There is a clear unmet need for new treatments in irritable bowel syndrome with diarrhea (IBS-D). Ondansetron, an old 5-hydroxy-tryptamine3 antagonist, used for chemotherapy-induced nausea and ...vomiting and with favorable side effect profile, has shown promising results in previous trials. In this issue, efficacy with a novel bimodal release ondansetron formulation was presented in IBS-D. The bimodal release ondansetron improved stool consistency, presumably by slowing transit time, and tended to improve other IBS symptoms as well. The authors proposed C-reactive protein levels as a tool to select responders because a better response was seen in patients with slightly elevated C-reactive protein levels. Future large-scale studies will determine the role of bimodal release ondansetron in IBS-D with and without low-grade inflammation.
Irritable bowel syndrome (IBS) is one of the most common disorders of the gut-brain axis, which affects approximately 4% of the global population. The Rome IV criteria define IBS as chronic or ...recurrent abdominal pain associated with altered bowel habits. Patients can be categorized in four subtypes: IBS with predominant constipation (IBS-C), predominant diarrhea (IBS-D), mixed bowel habits (IBS-M), and unclassified (IBS-U). IBS is associated with a lower quality of life, reduced work productivity, and high healthcare costs. When comparing subtypes, patients with IBS-D report lower disease related quality of life. Due to the scope of this review, we have solely focused on patients with IBS-D. Choosing the right pharmacological treatment in these patients remains challenging due to the heterogeneous patient population, patients' expectation of the treatment outcome, unavailability of efficacious drugs, and the multifactorial and incompletely understood underlying pathophysiology. Currently, pharmacological treatment options target individual symptoms, such as abdominal pain, altered bowel habits, and bloating. In this review, we aimed to summarize the current and recent pharmacological treatment options in IBS-D, targeting the predominant gastrointestinal symptoms. Additionally, we proposed a pharmacological treatment algorithm which healthcare professionals could use when treating individual patients with IBS-D.
This study focused on defining the global prevalence of clinically relevant levels of psychological distress and somatic symptoms and the prevalence of coexistence between these symptoms and ...disorders of gut-brain interaction (DGBI). We also analyzed how clinically relevant psychological distress and somatic symptoms and coexistent DGBI are associated with health-related outcomes.
We included a representative sample of 54,127 adult participants (49.1% women; mean age of 44.3 years) from 26 countries worldwide. Participants completed an Internet survey (the Rome Foundation Global Epidemiology Study) with validated self-report questionnaires.
Clinically relevant psychological distress and/or somatic symptom severity was reported by 37.5% of the sample. These participants had 4.45 times higher odds to have at least one DGBI than individuals without psychological distress and/or somatic symptoms. Compared with participants with psychological distress and/or somatic symptoms with vs without DGBI, participants with a DGBI reported increased healthcare and medication utilization (with OR from 1.6 to 2.8). Coexistent DGBI in participants with psychological distress and/or somatic symptoms was the variable most strongly associated with reduced mental (β = -0.77; confidence interval -0.86 to -0.68) and physical (β = -1.17; confidence interval -1.24 to -1.10) quality of life.
This global study shows that psychological distress, somatic symptoms, and DGBI are very common and frequently overlap. The coexistence between psychological distress/somatic symptoms and DGBI seems to be especially detrimental to quality of life and healthcare utilization. Individuals with psychological distress/somatic symptoms and DGBI coexistence seem to be a group vulnerable to psychosocial problems that should be studied further and would likely benefit from psychological/psychiatric interventions.
