Abdominal pain in patients with inflammatory bowel disease in remission: A prospective study on contributing factors.

BACKGROUND: Abdominal pain is highly prevalent in patients with inflammatory bowel disease (IBD) in remission, but the aetiology is incompletely understood. AIM: To investigate the association of clinical, lifestyle and psychosocial factors with abdominal pain in patients with IBD in remission. METHODS: We performed a prospective multicentre study enrolling consecutive patients with IBD. Data were collected between 1 January 2020 and 1 July 2021, using myIBDcoach, an established remote monitoring platform for IBD. Chronic abdominal pain in IBD in remission (IBDremissionPain+) was defined as abdominal pain score ≥3 (0-10 NRS) on ≥1/3 of all assessments, combined with faecal calprotectin <150 µg/g in 90 days around periodic assessments. Disease activity, lifestyle and psychosocial factors were assessed every 1-3 months during 18 months. Using linear mixed models, the association of these factors with abdominal pain over time was analysed. RESULTS: We included 559 patients, of whom 429 (76.7%) remained in biochemical remission. Of these, 198 (46.2%) fulfilled the criteria for chronic abdominal pain. IBDremissionPain+ patients were characterised by female sex, younger age, higher BMI, and shorter disease duration. They reported more often or higher levels of stress, fatigue, depressive and anxiety symptoms, and life events (all p < 0.001). In the multivariable analysis, sex, disease entity, fatigue, depressive symptoms and life events were associated with abdominal pain over time (all p < 0.05). CONCLUSION: In this cohort of patients with IBD in remission, abdominal pain was common and associated with psychosocial factors. A more holistic treatment approach for patients with IBD suffering from abdominal pain may improve quality of care and subjective wellbeing.

Participation in colorectal cancer screening trials after first-time invitation: a systematic review.

BACKGROUND AND STUDY AIM: Colorectal cancer (CRC) screening is implemented by an increasing number of countries. Participation rates of screening programs influence the health benefit and cost-effectiveness of the applied method. The aim was to systematically review participation rate after first-time invitation for CRC screening with fecal occult blood test (FOBT), sigmoidoscopy, colonoscopy, and/or computed tomography (CT) colonography. METHODS: A systematic literature search was performed prior to October 1 2009. Prospective CRC screening studies of unselected populations reporting participation rates were included. RESULTS: After meta-analyses, overall participation rates were found to be 47 % for FOBT, 42 % for fecal immunologic tests (FITs), 35 % for sigmoidoscopy, 41 % for sigmoidoscopy combined with FIT/FOBT, 28 % for colonoscopy, and 22 % for CT colonography. Studies comparing screening methods showed higher participation rates for less invasive methods. Studies comparing invitation methods showed higher participation rates with general practitioner involvement, a more personalized recruitment approach, and reduction of barriers that discourage participation. CONCLUSIONS: Knowledge of identified factors affecting CRC screening participation can be used to improve screening programs.

Opportunistic screening of hospital staff using primary colonoscopy: participation, discomfort and willingness to repeat the procedure.

BACKGROUND: Participation in and tolerability of primary colonoscopy screening are presumed to be relatively low. The present study aimed to test its feasibility in a well-informed population of hospital staff using an intensive information campaign, and to identify factors associated with screening colonoscopy rated as uncomfortable. METHODS: Data were collected using standardized forms. RESULTS: Out of 1,090 invited employees (50-65 years), 447 (41.0%) participated. Bowel preparation and colonoscopy were rated as 'somewhat to very uncomfortable' by 79.5 and 21.9%, respectively. 96.3% of participants were willing to repeat colonoscopy in the future. Participants rating colonoscopy as uncomfortable were more likely unwilling to repeat the procedure (OR 8.026, CI 2.667-24.154). Multivariate analysis (age- and gender-adjusted) showed an association of colonoscopy rated as uncomfortable with: abdominal pain during colonoscopy (OR 3.185, CI 1.642-6.178), other pain (OR 2.428, CI 1.335-4.416), flatulence (OR 2.175, CI 1.219-3.881), embarrassment (OR 2.843, CI 1.350-5.989), abdominal pain after colonoscopy (OR 1.976, CI 1.041-3.751), and a prolonged procedure time (OR 1.000, CI 1.000-1.001). CONCLUSIONS: Acceptance of primary colonoscopy screening for colorectal neoplasia was high, although participants with symptoms during and after colonoscopy were more likely to rate colonoscopy as uncomfortable. This type of opportunistic screening procedure is suitable for the introduction of screening programs and may be useful in areas that have no access to population-based screening.

