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1.
  • Moraes Holst, Luiza, et al. (author)
  • Downregulated Mucosal Autophagy, Alpha Kinase-1 and IL-17 Signaling Pathways in Active and Quiescent Ulcerative Colitis
  • 2022
  • In: Clinical and Experimental Gastroenterology. - : DOVE MEDICAL PRESS LTD. - 1178-7023. ; 15, s. 129-144
  • Journal article (peer-reviewed)abstract
    • Background: Improved mucosal immune profiling in active and quiescent colonic inflammatory bowel disease (IBD) is needed to develop therapeutic options for treating and preventing flares. This study therefore aimed to provide a comprehensive mucosal characterization with emphasis on immunological host response of patients with active ulcerative colitis (UC active), UC during remission (UC remission) and active colonic Crohn's disease (CD active).Methods: Colonic biopsies from 47 study subjects were collected for gene expression and pathway analyses using the NanoString host-response panel, including 776 genes and 56 immune-related pathways.Results: The majority of mucosal gene expression and signaling pathway scores were increased in active IBD (n=27) compared to healthy subjects (n=10). However, both active IBD and UC remission (n=10) demonstrated decreased gene expression and signaling pathway scores related to autophagy, alpha kinase-1 and IL-17 signaling pathways compared to healthy subjects. Further, UC remission was characterized by decreased scores of several signaling pathways linked to homeostasis along with increased mononuclear cell migration pathway score as compared to healthy subjects. No major differences in the colonic mucosal gene expression between CD active (n=7) and UC (n=20) active were observed.Conclusion: This study indicates that autophagy, alpha kinase-1 and IL-17 signaling pathways are persistently downregulated in UC irrespective of disease activity. Further, UC patients in remission present a unique mucosal environment, potentially preventing patients from reaching and sustaining true homeostasis. These findings may enable better comprehension of the remitting and relapsing pattern of colonic IBD and guide future treatment and prevention of flares.
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2.
  • Moraes, Luiza, et al. (author)
  • Systemic Inflammatory Protein Profiles Distinguish Irritable Bowel Syndrome (IBS) and Ulcerative Colitis, Irrespective of Inflammation or IBS-Like Symptoms.
  • 2020
  • In: Inflammatory bowel diseases. - : Oxford University Press (OUP). - 1536-4844 .- 1078-0998. ; 26:6, s. 874-884
  • Journal article (peer-reviewed)abstract
    • Inflammatory mechanisms of ulcerative colitis (UC) and irritable bowel syndrome (IBS) may overlap or are part of different spectrums. However, potential links between inflammation and IBS-like symptoms in these patient groups are still unclear. The aim of this study was to determine if the systemic inflammatory protein (SIP) profiles differ between UC patients, with presence of inflammation or in remission with or without IBS-like symptoms, and IBS patients.Serum from patients with active UC (UCA), UC patients in remission with or without IBS-like symptoms (UCR+IBS, UCR-IBS), IBS patients (IBS), and healthy subjects (HS) was analyzed using the ProSeek Multiplex Inflammation kit, which detects 92 proteins.The exploratory cohort consisted of 166 subjects (UCA, n = 40; UCR-IBS, n = 45; UCR+IBS, n = 20; IBS, n = 40; HS, n = 21). Systemic inflammatory protein profiles separated UC from non-UC (HS and IBS) patients in multivariate analysis, revealing caspase 8, axin 1, sulfotransferase 1A1, and tumor necrosis factor superfamily member 14 as the variables most important to clustering. Although minor differences were detected between UCR+IBS and UCR-IBS, SIP profiles discriminated UCA from UCR, and interleukin (IL) 17C, IL17A, chemokine ligand 9, and transforming growth factor-α characterized active inflammation. SIP profiles weakly discriminated HS from IBS, although fibroblast growth factor 21 and IL6 serum levels were higher in IBS. Results were confirmed in a validation cohort (UCA, n = 15; UCR+IBS, n = 9; IBS, n = 14).SIP profiles distinguish UC patients from IBS patients, irrespective of inflammation or IBS-like symptoms, suggesting that inflammatory mechanisms of the diseases are part of different spectrums.
