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1.
  • Kanberg, Nelly, et al. (author)
  • Neurochemical signs of astrocytic and neuronal injury in acute COVID-19 normalizes during long-term follow-up.
  • 2021
  • In: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 70
  • Journal article (peer-reviewed)abstract
    • Neurologic manifestations are well-recognized features of coronavirus disease 2019 (COVID-19). However, the longitudinal association of biomarkers reflecting CNS impact and neurological symptoms is not known. We sought to determine whether plasma biomarkers of CNS injury were associated with neurologic sequelae after COVID-19.Patients with confirmed acute COVID-19 were studied prospectively. Neurological symptoms were recorded during the acute phase of the disease and at six months follow-up, and blood samples were collected longitudinally. Healthy age-matched individuals were included as controls. We analysed plasma concentrations of neurofilament light-chain (NfL), glial fibrillary acidic protein (GFAp), and growth differentiation factor 15 (GDF-15).One hundred patients with mild (n=24), moderate (n=28), and severe (n=48) COVID-19 were followed for a median (IQR) of 225 (187-262) days. In the acute phase, patients with severe COVID-19 had higher concentrations of NfL than all other groups (all p < 0·001), and higher GFAp than controls (p < 0·001). GFAp was also significantly increased in moderate disease (p < 0·05) compared with controls. NfL (r=0·53, p < 0·001) and GFAp (r=0·39, p < 0·001) correlated with GDF-15 during the acute phase. After six months, NfL and GFAp concentrations had normalized, with no persisting group differences. Despite this, 50 patients reported persistent neurological symptoms, most commonly fatigue (n=40), "brain-fog" (n=29), and changes in cognition (n=25). We found no correlation between persistent neurological symptoms and CNS injury biomarkers in the acute phase.The normalization of CNS injury biomarkers in all individuals, regardless of previous disease severity or persisting neurological symptoms, indicates that post COVID-19 neurological sequelae are not accompanied by ongoing CNS injury.The Swedish State Support for Clinical Research, SciLifeLab Sweden, and the Knut and Alice Wallenberg Foundation have provided funding for this project.
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2.
  • Ahluwalia, Bani, et al. (author)
  • A Distinct Faecal Microbiota and Metabolite Profile Linked to Bowel Habits in Patients with Irritable Bowel Syndrome
  • 2021
  • In: Cells. - : MDPI AG. - 2073-4409. ; 10:6
  • Journal article (peer-reviewed)abstract
    • Patients with irritable bowel syndrome (IBS) are suggested to have an altered intestinal microenvironment. We therefore aimed to determine the intestinal microenvironment profile, based on faecal microbiota and metabolites, and the potential link to symptoms in IBS patients. The faecal microbiota was evaluated by the GA-map(TM) dysbiosis test, and tandem mass spectrometry (GC-MS/MS) was used for faecal metabolomic profiling in patients with IBS and healthy subjects. Symptom severity was assessed using the IBS Severity Scoring System and anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. A principal component analysis based on faecal microbiota (n = 54) and metabolites (n = 155) showed a clear separation between IBS patients (n = 40) and healthy subjects (n = 18). Metabolites were the main driver of this separation. Additionally, the intestinal microenvironment profile differed between IBS patients with constipation (n = 15) and diarrhoea (n = 11), while no clustering was detected in subgroups of patients according to symptom severity or anxiety. Furthermore, ingenuity pathway analysis predicted amino acid metabolism and several cellular and molecular functions to be altered in IBS patients. Patients with IBS have a distinct faecal microbiota and metabolite profile linked to bowel habits. Intestinal microenvironment profiling, based on faecal microbiota and metabolites, may be considered as a future non-invasive diagnostic tool, alongside providing valuable insights into the pathophysiology of IBS.
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3.
  • Ahluwalia, Bani, et al. (author)
  • Aloe barbadensis Mill. extract improves symptoms in IBS patients with diarrhoea: post hoc analysis of two randomized double-blind controlled studies
  • 2021
  • In: Therapeutic Advances in Gastroenterology. - : SAGE Publications. - 1756-283X .- 1756-2848. ; 14
  • Journal article (peer-reviewed)abstract
    • Background: Aloe barbadensis Mill. (Aloe) extract was found to be well-tolerated, safe and showed beneficial effects in subsets of irritable bowel syndrome (IBS) patients in two randomized, double-blind, controlled studies. However, the individual studies were underpowered to perform subgroup analyses. We therefore determined the effect of Aloe extract in IBS subgroups in a post hoc analysis combining the results from the two studies. Methods: Data from the two controlled studies comparing Aloe and control treatment taken orally for 4 weeks, were pooled. Both studies included IBS patients fulfilling the ROME III criteria and IBS Symptom Severity Score (IBS-SSS) was assessed. We analysed the effect of Aloe extract on IBS symptom severity and the proportion of responders (IBS-SSS reduction > 50) in IBS subgroups. Results: In total, 213 IBS patients were included in the post hoc subgroup analyses. A reduction in overall symptom severity, primarily driven by effect on pain severity and frequency, comparing baseline versus end of treatment, was recorded in IBS patients with diarrhoea (IBS-D) receiving Aloe (n = 38, p < 0.001) but not control treatment (n = 33, p = 0.33), with difference between the treatment groups (p = 0.01). Moreover, the frequency of responders was higher in IBS-D patients receiving Aloe (n = 22, 58%) compared to control treatment (n = 10, 30%) (p = 0.02). The effect of Aloe extract treatment on IBS symptom severity was not superior to control treatment in the other IBS subtypes. Conclusion: Aloe extract improves symptom severity in IBS-D patients and can be regarded as a safe and effective treatment option for this patient group.
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4.
  • Ahluwalia, Bani, et al. (author)
  • Randomized clinical trial: Effects of Aloe barbadensis Mill. extract on symptoms, fecal microbiota and fecal metabolite profiles in patients with irritable bowel syndrome
  • 2020
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 32:8
  • Journal article (peer-reviewed)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.
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5.
  • Alemany, S., et al. (author)
  • Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants
  • 2023
  • In: Journal of Translational Medicine. ; 21:1
  • Journal article (peer-reviewed)abstract
    • BackgroundIrritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining the high rates of comorbidity remain largely unclear and there are no conclusive data on the temporal relationship between them. Exploring the overlapping genetic architecture between IBS and mental conditions may help to identify novel genetic loci and biological mechanisms underlying IBS and causal relationships between them.MethodsWe quantified the genetic overlap between IBS, neuroticism, depression and anxiety, conducted a multi-trait genome-wide association study (GWAS) considering these traits and investigated causal relationships between them by using the largest GWAS to date.ResultsIBS showed to be a highly polygenic disorder with extensive genetic sharing with mental conditions. Multi-trait analysis of IBS and neuroticism, depression and anxiety identified 42 genome-wide significant variants for IBS, of which 38 are novel. Fine-mapping risk loci highlighted 289 genes enriched in genes upregulated during early embryonic brain development and gene-sets related with psychiatric, digestive and autoimmune disorders. IBS-associated genes were enriched for target genes of anti-inflammatory and antirheumatic drugs, anesthetics and opioid dependence pharmacological treatment. Mendelian-randomization analysis accounting for correlated pleiotropy identified bidirectional causal effects between IBS and neuroticism and depression and causal effects of the genetic liability of IBS on anxiety.ConclusionsThese findings provide evidence of the polygenic architecture of IBS, identify novel genome-wide significant variants for IBS and extend previous knowledge on the genetic overlap and relationship between gastrointestinal and mental disorders.
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6.
  • Algera, Joost, 1993, et al. (author)
  • Associations between postprandial symptoms, hydrogen and methane production, and transit time in irritable bowel syndrome
  • 2023
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 35:2
  • Journal article (peer-reviewed)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.
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7.
