in the context of visceral pain.

This study aimed to investigate affective modulation of eye blink startle by aversive visceral stimulation. Startle blink EMG responses were measured in 31 healthy participants receiving painful, intermittent balloon distentions in the distal esophagus during 4 blocks (positive, negative, neutral or no pictures), and compared with startles during 3 'safe' blocks without esophageal stimulations (positive, negative or neutral emotional pictures). Women showed enhanced startle during blocks with distentions (as compared with 'safe' blocks), both when the balloon was in inflated and deflated states, suggesting that fear and/or expectations may have played a role. Men's startle did not differ between distention and non-distention blocks. In this particular study context affective picture viewing did not further impose any effect on startle eye blink responses. The current results may contribute to a better understanding of emotional reactions to aversive interoceptive stimulation.

Complications of bariatric surgery: dumping syndrome, reflux and vitamin deficiencies.

Bariatric surgical procedure are increasingly and successfully applied in the treatment of morbid obesity. Nevertheless, these procedures are not devoid of potential long-term complications. Dumping syndrome may occur after procedures involving at least partial gastric resection or bypass, including Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy. Diagnosis is based on clinical alertness and glucose tolerance testing. Treatment may involve dietary measures, acarbose and somatostatin analogues, or surgical reintervention for refractory cases. Gastro-esophageal reflux disease (GERD) can be aggravated by vertical banded gastroplasty and sleeve gastrectomy procedures, but pre-existing GERD may improve after RYGB and with adjustable gastric banding. Nutrient deficiencies constitute the most important long-term complications of bariatric interventions, as they may lead to haematological, metabolic and especially neurological disorders which are not always reversible. Malabsorptive procedures, poor postoperative nutrient intake, recurrent vomiting and poor compliance with vitamin supplement intake and regular follow-up are important risk factors. Preoperative nutritional assessment and rigourous postoperative follow-up plan with administration of multi-vitamin supplements and assessment of serum levels is recommended in all patients.

Treatment of abdominal pain in irritable bowel syndrome.

Functional abdominal pain in the context of irritable bowel syndrome (IBS) is a challenging problem for primary care physicians, gastroenterologists and pain specialists. We review the evidence for the current and future non-pharmacological and pharmacological treatment options targeting the central nervous system and the gastrointestinal tract. Cognitive interventions such as cognitive behavioral therapy and hypnotherapy have demonstrated excellent results in IBS patients, but the limited availability and labor-intensive nature limit their routine use in daily practice. In patients who are refractory to first-line therapy, tricyclic antidepressants (TCA) and selective serotonin reuptake inhibitors are both effective to obtain symptomatic relief, but only TCAs have been shown to improve abdominal pain in meta-analyses. A diet low in fermentable carbohydrates and polyols (FODMAP) seems effective in subgroups of patients to reduce abdominal pain, bloating, and to improve the stool pattern. The evidence for fiber is limited and only isphagula may be somewhat beneficial. The efficacy of probiotics is difficult to interpret since several strains in different quantities have been used across studies. Antispasmodics, including peppermint oil, are still considered the first-line treatment for abdominal pain in IBS. Second-line therapies for diarrhea-predominant IBS include the non-absorbable antibiotic rifaximin and the 5HT3 antagonists alosetron and ramosetron, although the use of the former is restricted because of the rare risk of ischemic colitis. In laxative-resistant, constipation-predominant IBS, the chloride-secretion stimulating drugs lubiprostone and linaclotide, a guanylate cyclase C agonist that also has direct analgesic effects, reduce abdominal pain and improve the stool pattern.

The complexity of globus: a multidisciplinary perspective.

Globus is a topic of interest for many specialties including otorhinolaryngology, gastroenterology and psychiatry/psychosomatic medicine, but, although many hypotheses have been suggested, key questions about its aetiology remain. This Review provides an overview of the extensive literature concerning this topic and discusses the quality of the evidence to date. Globus has been associated with oropharyngeal structural lesions, upper oesophageal sphincter disorders, oesophageal disorders, GERD, psychosocial factors and psychiatric comorbidity. However, findings are often contradictory and the literature remains highly inconclusive. Indeed, with the exception of patients with structural-based globus, the Rome III criteria for functional globus only apply to a subgroup of patients with idiopathic globus. In clinical reality, there exists a group of patients who present with idiopathic (nonstructural) globus, but nevertheless have dysphagia, odynophagia or GERD-exclusion criteria for globus diagnosis according to Rome III. The symptomatology of patients with globus might be broader than previously thought. It is therefore crucial to approach globus not from one single perspective, but from a multifactorial point of view, with focus on the coexistence and/or interactions of different mechanisms in globus pathogenesis. This approach could be translated to clinical practice by adopting a multidisciplinary method to patients presenting with globus.

Microbiota in health and irritable bowel syndrome: current knowledge, perspectives and therapeutic options.

The gastrointestinal tract is a natural reservoir of microbiota. The gut is germ-free at birth, but rapidly becomes host to various bacteria establishing a progressively mutual relationship. The composition of gut microbiota is individual-specific and depends on the genotype of the host and environmental factors. Novel techniques have been used to characterize gastrointestinal microbiota, including genomic approaches. The bacterial profile shows that dominant and minor phyla are present in the gastrointestinal tract. From the proximal to the distal segments of the gut the bacterial density gradually increases, reaching an estimated 10(11) to 10(12) bacteria per gram of colonic content. Dynamic interactions between gut and microbiota play a physiological role in metabolic, protective and structural functions, while dysbiosis contributes to several diseases. Microbiota appear to play a role in IBS, where qualitative and quantitative changes of bacteriaoccur in IBS subtypes. Initial therapeutic approaches in IBS have focused on microbiota. The relationship between perturbations of the microbiota, mucosal inflammation and IBS remains to be further investigated.

A multidimensional model of psychobiological interactions in functional dyspepsia: a structural equation modelling approach.

OBJECTIVE: Gastric sensorimotor function, abuse history, 'trait' and 'state' psychological factors and 'somatisation' all play a role in functional dyspepsia (FD) and its associated impaired quality of life (QoL), but their interplay remains poorly understood. We aimed to test a comprehensive, a priori hypothesised model of interactions between these dimensions in FD. DESIGN: In 259 FD patients, we studied gastric sensitivity with a barostat. We measured abuse history (sexual/physical, childhood/adulthood), 'trait' (alexithymia, trait anxiety) and 'state' (positive/negative affect, depression, panic disorder) psychological factors, somatic symptom reporting (somatic symptom count, dyspepsia, irritable bowel syndrome and fatigue symptoms) and QoL (physical, mental) using validated questionnaires. Confirmatory factor analysis (CFA) was used to assess whether four a priori hypothesised latent variables ('abuse', 'trait affectivity', 'state affect' and 'somatic symptom reporting') were adequately supported by the data. Structural equation modelling (SEM) was used to test the a priori hypothesised relationships between these latent variables and the observed variables gastric sensitivity and QoL. RESULTS: Both the CFA and SEM models fitted the data adequately. Abuse exerted its effect directly on 'somatic symptom reporting', rather than indirectly through psychological factors. A reciprocal relationship between 'somatic symptom reporting' and 'state affect' was found. Gastric sensitivity influences 'somatic symptom reporting' but not vice versa. 'Somatic symptom reporting' and 'trait affectivity' are the main determinants of physical and mental QoL, respectively. CONCLUSIONS: We present the first comprehensive model elucidating the complex interactions between multiple dimensions (gastric sensitivity, abuse history, 'state' and 'trait' psychological factors, somatic symptom reporting and QoL) in FD.