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1.	Ahluwalia, Bani, et al. (författare) Randomized clinical trial: Effects of Aloe barbadensis Mill. extract on symptoms, fecal microbiota and fecal metabolite profiles in patients with irritable bowel syndrome 2020 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 32:8 Tidskriftsartikel (refereegranskat)abstract Background Aloe barbadensis Mill.(Aloe) with potential prebiotic effects has been suggested to reduce symptoms in patients with irritable bowel syndrome (IBS). We therefore aimed to determine the effects of an Aloe extract on symptoms of IBS, and evaluate whether effects may be mediated by fecal microbiota and metabolites in a randomized, double-blind, controlled trial. Methods Patient with IBS diagnosed according to the ROME III criteria (all subtypes), received Aloe or control treatment (inulin) for 4 weeks. IBS Symptom Severity Score (IBS-SSS) was assessed, and fecal samples collected before and at end of treatment. Fecal microbiota composition and metabolomic profile were determined. Key results In total, 160 IBS patients completed the study. The overall severity of IBS symptoms was reduced in both Aloe and control treatment groups (P < .001, both groups, comparing baseline vs end of treatment), without difference between groups (P = .62). The frequency of responders (IBS-SSS reduction >= 50) did not differ between Aloe treatment (n = 33, 39%) and control (n = 34, 45%) (P = .49). However, fecal microbiota and metabolite profiles differed between Aloe, but not control treatment responders and non-responders both before and after treatment. Conclusion In a mixed group of IBS patients, Aloe was not superior to control treatment, although it showed potential to reduce IBS symptom severity in subsets of IBS patients which could be predicted by fecal microbiota and metabolite profiles. ClinicalTrials.gov no: NCT01400048.
2.	Algera, Joost, 1993, et al. (författare) Associations between postprandial symptoms, hydrogen and methane production, and transit time in irritable bowel syndrome 2023 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 35:2 Tidskriftsartikel (refereegranskat)abstract 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.
3.	Beeckmans, Dorien, et al. (författare) Relationship between bile salts, bacterial translocation, and duodenal mucosal integrity in functional dyspepsia 2020 Ingår i: Neurogastroenterology and Motility. - : WILEY. - 1350-1925 .- 1365-2982. ; 32:5 Tidskriftsartikel (refereegranskat)abstract Background Functional dyspepsia (FD) is a complex disorder, in which multiple mechanisms underlie symptom generation, including impaired duodenal barrier function. Moreover, an altered duodenal bile salt pool was recently discovered in patients with FD. We aimed to evaluate the relationship between bile salts, bacterial translocation, and duodenal mucosal permeability in FD. Methods Duodenal biopsies from patients with FD and healthy volunteers (HV) were mounted in Ussing chambers to measure mucosal resistance and bacterial passage in the absence and presence of fluorescein-conjugated Escherichia coli and glyco-ursodeoxycholic acid (GUDCA) exposure. In parallel, duodenal fluid aspirates were collected from patients and bile salts were analyzed. Key results The transepithelial electrical resistance of duodenal biopsies from patients was lower compared with HV (21.4 +/- 1.3 omega.cm(2) vs. 24.4 +/- 1.2 omega.cm(2); P = .02; N = 21). The ratio of glyco-cholic and glyco-chenodeoxycholic acid (GCDCA) to tauro- and GUDCA correlated positively with transepithelial electrical resistance in patients. Glyco-ursodeoxycholic acid slightly altered the mucosal resistance, resulting in similar values between patient and healthy biopsies (22.1 +/- 1.0 omega.cm(2) vs. 23.0 +/- 1.0 omega.cm(2); P = .5). Bacterial passage after 120 minutes was lower for patient than for healthy biopsies (0.0 [0.0-681.8] vs. 1684.0 [0.0-4773.0] E coli units; P = .02). Glyco-ursodeoxycholic acid increased bacterial passage in patient biopsies (102.1 [0.0-733.0] vs. 638.9 [280.6-2124.0] E coli units; P = .009). No correlation was found between mucosal resistance and bacterial passage. Conclusions amp; inferences Patients with FD displayed decreased duodenal mucosal resistance associated with bile salts, however, not associated with bacterial passage in vitro. In addition, the hydrophilic bile salt glyco-ursodeoxycholic acid abolished differences in mucosal resistance and bacterial passage between patient and control group.