Control Crohn Safe with episodic adalimumab monotherapy as first-line treatment study (CoCroS): study protocol for a randomised controlled trial.

INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory bowel disease with a heterogeneous clinical presentation, relapse rate and treatment response. At present, no markers are available to adequately predict disease course at diagnosis. To prevent overtreatment of patients with a relative mild disease course, a step-up approach starting with corticosteroids is usually applied. Timely introduction of potentially disease modifying drugs and tight control of mucosal inflammation are crucial to prevent disease-related complications in patients with a complex disease course. We hypothesise that episodic treatment with adalimumab monotherapy in combination with close monitoring after drug discontinuation improves long-term outcome and reduces drug-related side effects, while preventing overtreatment. METHODS AND ANALYSIS: In this pragmatic multicentre randomised controlled trial, newly diagnosed CD patients or CD patients with a flare, naïve to thiopurines and biologicals, will be included and randomised 1:1 to open-label episodic (ie, 24 weeks) adalimumab monotherapy or step-up care starting with corticosteroids. The primary outcome is the number of yearly quarters of corticosteroid free clinical (Monitor Inflammatory Bowel Disease At Home score ≤3) and biochemical (C reactive protein within normal range and faecal calprotectin ≤200 µg/g) remission at week 96. Secondary outcomes are total healthcare costs, cumulative corticosteroid dose, proportion of patients with endoscopic remission at week 24, corticosteroid-free clinical remission, time to remission and patient-reported outcome measures on quality of life, (work) disability and treatment adherence. Safety outcomes are drug-related and disease-related adverse events and disease progression on MRI-enterography at week 96. ETHICS AND DISSEMINATION: This study is approved by the Medical Research Ethics Committee of azM/UM in Maastricht dated 21 August 2019 (METC18-076) and is monitored by the Clinical Trial Centre Maastricht according to Good Clinical Practice guidelines. Written informed consent will be obtained from all patients. Study results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT03917303.

A combination of fecal calprotectin and human beta-defensin 2 facilitates diagnosis and monitoring of inflammatory bowel disease.

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) show a large overlap in clinical presentation, which presents diagnostic challenges. As a consequence, invasive and burdensome endoscopies are often used to distinguish between IBD and IBS. Here, we aimed to develop a noninvasive fecal test that can distinguish between IBD and IBS and reduce the number of endoscopies.We used shotgun metagenomic sequencing to analyze the composition and function of gut microbiota of 169 IBS patients, 447 IBD patients and 1044 population controls and measured fecal Calprotectin (FCal), human beta defensin 2 (HBD2), and chromogranin A (CgA) in these samples. These measurements were used to construct training sets (75% of data) for logistic regression and machine learning models to differentiate IBS from IBD and inactive from active IBD. The results were replicated on test sets (remaining 25% of the data) and microbiome data obtained using 16S sequencing.Fecal HBD2 showed high sensitivity and specificity for differentiating between IBD and IBS (sensitivity = 0.89, specificity = 0.76), while the inclusion of microbiome data with biomarkers (HBD2 and FCal) showed a potential for improvement in predictive power (optimal sensitivity = 0.87, specificity = 0.93). Shotgun sequencing-based models produced comparable results using 16S-sequencing data. HBD2 and FCal were found to have predictive power for IBD disease activity (AUC ≈ 0.7).HBD2 is a novel biomarker for IBD in patients with gastro-intestinal complaints, especially when used in combination with FCal and potentially in combination with gut microbiome data.

Dynamics and ecological consequences of avian influenza virus infection in greater white-fronted geese in their winter staging areas.

