Review article: A practical approach to persistent gastrointestinal symptoms in inflammatory bowel disease in remission.

BACKGROUND: Persistent gastrointestinal symptoms are prevalent in adult patients with inflammatory bowel disease (IBD), even when endoscopic remission is reached. These symptoms can have profound negative effects on the quality of life of affected patients and can be difficult to treat. They may be caused by IBD-related complications or comorbid disorders, but they can also be explained by irritable bowel syndrome (IBS)-like symptoms. AIMS: To provide a practical step-by-step guide to diagnose and treat persistent gastrointestinal symptoms in patients with IBD in remission via a personalised approach. METHODS: We scrutinised relevant literature on causes, diagnostics and treatment of persistent gastrointestinal symptoms (abdominal pain or discomfort, bloating, abdominal distension, diarrhoea, constipation and faecal incontinence) in patients with IBD in remission. RESULTS: A graphical practical guide for several steps in diagnosing, identifying potential triggers and adequate treatment of persistent gastrointestinal symptoms in IBD in remission is provided based on supporting literature. The first part of this review focuses on the diagnostic and treatment approaches for potential IBD-related complications and comorbidities. The second part describes the approach to IBS-like symptoms in IBD in remission. CONCLUSIONS: Persistent gastrointestinal symptoms in IBD in remission can be traced back to potential pathophysiological mechanisms in individual patients and can be treated adequately. For both IBD-related complications and comorbidities and IBS-like symptoms in IBD in remission, pharmacological, dietary, lifestyle or psychological treatments can be effective. A systematic and personalised approach is required to reduce the burden for patients, healthcare systems, and society.

A low FODMAP diet plus traditional dietary advice versus a low-carbohydrate diet versus pharmacological treatment in irritable bowel syndrome (CARBIS): a single-centre, single-blind, randomised controlled trial.

BACKGROUND: Dietary advice and medical treatments are recommended to patients with irritable bowel syndrome (IBS). Studies have not yet compared the efficacy of dietary treatment with pharmacological treatment targeting the predominant IBS symptom. We therefore aimed to compare the effects of two restrictive dietary treatment options versus optimised medical treatment in people with IBS. METHODS: This single-centre, single-blind, randomised controlled trial was conducted in a specialised outpatient clinic at the Sahlgrenska University Hospital, Gothenburg, Sweden. Participants (aged ≥18 years) with moderate-to-severe IBS (Rome IV; IBS Severity Scoring System [IBS-SSS] ≥175) and no other serious diseases or food allergies were randomly assigned (1:1:1) by web-based randomisation to receive a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) plus traditional IBS dietary advice recommended by the UK National Institute for Health and Care Excellence (hereafter the LFTD diet), a fibre-optimised diet low in total carbohydrates and high in protein and fat (hereafter the low-carbohydrate diet), or optimised medical treatment based on predominant IBS symptom. Participants were masked to the names of the diets, but the pharmacological treatment was open-label. The intervention lasted 4 weeks, after which time participants in the dietary interventions were unmasked to their diets and encouraged to continue during 6 months' follow-up, participants in the LFTD group were instructed on how to reintroduce FODMAPs, and participants receiving pharmacological treatment were offered diet counselling and to continue with their medication. The primary endpoint was the proportion of participants who responded to the 4-week intervention, defined as a reduction of 50 or more in IBS-SSS relative to baseline, and was analysed per modified intention-to-treat (ie, all participants who started the intervention). Safety was analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02970591, and is complete. FINDINGS: Between Jan 24, 2017, and Sept 2, 2021, 1104 participants were assessed for eligibility and 304 were randomly assigned. Ten participants did not receive their intervention after randomisation and thus 294 participants were included in the modified intention-to-treat population (96 assigned to the LFTD diet, 97 to the low-carbohydrate diet, and 101 to optimised medical treatment). 241 (82%) of 294 participants were women and 53 (18%) were men and the mean age was 38 (SD 13). After 4 weeks, 73 (76%) of 96 participants in the LFTD diet group, 69 (71%) of 97 participants in the low-carbohydrate diet group, and 59 (58%) of 101 participants in the optimised medical treatment group had a reduction of 50 or more in IBS-SSS compared with baseline, with a significant difference between the groups (p=0·023). 91 (95%) of 96 participants completed 4 weeks in the LFTD group, 92 (95%) of 97 completed 4 weeks in the low-carbohydrate group, and 91 (90%) of 101 completed 4 weeks in the optimised medical treatment group. Two individuals in each of the intervention groups stated that adverse events were the reason for discontinuing the 4-week intervention. Five (5%) of 91 participants in the optimised medical treatment group stopped treatment prematurely due to side-effects. No serious adverse events or treatment-related deaths occurred. INTERPRETATION: Two 4-week dietary interventions and optimised medical treatment reduced the severity of IBS symptoms, with a larger effect size in the diet groups. Dietary interventions might be considered as an initial treatment for patients with IBS. Research is needed to enable personalised treatment strategies. FUNDING: The Healthcare Board Region Västra Götaland, the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, AFA Insurance, grants from the Swedish state, the Wilhelm and Martina Lundgren Science Foundation, Skandia, the Dietary Science Foundation, and the Nanna Swartz Foundation.