4.	Bosman, M., et al. (författare) Placebo response in pharmacological trials in patients with functional dyspepsia-A systematic review and meta-analysis 2023 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 35:2 Forskningsöversikt (refereegranskat)abstract Background Pharmacological trials in functional dyspepsia (FD) are associated with high placebo response rates. We aimed to identify the magnitude and contributing factors to the placebo response. Methods We conducted a systematic review and meta-analysis including randomized controlled trials (RCTs) with a dichotomous outcome in adult patients with FD that compared an active pharmacotherapeutic treatment with placebo. Our main outcome was identification of the magnitude of the pooled placebo response rate for the following endpoints: symptom responder, symptom-free responder, adequate relief responder, and combined endpoint responder (i.e., the primary endpoint of each specific trial regarding treatment response). Several putative moderators (i.e., patient, disease, and trial characteristics) were examined. Key Results We included 26 RCTs in our analysis. The pooled placebo response rate was 39.6% (95% CI 30.1-50.0) using the symptom responder definition, 20.5% (12.8-31.0) using the symptom-free responder definition, 38.5% (33.8-43.6) using the adequate relief responder definition, and 35.5% (31.6-39.7) using the combined endpoint responder definition. A lower overall baseline symptom score was significantly associated with a higher placebo response rate. No other moderators were found to significantly impact the placebo response rate. Due to the lack of data, no analyses could be performed according to individual FD subtypes or symptoms. Conclusions and Inferences The pooled placebo response rate in pharmacological trials in FD is about 39%, depending on which responder definitions is used. Future trials should consider applying an entry criterion based on minimal level of symptom severity to decrease the placebo response. We also suggest separate reporting of core FD symptoms pending more concrete harmonization efforts in FD trials.
5.	Bureychak, Tetyana, et al. (författare) Symptoms and health experience in irritable bowel syndrome with focus on men 2022 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 34:11 Tidskriftsartikel (refereegranskat)abstract Background Irritable bowel syndrome (IBS) is a disorder with a predominance in women; IBS in men is less studied. The present study evaluated symptoms as well as health and social experiences of men with IBS. Methods This cross-sectional study included 293 patients with IBS (64 men) and 363 non-IBS controls (62 men). Gastrointestinal symptom diaries were filled in prospectively, and data on comorbidities and healthcare-seeking behavior were assessed by questionnaires. Men with IBS were compared with men without IBS and women with IBS. Key results Compared with women with IBS, men with IBS had fewer contacts with the healthcare system, fewer psychiatric comorbidities, fewer sleeping problems, and less chronic pain. Urgency to defecate and nausea were less common, and stool frequency was higher in men with IBS. There was no difference between men with and without IBS in terms of educational level, satisfaction with household economy, or living with a partner. In contrast, women with IBS more often lived alone, were more often dissatisfied with household economy, and had a lower educational level than women without IBS. Men with IBS had the same proportion of full-time employment as men without IBS but in contrast, the proportion of women with IBS in full-time employment was only 34%, compared to 50% of the women without IBS. Conclusion and inferences The present study improves the understanding of mens experiences of IBS and suggests that sex and gender may be integrated into the biopsychosocial model of IBS.
6.	Böhn, Lena, et al. (författare) A randomized double-blind placebo-controlled crossover pilot study: Acute effects of the enzyme alpha-galactosidase on gastrointestinal symptoms in irritable bowel syndrome patients 2021 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 33:7 Tidskriftsartikel (refereegranskat)abstract Background Postprandial symptoms presumably related to intestinal gas production are common in patients with irritable bowel syndrome (IBS). The aim of the study was to assess if oral alpha-galactosidase is superior to placebo in reducing gastrointestinal (GI) symptoms and intestinal gas production after ingestion of carbohydrate-rich meals in adult patients with IBS. Methods We studied the effect of 1200 GaIU/meal alpha-galactosidase (Nogasin(R)) or placebo capsules on GI symptoms in patients with IBS after three standardized, meals high in oligosaccharides, in a randomized, double-blind, crossover study. The intensity of eight GI symptoms was rated, and breath hydrogen and methane were measured every 30 min during 7.5 h. The severity of GI symptoms the following morning was assessed and compared with baseline.S Key Results Twenty adult patients with IBS (19 females), mean age 49 years (range 22-75 years), were included. All test meals were well tolerated but induced a gradual increase in GI symptom severity. Neither GI symptom ratings over time, nor hydrogen and methane concentrations differed between the days with alpha-galactosidase or placebo. The severity of abdominal pain and bloating was lower the following morning, but with no differences between alpha-galactosidase and placebo. Conclusions & Inferences The use of alpha-galactosidase together with meals high in oligosaccharides was in this pilot study not superior to placebo in reducing postprandial GI symptoms or the concentration of hydrogen and methane in expired air in IBS.
