Electrogastrography as a diagnostic tool for delayed gastric emptying in functional dyspepsia and irritable bowel syndrome

Several pathophysiological mechanisms have been proposed in functional gastrointestinal (GI) disorders, e.g. altered GI motility and sensitivity. The aim of this study was to investigate gastric electrical activity (GEA) in patients with functional dyspepsia (FD) or irritable bowel syndrome (IBS) compared with healthy controls (HC), and to assess if abdominal symptoms and delayed gastric emptying are associated with alterations in GEA, as determined by electrogastrography (EGG). Forty patients with FD, IBS or both were compared with 22 HC. EGG was performed before and after a standard meal. Frequencies and amplitudes pre- and post-prandially were analysed. Furthermore, gastric emptying and symptom scores were assessed. Eight of 40 patients (20%; three FD, three IBS, two FD and IBS) had delayed gastric emptying. Disturbed gastric emptying and lack of a postprandial increase in the EGG amplitude were significantly correlated (r = 0.8; P < 0.005). No differences between controls and patients were observed in the distribution of EGG frequencies. Treatment with the prokinetically active macrolide erythromycin improved gastric emptying, GEA and symptoms (n = 4). The data suggest that EGG could be useful as a diagnostic tool in patients with FD and IBS to identify a subgroup of patients with delayed gastric emptying.     

Children with functional gastrointestinal disorders with and without co-existing nausea: A comparison of clinical and psychological characteristics

Background

Nausea co-existing with functional gastrointestinal disorders (FGIDs) has been suggested to negatively impact physical and psychological factors in children. This study aims to compare clinical and psychological characteristics of a large cohort of pediatric patients with an FGID with and without nausea.

Methods

Patients of two previous randomized controlled trials were included, the first assessing the effect of hypnotherapy (HT) in 260 children fulfilling Rome criteria of irritable bowel syndrome (IBS) or functional abdominal pain (FAP), the second examining the effect of HT in 100 children with nausea in children with either functional nausea (FN) or functional dyspepsia (FD). At inclusion, demographics, clinical features, including the presence of nausea, depression and anxiety, somatization, and health-related quality of life (QoL) were assessed in patients.

Key Results

In total, 355 patients with IBS (n = 131), FAP (n = 127), FN (n = 62), and FD (n = 35) were included, of which 255 (72%) patients experienced nausea versus 100 (28%) without nausea. Age at onset of symptoms was higher in children experiencing nausea (12.0y vs. 9.0y, p = 0.000). Significantly higher somatization, anxiety and depression scores, and lower health-related QoL were reported for children with nausea. There were no significant differences between children with only nausea and children with nausea and abdominal pain.

Conclusions and Inferences

Children with nausea, either with or without abdominal pain, report higher somatization scores, increased anxiety and depression, and lower overall QoL, compared to children with pain-related FGIDs without accompanying nausea. Addressing the presence of nausea in children with FGIDs seems essential to customize their treatment and improve overall quality of life.     

The trials and tribulations of drug development for functional gastrointestinal disorders

Abstract  Functional gastrointestinal disorders (FGID) are common conditions seen in primary care and specialty practices but many affected individuals report a lack of satisfaction with available treatments. Despite the unmet need for more effective pharmacotherapy, drug development for these conditions can be challenging on many levels. This review will discuss the rationale and challenges of drug development for FGID. The reasons for engaging in drug development include that these conditions are highly prevalent, associated with a significant economic and healthcare burden, and associated with a lack of satisfaction with current therapies. The challenges include the lack of perception that FGID are legitimate disorders, the multidimensional and complex pathophysiology of FGID, the lack of a biological marker for diagnosis and treatment response, the heterogeneity of the patient population, the lack of consensus regarding the best outcome measures for clinical trials and the perceived increased risk–benefit ratio associated with drugs for FGID. Ongoing efforts are being taken to work towards a better understanding of pathophysiology, illness severity, patient-reported outcome measures, and benefit : risk assessment, and towards increasing education and communication amongst patients, clinicians, investigators, industry and regulatory agencies which will hopefully help optimize drug development strategies for FGID.     

A comparative study of disorders of gut–brain interaction in Western Europe and Asia based on the Rome foundation global epidemiology study

Objective

Many studies have been published on disorders of the gut–brain interaction (DGBI) in Asia and Western Europe, but no previous study has directly assessed the difference between the two regions. The aim was to compare the prevalence of DGBI in Asia and Western Europe.

Methods

We used data collected in a population-based Internet survey, the Rome Foundation Global Epidemiology Study, from countries in Western Europe (Belgium, France, Germany, Netherlands, Italy, Spain, Sweden, and the United Kingdom) and Asia (China, Japan, South Korea, and Singapore). We assessed DGBI diagnoses (Rome IV Adult Diagnostic Questionnaire), anxiety/depression (Patient Health Questionnaire-4, PHQ-4), non-GI somatic symptoms (PHQ-12), and access to and personal costs of doctor visits.

