Coffee, Alcohol, and Artificial Sweeteners Have Temporal Associations with Gastrointestinal Symptoms.

BACKGROUND: Various dietary strategies for managing irritable bowel syndrome (IBS) target mechanisms such as brain-gut interactions, osmotic actions, microbial gas production, and local immune activity. These pathophysiological mechanisms are diverse, making it unclear which foods trigger IBS symptoms for a substantial proportion of patients. AIM: To identify associations between foods and gastrointestinal symptoms. METHODS: From the mySymptoms smartphone app, we collected anonymized diaries of food intake and symptoms (abdominal pain, diarrhea, bloating, and gas). We selected diaries that were at least 3 weeks long. The diaries were analyzed for food-symptom associations using a proprietary algorithm. As the participants were anonymous, we conducted an app-wide user survey to identify IBS diagnoses according to Rome IV criteria. RESULTS: A total of 9,710 food symptom diaries that met the quality criteria were collected. Of the survey respondents, 70% had IBS according to Rome IV criteria. Generally, strong associations existed for caffeinated coffee (diarrhea, 1-2 h postprandial), alcoholic beverages (multiple symptoms, 4-72 h postprandial), and artificial sweeteners (multiple symptoms, 24-72 h postprandial). Histamine-rich food intake was associated with abdominal pain and diarrhea. Some associations are in line with existing literature, whilst the absence of an enriched FODMAP-symptom association contrasts with current knowledge. CONCLUSIONS: Coffee, alcohol, and artificial sweeteners were associated with GI symptoms in this large IBS-predominant sample. Symptom onset is often within 2 h postprandial, but some foods were associated with a delayed response, possibly an important consideration in implementing dietary recommendations. Clinical trials must test the causality of the demonstrated food-symptom associations.

Gastroesophageal Reflux Disease-Functional Dyspepsia Overlap: Do Birds of a Feather Flock Together?

INTRODUCTION: Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) are 2 of the most prevalent upper gastrointestinal (GI) disorders in the Western world. Previous Rome definitions excluded patients with predominant heartburn from the definition of FD because they were considered to have GERD. However, more recent studies showed that heartburn and acid regurgitation are also common symptoms in patients with FD. The aim of this study is to provide an overview of the prevalence of overlap between GERD and FD, the underlying pathophysiology and implications for treatment. METHODS: A review of the literature was performed using the PubMed database, and a meta-analysis with random effects model was completed. RESULTS: This review showed considerable overlap between GERD and FD. A meta-analysis on the data included in this review showed 7.41% (confidence interval [CI]: 4.55%-11.84%) GERD/FD overlap in the general population, 41.15% (CI: 29.46%-53.93%) GERD with FD symptoms, and 31.32% (CI: 19.43%-46.29%) FD with GERD symptoms. Although numerous committees and consensus groups attempted to develop uniform definitions for the diagnosis of GERD and FD, various diagnostic criteria are used across studies and clinical trials (frequency, severity, and location of symptoms). Several studies showed that the overlap between GERD and FD can be explained by a shared pathophysiology, including delayed gastric emptying and disturbed gastric accommodation. DISCUSSION: For diagnoses of GERD and FD, uniform definitions that are easy to implement in population studies, easy to interpret for physicians, and that need to be well explained to patients to avoid overestimation or underestimation of true prevalence are needed. Both GERD and FD coexist more frequently than expected, based on coincidence, suggesting a potential pathophysiological link. More research is needed to explore the common GERD/FD overlap population to identify the underlying pathophysiological mechanisms, which may lead to a more effective therapeutic approach.

Accuracy of Nutrient Calculations Using the Consumer-Focused Online App MyFitnessPal: Validation Study.