Recent outbreaks of highly pathogenic avian influenza (HPAI) in poultry have raised interest in the interplay between avian influenza (AI) viruses and their wild hosts. Studies linking virus ecology to host ecology are still scarce, particularly for non-duck species. Here, we link capture-resighting data of greater white-fronted geese Anser albifrons albifrons with the AI virus infection data collected during capture in The Netherlands in four consecutive winters. We ask what factors are related to AI virus prevalence and whether there are ecological consequences associated with AI virus infection in staging white-fronted geese. Mean seasonal (low pathogenic) AI virus prevalence ranged between 2.5 and 10.7 per cent, among the highest reported values for non-duck species, and occurred in distinct peaks with near-zero prevalence before and after. Throat samples had a 2.4 times higher detection frequency than cloacal samples. AI virus infection was significantly related to age and body mass in some but not other winters. AI virus infection was not related to resighting probability, nor to maximum distance travelled, which was at least 191 km during the short infectious lifespan of an AI virus. Our results suggest that transmission via the respiratory route could be an important transmission route of AI virus in this species. Near-zero prevalence upon arrival on their wintering grounds, in combination with the epidemic nature of AI virus infections in white-fronted geese, suggests that white-fronted geese are not likely to disperse Asian AI viruses from their Siberian breeding grounds to their European wintering areas.

Rome III vs Rome IV criteria for irritable bowel syndrome: A comparison of clinical characteristics in a large cohort study.

BACKGROUND: The Rome criteria for irritable bowel syndrome (IBS) have been revised and are expected to apply only to the subset of Rome III IBS subjects with abdominal pain as predominant symptom, occurring at least once a week. The aim of this study was to determine the percentage of Rome III IBS subjects that fulfills Rome IV criteria and to evaluate differences between Rome IV-positive and Rome IV-negative subjects. METHODS: Four hundred and four Rome III IBS subjects completed a 14-day end-of-day symptom diary, the Gastrointestinal Symptom Rating Scale (GSRS), Hospital Anxiety and Depression Scale, and RAND 36-item Short-Form Health Survey (SF-36). Diary-based surrogate Rome IV criteria were defined as occurrence of abdominal pain at least 1 day each week with a severity of ≥2 (mild; definition 1) or ≥3 (considerable; definition 2). KEY RESULTS: Using surrogate Rome IV criteria, 353 (87.4%, definition 1) and 249 (61.6%, definition 2) subjects were defined as Rome IV positive. These patients were more often female, younger, and recruited from secondary/tertiary care compared with Rome IV-negative subjects. They also presented with higher abdominal pain scores and gastrointestinal (GI) symptom severity on both end-of-day diary and GSRS, higher psychological symptom scores, and lower quality of life compared with Rome IV-negative subjects. CONCLUSIONS AND INFERENCES: The Rome IV IBS population likely reflects a subgroup of Rome III IBS patients with more severe GI symptomatology, psychological comorbidities, and lower quality of life. This implies that results from Rome III IBS studies may not be directly comparable to those from Rome IV IBS populations.

The potential of volatile organic compounds for the detection of active disease in patients with ulcerative colitis.

BACKGROUND: To optimise treatment of ulcerative colitis (UC), patients need repeated assessment of mucosal inflammation. Current non-invasive biomarkers and clinical activity indices do not accurately reflect disease activity in all patients and cannot discriminate UC from non-UC colitis. Volatile organic compounds (VOCs) in exhaled air could be predictive of active disease or remission in Crohn's disease. AIM: To investigate whether VOCs are able to differentiate between active UC, UC in remission and non-UC colitis. METHODS: UC patients participated in a 1-year study. Clinical activity index, blood, faecal and breath samples were collected at each out-patient visit. Patients with clear defined active faecal calprotectin >250 µg/g and inactive disease (Simple Clinical Colitis Activity Index <3, C-reactive protein <5 mg/L and faecal calprotectin <100 µg/g) were included for cross-sectional analysis. Non-UC colitis was confirmed by stool culture or radiological evaluation. Breath samples were analysed by gas chromatography time-of-flight mass spectrometry and kernel-based method to identify discriminating VOCs. RESULTS: In total, 72 UC (132 breath samples; 62 active; 70 remission) and 22 non-UC-colitis patients (22 samples) were included. Eleven VOCs predicted active vs. inactive UC in an independent internal validation set with 92% sensitivity and 77% specificity (AUC 0.94). Non-UC colitis patients could be clearly separated from active and inactive UC patients with principal component analysis. CONCLUSIONS: Volatile organic compounds can accurately distinguish active disease from remission in UC and profiles in UC are clearly different from profiles in non-UC colitis patients. VOCs have demonstrated potential as new non-invasive biomarker to monitor inflammation in UC.

Habitual diet and diet quality in Irritable Bowel Syndrome: A case-control study.