7.	Cajander, Per, 1976-, et al. (författare) Effects of dexmedetomidine on pharyngeal swallowing and esophageal motility : A double-blind randomized cross-over study in healthy volunteers 2023 Ingår i: Neurogastroenterology and Motility. - : Wiley-Blackwell Publishing Inc.. - 1350-1925 .- 1365-2982. ; 35:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Sedative agents increase the risk of pulmonary aspiration, where an intact swallowing function is an important defense mechanism. Dexmedetomidine is an α2 -adrenoceptor agonist widely used during procedural sedation due to beneficial properties with minimal respiratory effects. The effects of dexmedetomidine on pharyngeal swallowing and esophageal motility are not known in detail.METHODS: To determine the effects of dexmedetomidine on pharyngeal swallowing and esophageal motility, nineteen volunteers were included in this double-blinded, randomized placebo-controlled cross-over study. Study participants received target-controlled dexmedetomidine and placebo infusions. Recordings of pressure and impedance data were acquired using a manometry and impedance solid-state catheter. Data were analyzed from three bolus swallows series: baseline, during dexmedetomidine/placebo infusion at target plasma concentrations 0.6 ng ml-1 and 1.2 ng ml-1 . Subjective swallowing difficulties were also recorded.KEY RESULTS: On pharyngeal swallowing, dexmedetomidine affected the upper esophageal sphincter with decreased pre- and post-swallow contractile pressures and an increase in residual pressure during swallow-related relaxation. On esophageal function, dexmedetomidine decreased contractile vigor of the proximal esophagus and increased velocity of the peristaltic contraction wave. Residual pressures during swallow-related esophagogastric junction (EGJ) relaxation decreased, as did basal EGJ resting pressure. The effects on the functional variables were not clearly dose-dependent, but mild subjective swallowing difficulties were more common at the higher dose level.CONCLUSIONS AND INFERENCES: Dexmedetomidine induces effects on pharyngeal swallowing and esophageal motility, which should be considered in clinical patient management and also when a sedative agent for procedural sedation or for manometric examination is to be chosen.
8.	Cajander, Per, 1976-, et al. (författare) Response to Letter to the Editor 2023 Ingår i: Neurogastroenterology and Motility. - : Wiley-Blackwell. - 1350-1925 .- 1365-2982. ; 35:8 Tidskriftsartikel (refereegranskat)abstract It is crucial to consider the possible influence of anesthetic agents on esophageal function testing. Dexmedetomidine has been shown to affect primary peristalsis during esophageal manometry. In the two case reports presented by Toaz et al., secondary peristalsis during FLIP panometry was also affected. This may be attributed to an alternate pharmacodynamic effect, with a transient direct α2-mediated effect on esophageal smooth muscle, associated with a high plasma concentration following bolus injection, prior to the onset of sympathetic inhibition.
9.	Clevers, Egbert, et al. (författare) Food-symptom diaries can generate personalized lifestyle advice for managing gastrointestinal symptoms: A pilot study 2020 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 32:8 Tidskriftsartikel (refereegranskat)abstract 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.
10.	Corsetti, M., et al. (författare) Chronic constipation in adults: Contemporary perspectives and clinical challenges. 2: Conservative, behavioural, medical and surgical treatment 2021 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. Tidskriftsartikel (refereegranskat)abstract Background: Chronic constipation is a prevalent disorder that affects quality of life of patients and consumes resources in healthcare systems worldwide. In clinical practice, it is still considered a challenge as clinicians frequently are unsure as to which treatments to use and when. Over a decade ago, a Neurogastroenterology and Motility journal supplement devoted to the investigation and management of constipation was published (Neurogastroenterol Motil 2009;21(Suppl 2):1). In October 2018, the 3rd London Masterclass, entitled "Contemporary management of constipation" was held. The faculty members of this symposium were invited to write two reviews to present a collective synthesis of talks presented and discussions held during this meeting. The first review addresses epidemiology, diagnosis, clinical associations, pathophysiology, and investigation. Purpose: The present is the second of these reviews, providing contemporary perspectives and clinical challenges regarding behavioral, conservative, medical, and surgical treatments for patients presenting with constipation. It includes a management algorithm to guide clinical practice.