BACKGROUND: Digital food registration via online platforms that are coupled to large food databases obviates the need for manual processing of dietary data. The reliability of such platforms depends on the quality of the associated food database. OBJECTIVE: In this study, we validate the database of MyFitnessPal versus the Belgian food composition database, Nubel. METHODS: After carefully given instructions, 50 participants used MyFitnessPal to each complete a 4-day dietary record 2 times (T1 and T2), with 1 month in between T1 and T2. Nutrient intake values were calculated either manually, using the food composition database Nubel, or automatically, using the database coupled to MyFitnessPal. First, nutrient values from T1 were used as a training set to develop an algorithm that defined upper limit values for energy intake, carbohydrates, fat, protein, fiber, sugar, cholesterol, and sodium. These limits were applied to the MyFitnessPal dataset extracted at T2 to remove extremely high and likely erroneous values. Original and cleaned T2 values were correlated with the Nubel calculated values. Bias was estimated using Bland-Altman plots. Finally, we simulated the impact of using MyFitnessPal for nutrient analysis instead of Nubel on the power of a study design that correlates nutrient intake to a chosen outcome variable. RESULTS: Per food portion, the following upper limits were defined: 1500 kilocalories for total energy intake, 95 grams (g) for carbohydrates, 92 g for fat, 52 g for protein, 22 g for fiber, 70 g for sugar, 600 mg for cholesterol, and 3600 mg for sodium. Cleaning the dataset extracted at T2 resulted in a 2.8% rejection. Cleaned MyFitnessPal values demonstrated strong correlations with Nubel for energy intake (r=0.96), carbohydrates (r=0.90), fat (r=0.90), protein (r=0.90), fiber (r=0.80), and sugar (r=0.79), but weak correlations for cholesterol (ρ=0.51) and sodium (ρ=0.53); all P values were ≤.001. No bias was found between both methods, except for a fixed bias for fiber and a proportional bias for cholesterol. A 5-10% power loss should be taken into account when correlating energy intake and macronutrients obtained with MyFitnessPal to an outcome variable, compared to Nubel. CONCLUSIONS: Dietary analysis with MyFitnessPal is accurate and efficient for total energy intake, macronutrients, sugar, and fiber, but not for cholesterol and sodium.

Prucalopride in Gastroparesis: A Randomized Placebo-Controlled Crossover Study.

OBJECTIVES: Prokinetics are considered the preferred treatment option for gastroparesis, but evidence of their efficacy is scarce. Prucalopride, a selective 5-hydroxytryptamine 4 receptor agonist used in the treatment of constipation, is able to enhance the gastric emptying rate. In a double-blind, randomized, placebo-controlled crossover study, we evaluated the efficacy of prucalopride to improve the gastric emptying rate and symptoms in patients with gastroparesis. METHODS: Thirty-four patients with gastroparesis (28 idiopathic, 7 men, mean age 42 ± 13 years) were evaluated in a double-blind crossover trial of 4-week treatment periods with placebo or prucalopride 2 mg q.d., separated by 2 weeks of washout. The primary end point was the change in symptom severity, assessed by the Gastroparesis Cardinal Symptom Index; secondary end points comprised the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index, the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life, and daily diaries, and the gastric emptying rate was assessed by the C-octanoic acid breath test. RESULTS: Three patients were lost to follow-up. One serious adverse event occurred (small bowel volvulus in the prucalopride group), and 3 patients dropped out because of adverse events of nausea and headache (all prucalopride). For the entire patient group, compared with placebo, prucalopride significantly improved the total Gastroparesis Cardinal Symptom Index (1.65 ± 0.19 vs 2.28 ± 0.20, P < 0.0001) and the subscales of fullness/satiety, nausea/vomiting, and bloating/distention. Prucalopride significantly improved the overall Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life score (1.15 ± 0.16 vs 1.44 ± 0.16, P < 0.05) and the domains of clothing and diet. The gastric half emptying time was significantly enhanced by prucalopride compared with placebo and baseline (98 ± 10 vs 143 ± 11 and 126 ± 13 minutes, P = 0.005 and <0.001, respectively). These significant improvements were also found when considering only the idiopathic gastroparesis subgroup. DISCUSSION: In a cohort of patients with predominantly idiopathic gastroparesis, 4 weeks of prucalopride treatment significantly improved symptoms and quality of life and enhanced gastric emptying compared with placebo.

Development of Irritable Bowel Syndrome Features Over a 5-year Period.