BACKGROUND: Diet is considered to be a key factor in symptom generation in Irritable Bowel Syndrome (IBS) and patients tend to exclude food products from their diet in pursue of symptom relief, which may impair diet quality. METHODS: We evaluated habitual dietary intake in IBS patients with regard to nutrients and food products using an extensive food frequency questionnaire. One hundred ninety-four IBS patients were compared to 186 healthy controls using multiple logistic regression analysis. An overall diet quality score was calculated for each participant based on the criteria of the Dutch Healthy Diet (DHD) index. KEY RESULTS: A lower DHD-score was found for IBS (mean [SD]: 52.9 [9.6]) vs controls (55.1 [9.2], P=.02). The diet of patients was lower in fibers (21 g vs 25 g per day, P=.002) and fructose (14 g vs 16 g, P=.033), while higher in total fat (37% vs 36% of total energy intake, P=.010) and added sugars (46 g vs 44 g, P=.029). Differences in daily intake of food products included lower consumption of apples (40 g vs 69 g, P<.001), pasta (28 vs 37 g, P=.029) and alcoholic beverages (130 g vs 193 g, P=.024) and higher consumption of processed meat (38 g vs 29 g, P<.001). Some of these findings correlated with gastrointestinal symptoms, showing differences between IBS subtypes. CONCLUSIONS AND INFERENCES: Differences in habitual diet were described, showing lower diet quality in IBS patients compared to controls, with increased consumption of fat and lower intake of fibers and fructose. Our data support the importance of personalized and professional nutritional guidance of IBS patients.

Biomarkers for visceral hypersensitivity in patients with irritable bowel syndrome.

BACKGROUND: Increased visceral sensitivity is observed in up to 60% of patients with Irritable Bowel Syndrome (IBS). Mucosal inflammation, altered neuroendocrine activity and intraluminal metabolic processes may contribute to the development of visceral hypersensitivity. Previously, we demonstrated that biomarkers, indicative for these biological processes, were altered in IBS patients compared to healthy controls. However, how these processes relate to visceral hypersensitivity is unknown. AIM: The aim of this study was to provide insight in biological processes associated with visceral hypersensitivity. Fecal and plasma biomarkers were measured in normosensitive and hypersensitive IBS patients. METHODS: A total of 167 IBS patients underwent a rectal barostat procedure to assess visceral sensitivity to pain. Based on the outcome, patients were classified into a normosensitive or hypersensitive group. Calprotectin, human ß-defensin 2 (HBD2), chromogranin A (CgA), and short chain fatty acids (SCFAs) were measured in feces, citrulline in plasma, and serotonin and its main metabolite 5-hydroxyindoleacetic acid (5-HIAA) in platelet-poor plasma. KEY RESULTS: Fecal markers and plasma citrulline were measured in 83 hypersensitive and 84 normosensitive patients, while platelet-poor plasma for the assessment of serotonin and 5-HIAA was available for a subgroup, i.e. 53 hypersensitive and 42 normosensitive patients. No statistically significant differences were found in concentrations of biomarkers between groups. Adjustment of the analyses for potential confounders, such as medication use, did not alter this conclusion. CONCLUSIONS & INFERENCES: Our findings do not support a role for the biological processes as ascertained by biomarkers in visceral hypersensitivity in IBS patients. This study is registered in the US National Library of Medicine (clinicaltrials.gov, NCT00775060).

[Changes in the treatment of Crohn's disease: fewer hospitalizations, less surgery, and reduced glucocorticoid use]. / Veranderingen in de behandeling van ziekte van Crohn.

OBJECTIVE: To study changes in treatment and disease course in patients with Crohn's disease (CD) in the South Limburg region of the Netherlands between 1991 and 2014. DESIGN: Population-based cohort study. METHODS: All 1162 CD patients in the 'IBD South Limburg cohort' were divided across three subcohorts on the basis of year of diagnosis: 1991-1998 (N = 316), 1999-2005 (N = 387) and 2006-2011 (N = 459). We compared the risk of hospitalization, bowel resection and the development of strictures and/or fistulas across the subcohorts. We also compared cumulative corticosteroid use and the relationship between the outcome measures and maintenance medication. RESULTS: In the period 1991-2014 there was an increase in the number of patients treated within 5 years with immunomodulators from 30.6% to 70.8%. For treatment with biologicals there was an increase from 3.1% to 41.2%. In parallel, the risk of hospitalization decreased from 65.9% to 44.2% and the risk of bowel resection decreased from 42.9% to 17.4%. The risk of developing strictures or fistulas remained stable (21.2%). There was no significant association between the outcome measures and the use of immunomodulators or biologicals. Furthermore, corticosteroid use decreased over time; this was linked to use of immunomodulators and biologicals. CONCLUSION: Treatment of Crohn's disease has changed over the past two decades, and the disease course has improved. We found no association between changes in maintenance medication and disease course.