11.	Dreja, Julia, et al. (författare) Volumetric analysis of small bowel motility in an unselected cohort of patients with Crohn’s disease 2020 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 32:10 Tidskriftsartikel (refereegranskat)abstract Background: Quantified terminal ileal motility during magnetic resonance enterography (MRE) has been suggested to be used as a biomarker of Crohn's disease (CD). The aim of the present study was to evaluate this method in clinical practice. Methods: Healthy volunteers and all consecutive patients referred to MRE during a 2-year period were asked to participate and complete the Irritable Bowel Syndrome-Symptom Severity Scale (IBS-SSS) to assess gastrointestinal symptoms. Medical records were scrutinized, and motility indices (MIs) were calculated from MR images. Key Results: Twenty-two healthy controls and 134 examinations with CD were included (inclusion rate: 76.3%). Patients with CD had increased mural thickness of the terminal ileum, increased fecal calprotectin, and more symptoms than controls. Patients with active CD had increased mural thickness of ileum and terminal ileum, higher MR activity indices, and signs of inflammation in laboratory analyses, but similar symptoms, compared with inactive disease. After exclusion of sole colon disease (n = 13), MI inversely correlated with mural thickness in terminal ileum, and MI was lower in active disease versus controls in ileum (P =.019) and terminal ileum (P =.005), and versus inactive disease in terminal ileum (P =.044). The area under the curve of MI in terminal ileum was 0.736 for active CD against healthy controls (P =.002) and 0.682 for active against inactive CD (P =.001). MIs were similar in controls and inactive CD. Conclusions and Interferences: MI reflects inflammatory activity in the intestine. Alterations in MI did not explain symptomatology in inactive CD, without measurable inflammatory parameters in morphology or laboratory analyses.
12.	Garcia-Etxebarria, K, et al. (författare) A survey of functional dyspepsia in 361,360 individuals: Phenotypic and genetic cross-disease analyses 2022 Ingår i: Neurogastroenterology and motility. - : Wiley. - 1365-2982 .- 1350-1925. ; 34:6, s. e14236- Tidskriftsartikel (refereegranskat)
13.	Grinsvall, Cecilia, et al. (författare) Association between pain sensitivity and gray matter properties in the sensorimotor network in women with irritable bowel syndrome 2021 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 33:4 Tidskriftsartikel (refereegranskat)abstract Background Enhanced perception of visceral stimuli is an important feature of Irritable Bowel Syndrome (IBS), but it is not known whether visceral sensitivity is associated with regional structural brain properties in IBS. Methods Structural brain magnetic resonance imaging data from 216 women with IBS and 138 healthy women were parcellated with FreeSurfer to define regional gray matter morphometry (volume, cortical thickness, surface area and mean curvature) in the sensorimotor network. General linear models were used to detect group differences between IBS and health. In a second set of 48 female IBS patients, pain threshold, pain intensity ratings during rectal balloon distension, and reported levels of abdominal pain and bloating were correlated with brain regions that showed differences between IBS and health in the first data set. Key Results Several statistically significant differences between IBS patients and healthy controls were found, mainly higher gray matter volume and cortical thickness in primary somatosensory cortex, secondary somatosensory cortex, and subcortical regions, and lesser gray matter volume, surface area and cortical thickness in posterior insula and superior frontal gyrus. Pain intensity ratings during rectal distension were associated with left primary somatosensory cortical thickness, and pain threshold was associated with right nucleus accumbens volume. Conclusions and Inferences Regional gray matter differences in sensorimotor network are associated with visceral sensitivity and may represent neuroplastic changes in female IBS patients.
14.	Hreinsson, Johann P., 1987, et al. (författare) A comparative study of disorders of gut-brain interaction in Western Europe and Asia based on the Rome foundation global epidemiology study 2023 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 35:6 Tidskriftsartikel (refereegranskat)abstract ObjectiveMany studies have been published on disorders of the gut-brain interaction (DGBI) in Asia and Western Europe, but no previous study has directly assessed the difference between the two regions. The aim was to compare the prevalence of DGBI in Asia and Western Europe. MethodsWe used data collected in a population-based Internet survey, the Rome Foundation Global Epidemiology Study, from countries in Western Europe (Belgium, France, Germany, Netherlands, Italy, Spain, Sweden, and the United Kingdom) and Asia (China, Japan, South Korea, and Singapore). We assessed DGBI diagnoses (Rome IV Adult Diagnostic Questionnaire), anxiety/depression (Patient Health Questionnaire-4, PHQ-4), non-GI somatic symptoms (PHQ-12), and access to and personal costs of doctor visits. ResultsThe study included 9487 subjects in Asia and 16,314 in Western Europe. Overall, 38.0% had at least one DGBI; younger age, female sex, and higher scores on PHQ4 and PHQ12 were all associated with DGBI. The prevalence of having at least one DGBI was higher in Western Europe than in Asia (39.1% vs 36.1%, OR 1.14 [95% CI 1.08-1.20]). This difference was also observed for DGBI by anatomical regions, most prominently esophageal DGBI (OR 1.67 [1.48-1.88]). After adjustment, the difference in DGBI prevalence diminished and psychological (PHQ-4) and non-GI somatic symptoms (PHQ-12) had the greatest effect on the odds ratio estimates. ConclusionThe prevalence of DGBI is generally higher in Western Europe compared to Asia. A considerable portion of the observed difference in prevalence rates seems to be explained by more severe psychological and non-GI somatic symptoms in Western Europe.