Association Between Celiac Disease and Irritable Bowel Syndrome: A Nationwide Cohort Study.

BACKGROUND & AIMS: The aim of this study was to determine the risk of irritable bowel syndrome (IBS) diagnosis in patients with celiac disease (CD) compared with general population comparators. METHODS: Using Swedish histopathology and register-based data, we identified 27,262 patients with CD diagnosed in 2002-2017 and 132,922 age- and sex-matched general population comparators. Diagnoses of IBS were obtained from nationwide inpatient and non-primary outpatient records. Cox regression estimated hazard ratios (aHRs) for IBS adjusted for education level and Charlson Comorbidity Index. To reduce potential surveillance bias our analyses considered incident IBS diagnosis ≥1 year after CD diagnosis. Using conditional logistic regression, secondary analyses were calculated to estimate odds ratios (ORs) for IBS diagnosis ≥1 year before CD diagnosis. RESULTS: During an average of 11.1 years of follow-up, 732 celiac patients (2.7%) were diagnosed with IBS vs 1131 matched general population comparators (0.9%). Overall (≥1-year of follow-up), the aHR for IBS was 3.11 (95% confidence interval [CI], 2.83-3.42), with aHR of 2.00 (95% CI, 1.63-2.45) after ≥10 years of follow-up. Compared with siblings (n = 32,010), celiac patients (n = 19,211) had ≥2-fold risk of later IBS (aHR, 2.42; 95% CI, 2.08-2.82). Compared with celiac patients with mucosal healing, those with persistent villus atrophy on follow-up biopsy were less likely to be diagnosed with IBS (aHR, 0.66; 95% CI, 0.46-0.95). CD was also associated with having an earlier IBS diagnosis (OR, 3.62; 95% CI, 3.03-4.34). CONCLUSIONS: In patients with CD, the risk of IBS is increased long before and after diagnosis. Clinicians should be aware of these long-term associations and their implications on patient management.

Temporal stability of fecal metabolomic profiles in irritable bowel syndrome.

BACKGROUND: The potential of the fecal metabolome to serve as a biomarker for irritable bowel syndrome (IBS) depends on its stability over time. Therefore, this study aimed to determine the temporal dynamics of the fecal metabolome, and the potential relationship with stool consistency, in patients with IBS and healthy subjects. METHODS: Fecal samples were collected in two cohorts comprising patients with IBS and healthy subjects. For Cohort A, fecal samples collected during 5 consecutive days were analyzed by gas chromatography-tandem mass spectrometry (GC-MS/MS). For Cohort B, liquid chromatography-MS (LC-MS) was used to analyze fecal samples collected at week 0 (healthy and IBS) and at week 4 (patients only). Stool consistency was determined by the Bristol Stool Form scale. KEY RESULTS: Fecal samples were collected from Cohort A (seven healthy subjects and eight IBS patients), and Cohort B (seven healthy subjects and 11 IBS patients). The fecal metabolome of IBS patients was stable short-term (Cohort A, 5 days and within the same day) and long-term (Cohort B, 4 weeks). A similar trend was observed over 5 days in the healthy subjects of Cohort A. The metabolome dissimilarity was larger between than within participants over time in both healthy subjects and IBS patients. Further analyses showed that patients had greater range of stool forms (types) than healthy subjects, with no apparent influence on metabolomic dynamics. CONCLUSION & INFERENCES: The fecal metabolome is stable over time within IBS patients as well as healthy subjects. This supports the concept of a stable fecal metabolome in IBS despite fluctuations in stool consistency, and the use of single timepoint sampling to further explore how the fecal metabolome is related to IBS pathogenesis.