  • Algera, Joost, 1993, et al. (author)
  • Gluten and fructan intake and their associations with gastrointestinal symptoms in irritable bowel syndrome: A food diary study
  • 2021
  • In: Clinical Nutrition. - : Elsevier BV. - 0261-5614. ; 40:10, s. 5365-5372
  • Journal article (peer-reviewed)abstract
    • Background & aims: Wheat contains several components, including gluten and fructan, that may be associated with gastrointestinal symptoms (GI) in irritable bowel syndrome (IBS). The aims of the study were to determine the average daily intake of gluten, investigate the association of gluten and GI symptoms, as well as the association between fructan and GI symptoms in IBS subjects. Methods: We assessed dietary intake, including total energy, and calculated average gluten and fructan intake in this 4-day food diary study. The subjects reported GI symptoms using the validated Gastrointestinal Symptom Rating Scale-IBS (GSRS-IBS). Results: In total, 147 IBS subjects (116 females) were included in this study. The median (IQR) intake of gluten was 11.0 (7.5-15.4) (range: 0.6-52.1) g/day, and this intake was significantly higher for males (16.2 (11.5-18.8), g/day) compared with females (10.3 (7.3-13.2), g/day) (P < 0.001). For analyses purposes, the subjects were stratified in tertiles of gluten intake. Median (IQR) overall GI symptom severity (GSRS-IBS) was significantly worse for the subjects with the lowest (52 (45-57)) and intermediate gluten intake (51 (43-58)), compared with the highest gluten intake (45 (37-50), P < 0.05, and P < 0.01 respectively). In addition, caloric intake was significantly lower in subjects with the lowest (1905 +/- 446, kcal/day) and intermediate gluten intake (1854 +/- 432, kcal/day), compared with subjects with the highest gluten intake (2305 +/- 411, kcal/day), P < 0.001 for both. Analyses of the stratified fructan tertiles resulted in no significant differences in GSRS-IBS. Conclusions: The mean intake of gluten varies substantially among subjects with IBS, and IBS subjects with more severe GI symptoms have lower intake of gluten and calories. Trial registry: (http://www.clinicaltrials.gov): Registered under Clinical Trial number NCT02970591. (c) 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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8.
  • Algera, Joost, 1993, et al. (author)
  • Low FODMAP diet reduces gastrointestinal symptoms in irritable bowel syndrome and clinical response could be predicted by symptom severity: A randomized crossover trial
  • 2022
  • In: Clinical Nutrition. - : Elsevier BV. - 0261-5614. ; 41:12, s. 2792-2800
  • Journal article (peer-reviewed)abstract
    • Background & aims: Fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) can provoke symptoms in patients with irritable bowel syndrome (IBS). We aimed to compare the effects of diets with low vs. moderate FODMAP content on gastrointestinal (GI) symptoms and bowel habits, and to identify possible predictors of clinical response to a low FODMAP diet and FODMAP sensitivity in IBS. Methods: Adult participants with IBS (Rome IV criteria, n = 29) were included and adhered to two 7-day diet periods, with either low (4 g/day) or moderate (23 g/day) amounts of FODMAPs, in this randomized, double-blind, crossover study. The periods were separated by a wash-out period (≥14 days). IBS-Severity Scoring System (IBS-SSS) and a stool diary (Bristol Stool Form) were completed before and after the diet periods. At baseline, severity of GI symptoms and gut microbial fermentation were assessed (every 15 min, 4 h) during the Lactulose Nutrient Challenge Test (LNCT). Clinical response and FODMAP sensitivity were defined by reduction after low FODMAP period, and increase after moderate FODMAP period in IBS-SSS (≥50 points), respectively. Results: Severity of GI symptoms (P = 0.04), stool consistency (P = 0.01), and stool frequency (P = 0.01) differed between the interventions, with reduced overall GI symptom severity, abdominal pain intensity and frequency, bowel habits dissatisfaction, and daily life interference (P < 0.05 for all), as well as more firm (P = 0.03) and less frequent (P < 0.01) stools after low FODMAP intervention, but not after moderate FODMAP intervention. A third (34%) responded clinically to the low FODMAP diet, and the response could be predicted by higher IBS-SSS at baseline (P = 0.02). Although modest associations between FODMAP sensitivity (22%) and GI symptoms during LNCT were observed, no independent predictors could be identified. Conclusions: A diet low in FODMAPs reduces GI symptoms and affects bowel habits in IBS, compared with a moderate FODMAP diet. Assessment of IBS severity before the intervention may be used to predict clinical response to a low FODMAP diet. Trial registry (http://www.clinicaltrials.gov): Registered under Clinical Trial number NCT05182593.
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9.
  • Algera, Joost, 1993, et al. (author)
  • Randomised controlled trial: effects of gluten-free diet on symptoms and the gut microenvironment in irritable bowel syndrome
  • 2022
  • In: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 56:9, s. 1318-1327
  • Journal article (peer-reviewed)abstract
    • Background A gluten-free diet reduces symptoms in some patients with irritable bowel syndrome (IBS) through unclear mechanisms. Aims To assess the effects of gluten-free versus gluten-containing diet on symptoms and the gut microenvironment, and to identify predictors of response to the gluten-free diet in IBS. Methods Twenty patients with IBS and 18 healthy controls (HC) followed a gluten-free diet during two 14-day intervention periods where they sprinkled either gluten (14 g/day) or rice flour powder over their meals. Primary outcomes included effects of the interventions on IBS symptoms (IBS-SSS) and bowel habits. Secondary outcomes included effects of gluten-free diet on faecal microbiota and metabolite profile. Results IBS symptoms improved during the gluten-free (p = 0.02), but not the gluten-containing period, with no difference between the interventions. IBS patients reported fewer loose stools during the gluten-free intervention (p = 0.01). Patients with IBS and HC presented distinct metabolite profiles based on the effects of the gluten-free diet (p < 0.001). True responders (reduced IBS-SSS by >= 50 solely after gluten-free period) and non-responders were discriminated based on the effects of the gluten-free diet on the microbiota (p < 0.01) and metabolite profiles (p < 0.001). The response to the gluten-free diet could be predicted by the metabolite profile before the intervention (p < 0.001). Conclusions A gluten-free diet may influence symptoms in a subset of patients with IBS, with a particular effect on bowel habits. A gluten-free diet seems to impact the gut microenvironment. Responsiveness to the gluten-free diet may be predicted by the metabolite profile. : NCT03869359.
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10.
  • Algera, Joost, 1993, et al. (author)
  • Treatments targeting the luminal gut microbiota in patients with irritable bowel syndrome
  • 2022
  • In: Current Opinion in Pharmacology. - : Elsevier BV. - 1471-4892. ; 66
  • Journal article (peer-reviewed)abstract
    • Irritable bowel syndrome (IBS) is a common disorder of gut -brain interaction affecting 4% of the world's population. Pa-tients with IBS experience chronic or recurrent abdominal pain in combination with altered bowel habits (diarrhea and/or constipation), and have reduced quality of life. Despite the high prevalence and substantial burden of IBS, its pathophysiology is incompletely understood and remains to be elucidated. The importance of the gut microenvironment has been highlighted in IBS, as there are signs that the gut microbiota of patients differs from healthy controls. Recent studies have aimed to alter the gut microbiota and thereby, attempted to alleviate gastrointestinal symptoms in IBS patients. We highlighted recent advances in common treatments that are targeting the luminal gut microbiota in IBS.
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11.