The effect of a probiotic drink with Lactobacillus plantarum 299v on the bacterial composition in faeces and mucosal biopsies of rectum and ascending colon.

BACKGROUND: Studies on probiotics mainly base their results on faecal samples, which may not represent the situation in the mucosa of distal and proximal colon. AIM: In a placebo-controlled study, to assess the effect of Lactobacillus plantarum 299v on the bacterial composition of faecal vs. mucosal samples. METHODS: Twenty-nine patients undergoing colonoscopic examination for polyps consumed a twice-daily drink with or without L. plantarum 299v (10(11) CFU/day) for 2 weeks. Faecal samples were collected before and after consumption. During colonoscopy, biopsies were collected from the ascending colon and rectum. The faecal and mucosal bacterial concentrations and prevalence were determined. RESULTS: L. plantarum 299v significantly increased the concentration of faecal lactic acid bacteria, lactobacilli and clostridia, and was identified in two rectal biopsies but not in the ascending colon biopsies of probiotic-treated subjects. Concentrations and prevalence in ascending colon and rectum biopsies were comparable, but were significantly lower compared with faecal samples. CONCLUSIONS: After probiotic consumption, a significant increase in the faecal concentration of lactobacilli was found but concentrations were low in biopsies. The bacterial composition in biopsies of the ascending colon and rectum did not differ based on culture techniques. To further elucidate the modes of action of probiotics, it might be necessary to study differences in colonization with molecular techniques.

High risk of drug-induced microscopic colitis with concomitant use of NSAIDs and proton pump inhibitors.

BACKGROUND: Microscopic colitis (MC) is a chronic bowel disorder characterised by watery diarrhoea. Nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), selective serotonin reuptake inhibitors (SSRIs) and statins have been associated with MC. However, underlying mechanisms remain unclear. AIM: To study the association between exposure to these drugs and MC, with attention to time of exposure, duration, dosage and combined exposure, and to test hypotheses on underlying pharmacological mechanisms. METHODS: A case-control study was conducted using the British Clinical Practice Research Datalink. MC cases (1992-2013) were matched to MC-naive controls on age, sex and GP practice. Drug exposure was stratified according to time of exposure, duration of exposure or dosage. Conditional logistic regression analysis was applied to calculate adjusted odds ratios (AORs). RESULTS: In total, 1211 cases with MC were matched to 6041 controls. Mean age was 63.4 years, with 73.2% being female. Current use of NSAIDs (AOR 1.86, 95% CI 1.39-2.49), PPIs (AOR 3.37, 95% CI 2.77-4.09) or SSRIs (AOR 2.03, 95% CI 1.58-2.61) was associated with MC compared to never or past use. Continuous use for 4-12 months further increased the risk of MC. Strongest associations (fivefold increased risk) were observed for concomitant use of PPIs and NSAIDs. Statins were not associated with MC. CONCLUSIONS: Current exposure to NSAIDs, PPIs or SSRIs and prolonged use for 4-12 months increased the risk of MC. Concomitant use of NSAIDs and PPIs showed the highest risk of MC. Acid suppression related dysbiosis may contribute to the PPI effect, which may be exacerbated by NSAID-related side-effects.

Alterations in serotonin metabolism in the irritable bowel syndrome.