BACKGROUND & AIMS: There are few data from longitudinal studies of the gastrointestinal and psychologic features of irritable bowel syndrome (IBS). We studied within-person correlations among features of IBS, along with progression of gastrointestinal (GI) symptoms and quality of life, and factors associated with changes over time. METHODS: We performed a longitudinal study of 276 patients with IBS in Sweden (70% female; ages, 19-76 years) who completed questionnaires, each year for 5 years, about their GI symptom severity, quality of life, GI-specific anxiety, general anxiety, depression, and coping resources. We performed within-person correlation analyses, latent class growth analysis, and random-intercept cross-lagged panel analysis. RESULTS: Within-person correlations with GI symptom severity were strongest for quality of life (r = -0.56) and GI-specific anxiety (r = 0.47). Progression of GI symptom severity was defined based on 3 classes; the class with the highest mean levels of GI, depression, and (GI-specific) anxiety symptoms at baseline did not improve over the 5-year period, contrary to the other classes. GI-specific anxiety was associated with an increase in GI symptom severity and decrease in quality of life 1 year later (P < .05) but other features of IBS were not. CONCLUSIONS: In a 5-year study of patients with IBS in Sweden, we found 3 classes of GI symptom development. We found levels of GI-specific anxiety to associate with GI symptom severity and quality of life 1 year later. Clinicians should be aware of GI-specific anxiety in patients with IBS, to identify patients at risk for lack of long-term symptom improvement with standard medical treatment.

Factor Analysis Defines Distinct Upper and Lower Gastrointestinal Symptom Groups Compatible With Rome IV Criteria in a Population-based Study.

BACKGROUND & AIMS: The Rome IV criteria define functional gastrointestinal (GI) disorders by specific combinations of symptoms. It is possible to empirically evaluate these symptom combinations by factor analysis (a statistical procedure that groups variables that correlate). However, this analysis has not been performed for the Rome IV criteria, and factor analyses based on the previous versions of the Rome criteria did not use population-based data. We therefore investigated symptom grouping by the Rome IV questionnaire using factor analysis of a population-based sample. METHODS: The Rome IV questionnaire was completed online in English by 5931 respondents from the United Kingdom, United States, and Canada (49% female, age range, 18-92 years). We performed an exploratory factor analysis on the Rome IV questions. Next, we performed a confirmatory factor analysis to compare the exploratory factor result to that of the Rome IV criteria. RESULTS: The exploratory factor analysis identified 8 factors that accounted for 45% of the variance in response: constipation, diarrhea, irritable bowel syndrome, abdominal pain, heartburn, nausea or vomiting, globus, and other upper GI symptoms. Most factors corresponded to distinct functional GI disorders defined by the Rome IV criteria-exceptions included abdominal pain and upper GI symptoms. In confirmatory factor analysis, the exploratory model fitted slightly better than that based on the Rome IV criteria (root mean square error of approximation, 0.063 vs 0.077). CONCLUSIONS: We used factor analysis to identify distinct upper and lower GI symptom groups that are compatible with the Rome IV criteria. Our findings support the use of the Rome IV criteria in research and clinical practice as a basis for development of diagnostics and management of patients.

Associations between postprandial symptoms, hydrogen and methane production, and transit time in irritable bowel syndrome.