  • Aziz, I., et al. (author)
  • The overlap between irritable bowel syndrome and organic gastrointestinal diseases
  • 2021
  • In: The Lancet Gastroenterology and Hepatology. - 2468-1253. ; 6:2, s. 139-148
  • Journal article (peer-reviewed)abstract
    • Irritable bowel syndrome (IBS) is a common functional bowel disorder characterised by symptoms of recurrent abdominal pain associated with a change in bowel habit. This condition is one of the most frequent reasons to seek a gastroenterology consultation in primary and secondary care. The diagnosis of IBS is made by identifying characteristic symptoms, as defined by the Rome criteria, and excluding organic gastrointestinal diseases that might otherwise explain these symptoms. Organic conditions that can be mistaken for IBS include coeliac disease, inflammatory bowel disease (IBD), colorectal cancer, and, in those with diarrhoea-predominant symptoms, chronic gastrointestinal infections, microscopic colitis, and primary bile acid diarrhoea. The concept of small intestinal bacterial overgrowth being associated with IBS is shrouded with controversy and uncertainty, mainly because of invalid tests due to poor sensitivity and specificity, potentially leading to incorrect assumptions. There is insufficient evidence to link IBS-type symptoms with exocrine pancreatic insufficiency or with symptomatic uncomplicated diverticular disease, since both are hampered by conflicting data. Finally, there is growing appreciation that IBS can present in patients with known but stable organic gastrointestinal diseases, such as quiescent IBD or coeliac disease. Recognising functional gut symptoms in these individuals is paramount so that potentially harmful escalations in immunosuppressive therapy can be avoided and attention can be focused on addressing disorders of gut–brain interaction. This Review endeavours to aid clinicians who practise adult gastroenterology in recognising the potential overlap between IBS and organic gastrointestinal diseases and highlights areas in need of further research and clarity. © 2020 Elsevier Ltd
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12.
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13.
  • Bocci, Matteo, et al. (author)
  • Infection of Brain Pericytes Underlying Neuropathology of COVID-19 Patients.
  • 2021
  • In: International journal of molecular sciences. - : MDPI AG. - 1422-0067 .- 1661-6596. ; 22:21
  • Journal article (peer-reviewed)abstract
    • A wide range of neurological manifestations have been associated with the development of COVID-19 following SARS-CoV-2 infection. However, the etiology of the neurological symptomatology is still largely unexplored. Here, we used state-of-the-art multiplexed immunostaining of human brains (n = 6 COVID-19, median age = 69.5 years; n = 7 control, median age = 68 years) and demonstrated that expression of the SARS-CoV-2 receptor ACE2 is restricted to a subset of neurovascular pericytes. Strikingly, neurological symptoms were exclusive to, and ubiquitous in, patients that exhibited moderate to high ACE2 expression in perivascular cells. Viral dsRNA was identified in the vascular wall and paralleled by perivascular inflammation, as signified by T cell and macrophage infiltration. Furthermore, fibrinogen leakage indicated compromised integrity of the blood-brain barrier. Notably, cerebrospinal fluid from additional 16 individuals (n = 8 COVID-19, median age = 67 years; n = 8 control, median age = 69.5 years) exhibited significantly lower levels of the pericyte marker PDGFRβ in SARS-CoV-2-infected cases, indicative of disrupted pericyte homeostasis. We conclude that pericyte infection by SARS-CoV-2 underlies virus entry into the privileged central nervous system space, as well as neurological symptomatology due to perivascular inflammation and a locally compromised blood-brain barrier.
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14.
  • Bonfiglio, Ferdinando, et al. (author)
  • GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome
  • 2021
  • In: Cell Genomics. - Cambridge, MA, United States : Elsevier. - 2666-979X. ; 1:3
  • Journal article (peer-reviewed)abstract
    • Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p ≤ 5.0 × 10-8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes.
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15.
  • Bosman, M., et al. (author)
  • Discontinuation of infliximab in patients with ulcerative colitis in remission (HAYABUSA): a multicentre, open-label, randomised controlled trial
  • 2021
  • In: The Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 6:6, s. 459-473
  • Journal article (peer-reviewed)abstract
    • Findings Between June 16, 2014, and July 28, 2017, 122 patients were eligible for screening and a total of 95 patients were randomly assigned to the infliximab-continued group (n=48) or the infliximab-discontinued group (n=47). 92 patients (n=46 for both groups) were included in the full analysis set. 37 (80.4% [95% CI 66.1-90.6]) of 46 patients in the infliximab-continued group and 25 (54.3% [39.0-69.1]) of 46 patients in the infliximab-discontinued group were in remission at week 48. The between-group difference was 26.1% (95% CI 7.7-44.5; p=0.0076) before adjustment and 27.3% (95% CI 8.0-44.1; p=0.0059) after adjustment for stratification factors. Eight (17%) of 48 patients in the infliximab-continued group and six (13%) of 47 in the infliximab-discontinued group developed adverse events (between-group difference 3.9% [95% CI -10.3 to 18.1]; p=0.59). In the infliximab-continued group, one patient had an infusion reaction and two patients had psoriatic skin lesions. Eight (66.7%, 95% CI 34.9-90.1) of the 12 patients in the infliximab-discontinuation group who were re-treated with infliximab after relapsing were in remission within 8 weeks of re-treatment; none had infusion reactions. Background Anti-tumour necrosis factor (TNF) agents are the mainstay of long-term treatment for refractory ulcerative colitis. However, long-term use of anti-TNF therapy might lead to an increased risk of malignancy or infection. To date, no randomised controlled trial has evaluated whether anti-TNF agents can be safely discontinued in patients with ulcerative colitis in remission. We therefore aimed to compare outcomes in these patients who continued infliximab with those who discontinued infliximab. Methods We did a multicentre, open-label randomised controlled trial at 24 specialist centres in Japan. We enrolled patients with ulcerative colitis who were in remission, had been treated with intravenous infliximab (5 mg/kg) every 8 weeks, and had started infliximab at least 14 weeks before study enrolment. No restrictions regarding age and comorbidities were used to exclude participation. Patients who were confirmed to be in remission for more than 6 months, to be corticosteroid-free, and to have a Mayo Endoscopic Subscore (MES) of 0 or 1 were centrally randomised. An independent organisation randomly assigned patients (1:1) into either the infliximab-continued group or infliximab-discontinued group, using a computer-generated stratified randomisation procedure. The stratified factors were the use of immunomodulators (yes or no) and MES (0 or 1). Neither patients nor health-care providers were masked to the randomisation. The primary endpoint was the remission rate at week 48 in the full analysis set, which was based on the intention-to-treat principle and excluded participants with no efficacy data after randomisation. This study was registered with the University Hospital Medical Information Network Center Trials registry, UMIN000012092. Findings Between June 16, 2014, and July 28, 2017, 122 patients were eligible for screening and a total of 95 patients were randomly assigned to the infliximab-continued group (n=48) or the infliximab-discontinued group (n=47). 92 patients (n=46 for both groups) were included in the full analysis set. 37 (80.4% [95% CI 66.1 & ndash;90.6]) of 46 patients in the infliximab-continued group and 25 (54.3% [39.0 & ndash;69.1]) of 46 patients in the infliximab-discontinued group were in remission at week 48. The between-group difference was 26.1% (95% CI 7.7 & ndash;44.5; p=0.0076) before adjustment and 27.3% (95% CI 8.0 & ndash;44.1; p=0.0059) after adjustment for stratification factors. Eight (17%) of 48 patients in the infliximab-continued group and six (13%) of 47 in the infliximab-discontinued group developed adverse events (between-group difference 3.9% [95% CI & minus;10.3 to 18.1]; p=0.59). In the infliximab-continued group, one patient had an infusion reaction and two patients had psoriatic skin lesions. Eight (66.7%, 95% CI 34.9 & ndash;90.1) of the 12 patients in the infliximab-discontinuation group who were re-treated with infliximab after relapsing were in remission within 8 weeks of re-treatment; none had infusion reactions. Interpretation Maintenance of remission was significantly more common in patients who continued infliximab than in those who discontinued. Discontinuing infliximab should therefore be discussed with caution, taking both risk of relapse and efficacy of re-treatment into account. Funding Mitsubishi Tanabe Pharma Corporation and the Intractable Disease Project of the Ministry of Health, Labour and Welfare of Japan. Copyright (c) 2021 Elsevier Ltd. All rights reserved.
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16.
  • Bosman, M., et al. (author)
  • Placebo response in pharmacological trials in patients with functional dyspepsia-A systematic review and meta-analysis
  • 2023
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 35:2
  • Research review (peer-reviewed)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.
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17.