Results

The study included 9487 subjects in Asia and 16,314 in Western Europe. Overall, 38.0% had at least one DGBI; younger age, female sex, and higher scores on PHQ4 and PHQ12 were all associated with DGBI. The prevalence of having at least one DGBI was higher in Western Europe than in Asia (39.1% vs 36.1%, OR 1.14 [95% CI 1.08–1.20]). This difference was also observed for DGBI by anatomical regions, most prominently esophageal DGBI (OR 1.67 [1.48–1.88]). After adjustment, the difference in DGBI prevalence diminished and psychological (PHQ-4) and non-GI somatic symptoms (PHQ-12) had the greatest effect on the odds ratio estimates.

Conclusion

The prevalence of DGBI is generally higher in Western Europe compared to Asia. A considerable portion of the observed difference in prevalence rates seems to be explained by more severe psychological and non-GI somatic symptoms in Western Europe.     

Is there a role of food allergy in irritable bowel syndrome and functional dyspepsia? A systematic review

A significant proportion of adults believe they suffer from food allergy, and 20-65% of patients with irritable bowel syndrome (IBS) attribute their symptoms to something in food that activates an abnormal response. This systematic review evaluates the role of food allergy in aetiology and management of these disorders. Activation of gastrointestinal mucosal immune system may be one of the causative factors in the pathogenesis of functional dyspepsia and IBS. This activation may result from effects of bacterial infection or other luminal factors including commensal microbial flora and food antigens. Some studies have reported on the role of food allergy in IBS; only one epidemiological study on functional dyspepsia and food allergy has been published. The mechanism by which food activates mucosal immune system is uncertain, but food specific IgE and IgG4 appeared to mediate the hypersensitivity reaction in a subgroup of IBS patients. Exclusion diets based on skin prick test, RAST for IgE or IgG4, hypoallergic diet and clinical trials with oral disodium cromoglycate have been conducted, and some success has been reported in a subset of IBS patients. Further well-controlled studies are needed to establish whether food allergy plays a role in the pathophysiology of functional dyspepsia and IBS.     

Unraveling functional abdominal bloating and distension: the role of thoraco-abdominal accommodation and a physical sign to aid its detection

Bloating and distension are common complaints in patients with irritable bowel syndrome of which the cause has remained elusive, although it has been shown that the obvious explanation of excessive gas is unlikely. The recent application of technologies such as the gas challenge technique, abdominal inductance plethysmography, CT scanning, as well as electromyography of the diaphragm and anterior abdominal wall, have allowed the situation to be slowly unraveled. It is now seems probable that the pathophysiology of bloating and distension are subtly different with the former having a sensory component whereas mechanical factors, such as disordered abdominal accommodation, contribute more to the latter.     

Brain–gut connections in functional GI disorders: anatomic and physiologic relationships

Understanding the neural regulation of gut function and sensation makes it easier to understand the interrelatedness of emotionality, symptom-attentive behavior or hypervigilance, gut function and pain. The gut and the brain are highly integrated and communicate in a bidirectional fashion largely through the ANS and HPA axis. Within the CNS, the locus of gut control is chiefly within the limbic system, a region of the mammalian brain responsible for both the internal and external homeostasis of the organism. The limbic system also plays a central role in emotionality, which is a nonverbal system that facilitates survival and threat avoidance, social interaction and learning. The generation of emotion and associated physiologic changes are the work of the limbic system and, from a neuroanatomic perspective, the 'mind-body interaction' may largely arise in this region. Finally, the limbic system is also involved in the 'top down' modulation of visceral pain transmission as well as visceral perception. A better understanding of the interactions of the CNS, ENS and enteric immune system will significantly improve our understanding of 'functional' disorders and allow for a more pathophysiologic definition of categories of patients currently lumped under the broad umbrella of FGID.     

Visceral and somatic sensory function in functional dyspepsia

Background Visceral hypersensitivity is one of the proposed underlying mechanisms in functional dyspepsia (FD). It is not clear whether visceral hypersensitivity in FD is a manifestation of a central sensitization also encompassing somatic sensitization. Transient receptor potential vanilloid‐1 (TRPV₁) pathways are involved in gastric mechanosensory physiology and the TRPV₁ receptor agonist, capsaicin, has been used as a chemical stimulant. Methods In this double‐blind, randomized study we evaluated both visceral and somatic sensory function in 34 FD patients and 42 healthy controls using quantitative sensory testing. Visceral pain sensitivity was assessed using a validated gastric pain model with oral capsaicin capsule titration and somatic pain sensitivity was determined by foot heat and hand electric stimulation. Key Results The median capsaicin dose required to attain moderate pain was 0.5mg in FD and 1mg in controls (P = 0.03). At these doses, mean pain intensities on a 0–100 visual analog scale were greater for FD than controls [56.9 (95% confidence intervals, 52.2–61.5) vs 45.1 (41.6–48.6), resp.] (P = 0.005). Overall, mean somatic sensory and pain thresholds were similar in FD and control groups, but in a subgroup of FD pain hypersensitivity was seen on the hand and on the foot at different stimulation thresholds. Conclusions & Inferences A majority of patients with FD have visceral chemo‐hypersensitivity involving TRPV₁ pathways. A substantial subgroup also has somatic hypersensitivity as evidence of central sensitization.     