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4.
  • Abell, T. L., et al. (author)
  • Neurostimulation of the Gastrointestinal Tract: Review of Recent Developments
  • 2015
  • In: Neuromodulation. - : Elsevier BV. - 1094-7159. ; 18:3, s. 221-227
  • Journal article (peer-reviewed)abstract
    • ObjectiveNeurostimulation is one manifestation of neuromodulation of the gastrointestinal (GI) tract. This manuscript reviews the history of neurostimulation of the GI tract with emphasis on current methods of stimulation. Materials and MethodsA review was completed of the current research on GI neurostimulation methods with an emphasis on their clinical applications. ResultsUpper GI disorders can be modulated with both temporary (placed endoscopically or surgically) or permanent (placed surgically) gastric electrical stimulation (GES) devices. The current GI neurostimulation of stomach (GES) devices have been used in both children and adults, and some patients have been followed in excess of 15 years with good long-term results. Similar GES devices also have been used for a variety of lower GI disorders, including constipation and fecal incontinence, for a number of years. ConclusionsGI neurostimulation, as a type of neuromodulation, has been demonstrated to function at several locations in the GI tract for a variety of disorders. The future of neurostimulation in the GI tract will likely be influenced by a better understanding of pathophysiology as well as the development of new techniques and devices for neuromodulation.
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5.
  • Adolfsson, Jan, et al. (author)
  • Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005 : Data from the national prostate cancer register in Sweden
  • 2007
  • In: Scandinavian Journal of Urology and Nephrology. - Stockholm : Taylor & Francis. - 0036-5599 .- 1651-2065. ; 41:6, s. 456-477
  • Journal article (peer-reviewed)abstract
    • Objective. The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. Material and methods. Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. Results. In total, 72 028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of >100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score ≤6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged ≥75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. Conclusions. All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer
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6.
  • Adolfsson, Jan, et al. (author)
  • Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005
  • 2007
  • In: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 0036-5599 .- 1651-2065. ; 41:6, s. 456-477
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. MATERIAL AND METHODS: Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. RESULTS: In total, 72,028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of > 100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score <6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged > or =75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. CONCLUSIONS: All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer.
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7.
  • 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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8.
  • 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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9.
  • 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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10.
  • 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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11.
  • Algera, Joost, 1993, et al. (author)
  • Managing pain in irritable bowel syndrome: current perspectives and best practice
  • 2023
  • In: Expert Review of Gastroenterology & Hepatology. - 1747-4124. ; 17:9, s. 871-881
  • Research review (peer-reviewed)abstract
    • IntroductionIrritable bowel syndrome (IBS) is characterized by chronic symptoms (>6 months) of abdominal pain in combination with a disturbed bowel habit. There is an association between the intensity of abdominal pain and the need for health care utilization. A bidirectionally disordered gut-brain interaction is central in the pathophysiology of IBS where a number of factors, gastrointestinal and non-gastrointestinal, can contribute to the illness experience. In order to treat abdominal pain in IBS, mapping these factors in a multidimensional clinical profile is helpful.Areas coveredThis review covers basic epidemiology and pathophysiology of abdominal pain in IBS, the diagnostic approach, and a multidimensional treatment model where the management of abdominal pain is in focus.Expert opinionA personalized treatment of abdominal pain in IBS is possible in patients who understand the diagnosis, the potential of therapies used, and where a good continuity in the patient-doctor relationship is established.
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12.
  • 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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13.
  • 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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14.
  • Almquist, Ellinor, et al. (author)
  • Practical management of irritable bowel syndrome: a clinical review.