BACKGROUND: Abnormal oroanal transit time (OATT) and visceral hypersensitivity are key pathophysiological factors in irritable bowel syndrome (IBS). The lactulose nutrient challenge test (LNCT) has been developed to assess the postprandial symptoms and gut microbial fermentation. We aimed to investigate associations between OATT, rectal sensitivity, and LNCT in IBS patients. METHODS: We included 263 IBS patients from two study cohorts, where the link between pathophysiology and symptoms was investigated. During the LNCT, severity of postprandial symptoms was graded, and breath hydrogen/methane concentrations were measured after ingestion of a combined lactulose nutrient drink every 15 min for 4 h. The patients underwent rectal sensitivity (rectal barostat) and OATT (radiopaque markers) investigations. Comorbid conditions (functional dyspepsia, anxiety, depression, and somatization) were assessed with questionnaires. KEY RESULTS: After controlling for comorbid conditions, rectal sensitivity was associated with abdominal pain (p < 0.05), and more rapid OATT was associated with higher severity of abdominal discomfort, rumbling, nausea, and urgency (p < 0.05 for all) both pre- and post-prandially. Postprandial nausea, urgency, and abdominal pain changed differently over time depending on OATT (p < 0.05 for all). OATT, but not rectal sensitivity, was associated with hydrogen and methane concentrations (p = 0.002 for both). Trajectories over time of postprandial symptoms and exhaled hydrogen/methane concentrations were correlated with different correlations depending on OATT. CONCLUSION AND INFERENCES: This study highlights the importance of oroanal transit and hydrogen and methane production in the pathophysiology of IBS and increases our understanding of pathophysiological factors involved in postprandial symptom generation. Treatments targeting oroanal transit and hydrogen and methane production may improve specific postprandial symptoms.

Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome: A multicenter retrospective study.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) of the serotonin type 3 receptor subunit (HTR3) genes have been associated with psychosomatic symptoms, but it is not clear whether these associations exist in irritable bowel syndrome (IBS). AIM: To assess the association of HTR3 polymorphisms with depressive, anxiety, and somatization symptoms in individuals with IBS. METHODS: In this retrospective study, 623 participants with IBS were recruited from five specialty centers in Germany, Sweden, the United States, the United Kingdom, and Ireland. Depressive, anxiety, and somatization symptoms and sociodemographic characteristics were collected. Four functional SNPs - HTR3A c.-42C>T, HTR3B c.386A>C, HTR3C c.489C>A, and HTR3E c.*76G>A - were genotyped and analyzed using the dominant and recessive models. We also performed separate analyses for sex and IBS subtypes. SNP scores were calculated as the number of minor alleles of the SNPs above. The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays. RESULTS: Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model (F depressive = 7.475, P depressive = 0.006; F anxiety = 6.535, P anxiety = 0.011). A higher SNP score (range 0-6) was linked to a worsened depressive symptoms score (F = 7.710, P-linear trend = 0.006) in IBS. The potential relevance of the HTR3C SNP was corroborated, showing changes in the expression level of 5-HT3AC variant receptors. CONCLUSION: We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS. The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.

A Distinct Faecal Microbiota and Metabolite Profile Linked to Bowel Habits in Patients with Irritable Bowel Syndrome.

Patients with irritable bowel syndrome (IBS) are suggested to have an altered intestinal microenvironment. We therefore aimed to determine the intestinal microenvironment profile, based on faecal microbiota and metabolites, and the potential link to symptoms in IBS patients. The faecal microbiota was evaluated by the GA-mapTM dysbiosis test, and tandem mass spectrometry (GC-MS/MS) was used for faecal metabolomic profiling in patients with IBS and healthy subjects. Symptom severity was assessed using the IBS Severity Scoring System and anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. A principal component analysis based on faecal microbiota (n = 54) and metabolites (n = 155) showed a clear separation between IBS patients (n = 40) and healthy subjects (n = 18). Metabolites were the main driver of this separation. Additionally, the intestinal microenvironment profile differed between IBS patients with constipation (n = 15) and diarrhoea (n = 11), while no clustering was detected in subgroups of patients according to symptom severity or anxiety. Furthermore, ingenuity pathway analysis predicted amino acid metabolism and several cellular and molecular functions to be altered in IBS patients. Patients with IBS have a distinct faecal microbiota and metabolite profile linked to bowel habits. Intestinal microenvironment profiling, based on faecal microbiota and metabolites, may be considered as a future non-invasive diagnostic tool, alongside providing valuable insights into the pathophysiology of IBS.

Codeine induces increased resistance at the esophagogastric junction but has no effect on motility and bolus flow in the pharynx and upper esophageal sphincter in healthy volunteers: A randomized, double-blind, placebo-controlled, cross-over trial.