Global Prevalence of Psychological Distress and Comorbidity With Disorders of Gut-Brain Interactions.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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 (ß = -0.77; confidence interval [-0.86 to -0.68]) and physical (ß = -1.17; confidence interval [-1.24 to -1.10]) quality of life. DISCUSSION: 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.

Natural history of symptoms and prognostic information of the rapid drink challenge and solid bolus swallows in esophagogastric junction outflow obstruction defined by manometry.

BACKGROUND/INTRODUCTION: Esophagogastric junction outflow obstruction (EGJOO) is a condition characterized by poor relaxation of the lower esophageal sphincter (LES), which can manifest as dysphagia and chest pain. The best treatment of EGJOO is unknown as some patients improve without any specific therapy, whereas some patients undergo invasive therapy. Currently, prognostic factors are lacking. We aimed to assess the long-term prognosis and predictors of dysphagia and chest pain by the rapid drink challenge and solid bolus swallows in EGJOO. METHODS: We retrospectively assessed high-resolution esophageal manometries (HRM) performed at our center between 2015 and 2018. The patients completed a dysphagia and chest pain questionnaire a median of 34 months after the HRM/baseline assessment, including the Impaction dysphagia questionnaire-10 (IDQ-10) complemented with questions regarding chest pain and esophageal treatments. Symptoms were compared with HRM findings. RESULTS: In all, 980 HRMs were analyzed and 66 (6.5%) were identified as having HRM findings compatible with EGJOO. Of these, 27 patients with EGJOO (41%) completed the follow-up questionnaires and had no exclusion criteria, and 70% of these patients had dysphagia and 44% chest pain at least once a week. Dysphagia at follow-up was more common in patients with elevated integrated relaxation pressure (IRP) on all three HRM metrics (water swallows, solid bolus swallows, and rapid drink challenge) (p = 0.03, odds ratio: 8.4 (95% CI: 1.2-56.0)), but this was not seen for chest pain (p = 0.45). Abnormal motility patterns on rapid drink challenge or solid bolus swallows were not associated with dysphagia or chest pain at follow-up. CONCLUSIONS: Having a high IRP on three HRM metrics-water swallows, solid bolus swallows, and rapid drink challenge-is associated with a worse prognosis in patients with EGJOO and could potentially be used to select candidates suitable for invasive procedures.

Quality of Life and Bidirectional Gut-Brain Interactions in Irritable Bowel Syndrome From Adolescence to Adulthood.