  • Broeders, B., et al. (author)
  • Epidemiology of disorders of gut-brain interaction in Belgium and differences between two language groups: Results from the Rome foundation global epidemiology study
  • 2023
  • In: Neurogastroenterology and Motility. - 1350-1925. ; 35:6
  • Journal article (peer-reviewed)abstract
    • BackgroundThe Rome Foundation carried out a worldwide epidemiology study on DGBI according to the Rome IV criteria in 33 countries, including Belgium. DGBI prevalence varied between continents and countries, but prevalence differences within language groups in a single country have not yet been described. MethodsWe analyzed the prevalence rates of 18 DGBI and their psychosocial impact in Belgium in the French and Dutch language groups. Key ResultsDGBI prevalence was similar in the French-speaking and Dutch-speaking population. Having one or more DGBI was negatively associated with psychosocial well-being. The scores for depression were lower in the Dutch-speaking participants with one or more DGBI compared to the French-speaking participants. Interestingly, we also found significantly lower scores in the general Dutch-speaking versus the French-speaking population for depression and non-gastrointesinal somatic symptoms, and higher global physical health and mental health quality-of-life component scores. In the Dutch-speaking group, medication use for gastric acid was lower, but use of prescribed analgesics was more common. Nevertheless, the use of non-prescribed pain medication was higher in the French-speaking group. Anxiety and sleep medication use was also higher in the latter group. Conclusions & InterferencesThe results of this first in-depth analysis of Rome IV DGBI in Belgium show a higher prevalence for some DGBI in the French-speaking cohort, and a larger associated disease burden. These differences between language/culture groups in the same country support the psychosocial pathophysiological model of DGBI.
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18.
  • Busby-Whitehead, J., et al. (author)
  • The aging gut: Symptoms compatible with disorders of gut-brain interaction (DGBI) in older adults in the general population
  • 2024
  • In: Journal of the American Geriatrics Society. - 0002-8614. ; 72:2, s. 479-489
  • Journal article (peer-reviewed)abstract
    • Background: Little is known about changes in gastrointestinal symptoms compatible with disorders of gut-brain interaction (DGBI) with increasing age at the population level. The objective of this study was to describe the patterns of DGBI in individuals 65 years of age and above and contrasting them with those of younger adults.Methods: A community sample of 6300 individuals ages 18 and older in the US, UK, and Canada completed an online survey. Quota-based sampling was used to ensure equal proportion of sex and age groups (40% aged 18-39, 40% aged 40-64, 20% aged 65+) across countries, and to control education distributions. The survey included the Rome IV Diagnostic Questionnaire for DGBI, demographic questions, questionnaires measuring overall somatic symptom severity and quality of life, and questions on healthcare utilization, medications, and surgical history.Results: We included 5926 individuals in our analyses; 4700 were 18-64 years of age and 1226 were ages 65+. Symptoms compatible with at least one DGBI were less prevalent in participants ages 65+ vs. ages 18-64 years (34.1% vs. 41.3%, p < 0.0001). For symptoms compatible with upper GI DGBI, lower prevalence for most disorders was noted in the 65+ group. For lower GI DGBI, a different pattern was seen. Prevalence was lower in ages 65+ for irritable bowel syndrome and anorectal pain, but no differences from younger participants for the disorders defined by abnormal bowel habits (constipation and/or diarrhea) were seen. Fecal incontinence was the only DGBI that was more common in ages 65+. Having a DGBI was associated with reduced quality of life, more severe non-GI somatic symptoms, and increased healthcare seeking, both in younger and older participants.Conclusion: Symptoms compatible with DGBI are common, but most of these decrease in older adults at the population level, with the exception of fecal incontinence which increases. This pattern needs to be taken into account when planning GI health care for the growing population of older adults.
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19.
  • Böhn, Lena, et al. (author)
  • 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
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 33:7
  • Journal article (peer-reviewed)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.
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20.
  • Clevers, Egbert, et al. (author)
  • Adherence to diet low in fermentable carbohydrates and traditional diet for irritable bowel syndrome
  • 2020
  • In: Nutrition. - : Elsevier BV. - 0899-9007. ; 73
  • Journal article (peer-reviewed)abstract
    • Objectives: Dietary interventions in irritable bowel syndrome (IBS) include a traditional IBS diet following the guidelines from the National Institute for Health and Clinical Excellence and a diet low in fermentable oligo-, di-, monosaccharides and polyols (FODMAPs). The aim of this study was to evaluate the adherence to these diets, food groups difficult to replace, and dietary determinants of symptom improvement. Methods: Sixty-six patients with IBS were randomized to a 4-wk low FODMAP or traditional IBS diet. Participants completed 4-d diet diaries before and during the intervention and reported symptoms on the IBS severity scoring system. We described adherence to the diets on the food group and product level and investigated the association between adherence and symptom improvement. Results: Adherence to the low FODMAP diet was good and consistent: All participants had a comparable shift in the diet's principal components compatible with the guidelines. Most high FODMAP products were well replaced with low FODMAP equivalents. However, total energy intake fell by 25%, mainly owing to a 69% decreased intake of snacks (P < 0.001). The traditional IBS diet did not shift the diet's principal components, and despite the guidelines, consumption of coffee and alcoholic beverages remained rather high (>50% of baseline). Total energy intake fell by 11% (P = 0.15). For both diets, there was a trend toward an association between adherence and symptom improvement (P < 0.10). Conclusion: In both the low FODMAP and traditional IBS diet, certain food groups were difficult to replace. Because adherence may predict symptom improvement, close dietary guidance might enhance the efficacy of both diets. © 2020 Elsevier Inc.
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21.
  • Clevers, Egbert, et al. (author)
  • Coffee, Alcohol, and Artificial Sweeteners Have Temporal Associations with Gastrointestinal Symptoms
  • 2024
  • In: DIGESTIVE DISEASES AND SCIENCES. - 0163-2116 .- 1573-2568.
  • Journal article (peer-reviewed)abstract
    • BackgroundVarious dietary strategies for managing irritable bowel syndrome (IBS) target mechanisms such as brain-gut interactions, osmotic actions, microbial gas production, and local immune activity. These pathophysiological mechanisms are diverse, making it unclear which foods trigger IBS symptoms for a substantial proportion of patients.AimTo identify associations between foods and gastrointestinal symptoms.MethodsFrom the mySymptoms smartphone app, we collected anonymized diaries of food intake and symptoms (abdominal pain, diarrhea, bloating, and gas). We selected diaries that were at least 3 weeks long. The diaries were analyzed for food-symptom associations using a proprietary algorithm. As the participants were anonymous, we conducted an app-wide user survey to identify IBS diagnoses according to Rome IV criteria.ResultsA total of 9,710 food symptom diaries that met the quality criteria were collected. Of the survey respondents, 70% had IBS according to Rome IV criteria. Generally, strong associations existed for caffeinated coffee (diarrhea, 1-2 h postprandial), alcoholic beverages (multiple symptoms, 4-72 h postprandial), and artificial sweeteners (multiple symptoms, 24-72 h postprandial). Histamine-rich food intake was associated with abdominal pain and diarrhea. Some associations are in line with existing literature, whilst the absence of an enriched FODMAP-symptom association contrasts with current knowledge.ConclusionsCoffee, alcohol, and artificial sweeteners were associated with GI symptoms in this large IBS-predominant sample. Symptom onset is often within 2 h postprandial, but some foods were associated with a delayed response, possibly an important consideration in implementing dietary recommendations. Clinical trials must test the causality of the demonstrated food-symptom associations.
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22.
  • Clevers, Egbert, et al. (author)
  • Food-symptom diaries can generate personalized lifestyle advice for managing gastrointestinal symptoms: A pilot study
  • 2020
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 32:8
  • Journal article (peer-reviewed)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.
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23.