  • 2016
  • In: Minerva gastroenterologica e dietologica. - 1827-1642. ; 62:1, s. 30-48
  • Research review (peer-reviewed)abstract
    • Irritable bowel syndrome is a functional gastrointestinal disorder, frequently managed by general practitioners and gastroenterologists. It is a complex condition, characterized by abdominal pain or discomfort associated with altered bowel habits, and it affects 11% of the population worldwide. It has a profound effect on quality of life for many patients and poses a substantial cost to society. Due to the complexity and diversity of IBS, diagnosis and treatment can be challenging. Common drawbacks in diagnosing and treating this disorder include unnecessary tests, failure to establish trust in the physician-patient relationship and difficulties in explaining the diagnosis. Research in recent years has however refined the diagnostic criteria and improved our ability to safely identify IBS with a limited number of investigations. A concise diagnostic evaluation, guided adequate information, prompt initiation of symptom-guided treatment and consistency in the patient-doctor relationship can help relieve the suffering experienced by patients with IBS. For patients with mild symptoms, reassurance, education, lifestyle changes and dietary advice are often sufficient. Patients with moderate to severe symptoms might need symptom modifying drugs, and psychological treatments such as CBT or hypnotherapy may be offered at this stage. For patients with severe and incapacitating symptoms, a multidisciplinary approach is recommended and psychotropic drugs are often used. This clinical review offers suggestions for a diagnostic approach as well as a treatment strategy, based on the current evidence on pathophysiology, diagnosis and treatment in IBS.
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16.
  • Amcoff, Karin, 1975- (author)
  • Serological and faecal biomarkers in inflammatory bowel disease
  • 2018
  • Doctoral thesis (other academic/artistic)abstract
    • The inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are relapsing and remitting disorders characterised by chronic inflammation at various sites in the gastrointestinal tract, resulting in diarrhoea and abdominal pain. Neither the aetiology nor the pathophysiology is yet fully understood, and there is currently no cure.The overall aim of this thesis was to add a piece of the puzzle to understanding the complex pathogenesis of IBD; to determine the role of genetic and environmental factors in the development of antibodies in IBD - which could provide insight to the aetiology of the diseases; and to find sensitive and specific faecal biomarkers to predict future flare in the diseases.By conducting twin-studies, we found that some serological antibodies associated with Crohn's disease seemed to be genetically predisposed (anti-OmpC and anti-I2). Genetic predisposition do not play a predominant role in the generation of other antibodies, such as ASCA, anti-CBir1 or the autoantibody most commonly found in ulcerative colitis; pANCA. Exposure to environmental factors during childhood are suggested to be of importance in the development of ASCA and anti-CBir1 in CD. Active smoking seemed to have a protective effect against development of pANCA.Faecal calprotectin is a known marker for intestinal inflammation. In our third study, three faecal calprotectin assays were compared, which revealed overall poor agreement. This implies that standardisation of the method is highly needed.In our final study, we measured faecal eosinophil derived neurotoxin (EDN) and eosinophil cationic protein (ECP) in patients with IBD every third month over a two-year period. The results revealed that the risk of relapse in UC can be predicted by measuring EDN consecutively.
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17.
  • Aziz, Imran, et al. (author)
  • Epidemiology, Clinical Characteristics, and Associations for Rome IV Functional Nausea and Vomiting Disorders in Adults
  • 2019
  • In: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 17:5, s. 878-886
  • Journal article (peer-reviewed)abstract
    • Background & Aims: Functional nausea and vomiting disorders (FNVDs) are classified as chronic nausea and vomiting syndrome (CNVS) or cyclic vomiting syndrome (CVS)—CVS includes cannabinoid hyperemesis syndrome. We investigated the population prevalence of FNVDs, their characteristics, and associated factors. Methods: In the year 2015, an Internet cross-sectional health survey was completed by 5931 adults in the general populations of 3 English-speaking countries; 2100 participants were in the United States, Canada, or the United Kingdom. Quota-based sampling was used to generate demographically balanced and population-representative samples. The survey collected data on demographics, health care visits, medications, somatic symptom severity, quality of life, and symptom-based diagnostic criteria for Rome IV FNVDs as well as for irritable bowel syndrome and functional dyspepsia. Subsequent comparisons were made between Rome IV FNVD subjects and individuals without FNVDs (controls). Results: Overall, 2.2% of the population (n = 131) fulfilled symptom-based diagnostic criteria for Rome IV FNVDs: the United States (3%) had a greater prevalence than Canada (1.9%) or the United Kingdom (1.8%) (P =.02). The prevalence of CNVS was similar among the countries, ranging from 0.8% to 1.2%. However, the prevalence of CVS was higher in the United States (2%) than in Canada (0.7%) or the United Kingdom (1%) (P =.03). The proportion of subjects with CVS taking cannabis did not differ significantly among countries (P =.31), although the 7 cases of cannabinoid hyperemesis syndrome were in the United States. A significantly higher proportion of subjects with CVS reported a compulsive need for hot water bathing to alleviate emetic symptoms than subjects with CNVS (44% vs 19%; P =.03); this behavior was independent of cannabis but augmented by its use. Subjects with FNVDs had significantly greater health impairment and health care utilization than controls. On multivariate analysis, independent factors associated with FNVDs were younger age, increasing somatic symptom severity, lower quality of life, presence of irritable bowel syndrome, and functional dyspepsia. However, on subgroup analysis, somatic symptom severity was associated with CVS but not CNVS, whereas poor quality of life was associated with CNVS but not CVS. Conclusions: Based on a cross-sectional health survey of adults in the general populations of 3 English-speaking countries, approximately 2% of subjects meet symptom-based criteria for Rome IV FNVDs and have considerable health impairments. Hot water bathing to alleviate emetic symptoms is reported for all FNVDs, and is perpetuated by cannabis use. © 2019 AGA Institute
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18.