BACKGROUND: Chronic opioid use can induce esophageal dysfunction with symptoms resembling achalasia and a manometric pattern of esophagogastric junction-outflow obstruction (EGJ-OO). However, the effect of opioids in acute setting on pharyngeal function and esophageal body contractility has not been investigated. METHODS: After positioning the high-resolution impedance manometry (HRiM) catheter, codeine (60 mg) or placebo (glucose syrup) was infused intragastrically. Forty-five minutes post-infusion, participants received liquid, semi-solid, and solid boluses to assess esophageal and pharyngeal function. HRiM analysis was performed adhering to the Chicago classification v3.0. (CC v3.0). Pressure flow analysis (PFA) for the esophageal body and the pharynx was performed using the SwallowGateway™ online platform. KEY RESULTS: Nineteen healthy volunteers (HV) [5 male; age 38.3] were included. After codeine administration, higher integrated relaxation pressure 4 s values resulted in significantly reduced deglutitive EGJ relaxation and distal latency was significantly shorter. Distal contractility was similar in both conditions. Bolus flow resistance at the EGJ and distention pressures increased significantly after codeine infusion. Based on CC v3.0, acute infusion of codeine induced EGJ-OO in six HV (p = 0.0003 vs. placebo). Codeine administration induced no significant alterations in any of the pharyngeal PFA metrics. CONCLUSIONS & INFERENCES: In HV, acute administration of codeine increased bolus resistance at the EGJ secondary to induced incomplete EGJ relaxation leading to major motility disorders in a subset of subjects including EGJ-OO. However, an acute single dose of codeine did not affect motility or bolus flow in pharynx and UES. ClinicalTrials.gov number, NCT03784105.

Gastrointestinal symptoms in office workers are predicted by psychological distress and short sleep duration.

OBJECTIVE: Gastrointestinal (GI) symptoms can be triggered by several lifestyle factors, including psychological distress, short sleep duration, and diet. It is poorly known which physiological mechanisms are involved, but the autonomic nervous system (as a key mediator of the stress response) is a likely candidate. We aimed to investigate the associations between selected lifestyle factors, measures of stress physiology, and GI symptoms. METHODS: This is a longitudinal study of 1002 office employees (52% male, mean age 39 ± 10 years), who were asked to report their GI symptoms, psychological distress, sleep times, and intake of caffeine, alcohol, and soft drinks for 5 days. Skin conductance, heart rate / variability, and acceleration were automatically recorded using wearable sensors. 850 participants from this study were eligible for analysis. We computed within-person correlations between the variables and used mediation analysis to test causal models. RESULTS: Sleep duration (ρ = -0.12, p < 0.001) and psychological distress (ρ = 0.19, p < 0.001) were significantly though weakly associated with GI symptoms. The physiological variables were not or weakly associated with GI symptoms in this study. The association between sleep duration and GI symptoms was largely mediated by psychological distress (61%). CONCLUSIONS: Short sleep and psychological distress predict GI symptoms in office workers. Further research is needed to unravel the physiological mechanisms mediate this association.

Adherence to diet low in fermentable carbohydrates and traditional diet for irritable bowel syndrome.

OBJECTIVES: Dietary interventions in irritable bowel syndrome (IBS) include a traditional IBS diet following the guidelines from the National Institute for Health and Clinical Excellence and a diet low in fermentable oligo-, di-, monosaccharides and polyols (FODMAPs). The aim of this study was to evaluate the adherence to these diets, food groups difficult to replace, and dietary determinants of symptom improvement. METHODS: Sixty-six patients with IBS were randomized to a 4-wk low FODMAP or traditional IBS diet. Participants completed 4-d diet diaries before and during the intervention and reported symptoms on the IBS severity scoring system. We described adherence to the diets on the food group and product level and investigated the association between adherence and symptom improvement. RESULTS: Adherence to the low FODMAP diet was good and consistent: All participants had a comparable shift in the diet's principal components compatible with the guidelines. Most high FODMAP products were well replaced with low FODMAP equivalents. However, total energy intake fell by 25%, mainly owing to a 69% decreased intake of snacks (P < 0.001). The traditional IBS diet did not shift the diet's principal components, and despite the guidelines, consumption of coffee and alcoholic beverages remained rather high (>50% of baseline). Total energy intake fell by 11% (P = 0.15). For both diets, there was a trend toward an association between adherence and symptom improvement (P < 0.10). CONCLUSION: In both the low FODMAP and traditional IBS diet, certain food groups were difficult to replace. Because adherence may predict symptom improvement, close dietary guidance might enhance the efficacy of both diets.