  • Colomier, Esther, 1995, et al. (author)
  • Global prevalence and burden of meal-related abdominal pain
  • 2022
  • In: Bmc Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 20:1
  • Journal article (peer-reviewed)abstract
    • Background Patients with disorders of gut-brain interaction (DGBI) report meal intake to be associated with symptoms. DGBI patients with meal-related symptoms may have more severe symptoms overall and worse health outcomes, but this subgroup has not been well characterized. We aimed to describe the global prevalence of meal-related abdominal pain and characterize this subgroup. Methods The data analyzed originated from the Internet survey component of the population-based Rome Foundation Global Epidemiology Study, completed in 26 countries (n = 54,127). Adult subjects were asked whether they had abdominal pain and how often this was meal-related. Respondents were categorized into "no," "occasional," and "frequent" meal-related abdominal pain groups based on 0%, 10-40%, and >= 50% of the pain episodes being meal-related, respectively. DGBI diagnoses, frequency of other GI symptoms, psychological distress, non-GI somatic symptoms, quality of life, and healthcare utilization were compared between groups. Mixed linear and ordinal regression was used to assess independent associations between psychological distress, non-GI somatic symptoms, quality of life, other GI symptoms, and meal-related abdominal pain. Results Overall, 51.9% of the respondents reported abdominal pain in the last 3 months, and 11.0% belonged to the group with frequent meal-related abdominal pain, which included more females and younger subjects. DGBI diagnoses were more common in subjects with frequent meal-related abdominal pain, and the frequency of several GI symptoms was associated with having more frequent meal-related abdominal pain. Having meal-related abdominal pain more frequently was also associated with more severe psychological distress, non-GI somatic symptoms, and a poorer quality of life. The group with frequent meal-related abdominal pain also more often consulted a doctor for bowel problems compared to the other groups of meal-related abdominal pain. Conclusion Reporting frequent meal-related abdominal pain is common across the globe and associated with other GI and non-GI somatic symptoms, psychological distress, healthcare utilization, and a poorer quality of life. Individuals who frequently experience meal-related abdominal pain also more frequently fulfill the diagnostic criteria for DGBI. Assessing meal-related symptoms in all DGBI patients could be of major importance to improve and individualize symptom management.
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24.
  • Colomier, Esther, 1995, et al. (author)
  • Mechanisms underlying food-related symptoms in disorders of gut-brain interaction: Course ahead in research and clinical practice
  • 2023
  • In: Baillière's Best Practice & Research : Clinical Gastroenterology. - : Elsevier BV. - 1521-6918. ; 62-63
  • Journal article (peer-reviewed)abstract
    • A subgroup of patients with a disorder of gut-brain interaction (DGBI) report symptoms such as abdominal pain, gas-related symptoms, dyspeptic symptoms and loose stool or urgency after meal intake. Therefore, the effect of several dietary therapies including fibre-rich or restrictive diets have already been studied in patients with ir-ritable bowel syndrome, functional abdominal bloating or distention, and functional dyspepsia. However, there is a paucity of studies in the literature on the mechanisms underlying food-related symptoms. Therefore, this review focuses on these potential mechanisms and explains the role of nutrient sensing and tasting, physical considerations, malabsorption or allergy-like reaction to food and its interaction with microbiota. In addition, it emphasizes the importance of future research and clinical practice regarding food-related symptoms in patients with a DGBI.
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25.
  • Colomier, Esther, 1995, et al. (author)
  • Predictors of Symptom-Specific Treatment Response to Dietary Interventions in Irritable Bowel Syndrome
  • 2022
  • In: Nutrients. - : MDPI AG. - 2072-6643. ; 14:2
  • Journal article (peer-reviewed)abstract
    • (1) Background: Predictors of dietary treatment response in irritable bowel syndrome (IBS) remain understudied. We aimed to investigate predictors of symptom improvement during the low FODMAP and the traditional IBS diet for four weeks. (2) Methods: Baseline measures included faecal Dysbiosis Index, food diaries with daily energy and FODMAP intake, non-gastrointestinal (GI) somatic symptoms, GI-specific anxiety, and psychological distress. Outcomes were bloating, constipation, diarrhea, and pain symptom scores treated as continuous variables in linear mixed models. (3) Results: We included 33 and 34 patients on the low FODMAP and traditional IBS diet, respectively. Less severe dysbiosis and higher energy intake predicted better pain response to both diets. Less severe dysbiosis also predicted better constipation response to both diets. More severe psychological distress predicted worse bloating response to both diets. For the different outcomes, several differential predictors were identified, indicating that baseline factors could predict better improvement in one treatment arm, but worse improvement in the other treatment arm. (4) Conclusions: Psychological, nutritional, and microbial factors predict symptom improvement when following the low FODMAP and traditional IBS diet. Findings may help individualize dietary treatment in IBS. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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26.
  • Corsetti, M., et al. (author)
  • Chronic constipation in adults: Contemporary perspectives and clinical challenges. 2: Conservative, behavioural, medical and surgical treatment
  • 2021
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982.
  • Journal article (peer-reviewed)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.
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27.
  • Edén, Arvid, 1975, et al. (author)
  • Neurochemical biomarkers to study CNS effects of COVID-19: a narrative review and synthesis.
  • 2021
  • In: Journal of neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 159:1, s. 61-77
  • Journal article (peer-reviewed)abstract
    • Neurological symptoms are frequently reported in patients suffering from COVID-19. Common CNS-related symptoms include anosmia, caused by viral interaction with either neurons or supporting cells in nasal olfactory tissues. Diffuse encephalopathy is the most common sign of CNS dysfunction, which likely results from the CNS consequences of the systemic inflammatory syndrome associated with severe COVID-19. Additionally, microvascular injuries and thromboembolic events likely contribute to the neurologic impact of acute COVID-19. These observations are supported by evidence of CNS immune activation in cerebrospinal fluid (CSF) and in autopsy tissue, along with detection of microvascular injuries in both pathological and neuroimaging studies. The frequent occurrence of thromboembolic events in patients with COVID-19 has generated different hypotheses, among which viral interaction with perivascular cells is particularly attractive, yet unproven. A distinguishing feature of CSF findings in SARS-CoV-2 infection is that clinical signs characteristic of neurotropic viral infections (CSF pleocytosis and blood brain barrier injury) are mild or absent. Moreover, virus detection in CSF is rare, and often of uncertain significance. In this review, we provide an overview of the neurological impact that occur in the acute phase of COVID-19, and the role of CSF biomarkers in the clinical management and research to better treat and understand the disease. In addition to aiding as diagnostic and prognostic tools during acute infection, the use of comprehensive and well characterized CSF and blood biomarkers will be vital in understanding the potential impact on the CNS in the rapidly increasing number of individuals recovering from COVID-19.
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28.
  • Eijsbouts, C., et al. (author)
  • Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders
  • 2021
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53:11, s. 1543-1552
  • Journal article (peer-reviewed)abstract
    • Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS. © 2021, The Author(s).
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29.
  • Ekerfors, Ulrika, et al. (author)
  • The influence of muscle performance and fatigue on prognosis in patients with compensated liver disease
  • 2023
  • In: BMC Gastroenterology. - 1471-230X. ; 23:1
  • Journal article (peer-reviewed)abstract
    • Background Poor muscle function is associated with a negative prognosis in advanced liver disease but the impact in compensated chronic liver disease is unknown. Similar prognostic uncertainty applies to fatigue. We aimed to assess the prognostic value of muscle performance and fatigue in a cohort of patients with compensated chronic liver disease. Methods We followed 241 patients with compensated chronic liver disease included in a study between 2010 and 2014. Subjects were 52 +/- 15 years (mean +/- SD; 134 females). All subjects performed four muscle function tests: "Timed Up and Go" test, walking speed, handgrip strength, and standing heel-rises. Fatigue was evaluated by fatigue impact scale. Follow up data was acquired through hospital records and registries. Results During follow up of 6.75 +/- 1.4 years, 13 patients died (5.5%) and 11 (4.5%) patients underwent liver transplantation. A timed up and go over 10 s was not significantly associated with a lower survival (Kaplan-Meier, log rank test p = 0.132), or with transplant free survival (p = 0.543), Fig. 3. It was also not specifically associated with liver related causes of death (p = 0.597). The other physical functioning tests and fatigue were not significantly associated with mortality or transplant-free survival (p > 0.05 for all) except for maximal walking speed (2.2 vs. 1.9 m/s, p = 0.007). Conclusions Our study suggests that muscle function and fatigue are not key prognostic factors in compensated chronic liver disease. However, further confirmation in future studies is needed.