ABSTRACT
Current fructose consumption levels often overwhelm the intestinal capacity to absorb fructose. We investigated the impact of fructose malabsorption on intestinal endocrine function and ...addressed the role of the microbiota in this process. To answer this question, a mouse model of moderate fructose malabsorption ketohexokinase mutant (KHK)−/− and wild‐type (WT) littermate mice were used and received a 20%‐fructose (KHK‐F and WT‐F) or 20%‐glucose diet. Cholecystokinin (Cck) mRNA and protein expression in the ileum and cecum, as well as preproglucagon (Gcg) and neurotensin (Nts) mRNA expression in the cecum, increased in KHK‐F mice. In KHK‐F mice, triple‐label immunohistochemistry showed major up‐regulation of CCK in enteroendocrine cells (EECs) that were glucagon‐like peptide‐1 (GLP‐1)+/Peptide YY (PYY−) in the ileum and colon and GLP‐1−/PYY− in the cecum. The cecal microbiota composition was drastically modified in the KHK‐F in association with an increase in glucose, propionate, succinate, and lactate concentrations. Antibiotic treatment abolished fructose malabsorption‐dependent induction of cecal Cck mRNA expression and, in mouse GLUTag and human NCI‐H716 cells, Cck mRNA expression levels increased in response to propionate, both suggesting a microbiota‐dependent process. Fructose reaching the lower intestine can modify the composition and metabolism of the microbiota, thereby stimulating the production of CCK from the EECs possibly in response to propionate.—Zhang, X., Grosfeld, A., Williams, E., Vasiliauskas, D., Barretto, S., Smith, L., Mariadassou, M., Philippe, C., Devime, F., Melchior, C., Gourcerol, G., Dourmap, N., Lapaque, N., Larraufie, P., Blottière, H. M., Herberden, C., Gerard, P., Rehfeld, J. F., Ferraris, R. P., Fritton, J. C., Ellero‐Simatos, S., Douard, V. Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism. FASEB J. 33, 7126–7142 (2019). www.fasebj.org
Patients with disorders of gut-brain interaction (DGBI) report meal intake to be associated with symptoms. DGBI patients with meal-related symptoms may have more severe symptoms overall and worse ...health outcomes, but this subgroup has not been well characterized. We aimed to describe the global prevalence of meal-related abdominal pain and characterize this subgroup.
The data analyzed originated from the Internet survey component of the population-based Rome Foundation Global Epidemiology Study, completed in 26 countries (n = 54,127). Adult subjects were asked whether they had abdominal pain and how often this was meal-related. Respondents were categorized into "no," "occasional," and "frequent" meal-related abdominal pain groups based on 0%, 10-40%, and ≥50% of the pain episodes being meal-related, respectively. DGBI diagnoses, frequency of other GI symptoms, psychological distress, non-GI somatic symptoms, quality of life, and healthcare utilization were compared between groups. Mixed linear and ordinal regression was used to assess independent associations between psychological distress, non-GI somatic symptoms, quality of life, other GI symptoms, and meal-related abdominal pain.
Overall, 51.9% of the respondents reported abdominal pain in the last 3 months, and 11.0% belonged to the group with frequent meal-related abdominal pain, which included more females and younger subjects. DGBI diagnoses were more common in subjects with frequent meal-related abdominal pain, and the frequency of several GI symptoms was associated with having more frequent meal-related abdominal pain. Having meal-related abdominal pain more frequently was also associated with more severe psychological distress, non-GI somatic symptoms, and a poorer quality of life. The group with frequent meal-related abdominal pain also more often consulted a doctor for bowel problems compared to the other groups of meal-related abdominal pain.
Reporting frequent meal-related abdominal pain is common across the globe and associated with other GI and non-GI somatic symptoms, psychological distress, healthcare utilization, and a poorer quality of life. Individuals who frequently experience meal-related abdominal pain also more frequently fulfill the diagnostic criteria for DGBI. Assessing meal-related symptoms in all DGBI patients could be of major importance to improve and individualize symptom management.
We aimed to determine the burden of opioid consumption in a cohort of patients with functional gastrointestinal disorders.
All patients diagnosed with functional gastrointestinal disorders and ...referred to our university hospital were evaluated from 2013 to the beginning of 2019. Irritable bowel syndrome and functional dyspepsia diagnoses were determined according to Rome criteria and severity according to irritable bowel syndrome severity scoring system. Vomiting was quantified using a 5-point Likert scale, and constipation severity was measured using the Knowles-Eccersley-Scott-Symptom questionnaires. Quality of life was quantified by the GastroIntestinal Quality of Life Index. Patients were categorized as being treated on a chronic basis with either tramadol, step II opioids, step III opioids or as being opioid-free.