15.	Iribarren, Cristina, 1993, et al. (författare) Fecal luminal factors from patients with irritable bowel syndrome induce distinct gene expression of colonoids 2022 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 34:10 Tidskriftsartikel (refereegranskat)abstract Background: Alteration of the host-microbiota cross talk at the intestinal barrier may participate in the pathophysiology of irritable bowel syndrome (IBS). Therefore, we aimed to determine effects of fecal luminal factors from IBS patients on the colonic epithelium using colonoids. Methods: Colon-derived organoid monolayers, colonoids, generated from a healthy subject, underwent stimulation with fecal supernatants from healthy subjects and IBS patients with predominant diarrhea, phosphate-buffered saline (PBS), or lipopolysaccharide (LPS). Cytokines in cell cultures and fecal LPS were measured by ELISA and mRNA gene expression of monolayers was analyzed using Qiagen RT2 Profiler PCR Arrays. The fecal microbiota profile was determined by the GA-map (TM) dysbiosis test and the fecal metabolite profile was analyzed by untargeted liquid chromatography/mass spectrometry. Key results: Colonoid monolayers stimulated with fecal supernatants from healthy subjects (n = 7), PBS (n = 4) or LPS (n = 3) presented distinct gene expression profiles, with some overlap ((RY)-Y-2 = 0.70, Q(2) = 0.43). Addition of fecal supernatants from healthy subjects and IBS patients (n = 9) gave rise to different gene expression profiles of the colonoid monolayers ((RY)-Y-2 = 0.79, Q(2) = 0.64). Genes (n = 22) related to immune response (CD1D, TLR5) and barrier integrity (CLDN15, DSC2) contributed to the separation. Levels of proinflammatory cytokines in colonoid monolayer cultures were comparable when stimulated with fecal supernatants from either donor types. Fecal microbiota and metabolite profiles, but not LPS content, differed between the study groups. Conclusions: Fecal luminal factors from IBS patients induce a distinct colonic epithelial gene expression, potentially reflecting the disease pathophysiology. The culture of colonoids from healthy subjects with fecal supernatants from IBS patients may facilitate the exploration of IBS related intestinal micro-environmental and barrier interactions.
16.	Iribarren, Cristina, 1993, et al. (författare) Human milk oligosaccharide supplementation in irritable bowel syndrome patients: A parallel, randomized, double-blind, placebo-controlled study 2020 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 32:10 Tidskriftsartikel (refereegranskat)abstract Objectives Human milk oligosaccharides safely and beneficially impact bifidobacteria abundance in healthy adults, while their effects in patients with irritable bowel syndrome (IBS) are unknown. Hence, we aimed to determine the dose of 4:1 mix of 2'-O-fucosyllactose and Lacto-N-neotetraose (2'FL/LNnT) that increases fecal bifidobacteria abundance without aggravating overall gastrointestinal symptoms in IBS patients in a randomized, double-blind, controlled study. Additionally, the impact of 2'FL/LNnT on the fecal bacterial profile was assessed. Methods Irritable bowel syndrome patients diagnosed according to the Rome IV criteria received placebo (glucose), or 5 g or 10 g 2'FL/LNnT for 4 weeks followed by a four-week follow-up period. Gastrointestinal Symptom Rating Scale-IBS was used to assess gastrointestinal symptom severity; fecal microbiota composition was evaluated by GA-map (TM) Dysbiosis Test. Results Of the included 60 patients, two (one placebo and one 10 g) discontinued prematurely. Fecal bifidobacteria abundance was increased at week 4, but not at week 8, in the 10 g group compared to the other groups. Severity of overall or individual gastrointestinal symptoms did not differ between the groups at week 4 or 8, and no symptom deterioration was seen in any of the groups. The 10 g dose influenced overall fecal microbiota composition, and responders-defined as bifidobacteria increase >= 50%-could be discriminated from non-responders based on fecal microbiota modulation. Conclusions The 10 g dose of 2'FL/LNnT induced an increase in the beneficialBifidobacteriumspp. without aggravating gastrointestinal symptoms in patients with IBS. This approach may be worthwhile to modulate gut microbiota of IBS patients toward a healthier profile.