BACKGROUNDS AND AIMS: Reports on cross-sectional and longitudinal associations between health-related quality of life (HRQoL), psychological distress, and irritable bowel syndrome (IBS) in the adolescent and young adult general population are few. We aimed to describe cross-sectional associations between HRQoL and IBS in adolescence and young adulthood, and examine bidirectional gut-brain interactions in the transition from childhood to adulthood. METHODS: We included 3391 subjects from a prospective birth cohort study, with data on IBS at 16 years of age and 24 years of age. IBS was assessed using the pediatric Rome III (16 years of age) and the adult Rome IV (24 years of age) diagnostic questionnaires. HRQoL and psychological distress were assessed through EQ-5D. Sex-adjusted logistic regression models were used to examine associations between overall HRQoL/psychological distress at 16 years of age and new-onset IBS at 24 years of age (brain-gut) and between IBS at 16 years of age and new-onset psychological distress at 24 years of age (gut-brain). RESULTS: In subjects with vs without IBS at 16 and 24 years of age, overall HRQoL (EQ visual analog scale, EQ-5D index value) was lower, and it was more common reporting problems in 4 of 5 EQ-5D dimensions (all P < .05). EQ-5D index value at 16 years of age was inversely associated (odds ratio [OR], 0.1, 95% confidence interval [CI], 0.01-0.6), and psychological distress at 16 years of age was positively associated (OR, 1.6; 95% CI, 1.2-2.3), with new-onset IBS at 24 years of age. Having any abdominal pain-related disorder of gut-brain interaction at 16 years of age was associated with new-onset psychological distress at 24 years of age (OR, 1.7; 95% CI, 1.2-2.5). CONCLUSIONS: Adolescents and young adults with IBS in the general population have impaired HRQoL. Bidirectional gut-brain interactions are relevant for symptom generation in abdominal pain-related disorders of gut-brain interaction, and for HRQoL impairment and psychological distress in the transition from childhood to adulthood.

Antibiotic use as a risk factor for irritable bowel syndrome: Results from a nationwide, case-control study.

BACKGROUND: The microbiome plays an important role in the pathophysiology of irritable bowel syndrome (IBS). Antibiotic use can fundamentally alter gut microbial ecology. We examined the association of antibiotic use with IBS in a large population-based investigation. METHODS: A case-control study with prospectively collected data on 29,111 adult patients diagnosed with IBS in Sweden between 2007 and 2016 matched with 135,172 controls. Using a comprehensive histopathology cohort, the Swedish Patient Register, and the Prescribed Drug Register, we identified all consecutive cases of IBS in addition to cumulative antibiotic dispensations accrued until 1 year prior to IBS (exclusionary period) for cases and time of matching for up to five general population controls matched on the basis of age, sex, country and calendar year. Conditional logistic regression estimated multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of IBS. RESULTS: Patients with IBS (n = 29,111) were more likely than controls (n = 135,172) to have used antibiotics up to 1 year prior to diagnosis (74.9% vs. 57.8%). After multivariable adjustment, this translated to a more than twofold increased odds of IBS (OR 2.21, 95% CI 2.14-2.28) that did not differ according to age, sex, year of IBS diagnosis or IBS subtype. Compared to none, 1-2 (OR 1.67, 95% CI 1.61-1.73) and ≥3 antibiotics dispensations (OR 3.36, 95% CI 3.24-3.49) were associated with increased odds of IBS (p for trend <0.001) regardless of the antibiotic class. CONCLUSIONS: Prior antibiotics use was associated with an increased odds of IBS with the highest risk among people with multiple antibiotics dispensations.

Managing pain in irritable bowel syndrome: current perspectives and best practice.

INTRODUCTION: Irritable bowel syndrome (IBS) is characterized by chronic symptoms (>6 months) of abdominal pain in combination with a disturbed bowel habit. There is an association between the intensity of abdominal pain and the need for health care utilization. A bidirectionally disordered gut-brain interaction is central in the pathophysiology of IBS where a number of factors, gastrointestinal and non-gastrointestinal, can contribute to the illness experience. In order to treat abdominal pain in IBS, mapping these factors in a multidimensional clinical profile is helpful. AREAS COVERED: This review covers basic epidemiology and pathophysiology of abdominal pain in IBS, the diagnostic approach, and a multidimensional treatment model where the management of abdominal pain is in focus. EXPERT OPINION: A personalized treatment of abdominal pain in IBS is possible in patients who understand the diagnosis, the potential of therapies used, and where a good continuity in the patient-doctor relationship is established.

Work productivity and activity impairment in disorders of gut-brain interaction: Data from the Rome Foundation Global Epidemiology Study.