  • Aziz, Imran, et al. (author)
  • Epidemiology, clinical characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults in the USA, Canada, and the UK: a cross-sectional population-based study
  • 2018
  • In: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 3:4, s. 252-262
  • Journal article (peer-reviewed)abstract
    • Background The population prevalence, clinical characteristics, and associations for Rome IV functional dyspepsia are not known. Following the publication of the Rome IV criteria for functional gastrointestinal disorders, we aimed to assess the prevalence, characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults across the USA, Canada, and the UK. Methods We sent an internet-based cross-sectional health survey to adults in the general population of three English-speaking countries: the USA, Canada, and the UK. We used quota-based sampling to generate demographically balanced and population-representative samples. Individuals were invited to complete an online questionnaire on general health, without mention that the purpose of this survey was to examine gastrointestinal symptoms. We excluded participants who failed two attention-test questions or were excessively inconsistent on the three gastrointestinal questions that were presented twice in the survey for this particular purpose. The survey enquired about demographics, health-care visits, medications, somatisation, quality of life, and symptom-based criteria for Rome IV functional dyspepsia as well as for irritable bowel syndrome (IBS) and functional heartburn. We made subsequent comparisons between participants with Rome IV functional dyspepsia and controls without dyspepsia. The primary objective was to identify participants who fulfilled symptom-based criteria for Rome IV functional dyspepsia and categorise them into postprandial distress syndrome, epigastric pain syndrome, or overlapping subtypes. Findings 6300 general population adults completed the health survey; 2100 each from the USA, Canada, and the UK. 369 responses were deemed inconsistent, leaving data for 5931 adults. Rome IV functional dyspepsia was significantly more prevalent in the USA (232 [12%] of 1949) than in Canada (167 [8%] of 1988) and the UK (152 [8%] of 1994; p< 0 . 0001). The subtype distribution was 61% postprandial distress syndrome, 18% epigastric pain syndrome, and 21% overlapping variant with both syndromes; this pattern was similar across the countries. Participants with functional dyspepsia had significantly greater health impairment and health-care usage than those without dyspepsia. Participants with the overlapping variant showed greater somatisation and poorer quality-of-life scores than did individuals with either postprandial distress syndrome or epigastric pain syndrome alone. In multivariate analysis, independent factors associated with all functional dyspepsia subtypes included worsening quality of life and the presence of symptoms compatible with functional heartburn and IBS, with functional heartburn and IBS having the strongest association with overlapping postprandial distress syndrome and epigastric pain syndrome. Notably, somatisation showed a positive association with postprandial distress syndrome and the overlapping variant, and use of antidepressants showed a negative association with postprandial distress syndrome. Interpretation Approximately 10% of the adult population fulfils symptom-based criteria for Rome IV functional dyspepsia and incurs considerable associated health impairment. The functional dyspepsia subtypes show differing associations, suggesting differences in pathophysiological processes or influences.
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19.