17.	Iribarren, Cristina, 1993, et al. (författare) Temporal stability of fecal metabolomic profiles in irritable bowel syndrome 2024 Ingår i: Neurogastroenterology and Motility. - 1350-1925 .- 1365-2982. ; 36:3 Tidskriftsartikel (refereegranskat)abstract 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.
18.	Josefsson, Axel, 1984, et al. (författare) Natural history of symptoms and prognostic information of the rapid drink challenge and solid bolus swallows in esophagogastric junction outflow obstruction defined by manometry 2024 Ingår i: Neurogastroenterology and Motility. - 1350-1925 .- 1365-2982. ; 36:2 Tidskriftsartikel (refereegranskat)abstract 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.
19.	Klaassen, T., et al. (författare) Psychometric evaluation of an experience sampling method-based patient-reported outcome measure in functional dyspepsia 2021 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 33:9 Tidskriftsartikel (refereegranskat)abstract Background Due to important biases, conventional end-of-day and end-of-week assessment methods of gastrointestinal symptoms in functional dyspepsia (FD) are considered suboptimal. Real-time symptom assessment based on the experience sampling method (ESM) could be a more accurate measurement method. This study aimed to evaluate validity and reliability of an ESM-based patient-reported outcome measure (PROM) for symptom assessment in FD. Methods Thirty-five patients with FD (25 female, mean age 44.7 years) completed the ESM-based PROM (a maximum of 10 random moments per day) and an end-of-day symptom diary for 7 consecutive days. On day 7, end-of-week questionnaires were completed including the Nepean Dyspepsia Index (NDI) and Patient Assessment of Gastrointestinal Symptom Severity Index (PAGI-SYM). Key Results Experience sampling method and corresponding end-of-day scores for gastrointestinal symptoms were significantly associated (ICCs range 0.770-0.917). However, end-of-day scores were significantly higher (Delta 0.329-1.031) than mean ESM scores (p < 0.05). Comparing ESM with NDI and PAGI-SYM scores, correlations were weaker (Pearson's r range 0.467-0.846). Cronbach's alpha coefficient was good for upper gastrointestinal symptoms (alpha = 0.842). First half-week and second half-week scores showed very good consistency (ICCs range 0.913-0.975). Conclusion and Inferences Good validity and reliability of a novel ESM-based PROM for assessing gastrointestinal symptoms in FD patients was demonstrated. Moreover, this novel PROM allows to evaluate individual symptom patterns and can evaluate interactions between symptoms and environmental/contextual factors. ESM has the potential to increase patients' disease insight, provide tools for self-management, and improve shared decision making. Hence, this novel tool may aid in the transition toward personalized health care for FD patients.
20.	Leven, Patrick, et al. (författare) Application of a RiboTag-based approach to generate and analyze mRNA from enteric neural cells 2022 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 34:7 Tidskriftsartikel (refereegranskat)abstract Background Transcriptional profiling of specific intestinal cell populations under health and disease is generally based on traditional sorting approaches followed by gene expression analysis. Therein, specific cell populations are identified either by expressing reporter genes under a cell type-specific promotor or by specific surface antigens. This method provides adequate results for blood-derived and tissue-resident immune cells. However, in stromal cell analysis, cellular stress due to digestion often results in degraded RNA. Particularly, ramified cells integrated into the tissue, such as enteric neurons and glial cells, suffer from these procedures. These cell types are involved in various intestinal processes, including a prominent immune-regulatory role, which requires suitable approaches to generate cell-specific transcriptional profiles. Methods Sox10(iCreERT2) and choline acetyltransferase (ChAT(Cre)) mice were crossed with mice labeling the ribosomal Rpl22 protein upon Cre activity with a hemagglutinin tag (Rpl22-HA, termed RiboTag). This approach enabled cellular targeting of enteric glia and neurons and the immediate isolation of cell-specific mRNA from tissue lysates without the need for cell sorting. Key results We verified the specific expression of Rpl22-HA in enteric glia and neurons and provided gene expression data demonstrating a successful enrichment of either Sox-10(+) glial or ChAT(+) neuronal mRNAs by the RiboTag-mRNA procedure using qPCR and RNA-Seq analysis. Conclusions and inferences We present a robust and selective protocol that allows the generation of cell type-specific transcriptional in vivo snapshots of distinct enteric cell populations that will be especially useful for various intestinal disease models involving peripheral neural cells.