BACKGROUND: Disorders of Gut-Brain Interaction (DGBI) are highly prevalent worldwide, but their effect on work productivity has not gained much attention. AIMS AND METHODS: We aimed to compare work productivity and activity impairment (WPAI) in persons with and without DGBI in a large population-based cohort and identify factors independently associated with WPAI in subjects with DGBI. Data were collected from Germany, Israel, Italy, Japan, the Netherlands, Poland, Spain and Sweden via Internet surveys as part of the Rome Foundation Global Epidemiology Study. Apart from the Rome IV diagnostic questionnaire, questionnaires evaluating WPAI related to general health (WPAI:GH), psychological distress (PHQ-4), somatic symptom severity (PHQ-15) and other factors were assessed. RESULTS: Of the 16,820 subjects, 7111 met the criteria for DGBI according to the Rome IV diagnostic questionnaire. Subjects with DGBI were younger (median (interquartile range) age 43 (31-58) vs. 47 (33-62)) and more often female (59.0% vs. 43.7%) compared to subjects without DGBI. Subjects with DGBI had higher absenteeism, presenteeism (poor work productivity due to illness), overall work impairment and activity impairment (p < 0.001) compared with subjects without. For subjects with DGBI affecting more than one anatomical region, WPAI was incrementally higher for each additional region. There were significant differences in WPAI for subjects with DGBI in different countries. Subjects from Sweden had the highest overall work impairment and from Poland the lowest. Using multiple linear regression, male sex, fatigue, psychological distress, somatic symptom severity and number of anatomical regions were independently associated with overall work impairment (p < 0.05 for all). CONCLUSION: In the general population, people with DGBI have substantial WPAI compared with those without DGBI. The reasons for these findings should be explored further, but having multiple DGBI, psychological distress, fatigue and somatic symptom severity seem to contribute to this impairment associated with DGBI.

Prevalence and impact of disorders of Gut-Brain interaction in Sweden.

BACKGROUND: Previous epidemiologic studies in Sweden have only covered some of the disorders of gut-brain interaction (DGBI) and are not representative of the general population. This study aimed to define the prevalence and impact of DGBI in Sweden. METHODS: We used Swedish data from the Rome Foundation Global Epidemiology Study which include information on DGBI diagnoses, psychological distress, quality of life (QoL), healthcare utilization, and the impact of stress on GI symptoms. KEY RESULTS: The prevalence of having any DGBI was 39.1% (95% CI 37.0-41.2); esophageal disorders 6.1% (5.1-7.3), gastroduodenal disorders 10.7% (9.3-12.0), bowel disorders 31.6% (29.6-33.6), and anorectal disorders 6.0% (5.1-7.2). Subjects with a DGBI more commonly reported anxiety and/or depression, reduced mental and physical QoL, and more frequent doctor visits due to health problems. Subjects with a DGBI reported bothersome gastrointestinal (GI) symptoms to a greater extent and more than 1/3 had visited a doctor due to GI problems and of those 1/3 had seen multiple doctors. Prescription medications were available among 36.4% (31.0-42.0) who had bothersome GI symptoms and a DGBI, with sufficient symptom relief in 73.2% (64.0-81.1). Psychological factors and eating were reported to worsen GI symptoms and stress during the last month was greater in subjects with a DGBI. CONCLUSIONS AND INFERENCES: DGBI prevalence and its impact in Sweden is in line with global data, including increased healthcare utilization. GI symptoms are commonly affected by psychological factors and eating, and a high proportion of those on prescription medication report sufficient GI symptom relief.

Factor Analysis of the Rome IV Criteria for Major Disorders of Gut-Brain Interaction (DGBI) Globally and Across Geographical, Sex, and Age Groups.