2933 consecutive patients were included. In our cohort, 12.5% had only irritable bowel syndrome, 39.3% had only functional dyspepsia, 24.9% had a combination of both, and 23.4% had other functional gastrointestinal disorders. Among them, the consumption of tramadol, step II (tramadol excluded) and step III opioids was 1.8, 1.3 and 0.3 % respectively in 2013 and 4.3, 3.4 and 1.9% in 2018 (
< 0.03). Opioid consumption was associated with increased vomiting (
= 0.0168), constipation (
< 0.0001), symptom severity (
< 0.001), more altered quality of life (
< 0.0001) and higher depression score (
= 0.0045).
In functional gastrointestinal disorders, opioid consumption has increased in the last years and is associated with more GI symptoms (vomiting, constipation and GI severity), higher depression and more altered quality of life.
Esophageal hypersensitivity is important in gastroesophageal reflux disease (GERD) patients who are refractory to acid-suppressive therapy. Stress affects visceral sensitivity and exacerbates ...heartburn in GERD. Peripheral CRH is a key mediator of the gut stress response. We hypothesize that CRH increases esophageal sensitivity and alters esophageal motility in health. Esophageal sensitivity to thermal, mechanical, electrical, and chemical stimuli was assessed in 14 healthy subjects after administration of placebo or CRH (100 μg iv). Perception scores were assessed for first perception, pain perception threshold (PPT), and pain tolerance threshold (PTT). Esophageal motility was investigated by high-resolution impedance manometry, before and after CRH and evaluated by distal contractile integral (DCI) and intrabolus pressure (IBP). Pressure flow analysis assessed bolus clearance (impedance ratio), degree of pressurization needed to propel bolus onward (IBP slope), and pressure flow (pressure flow index, PFI). Stress and mood were assessed during the study. Sensitivity to mechanical distention was increased after CRH compared with placebo (PPT:
= 0.0023; PTT:
= 0.0253). CRH had no influence on the other stimulations. DCI was increased for all boluses (liquid,
= 0.0012; semisolid,
= 0.0017; solid,
= 0.0107). Impedance ratio for liquid (
< 0.0001) and semisolid swallows (
= 0.0327) decreased after CRH. IBP slope increased after CRH for semisolid (
= 0.0041) and solid (
= 0.0003) swallows. PFI increased for semisolid (
= 0.0017) and solid swallows (
= 0.0031). CRH increased esophageal sensitivity to mechanical distention, not to the other stimulation modalities. CRH increased esophageal contractility and tone, decreased LES relaxation, increased esophageal bolus pressurization, improved esophageal bolus clearance, and increased pressure flow.
This is the first study to address the effect of corticotropin-releasing hormone (CRH) on esophageal sensitivity and alterations in motility in health. CRH administration increased esophageal sensitivity to mechanical distention. This effect is accompanied by an increase in esophageal contractility and tone and a decrease in lower esophageal sphincter relaxation. CRH increased esophageal bolus pressurization, improved esophageal bolus clearance, and increased pressure flow. The changes in esophageal contractile properties may underlie the increased sensitivity to mechanical distention after CRH.
Association between symptoms, quality of life and gastric emptying in dyspepsia is inconsistent in the literature. The aim of our study is to investigate if gastric emptying is associated with ...specific symptoms and quality of life in dyspeptic patients.
We reviewed retrospectively gastric emptying measured by
C-labelled octanoate breath testing for more than 6 hours in 198 consecutive patients with dyspepsia complaints. Gastrointestinal symptoms were assessed using a 5-points Likert scale and by a symptomatic composite score, whereas quality of life was measured by the GIQLI.
In our cohort, 90 patients (45%) had a delayed gastric emptying (half emptying time above 166 minutes when assessed over 6-8 hours). There was no difference in symptoms or quality of life between patients with or without delayed gastric emptying. However, patients with severely delayed gastric emptying (half emptying time above 200 minutes) had increased postprandial fullness (
= 0.012), abdominal pain (
= 0.026), bloating (
= 0.044), early satiety (
= 0.018), symptomatic composite score (
= 0.005), and a lower quality of life (
= 0.018). This association was no longer observed if the calculation of gastric emptying was limited to the first 4-hour samples.