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30.
  • Elmunzer, B. Joseph, et al. (author)
  • Prolonged Gastrointestinal Manifestations After Recovery From COVID-19
  • 2024
  • In: Clinical Gastroenterology and Hepatology. - 1542-3565 .- 1542-7714. ; 22:5
  • Journal article (peer-reviewed)abstract
    • Background & Aims: Acute enteric infections are well known to result in long-term gastrointestinal (GI) disorders. Although COVID-19 is principally a respiratory illness, it demonstrates significant GI tropism, possibly predisposing to prolonged gut manifestations. We aimed to examine the long-term GI impact of hospitalization with COVID-19. Methods: Nested within a large-scale observational cohort study of patients hospitalized with COVID-19 across North America, we performed a follow-up survey of 530 survivors 12–18 months later to assess for persistent GI symptoms and their severity, and for the development of disorders of gut-brain interaction (DGBIs). Eligible patients were identified at the study site level and surveyed electronically. The survey instrument included the Rome IV Diagnostic Questionnaire for DGBI, a rating scale of 24 COVID-related symptoms, the Gastrointestinal Symptoms Rating Scale, and the Impact of Events–Revised trauma symptom questionnaire (a measure of posttraumatic stress associated with the illness experience). A regression analysis was performed to explore the factors associated with GI symptom severity at follow-up. Results: Of the 530 invited patients, 116 responded (52.6% females; mean age, 55.2 years), and 73 of those (60.3%) met criteria for 1 or more Rome IV DGBI at follow-up, higher than the prevalence in the US general population (P <. 0001). Among patients who experienced COVID-related GI symptoms during the index hospitalization (abdominal pain, nausea, vomiting, or diarrhea), 42.1% retained at least 1 of these symptoms at follow-up; in comparison, 89.8% of respondents retained any (GI or non-GI) COVID-related symptom. The number of moderate or severe GI symptoms experienced during the initial COVID-19 illness by self-report correlated with the development of DGBI and severity of GI symptoms at follow-up. Posttraumatic stress disorder (Impact of Events–Revised score ≥33) related to the COVID-19 illness experience was identified in 41.4% of respondents and those individuals had higher DGBI prevalence and GI symptom severity. Regression analysis revealed that higher psychological trauma score (Impact of Events–Revised) was the strongest predictor of GI symptom severity at follow-up. Conclusions: In this follow-up survey of patients 12–18 months after hospitalization with COVID-19, there was a high prevalence of DGBIs and persistent GI symptoms. Prolonged GI manifestations were associated with the severity of GI symptoms during hospitalization and with the degree of psychological trauma related to the illness experience.
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31.
  • Fritz, N., et al. (author)
  • The serotonin receptor 3E variant is a risk factor for female IBS-D
  • 2022
  • In: Journal of Molecular Medicine-Jmm. - : Springer Science and Business Media LLC. - 0946-2716 .- 1432-1440. ; 100:11, s. 1617-1627
  • Journal article (peer-reviewed)abstract
    • Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT3 receptor family. 5-HT(3)Rs are encoded by HTR3 genes and control GI function, and peristalsis and secretion, in particular. Moreover, 5-HT3R antagonists are beneficial in the treatment of diarrhea predominant IBS (IBS-D). We previously reported on functionally relevant SNPs in HTR3A c.-42C > T (rs1062613), HTR3C p.N163K (rs6766410), and HTR3E c.*76G > A (rs56109847 = rs62625044) being associated with IBS-D, and the HTR3B variant p.Y129S (rs1176744) was also described within the context of IBS. We performed a multi-center study to validate previous results and provide further evidence for the relevance of HTR3 genes in IBS pathogenesis. Therefore, genotype data of 2682 IBS patients and 9650 controls from 14 cohorts (Chile, Germany (2), Greece, Ireland, Spain, Sweden (2), the UK (3), and the USA (3)) were taken into account. Subsequent meta-analysis confirmed HTR3E c.*76G > A (rs56109847 = rs62625044) to be associated with female IBS-D (OR = 1.58; 95% CI (1.18, 2.12)). Complementary expression studies of four GI regions (jejunum, ileum, colon, sigmoid colon) of 66 IBS patients and 42 controls revealed only HTR3E to be robustly expressed. On top, HTR3E transcript levels were significantly reduced in the sigma of IBS patients (p = 0.0187); more specifically, in those diagnosed with IBS-D (p = 0.0145). In conclusion, meta-analysis confirmed rs56109847 = rs62625044 as a risk factor for female IBS-D. Expression analysis revealed reduced HTR3E levels in the sigmoid colon of IBS-D patients, which underlines the relevance of HTR3E in the pathogenesis of IBS-D.
  •  
32.
  • Frändemark, Åsa, 1988, et al. (author)
  • Maintaining work life under threat of symptoms: a grounded theory study of work life experiences in persons with Irritable Bowel Syndrome
  • 2022
  • In: BMC Gastroenterology. - : Springer Science and Business Media LLC. - 1471-230X. ; 22:1
  • Journal article (peer-reviewed)abstract
    • Background Irritable Bowel Syndrome (IBS) is a highly prevalent functional gastrointestinal disorder. Earlier studies have shown that IBS can limit the ability to perform at work and lead to absenteeism. However, few studies focus on work life experiences based on patients' narratives. The purpose of this study was to construct a theory for how persons with IBS maintain their work life. Methods A qualitative study was performed using constructivist grounded theory. Semi-structured interviews with 15 women and 8 men with IBS (26-64 years of age) were conducted. Fourteen participants worked full-time, six worked part-time and three were on sick leave. The interviews were transcribed verbatim and coded line-by-line, incident-by-incident and thereafter focused coding was done. From the data and codes, categories were generated. Finally, a core category was constructed explaining the process of maintaining work life when living with IBS. Results Balancing work life while being under threat of symptoms constituted of four categories, being prepared, restricting impact, reconciling and adjusting. Persons with IBS restricted the impact of IBS on work by using strategies and upholding daily routines and strived to being prepared by exerting control over work life. These ongoing processes served to limit the influence of IBS on work by symptoms being less intense, perceived as less frequent, or not as bothersome. Reconciling IBS with work life was understood as a successful outcome from being prepared and restricting impact but was also influenced by the individual's outlook on life. Adjusting to other people at work interfered with the strategies of being prepared, restricting impact, and reconciling, leaving persons with IBS more susceptible to symptoms. Conclusions This study deepens the understanding of the work situation for persons with IBS. Health care professionals can use the results of this study in the dialogue with the patient discussing work ability and sick leave. The results imply that although balancing work life under threat of symptoms can be a struggle, there are strategies that persons with IBS and employers together can initiate and use to reduce impact on work on several different levels.
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33.
  • Frändemark, Åsa, 1988, et al. (author)
  • Work productivity and activity impairment in disorders of gut-brain interaction: Data from the Rome Foundation Global Epidemiology Study
  • 2023
  • In: United European Gastroenterology Journal. - 2050-6406. ; 11:6, s. 503-513
  • Journal article (peer-reviewed)abstract
    • BackgroundDisorders of Gut-Brain Interaction (DGBI) are highly prevalent worldwide, but their effect on work productivity has not gained much attention. Aims and MethodsWe 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. ResultsOf 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). ConclusionIn 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.
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34.