Influence of alcohol consumption on IBS and dyspepsia

The role of alcohol use in irritable bowel syndrome (IBS) and dyspepsia is not well understood. We hypothesised that people with psychological distress who drink no alcohol, or excess alcohol, are at increased risk of having IBS or dyspepsia. Valid gastrointestinal (GI) symptom surveys were mailed to randomly selected cohorts of community residents. Associations between IBS, dyspepsia and abdominal pain and alcohol use were assessed using logistic regression adjusted for a Somatic Symptom Checklist score (SSC). A total of 4390 (80%) responded; of these, 10.5% reported IBS, 2% dyspepsia and 22% abdominal pain. Alcohol consumption >7 drinks week(-1) was associated with a greater odds for dyspepsia (OR 2.3; 95% CI:1.1-5.0) and frequent abdominal pain (OR 1.5; 95% CI: 1.1-2.0) but not IBS. However, significant interactions among gender, alcohol use and SSC scores were detected (P < 0.005). In females with a low SSC score, consuming alcohol > or =7 drinks week(-1) increased the odds of IBS compared to drinking alcohol moderately. Alcohol consumption was associated with dyspepsia and abdominal pain. A relationship with IBS was identified when interactions with somatization and gender were appropriately considered. Whether these associations are due to the effects of alcohol on the gut, or a common central mechanism remains to be determined.     

A fresh look at IBS—opportunities for systems medicine approaches

NeuroGUT is a EU‐funded initial training network (ITN) of 14 research projects in neurogastroenterology that have employed an equal number of early‐stage researchers. Neurogut trainees have—among other activities—attended an international conference on irritable bowel syndrome (IBS) in Bologna in 2016 and were asked to critically review and evaluate the current knowledge on IBS for their respective research activities, and to state what they were missing. Most appreciated were the topics brain imaging of gut activity, the role of the gut microbiota, the pharmacology of gut functions, the IBS‐IBD interrelation, the new Rome IV criteria, the role of gas, and the placebo response in functional disorders. Missed were more detailed coverage of high‐resolution manometry, functional brain imaging, advanced “systems medicine” approaches and bioinformatics technology, better sub‐classification of IBS patients, and the development of disease biomarkers, extended at the molecular (genetic/epigenetic, proteonomic) level. They summarize that despite excellent specialized research, there is a gap open that should be filled with systems medicine. For this, it would be necessary that medical research learns even more from the data sciences and other basic disciplines, for example, information technology and system biology, and also welcomes a change in paradigm that enhances open sharing of data, information, and resources.     

Increased visceral sensitivity in Giardia-induced postinfectious irritable bowel syndrome and functional dyspepsia. Effect of the 5HT3-antagonist ondansetron

In an outbreak of waterborne giardiasis where 1300 subjects were diagnosed, with Giardia lamblia, 139 continued to have abdominal symptoms of whom two of three had negative stool culture and microscopy. These were considered to have a postinfectious functional gastrointestinal disorder. We investigated visceral hypersensitivity in patients with persisting abdominal symptoms after Giardia infection and assessed the effect of 5HT(3)-antagonist ondansetron. Twenty-two patients with Giardia negative stools and 19 controls were included. A subset of patients (n = 15) had both irritable bowel syndrome (IBS) and functional dyspepsia (FD). All subjects underwent a satiety test with a soup combined with three-dimensional ultrasound. Fifteen of 22 patients underwent double-blind, randomized, placebo-controlled study with the 5-HT(3) antagonist ondansetron given orally. Drinking capacity was lower in patients than in controls (P < 0.01) and gastric emptying was reduced (P < 0.05). Patients had more symptoms both fasting and postprandially (P < 0.001) compared to controls. Ondansetron had no effect on these parameters except from less nausea postprandially (P < 0.05). In conclusion, patients with Giardia-induced gastrointestinal symptoms developed both IBS and FD. They exhibited gastric hypersensitivity with lower drinking capacity and delayed gastric emptying. The 5-HT(3) antagonist ondansetron did not improve drinking capacity, gastric emptying or symptoms except nausea.