Food-symptom diaries can generate personalized lifestyle advice for managing gastrointestinal symptoms: A pilot study.

BACKGROUND: Gastrointestinal (GI) symptoms have a heterogeneous pathophysiology. Yet, clinical management uses group-level strategies. There is a need for studies exploring personalized management options in patients with GI symptoms. From diaries of GI symptoms, food intake, and psychological distress, we extracted and validated personalized lifestyle advice. Secondly, we investigated group-level GI symptom triggers using meta-analysis. METHODS: We collected 209 diaries of GI symptoms, food intake, and psychological distress, coming from 3 cohorts of patients with GI symptoms (n = 20, 26, and 163, median lengths 24, 17, and 38 days). Diaries were split into training and test data, analyzed, and the triggers emerging from the training data were tested in the test data. In addition, we did a random effects meta-analysis on the full data to establish the most common GI symptom triggers. KEY RESULTS: Analysis of the training data allowed us to predict symptom triggers in the test data (r = 0.27, P < .001), especially in the subset of patients with a strong global association between lifestyle factors and symptoms (r = 0.45, P < .001). Low exposure to these triggers in the test data was associated with symptom reduction (P = .043). Meta-analysis showed that caloric intake in the late evening or night predicted an increase in GI symptoms, especially bloating. Several food-symptom associations were found, whereas psychological distress did not clearly lead to more severe GI symptoms. CONCLUSIONS & INFERENCES: Diaries of GI symptoms, food intake, and psychological distress can lead to meaningful personalized lifestyle advice in subsets of patients.

Relations between food intake, psychological distress, and gastrointestinal symptoms: A diary study.

Background: Gastrointestinal symptoms can be triggered by food intake and psychological distress, but individual-level research on food-symptom and stress-symptom associations is scarce. Objective: We aimed to identify associations between food intake, psychological distress and gastrointestinal symptoms, and their implications for personalised clinical management. Methods: Through the mobile phone application mySymptoms, 163 users kept, for a median of five weeks, a diary of food intake, psychological distress and gastrointestinal symptoms. We quantified associations between these on the individual level. The presence of individual-level associations was compared over latent classes of daily symptom patterns. Results: Various gastrointestinal symptoms had demonstrable food-symptom associations (heartburn: 73%, discomfort: 67%, diarrhoea: 57%, bloating: 53%, and gas: 48%). Food-symptom associations for pain in the abdomen (33%) were concentrated in the latent class of individuals with pain in the morning (68%), rather than those with pain in the evening and night (27% and 10%, respectively, p < 0.001). Stress-symptom relations were also found, although only 18% of individuals reported psychological distress. Conclusion: Personal food-symptom and stress-symptom relations can be detected, and may translate into specific daily symptom patterns. A next step will be to let personal food-symptom and stress-symptom relations serve as the basis for personalised clinical management.

Expression of immune-related genes in rectum and colon descendens of Irritable Bowel Syndrome patients is unrelated to clinical symptoms.