  • Grinsvall, Cecilia, et al. (author)
  • Altered Structural Covariance of Insula, Cerebellum and Prefrontal Cortex Is Associated with Somatic Symptom Levels in Irritable Bowel Syndrome (IBS)
  • 2021
  • In: Brain Sciences. - 2076-3425. ; 11:12
  • Journal article (peer-reviewed)abstract
    • Somatization, defined as the presence of multiple somatic symptoms, frequently occurs in irritable bowel syndrome (IBS) and may constitute the clinical manifestation of a neurobiological sensitization process. Brain imaging data was acquired with T1 weighted 3 tesla MRI, and gray matter morphometry were analyzed using FreeSurfer. We investigated differences in networks of structural covariance, based on graph analysis, between regional gray matter volumes in IBS-related brain regions between IBS patients with high and low somatization levels, and compared them to healthy controls (HCs). When comparing IBS low somatization (N = 31), IBS high somatization (N = 35), and HCs (N = 31), we found: (1) higher centrality and neighbourhood connectivity of prefrontal cortex subregions in IBS high somatization compared to healthy controls; (2) higher centrality of left cerebellum in IBS low somatization compared to both IBS high somatization and healthy controls; (3) higher centrality of the anterior insula in healthy controls compared to both IBS groups, and in IBS low compared to IBS high somatization. The altered structural covariance of prefrontal cortex and anterior insula in IBS high somatization implicates that prefrontal processes may be more important than insular in the neurobiological sensitization process associated with IBS high somatization. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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35.
  • Grinsvall, Cecilia, et al. (author)
  • Association between pain sensitivity and gray matter properties in the sensorimotor network in women with irritable bowel syndrome
  • 2021
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 33:4
  • Journal article (peer-reviewed)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.
  •  
36.
  • Hreinsson, Johann P., 1987, et al. (author)
  • A comparative study of disorders of gut-brain interaction in Western Europe and Asia based on the Rome foundation global epidemiology study
  • 2023
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 35:6
  • Journal article (peer-reviewed)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.
  •  
37.
  • Hreinsson, J. P., et al. (author)
  • Factor Analysis of the Rome IV Criteria for Major Disorders of Gut-Brain Interaction (DGBI) Globally and Across Geographical, Sex, and Age Groups
  • 2023
  • In: Gastroenterology. - : Elsevier BV. - 0016-5085. ; 164:7, s. 1211-1222
  • Journal article (peer-reviewed)abstract
    • 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 per-formed 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: ir-ritable 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.
  •  
38.
  • Huang, I. H., et al. (author)
  • Worldwide prevalence and burden of gastroparesis-like symptoms as defined by the United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis
  • 2022
  • In: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 10:8, s. 888-897
  • Journal article (peer-reviewed)abstract
    • Background/Objectives The global epidemiology of gastroparesis is unknown. The European UEG and European Society for Neurogastroenterology and motility consensus defines Gastroparesis as a condition characterized by delayed gastric emptying in the absence of mechanical obstruction, with a symptom pattern of nausea and/or vomiting and overlapping postprandial distress syndrome (PDS). Real-world evidence of this gastroparesis-like symptom pattern is a crucial step in understanding the epidemiology of gastroparesis. Methods In the Rome Foundation Global Epidemiology Study, 54,127 respondents from 26 countries completed the Rome IV Diagnostic Questionnaire and variables associated with disorders of gut-brain interaction via Internet. We selected subjects with gastroparesis-like symptoms (GPLS) (nausea and/or vomiting >= 1 day/week and simultaneous PDS). Patients reporting organic gastrointestinal disease, or fulfilling criteria for self-induced vomiting, cyclic vomiting or cannabinoid hyperemesis syndrome were excluded. We determined prevalence, associated comorbidities, quality of life (QoL) (PROMIS Global-10), symptoms of anxiety and depression (PHQ-4), somatic symptoms (PHQ-12), and healthcare utilization. Results The global prevalence of GPLS was 0.9% overall and 1.3% among diabetic individuals. Subjects with GPLS showed frequent overlapping of epigastric pain syndrome and irritable bowel syndrome. Subjects with GPLS had significantly lower body mass index, QoL, more non-gastrointestinal somatic complaints, symptoms of anxiety and depression, higher medication usage and doctor visits in the overall and diabetic population, compared to subjects without these symptoms. Conclusions GPLS are common worldwide and more common in diabetic patients. The symptom complex is associated with multiple aspects of illness and an increased healthcare consumption.
  •  
39.
  • Imran, A., et al. (author)
  • An approach to the diagnosis and management of Rome IV functional disorders of chronic constipation
  • 2020
  • In: Expert Review of Gastroenterology & Hepatology. - : Informa UK Limited. - 1747-4124 .- 1747-4132. ; ´14:1
  • Journal article (peer-reviewed)abstract
    • Introduction: Chronic constipation is highly prevalent, affecting between 10% and 15% of the population. The Rome IV criteria categorizes disorders of chronic constipation into four subtypes: (a) functional constipation, (b) irritable bowel syndrome with constipation, (c) opioid-induced constipation, and (d) functional defecation disorders, including inadequate defecatory propulsion and dyssynergic defecation. The initial management approach for these disorders is similar, focusing on diet, lifestyle and the use of standard over-the-counter laxatives. If unsuccessful, further therapy is tailored according to subtype. Areas covered: This review covers the definition, epidemiology, diagnostic criteria, investigations and management of the Rome IV disorders of chronic constipation. Expert opinion: By adopting a logical step-wise approach toward the diagnosis of chronic constipation and its individual subtypes, clinicians have the opportunity to tailor therapy accordingly and improve symptoms, quality of life, and patient satisfaction.
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40.
  • Iribarren, Cristina, 1993, et al. (author)
  • Fecal luminal factors from patients with irritable bowel syndrome induce distinct gene expression of colonoids
  • 2022
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 34:10
  • Journal article (peer-reviewed)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.
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41.
  • Iribarren, Cristina, 1993, et al. (author)
  • Human milk oligosaccharide supplementation in irritable bowel syndrome patients: A parallel, randomized, double-blind, placebo-controlled study
  • 2020
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 32:10
  • Journal article (peer-reviewed)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.
  •  
42.
  • Iribarren, Cristina, 1993, et al. (author)
  • Temporal stability of fecal metabolomic profiles in irritable bowel syndrome
  • 2024
  • In: Neurogastroenterology and Motility. - 1350-1925 .- 1365-2982. ; 36:3
  • Journal article (peer-reviewed)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.
  •  
43.
  • Iribarren, Cristina, 1993, et al. (author)
  • The Effects of Human Milk Oligosaccharides on Gut Microbiota, Metabolite Profiles and Host Mucosal Response in Patients with Irritable Bowel Syndrome
  • 2021
  • In: Nutrients. - : MDPI AG. - 2072-6643. ; 13:11
  • Journal article (peer-reviewed)abstract
    • Background: Human milk oligosaccharide supplementation safely modulates fecal bifidobacteria abundance and holds the potential to manage symptoms in irritable bowel syndrome (IBS). Here, we aimed to determine the role of a 4:1 mix of 2 & PRIME;-O-fucosyllactose and lacto-N-neotetraose (2 & PRIME;FL/LNnT) on the modulation of the gut microbiota composition and host mucosal response, as well as the link between the bifidobacteria abundance and metabolite modulation, in IBS patients. Methods: Biological samples were collected from IBS patients (n = 58) at baseline and week 4 post-supplementation with placebo, 5 g or 10 g doses of 2 & PRIME;FL/LNnT. The gut microbiota composition, metabolite profiles and expression of genes related to host mucosal response were determined. Results: Moderate changes in fecal, but not mucosal, microbial composition (beta-diversity) was observed during the intervention with higher dissimilarity observed within individuals receiving 10g 2 & PRIME;FL/LNnT compared to placebo. Both fecal and mucosal Bifidobacterium spp. increased after 2 & PRIME;FL/LNnT intake, with increased proportions of Bifidobacterium adolescentis and Bifidobacterium longum. Moreover, the intervention modulated the fecal and plasma metabolite profiles, but not the urine metabolite profile or the host mucosal response. Changes in the metabolite profiles were associated to changes in bifidobacteria abundance. Conclusion: Supplementation with 2 & PRIME;FL/LNnT modulated the gut microbiota, fecal and plasma metabolite profiles, but not the host mucosal response in IBS. Furthermore, the bifidogenic effect was associated with metabolite modulation. Overall, these findings support the assertion that 2 & PRIME;FL/LNnT supplementation modulate the intestinal microenvironment of patients with IBS, potentially related to health.
  •  
44.