  • Aziz, Imran, et al. (author)
  • How the Change in IBS Criteria From Rome III to Rome IV Impacts on Clinical Characteristics and Key Pathophysiological Factors
  • 2018
  • In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270. ; 113:7, s. 1017-1025
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: The diagnostic criteria for irritable bowel syndrome (IBS) have recently been updated from Rome III to Rome IV. Whereas in Rome III a diagnosis of IBS entailed chronic abdominal pain or discomfort at least 3 days per month, in Rome IV the term discomfort has been removed and the frequency of abdominal pain increased to at least 1 day per week. We examined how this change in IBS criteria impacts on clinical characteristics and pathophysiological factors. METHODS: A total of 542 Swedish subjects with Rome III IBS completed a baseline questionnaire enquiring for the number of abdominal pain days in the last 10 days; this was subsequently used as a surrogate marker to identify Rome IV IBS, in that (a) those with 0 or 1 day of pain were classed as Rome IV-negative, and (b) those with >= 2 days of pain were classed as Rome IV-positive. Comparisons were made between Rome IV-positive and -negative IBS groups for demographics, IBS subtype, gastrointestinal and psychological symptoms, somatisation, fatigue, disease-specific quality of life, rectal sensitivity, and oro-anal transit time. RESULTS: Overall, 85% of Rome III IBS patients fulfilled the Rome IV criteria for IBS, but 15% did not. Rome IV-positive subjects were significantly more likely to be female, have poorer quality of life, greater pain severity, bloating, somatisation, fatigue, and rectal sensitivity than Rome IV-negative subjects. There were no differences in severity of anxiety or depression, IBS subtypes, bowel habit dissatisfaction, or oro-anal transit time. Finally, increasing number of pain days correlated positively with symptoms and visceral hypersensitivity. CONCLUSIONS: Most Rome III-positive IBS patients seeking healthcare fulfil the Rome IV IBS criteria. They constitute a more severe group than those who lose their IBS diagnosis.
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20.
  • Aziz, Imran, et al. (author)
  • Small intestinal bacterial overgrowth as a cause for irritable bowel syndrome: guilty or not guilty?
  • 2017
  • In: Current Opinion in Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0267-1379. ; 33:3, s. 196-202
  • Journal article (peer-reviewed)abstract
    • Purpose of review Small intestinal bacterial overgrowth (SIBO) has been proposed as a cause of irritable bowel syndrome (IBS). However, this relationship has been subject to controversy. This review aims to provide a current perspective on the SIBO-IBS hypothesis. Case-control studies evaluating the prevalence of SIBO in IBS and healthy individuals have shown conflicting results. Moreover, the tests available in routine clinical practice to diagnose SIBO are not valid and lack both sensitivity and specificity. Hence, interpreting the effect of interventions based on these tests is fraught with uncertainty. Furthermore, the SIBO-IBS hypothesis has paved the way to assess antibiotic therapy in nonconstipated IBS, with rifaximin, a nonabsorbable antibiotic, showing modest but significant clinical benefit. However, individuals were not tested for SIBO and the mechanism of action of rifaximin in IBS remains to be elucidated. Preliminary data suggest that rifaximin decreases microbial richness and previous studies have noted antibacterial interventions in IBS to reduce colonic fermentation and improve symptoms. The advent of rapid culture-independent molecular techniques is a promising tool that will seek to clarify and advance our understanding of the gut microbial function. The SIBO-IBS hypothesis lacks convincing evidence but remains under scrutiny. The mechanism resulting in symptom improvement after rifaximin treatment in some IBS individuals requires exploration. Novel molecular techniques provide an exciting and challenging opportunity to explore the host-gut microbiota interaction.
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21.