BACKGROUND: Alterations in serotonin (5-HT) metabolism have been postulated to play a role in the pathogenesis of irritable bowel syndrome (IBS). However, previous reports regarding 5-HT metabolism in IBS are contradicting. AIM: To compare platelet poor plasma (PPP) 5-HT and 5-hydroxyindole acetic acid (5-HIAA) levels and their ratio in a large cohort of IBS patients and healthy controls (HC), including IBS-subgroup analysis. METHODS: Irritable bowel syndrome patients and HC were evaluated for fasting PPP 5-HT and 5-HIAA levels. Furthermore, GI-symptom diary, GSRS, quality of life, anxiety and depression scores were assessed in the 2 weeks before blood sampling. RESULTS: One hundred and fifty four IBS patients and 137 HC were included. No differences were detected in plasma 5-HT between groups. The 5-HIAA concentrations and 5-HIAA/5-HT ratio were significantly lower in IBS compared to HC: 24.6 ± 21.9 vs. 39.0 ± 29.5 µg/L (P < 0.001) and 8.4 ± 12.2 vs. 13.5 ± 16.6 (P < 0.01), respectively. Subtype analysis for 5-HIAA showed all IBS subtypes to be significantly different from HC. The 5-HIAA/5-HT ratio was significantly lower in the IBS-M subtype vs. HC. Linear regression analysis points to an influence of gender but not of GI-symptoms, psychological scores or medication use. CONCLUSIONS: We demonstrated that fasting 5-HT plasma levels are not significantly different in IBS patients compared to controls. However, decreased 5-HIAA levels and 5-HIAA/5-HT ratio in IBS patients may reflect altered serotonin metabolism in IBS. Gender affects 5-HIAA levels in IBS patients, but no effects of drugs, such as SSRIs, or higher GI-symptom or psychological scores were found.

Volatile organic compounds in breath as markers for irritable bowel syndrome: a metabolomic approach.

BACKGROUND: The diagnosis of irritable bowel syndrome (IBS) is challenging because of its heterogeneity and multifactorial pathophysiology. No reliable biomarkers of IBS have been identified so far. AIMS: In a case-control study, using a novel application of breath analysis to distinguish IBS patients from healthy controls based on the analysis of volatile organic compounds (VOCs). Subsequently, the diagnostic VOC-biomarker set was correlated with self-reported gastrointestinal (GI) symptoms of subjects of the Maastricht IBS clinical cohort and of a general population cohort, LifeLines DEEP. METHODS: Breath samples were collected from 170 IBS patients and 153 healthy controls in the clinical cohort and from 1307 participants in general population cohort. Multivariate statistics were used to identify the most discriminatory set of VOCs in the clinical cohort, and to find associations between VOCs and GI symptoms in both cohorts. RESULTS: A set of 16 VOCs correctly predicted 89.4% of the IBS patients and 73.3% of the healthy controls (AUC = 0.83). The VOC-biomarker set correlated moderately with a set of GI symptoms in the clinical (r = 0.55, P = 0.0003) and general population cohorts (r = 0.54, P = 0.0004). A Kruskal-Wallis test showed no influence from possible confounding factors in distinguishing IBS patients from healthy controls. CONCLUSIONS: A set of 16 breath-based biomarkers that distinguishes IBS patients from healthy controls was identified. The VOC-biomarker set correlated significantly with GI symptoms in two independent cohorts. We demonstrate the potential use of breath analysis in the diagnosis and monitoring of IBS, and a possible application of VOC analyses in a general population cohort.

Survival of the probiotic, L. plantarum 299v and its effects on the faecal bacterial flora, with and without gastric acid inhibition.

INTRODUCTION: Probiotic bacteria have to survive passage through the gastrointestinal tract. In this placebo-controlled double-blind study, the effect of Lactobacillus plantarum 299v on the faecal flora was studied with and without gastric acid inhibition. METHODS: Thirty-two healthy volunteers were given pantoprazole (40 mg/day) or placebo for 3 weeks from week 2 until week 4. In addition, from week 3 until week 4, L. plantarum 299v in an oatmeal-fermented drink (10(9) CFU/ml) was given twice daily to both groups. From each healthy volunteer, faecal samples were collected at the end of week 1, 2, 4 and 8 (4 weeks after cessation of L. plantarum 299v and pantoprazole/placebo). Several aerobically and anaerobically growing bacteria were counted and short chain fatty acid concentrations were determined. RESULTS: In both the pantoprazole and the placebo group, median lactobacilli counts increased significantly in week 4 compared to week 1 (from log 4.5 to 8.0 CFU/g faeces in pantoprazole and from log 4.2 to 7.7 CFU/g faeces in placebo group) and decreased significantly in week 8 (to log 4.5 CFU/g faeces in pantoprazole and log 4.3 CFU/g faeces in placebo group). These lactobacilli were identified as L. plantarum 299v. No significant differences were observed in all other bacterial counts and short chain fatty acid concentrations. CONCLUSIONS: The comparable increase of faecal lactobacilli counts in both the pantoprazole and the placebo-treated group demonstrates that L. plantarum 299v survives passage through the gastrointestinal tract irrespective of gastric acidity. The increment of the intra-gastric pH in combination with L. plantarum 299v did not modulate bacterial composition and/or the production of short chain fatty acids.