BACKGROUND: Mucosal immune activation has been postulated to play an important role in the pathogenesis of irritable bowel syndrome (IBS). However, data are conflicting and often based on small patient cohorts. Here, we aimed to evaluate the gene expression of a large set of immune-related genes in mucosal biopsies from IBS patients and healthy volunteers (HV). METHODS: A total of 171 IBS patients and 127 HV were included in the study. Rectum biopsies were collected from a cohort of 70 HV and 77 IBS patients (Rome III) and colon descendens biopsies from another cohort of 57 HV and 94 IBS patients (Rome II). Gene expression was assessed using OpenArray technology, and validated questionnaires were used to evaluate clinical characteristics (GI symptoms, somatization, anxiety, and depression). KEY RESULTS: A subset of IBS patients (33%) with increased immune activation in the colon descendens was identified using multivariate analysis and displayed increased gene expression of IL1B (3-fold change), prostaglandin synthase PTGS2 (2.1-fold change), and the G-protein-coupled receptor MRGPRX2 (10.7-fold change). Clinical characteristics in this subgroup were however similar to the rest of the patient cohort. Analysis of rectal biopsies failed to identify such subgroup of "immuno-active" IBS patients in the other patient cohort. CONCLUSION: A subset of IBS patients reveals evidence of immune activation in the colon descendens, but not in the rectum; however, gene expression is unrelated to clinical symptoms. To what extent this subgroup might however respond to anti-inflammatory therapy remains to be investigated.

Effects of caloric and noncaloric sweeteners on antroduodenal motility, gastrointestinal hormone secretion and appetite-related sensations in healthy subjects.

Background: Activation of gastrointestinal (GI) sweet taste receptors by caloric sweeteners triggers secretion of anorexigenic and inhibition of orexigenic GI hormones to regulate food intake. The effect of noncaloric sweeteners on these mechanisms is controversial. We have recently shown that motilin-induced gastric phase III contractions signal hunger feelings, thereby identifying GI motility, and its regulatory hormone motilin, as novel players in food intake regulation. Objective: The objective of the present study was to determine the effect of caloric and noncaloric sweeteners on GI motility, GI hormone secretion, and hunger in humans. Design: The study was a randomized, double-blind, crossover trial. Twelve healthy volunteers underwent 4 gastroduodenal manometry recordings in which the occurrence of phase III contractions was followed by the intragastric (i.g.) administration of 250 mL tap water or equisweet caloric (1) 50 g glucose and 2) 25 g fructose) and noncaloric sweeteners [220 mg acesulfame-K (ace-K)] dissolved in 250 mL tap water. Measurement continued until ≥1 subsequent phase III. Blood samples were collected for the measurement of GI hormones. Visual analog scales were used to rate hunger and satiety feelings. Response curves were analyzed using (generalized) linear mixed models. Results: We found: 1) an inhibitory effect of the 2 caloric sweeteners on antral motility (P < 0.01), but no effect after ace-K, 2) an inhibitory effect of the 2 caloric sweeteners on motilin secretion (P < 0.01), but no effect after ace-K, 3) an early increase in cholecystokinin (CCK) secretion after the 2 caloric sweeteners (P < 0.01), but no effect after ace-K, and 4) an initial stronger decrease in hunger feelings and stronger increase in satiety after ace-K (P < 0.05), followed by a steeper return of hunger and decrease of satiety after ace-K (P < 0.05). Conclusions: Our results demonstrate, for the first time to our knowledge, that the caloric sweeteners glucose and fructose, but not the noncaloric sweetener ace-K, inhibit motilin secretion and antral motility while increasing CCK secretion. This trial was registered at clinicaltrials.gov as NCT02891525.

Analysis of advanced glycation endproducts in selected food items by ultra-performance liquid chromatography tandem mass spectrometry: Presentation of a dietary AGE database.

The aim of this study was to validate an ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS) method for the determination of advanced glycation endproducts (AGEs) in food items and to analyze AGEs in a selection of food items commonly consumed in a Western diet. N(ε)-(carboxymethyl)lysine (CML), N(ε)-(1-carboxyethyl)lysine (CEL) and N(δ)-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were quantified in the protein fractions of 190 food items using UPLC-MS/MS. Intra- and inter-day accuracy and precision were 2-29%. The calibration curves showed perfect linearity in water and food matrices. We found the highest AGE levels in high-heat processed nut or grain products, and canned meats. Fruits, vegetables, butter and coffee had the lowest AGE content. The described method proved to be suitable for the quantification of three major AGEs in food items. The presented dietary AGE database opens the possibility to further quantify actual dietary exposure to AGEs and to explore its physiological impact on human health.