21.	Mavroudis, Georgios, et al. (författare) Visceral hypersensitivity is together with psychological distress and female gender associated with severity of IBS-like symptoms in quiescent ulcerative colitis 2021 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 33:3 Tidskriftsartikel (refereegranskat)abstract Background: A subset of ulcerative colitis (UC) patients in remission demonstrate IBSlike symptoms. Visceral hypersensitivity is a key pathophysiological mechanism in IBS, but its relevance to IBS-like symptoms in inactive UC remains unclear. Methods: UC patients in remission (UCR) were screened for IBS-like symptoms. Rectal sensitivity was assessed with rectal balloon distensions, with determination of sensory thresholds and unpleasantness/pain intensity ratings. Patients completed questionnaires evaluating gastrointestinal (GI) and psychological symptoms. Age- and gendermatched IBS subjects and healthy controls (HC) also underwent a rectal sensitivity test. Key Results: We included 36 UCR patients (18 with IBS-like symptoms (UCR + IBS) and 18 without (UCR - IBS)), 36 IBS subjects, and 14 HC. UCR and IBS patients were more sensitive to rectal balloon distensions than HC, but no differences between UCR and IBS patients were observed. UCR + IBS patients had lower sensory thresholds and higher unpleasantness ratings than UCR - IBS. In UCR patients, the overall GI symptom severity, pain, and bloating, but not diarrhea, constipation or satiety, were associated with rectal sensitivity. In multivariate analyses, rectal sensitivity, psychological distress, and female gender were identified as factors independently associated with GI symptom severity. 61% of UCR patients demonstrated rectal hypersensitivity, and these patients more commonly reported at least mild bloating and pain, and overall GI symptoms, compared to those with normal rectal sensitivity. Conclusion & Inferences: Visceral hypersensitivity was associated with IBS-like symptoms, in particular pain and bloating, in inactive UC. Together with psychological factors and female gender, visceral hypersensitivity seems to be involved in GI symptom generation in quiescent UC.
22.	Meira de-Faria, Felipe, 1984-, et al. (författare) Altered interaction between enteric glial cells and mast cells in the colon of women with irritable bowel syndrome 2021 Ingår i: Neurogastroenterology and Motility. - : Blackwell Science Ltd.. - 1350-1925 .- 1365-2982. ; 33:11 Tidskriftsartikel (refereegranskat)abstract Background: Enteric glial cells (EGC) and mast cells (MC) are intimately associated with gastrointestinal physiological functions. We aimed to investigate EGC-MC interaction in irritable bowel syndrome (IBS), a gut-brain disorder linked to increased intestinal permeability, and MC.Methods: Parallel approaches were used to quantify EGC markers in colonic biopsies from healthy controls (HC) and patients with IBS. Data were correlated with MC, vasoactive intestinal polypeptide (VIP) and VIP receptors (VPAC1/VPAC2) expressions, and bacterial translocation through biopsies mounted in Ussing chambers. In addition, we investigated the effects of EGC mediators on colonic permeability and the pharmacological-induced responses of EGC and MC cell lines.Key Results: Immunofluorescence of IBS colonic mucosa, as well as Western blotting and ELISA of IBS biopsy lysates, revealed increased glial fibrillary intermediate filament (GFAP) expression, indicating EGC activation. Mucosal GFAP correlated with increased MC and VPAC1(+)MC numbers and decreased VIP+MC, which seemed to control bacterial translocation in HC. In the contrary, EGC activation in IBS correlated with less MC and VPAC1(+) MC numbers, and more VIP+ MC. In vitro, MC and EGC cell lines showed intracellular calcium responses to each other's mediators. Furthermore, EGC mediators prevented VIP-induced MC degranulation, while MC mediators induced a reactive EGC phenotype. In Ussing chambers, EGC mediators decreased paracellular passage through healthy colonic biopsies.Conclusions & Inferences: Findings suggest the involvement of EGC and MC in the control of barrier function in the human colon and indicate a potential EGC-MC interaction that seems altered in IBS, with detrimental consequences to colonic permeability. Altogether, results suggest that imbalanced EGC-MC communication contributes to the pathophysiology of IBS.