Visceral hypersensitivity in irritable bowel syndrome: evidence for involvement of serotonin metabolism--a preliminary study.

BACKGROUND: Altered serotonergic (5-HT) metabolism and visceral perception have been associated with the pathogenesis of irritable bowel syndrome (IBS). Aim of this preliminary study was to assess the effect of the direct precursor of 5-HT, 5-hydroxytryptophan (5-HTP), on systemic 5-HT metabolites and visceral perception and to assess potential differential responses between IBS and controls. METHODS: 15 IBS patients and 15 healthy volunteers participated in this randomized double-blind placebo controlled study. Visceroperception was measured by rectal barostat. The 100 mg 5-HTP or placebo was ingested orally. Serotonergic metabolites were assessed in platelet poor plasma. KEY RESULTS: 5-HTP induces rectal allodynia in a significant number of healthy controls; IBS patients exhibit lowered pain thresholds in both placebo and 5-HTP conditions. 5-HTP induces rectal hyperalgesia in hypersensitive but not in non-hypersensitive IBS patients. Administration of 5-HTP significantly increased plasma 5-HTP levels (p < 0.001), did not affect 5-HT levels (p > 0.05), while levels of the main metabolite of 5-HT, 5-hydroxyindoleacetic acid, increased significantly (p < 0.05) in both groups. The magnitude of these changes observed in 5-HT metabolites was significantly greater in IBS patients. CONCLUSIONS & INFERENCES: Oral administration of 5-HTP induced significant alterations in systemic 5-HT metabolites that were accompanied by increased visceroperception of pain in controls and hypersensitive IBS patients. Changes in 5-HT metabolism appear to be important factors involved in visceral hypersensitivity as the 5-HTP-induced pro-nociceptive response was observed in all hypersensitive IBS patients and to a lesser magnitude in a significant number of healthy controls but in none of the non-hypersensitive IBS patients.

The Experience Sampling Method--a new digital tool for momentary symptom assessment in IBS: an exploratory study.

BACKGROUND: Retrospective questionnaires are frequently used for symptom assessment in irritable bowel syndrome (IBS) patients, but are influenced by recall bias and circumstantial and psychological factors. These limitations may be overcome by random, repeated, momentary assessment during the day, using electronic Experience Sampling Methodology (ESM). Therefore, we compared symptom assessment by ESM to retrospective paper questionnaires in IBS patients. METHODS: Twenty-six IBS patients (Rome III) were included, of which 16 were diagnosed with panic disorder (DSM-IV-TR). Patients scored symptoms using end-of-day diaries during 14 days and the gastrointestinal symptom rating scale (GSRS) once. ESM was used on seven consecutive days during the same time period. KEY RESULTS: End-of-day diary abdominal pain scores were 0.4 (SE 0.1, p < 0.001) point higher (on a 1-to-5-point scale) compared to corresponding ESM mean-scores in IBS patients. The difference was even more pronounced for upper abdominal pain scores assessed by the GSRS (4.77 ± 1.50) compared to ESM mean-scores (2.44 ± 1.30, p < 0.001), both on 1-to-7-point scale. For flatulence, comparable results were found. Nausea and belching scores showed small, but significant differences between end-of-day diary and ESM. All tested symptoms were scored higher on GSRS compared to ESM mean-scores (p < 0.01). Affective comorbidity did not influence differences in pain reporting between methods. CONCLUSIONS & INFERENCES: IBS patients report higher scores for abdominal pain in retrospective questionnaires compared to ESM, with a tendency to report peak rather than average pain scores. ESM can provide more insight in symptom course and potential triggers, and may lead to a better understanding of IBS symptomatology.

Double gastric infection with Helicobacter pylori and non-Helicobacter pylori bacteria during acid-suppressive therapy: increase of pro-inflammatory cytokines and development of atrophic gastritis.