There is no association between symptoms, quality of life and gastric emptying in an overall dyspeptic population. However, there is an association between symptoms, quality of life of delayed gastric emptying in the subgroup of patients with severely delayed gastric emptying. An 8-hour measurement of gastric emptying should be recommended.
Sleep disturbances are common in patients with functional dyspepsia. Our aim was to assess the relationship between subjective sleep and quality of life and to identify factors associated with ...impaired sleep in functional dyspepsia.
One thousand two hundred and twenty patients referred for functional gastrointestinal disorders at a single tertiary care center between end 2017 and June 2019 were studied using a self-administered questionnaire. 355 patients with Rome IV-based functional dyspepsia were identified. Sleep was assessed using both the
(PSQI) and the
(ISI). The severity of dyspeptic symptoms was assessed using the
(TSS). Quality of life was assessed by the
(GIQLI). Anxiety and depression levels were evaluated using the
(HAD) scale.
Among the 355 patients with functional dyspepsia, 66 (18.6%) patients displayed normal sleep quality whereas 289 (81.4%) patients had altered sleep quality. Functional dyspepsia patients with sleep disturbances were older (48.1 ± 15.4 vs. 41.4 ± 16.0,
= 0.0009), had decreased quality of life (GIQLI: 75.3 ± 18.5 vs. 92.1 ± 15.4,
< 0.0001), greater severity of their symptoms (TSS: 18.9 ± 3.6 vs. 17.2 ± 3.9,
= 0.0007), and higher anxiety and depression scores (HADS: 17.7 ± 7.2 vs. 11.9 ± 5.1,
< 0.0001). A correlation was found between sleep quality and quality of life
= -0.43 (95% CI: -0.51 to -0.34),
< 0.0001. Independent factors predicting poor sleep quality were age OR 1.03 (95% CI = 1.01-1.05),
= 0.006, depression level OR 1.27 (95% CI = 1.16-1.39);
< 0.0001, and the severity of dyspeptic symptoms OR 1.13 (95% CI = 1.04-1.22);
= 0.004.
A high prevalence of sleep disturbances was found in patients suffering from functional dyspepsia, with 81% of them having altered sleep quality and 61% having insomnia based on subjective assessment. Altered sleep quality and insomnia were associated with altered quality of life, higher severity of symptoms, and higher anxiety and depression scores in this disorder.
To compare the prevalence of anxiety and depression states and eating disorders (EDs) between patients with irritable bowel syndrome (IBS) and healthy volunteers without IBS.
IBS patients according ...to Rome III criteria referred to our tertiary care center for therapeutic management and matched volunteers without IBS were prospectively included. EDs were screened by Sick, Control, One stone, Fat, Food-French version (SCOFF-F) questionnaire. IBS symptom severity (IBS symptom severity score), stool consistency (Bristol stool scale), anxiety and depression levels (Hospital Anxiety and Depression scale), and quality of life (validated Gastrointestinal Quality of Life Index) were assessed by validated self-questionnaires.
IBS (228) patients and healthy volunteers (228) were included. Mean age was 42.5 ± 13.9 years with mainly women (76.7%). Among IBS patients, 25.4% had positive SCOFF-F compared to 21.1% of volunteers. IBS patients more frequently had a lower body mass index (BMI) than volunteers (p < 0.0001). IBS patients with ED had poorer quality of life and more stressful life events (p = 0.02) than IBS patients without ED. The prevalence of anxiety and depression was significantly higher in IBS patients with ED than in volunteers without ED, respectively (19.0% vs 1.9%, p=0.00, and 60.3% vs 19.7%, p < 0.0001).
The prevalence of ED assessed with positive SCOFF-F questionnaire was not significantly different between IBS patients and healthy volunteers. The combination of IBS and ED was associated with higher levels of anxiety or depression and poorer quality of life.
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