  • Jabbar, Karolina S., et al. (author)
  • Association between Brachyspira and irritable bowel syndrome with diarrhoea
  • 2021
  • In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 70, s. 1117-1129
  • Journal article (peer-reviewed)abstract
    • Objective: The incidence of IBS increases following enteric infections, suggesting a causative role for microbial imbalance. However, analyses of faecal microbiota have not demonstrated consistent alterations. Here, we used metaproteomics to investigate potential associations between mucus-resident microbiota and IBS symptoms. Design: Mucus samples were prospectively collected from sigmoid colon biopsies from patients with IBS and healthy volunteers, and their microbial protein composition analysed by mass spectrometry. Observations were verified by immunofluorescence, electron microscopy and real-Time PCR, further confirmed in a second cohort, and correlated with comprehensive profiling of clinical characteristics and mucosal immune responses. Results: Metaproteomic analysis of colon mucus samples identified peptides from potentially pathogenic Brachyspira species in a subset of patients with IBS. Using multiple diagnostic methods, mucosal Brachyspira colonisation was detected in a total of 19/62 (31%) patients with IBS from two prospective cohorts, versus 0/31 healthy volunteers (p<0.001). The prevalence of Brachyspira colonisation in IBS with diarrhoea (IBS-D) was 40% in both cohorts (p=0.02 and p=0.006 vs controls). Brachyspira attachment to the colonocyte apical membrane was observed in 20% of patients with IBS and associated with accelerated oro-Anal transit, mild mucosal inflammation, mast cell activation and alterations of molecular pathways linked to bacterial uptake and ion-fluid homeostasis. Metronidazole treatment paradoxically promoted Brachyspira relocation into goblet cell secretory granules-possibly representing a novel bacterial strategy to evade antibiotics. Conclusion: Mucosal Brachyspira colonisation was significantly more common in IBS and associated with distinctive clinical, histological and molecular characteristics. Our observations suggest a role for Brachyspira in the pathogenesis of IBS, particularly IBS-D. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
  •  
45.
  • Jakobsson, Sofie, 1968, et al. (author)
  • Patient safety before and after implementing person-centred inpatient care - A quasi-experimental study.
  • 2020
  • In: Journal of clinical nursing. - : Wiley. - 1365-2702 .- 0962-1067. ; 29:3-4, s. 602-612
  • Journal article (peer-reviewed)abstract
    • To evaluate aspects of patient safety before and after a person-centred (PC) inpatient care intervention.Transitioning from disease-centred to person-centred care requires great effort but can improve patient safety.A quasi-experimental study with data collection preceding and 12months after a PC inpatient care intervention.The study consecutively recruited adult patients (2014, n=263; 2015/2016, n=221) admitted to an inpatient care unit. The patients reported experiences of care at discharge and their perceived pain at admission and discharge. Medical records were reviewed to gather data on medications, planned care and clinical observations. The study is reported according to TREND guidelines.At discharge, patients receiving PC inpatient care reported competent medical-technical care. Patients receiving PC inpatient care reported more effective pain relief. Updated prescribed medications at the ward were maintained, and patients were made aware of planned medical care to higher extent during PC inpatient care. The assessment of pulse and body temperature was maintained, but fewer elective care patients had their blood pressure taken during PC inpatient care. Weight assessment was not prioritised during usual or PC inpatient care.Patients receiving PC inpatient care reported that they were given the best possible care and had less pain at discharge. The PC inpatient care included improved documentation and communication of planned medical care to the patients. Vital signs were more frequently recorded for patients admitted for acute care than patients admitted for elective care. PC inpatient care had no effect on frequency of weight measurements.PC inpatient care seems beneficial for the patients. Aspects of patient safety such as prescribed medications were maintained, and PC inpatient care seems to enhance the continuity of care. Inpatient clinical observations need further evaluation as healthcare transitions from disease-centred to person-centred care.
  •  
46.
  • Jansson-Rehnberg, Ann-Sofie, et al. (author)
  • Diarrhoea of unknown cause: medical treatment in a stepwise manner Management of Idiopathic Diarrhoea Based on Experience of Step-Up Medical Treatment
  • 2024
  • In: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. - : TAYLOR & FRANCIS LTD. - 0036-5521 .- 1502-7708.
  • Research review (peer-reviewed)abstract
    • The basic principle for the treatment of idiopathic diarrhoea (functional diarrhoea K59.1) is to delay transit through the gut in order to promote the absorption of electrolytes and water. Under mild conditions, bulking agents may suffice. With increasing severity, antidiarrhoeal pharmaceuticals may be added in a stepwise manner. In diarrhoea of unknown aetiology, peripherally-acting opioid receptor agonists, such as loperamide, are first-line treatment and forms the pharmaceutical basis of antidiarrheal treatment. As second-line treatment opium drops have an approved indication for severe diarrhoea when other treatment options fail. Beyond this, various treatment options are built on experience with more advanced treatments using clonidine, octreotide, as well as GLP-1 and GLP-2 analogs which require specialist knowledge the field.
  •  
47.
  • Jansson-Rehnberg, Ann Sofie, et al. (author)
  • Viktigt att stegvis öka insatser vid farmakologisk diarrébehandling : Pharmacological treatment of idiopathic diarrhea
  • 2023
  • In: Läkartidningen. - 0023-7205. ; 120
  • Journal article (other academic/artistic)abstract
    • The basic principle for treatment of idiopathic diarrhea is to delay transit through the gut in order to promote absorption of electrolytes and water. Under mild conditions bulking agents may suffice. With increasing severity, antidiarrheal pharmaceuticals may be added in a stepwise manner. Bile salt malabsorption is a clear indication for adsorptive resins, while in idiopathic diarrhea peripherally-acting opioid receptor agonists, such as loperamide, is the first-line treatment. Second-line treatment with approved indication for severe diarrhea when other treatment options fail includes opium drops. More advanced treatments are to be used by clinicians with specialist knowledge and experience in the field.
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48.
  •  
49.
  • Josefsson, Axel, 1984, et al. (author)
  • Global Prevalence and Impact of Rumination Syndrome
  • 2022
  • In: Gastroenterology. - : Elsevier BV. - 0016-5085. ; 162:3
  • Journal article (peer-reviewed)abstract
    • Background & aims: Rumination syndrome is a Disorder of Gut-Brain Interaction (DGBI) of unknown etiology. We aimed to assess its global prevalence and potential associations with other medical conditions. Methods: Data were collected via the Internet in 26 countries. Subjects were evenly distributed by country, sex, and age groups and were invited for a “health survey” using the Rome IV diagnostic questionnaire and a supplementary questionnaire addressing factors potentially associated with DGBI. Results: In all, 54,127 subjects completed the survey (51% male; mean age, 44.3 years). The overall prevalence of rumination syndrome was 3.1% (95% confidence interval [CI], 3.0–3.3%). It was highest in Brazil (5.5% CI, 4.5–6.5) and lowest in Singapore (1.7% CI, 1.1–2.2). The mean age of people with rumination syndrome was 44.5 years (standard deviation, 15.6) and it was more common in females (54.5% vs 45.5%). Factors independently associated with rumination syndrome were depression (odds ratio [OR], 1.46), anxiety (OR, 1.8), body mass index (OR, 1.04), and female sex (OR, 1.19). Subjects with multiple DGBI were at increased risk of having rumination syndrome, with the highest risk in subjects with 4 gastrointestinal regions with DGBI (OR, 15.9 compared with none). Quality of life (QoL) was lower in subjects with rumination syndrome compared with the rest of the cohort (PROMIS-10 score: physical QoL mean 12.9 vs 14.5; mental QoL mean 12.0 vs 13.6). Conclusions: The prevalence of rumination syndrome is higher than reported in most previous population studies and is likely underdiagnosed in clinical practice. Awareness of rumination syndrome should be raised among clinicians to improve care for these patients. © 2022 AGA Institute
  •  
50.
  • Josefsson, Axel, 1984, et al. (author)
  • 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
  • In: Neurogastroenterology and Motility. - 1350-1925 .- 1365-2982. ; 36:2
  • Journal article (peer-reviewed)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.
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