BACKGROUND: Long-term acid suppression may accelerate the development of atrophic gastritis in Helicobacter pylori-positive subjects. The pathogenetic mechanism remains unclear. AIM: To test the hypothesis that gastric double infection with H. pylori and non-H. pylori bacterial species-during acid suppression-may result in an enhanced inflammatory response, contributing to the development of atrophic gastritis. PATIENTS AND METHODS: A consecutive series of patients with gastro-oesophageal reflux disease undergoing treatment with proton pump inhibitors (n=113) or histamine2-receptor antagonists (H2-RAs) (n=37), and 76 non-treated dyspeptic controls were investigated. Gastric mucosal H. pylori and non-H. pylori bacteria, histological gastritis, H. pylori serology, and circulating interleukin (IL)-1beta, IL-6, and IL-8 were examined. RESULTS: Patients on acid suppression with either proton pump inhibitors or H2-RAs had a similar prevalence of H. pylori infection to the controls, but a higher prevalence of non-H. pylori bacteria (61% and 60% vs. 29%, P < 0.0001 and P < 0.002). Both the presence of H. pylori and non-H. pylori bacteria were independent risk factors of atrophic gastritis (antrum: relative risks (RRs), 10.1 and 5.07; corpus: RRs, 11.74 and 6.38). A simultaneous presence of H. pylori and non-H. pylori bacteria was associated with a markedly increased risk of atrophic gastritis (antrum: RR, 20.25; corpus: RR, 20.38), compatible with a synergistic effect. Furthermore, the simultaneous presence of both types of bacteria was associated with higher cytokine levels than in patients without any type of bacteria. This increase was also greater than in patients with H. pylori infection alone (P < 0.001, for both IL-1beta and IL-8). SUMMARY AND CONCLUSIONS: H. pylori-positive patients on long-term acid inhibition displayed three features: non-H. pylori bacterial growth; increased cytokine levels; and a higher risk of atrophic gastritis. We suggest that double infection with H. pylori and non-H. pylori bacteria is a major factor in the development of atrophic gastritis during gastric acid inhibition.

Non-Helicobacter pylori bacterial flora during acid-suppressive therapy: differential findings in gastric juice and gastric mucosa.

BACKGROUND: Intragastric growth of non-Helicobacter pylori bacteria commonly occurs during acid-suppressive therapy. The long-term clinical consequences are still unclear. AIM: To investigate the luminal and mucosal bacterial growth during gastric acid inhibition, in relation to the type and duration of acid-inhibitory treatment, as well as to concomitant H. pylori infection. METHODS: A total of 145 patients on continuous acid inhibition with either proton pump inhibitors (n=109) or histamine2-receptor antagonists (H(2)RAs, n=36) for gastro-oesophageal reflux disease, and 75 dyspeptic patients without acid inhibition (control group) were included. At endoscopy, fasting gastric juice was obtained for pH measurement and bacteriological culture. Gastric biopsy specimens were examined for detection of H. pylori (immunohistochemistry) and of non-H. pylori bacteria (modified Giemsa stain-positive and immunohistochemistry-negative at the same location). RESULTS: Non-H. pylori flora was detected in the gastric juice of 92 (41.8%) patients and in the gastric mucosa of 109 (49.6%) patients. In gastric juice, prevalence rate for non-H. pylori bacteria was higher in patients taking proton pump inhibitors than controls and those taking H(2)RAs (58.7% vs. 22.6% and vs. 30.6%, P < 0.0001 and P < 0.003, respectively), but did not differ statistically between H(2)RAs and controls. In gastric mucosa, prevalence rates for non-H. pylori bacteria were higher in patients taking proton pump inhibitors and H(2)RAs than in the controls (antrum: 46.9% and 48.6% vs. 25%, P < 0.05 for both; corpus: 52.2% and 56.8% vs. 23.7%, P < 0.001 for both), but did not differ between proton pump inhibitors and H(2)RAs. Both luminal and mucosal growth of non-H. pylori bacteria were significantly greater in H. pylori-positive than -negative patients taking proton pump inhibitors (P < 0.05 for both). Luminal growth of non-H. pylori flora increased with the intragastric pH level, whilst mucosal bacterial growth increased with the duration of acid inhibition. CONCLUSIONS: Non-H. pylori flora not only contaminates the gastric juice but also colonizes the gastric mucosa of a large proportion of patients treated long-term with acid inhibition. The relationship between H. pylori and non-H. pylori bacteria in the pathogenesis of atrophic gastritis and gastric cancer needs further elucidation.