23.	Midenfjord, Irina, et al. (författare) Central sensitization and severity of gastrointestinal symptoms in irritable bowel syndrome, chronic pain syndromes, and inflammatory bowel disease 2021 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 33:12 Tidskriftsartikel (refereegranskat)abstract Background Central sensitization has been suggested as an explanation of the wide range of gastrointestinal and extraintestinal symptoms commonly seen in irritable bowel syndrome (IBS). In this study, the presence and level of central sensitization, and its association to gastrointestinal (GI) symptoms were explored in IBS in comparison with control groups. Methods We investigated patients with IBS (n = 215), chronic pain disorders (n = 36), and inflammatory bowel disease (IBD) (n = 40) and volunteers without chronic diseases (n = 112). The Central Sensitization Inventory (CSI) was translated and validated in Swedish and used together with the Highly Sensitive Person (HSP) scale to measure the presence and level of central sensitization. Furthermore, severity of GI symptoms (GSRS-IBS and IBS-SSS), and anxiety and depression (HAD) were determined. Key results The Swedish translation of CSI demonstrated excellent validity. Central sensitization, defined by validated cut-off levels for CSI and HSP, was common in the whole cohort (40% and 28%) and in IBS (57% and 35%). Study participants with central sensitization had more severe GI symptoms, anxiety and depression, than participants without central sensitization. Strong associations were seen between CSI and GI symptom severity in the whole cohort (GSRS-IBS: partial eta(2) = 0.455, p < 0.001; IBS-SSS: partial eta(2) = 0.408, p < 0.001), with decreasing strength in patients with chronic pain, IBD, IBS, and volunteers. Conclusion and Inferences Central sensitization was common in IBS and associated with GI symptom severity, but with stronger associations in chronic pain disorders and IBD. This implies that other mechanisms may be of equal or greater importance for GI symptom severity in IBS.
24.	O'Grady, G., et al. (författare) Gastric sensorimotor function and its clinical measurement 2022 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 34:12 Tidskriftsartikel (refereegranskat)abstract Background: Gastroduodenal symptoms are highly prevalent, with underlying sensorimotor dysfunction contributing in many patients. Common symptoms include early satiation, postprandial fullness, epigastric bloating, pain or burning, nausea and vomiting, which collectively affect over 7% of adults. However, the clinical evaluation of these symptoms remains challenging, with current tests of gastric function remaining limited in their ability or availability to separate specific patient subgroups or guide-targeted care. Purpose: In the current edition of Neurogastroenterology & Motility, Silver et al. present new data showing correlations between patterns of intragastric meal distribution and symptom profiles in a large series of patients undergoing gastric emptying scintigraphy. Studies of this type are important, as they motivate understanding beyond existing disease labels, and orient focus toward deeper mechanistic profiling. This brief review provides an overview of gastric sensorimotor function and profiles several current and emerging methods of clinical evaluation. Perspectives are provided on accommodation testing, gastric emptying, measuring gastric myoelectrical activity including new approaches, and antroduodenal manometry. Although gastric physiology is complex, recent progress has been encouraging, with the heterogenous pathophysiology of gastric symptoms continuing to be unraveled, and new techniques for evaluating gastric function and symptoms emerging. Conclusions and Inferences: Ongoing progress will now depend on continuing to accurately profile the underlying mechanisms of gastroduodenal disorders to identify specific disease phenotypes that inform care.
25.	Ronkainen, Jukka, et al. (författare) Duodenal eosinophilia and the link to anxiety : A population-based endoscopic study 2021 Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 33:10 Tidskriftsartikel (refereegranskat)abstract Introduction: The concept of gut-to-brain communication via microbial or inflammatory pathways is gaining increased attention but genuine pathology directly linking gut perturbation to anxiety is lacking. We hypothesized that duodenal eosinophilia, as known to occur in functional dyspepsia (FD), may be an underlying cause of anxiety and may help explain the striking association between FD and anxiety.Methods: Randomly selected subjects from the national population register of Sweden completed the validated Abdominal Symptom Questionnaire; 1000 completed esophagogastroduodenoscopy and the Hospital Anxiety and Depression Scale questionnaire. Duodenal biopsies were obtained from 1(st) (D1) and 2(nd) portion (D2). Eligible subjects who underwent endoscopy (n = 887) were invited to participate in a 10-year follow-up study with the same questionnaires. Among endoscopy normal subjects, FD was identified by Rome criteria, and controls were symptom free. Duodenal eosinophilia was based on pre-defined cut-offs. Finding are reported as odds ratios (ORs) with 95% confidence interval and p-value.Results: The study population comprised 89 cases with FD and 124 healthy controls (mean age 62 years, SD 12, 34% male). Clinical anxiety at follow-up was elevated in those with D1 eosinophilia at baseline considering either new-onset anxiety (OR = 4.5, 95% CI 0.8, 23.8; p = 0.08) or follow-up anxiety adjusting for baseline anxiety (OR = 4.51 (95% CI 1.03, 19.81; p = 0.046).Conclusion: Duodenal eosinophilia may potentially be a mechanism linked to anxiety independent of FD.

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