BACKGROUND & AIMS: The Rome criteria are widely accepted for diagnosing disorders of gut-brain interaction, but their global applicability has been debated. This study aimed to evaluate the validity of the Rome IV criteria by factor analysis globally, across geographical regions, by sex, and by age groups. METHODS: Data were collected in 26 countries using the Rome IV questionnaire. Forty-nine ordinal variables were used in exploratory factor analysis (EFA) to identify clusters of inter-correlated variables (factors) within the data set. Confirmatory factor analysis with predefined factors of the disorders of gut-brain interaction was compared with the factors in the EFA. Analyses were performed globally, for each geographical region (North and Latin America, Western and Eastern Europe, Middle East, Asia), sex, and age groups (18-34, 35-49, 50-64, ≥65). RESULTS: A total of 54,127 people were included. The EFA identified 10 factors accounting for 57% of the variance: irritable bowel syndrome, constipation, diarrhea, upper gastrointestinal symptoms, globus, regurgitation/retching, chest pain, nausea/vomiting, and 2 right upper quadrant pain factors. Most factors had close correspondence to a Rome IV criteria diagnosis, but notably, functional dysphagia and heartburn symptoms were often included in the same factor and/or in upper gastrointestinal symptoms. Most factors were consistent across geographical regions, sex, and age groups, and compatible to the global results. All prespecified factors in the confirmatory analysis had a loading ≥0.4, indicating validity of the Rome IV criteria. CONCLUSIONS: The results indicate that the Rome IV criteria for irritable bowel syndrome, functional dyspepsia, functional constipation, globus, and biliary pain are globally valid and represent universal diagnostic entities that are similar across sex and age groups.

Identification of irritable bowel syndrome in the Swedish National Patient Register: a validation study.

BACKGROUND AND OBJECTIVE: National patient registers are valuable in epidemiological studies. To ensure high-quality data for studies of irritable bowel syndrome (IBS), this study aimed to validate the ICD-10 code for IBS in the Swedish National Patient Register. METHODS: The positive predictive values (PPV) for IBS defined by the Rome criteria were calculated based on a review of medical records of randomly selected individuals with a first-ever diagnostic listing of IBS in the Swedish National Patient register in the year 2005 (Rome II criteria) or 2010 (Rome III criteria). KEY RESULTS: 340 medical records were reviewed (172 from 2005 and 168 from 2010). The majority of patients were females (74%), and the mean age was 42 years. IBS used in any type of department had a PPV of 76% (95% confidence interval 71-80%), which increased to 80% (76-84%) when we included individuals likely to have IBS but where information about some aspects of the Rome criteria was lacking in the medical record. Two highly specialized gastroenterological departments had the best PPV, 96%, while departments of internal medicine in general had a PPV of 82% (80-95%). The PPV for the IBS subtype was 62% (55-67%). The PPVs were not significantly different comparing the two time periods investigated. CONCLUSION AND INFERENCES: The validity of a register-based definition of IBS in the Swedish National Patient register is high and can be used to identify patients with IBS in observational research. The data source, i.e., type of hospital and department, influences reliability.

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.

Fecal Luminal Factors from Patients with Gastrointestinal Diseases Alter Gene Expression Profiles in Caco-2 Cells and Colonoids.

Previous in vitro studies have shown that the intestinal luminal content, including metabolites, possibly regulates epithelial layer responses to harmful stimuli and promotes disease. Therefore, we aimed to test the hypothesis that fecal supernatants from patients with colon cancer (CC), ulcerative colitis (UC) and irritable bowel syndrome (IBS) contain distinct metabolite profiles and establish their effects on Caco-2 cells and human-derived colon organoids (colonoids). The metabolite profiles of fecal supernatants were analyzed by liquid chromatography-mass spectrometry and distinguished patients with CC (n = 6), UC (n = 6), IBS (n = 6) and healthy subjects (n = 6). Caco-2 monolayers and human apical-out colonoids underwent stimulation with fecal supernatants from different patient groups and healthy subjects. Their addition did not impair monolayer integrity, as measured by transepithelial electrical resistance; however, fecal supernatants from different patient groups and healthy subjects altered the gene expression of Caco-2 monolayers, as well as colonoid cultures. In conclusion, the stimulation of Caco-2 cells and colonoids with fecal supernatants derived from CC, UC and IBS patients altered gene expression profiles, potentially reflecting the luminal microenvironment of the fecal sample donor. This experimental approach allows for investigating the crosstalk at the gut barrier and the effects of the gut microenvironment in the pathogenesis of intestinal diseases.