  • Aziz, Imran, et al. (author)
  • The Prevalence and Impact of Overlapping Rome IV-Diagnosed Functional Gastrointestinal Disorders on Somatization, Quality of Life, and Healthcare Utilization: A Cross-Sectional General Population Study in Three Countries
  • 2018
  • In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270. ; 113:1, s. 86-96
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: The population prevalence of Rome IV-diagnosed functional gastrointestinal disorders (FGIDs) and their cumulative effect on health impairment is unknown. METHODS: An internet-based cross-sectional health survey was completed by 5,931 of 6,300 general population adults from three English-speaking countries (2100 each from USA, Canada, and UK). Quota-based sampling was used to generate demographically balanced and population representative samples with regards to age, sex, and education level. The survey enquired for demographics, medication, surgical history, somatization, quality of life (QOL), doctor-diagnosed organic GI disease, and criteria for the Rome IV FGIDs. Comparisons were made between those with Rome IV-diagnosed FGIDs against non-GI (healthy) and organic GI disease controls. RESULTS: The number of subjects having symptoms compatible with a FGID was 2,083 (35%) compared with 3,421 (57.7%) non-GI and 427 (7.2%) organic GI disease controls. The most frequently met diagnostic criteria for FGIDs was bowel disorders (n = 1,665, 28.1%), followed by gastroduodenal (n = 627, 10.6%), anorectal (n = 440, 7.4%), esophageal (n = 414, 7%), and gallbladder disorders (n = 10, 0.2%). On average, the 2,083 individuals who met FGID criteria qualified for 1.5 FGID diagnoses, and 742 of them (36%) qualified for FGID diagnoses in more than one anatomic region. The presence of FGIDs in multiple regions was associated with increasing somatization, worse mental/physical QOL, more medical therapies, and a higher prevalence of abdominal surgeries; all P < 0.001. Notably, individuals with FGIDs in multiple regions had greater somatization and worse QOL than organic GI disease controls. CONCLUSIONS: Roughly a third of the general adult population fulfils diagnostic criteria for a Rome IV FGID. In a third of this subset multiple GI regions are involved and this overlap is associated with increased health impairment.
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22.
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23.
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24.
  • Bennet, Sean, et al. (author)
  • Altered intestinal antibacterial gene expression response profile in irritable bowel syndrome is linked to bacterial composition and immune activation
  • 2018
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 30:12
  • Journal article (peer-reviewed)abstract
    • Background Immune activity and gut microbiota may impact the pathophysiology of irritable bowel syndrome (IBS). We aimed to determine whether antibacterial gene expression of immune activity-defined IBS patients differed compared to healthy subjects (HS) and ulcerative colitis (UC) patients and whether antibacterial profiles reflected gut microbiota composition and IBS symptoms. Methods Key Results Expression of 84 antibacterial genes in biopsies from HS, IBS patients (clustered according to immune activity (systemic and intestinal cytokines): immunonormal or immunoactive), and UC patients was assessed by Human Antibacterial Response RT2 Profiler PCR Array. In IBS patients, 16S rRNA gene sequencing of fecal and mucosal bacteria was performed and symptom pattern and severity were assessed. Intestinal antibacterial gene expression profiles differed between IBS patients (n = 31) and HS (n = 16), but did not differ between IBS subgroups based on bowel habit predominance or symptom severity. Based on previously identified IBS clusters, IBS patients with normal (n = 15) and enhanced immune activity (n = 16) had clearly separate antibacterial gene expression profiles from active UC patients (n = 12) and differed compared to each other and to HS. The differences in antibacterial gene expression profiles between immunonormal and immunoactive IBS patients were also reflected in distinct fecal and mucosal microbiota composition profiles, but not in symptom pattern or severity. Conclusions & Inferences This study demonstrates an altered antibacterial gene expression profile in IBS patients compared to HS and UC patients. While not linked to symptoms, immune activity-defined IBS clusters showed different intestinal antibacterial gene expression and distinct fecal and mucosal bacterial profiles.
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25.
  • Bennet, Sean, et al. (author)
  • Global Cytokine Profiles and Association With Clinical Characteristics in Patients With Irritable Bowel Syndrome
  • 2016
  • In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 111:8, s. 1165-1176
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: Evidence suggests that patients with irritable bowel syndrome (IBS) have an altered cytokine profile, although it is unclear whether cytokines are linked with symptom severity. We aimed to determine whether global serum and mucosal cytokine profiles differ between IBS patients and healthy subjects and whether cytokines are associated with IBS symptoms. METHODS: Serum from 144 IBS patients and 42 healthy subjects was analyzed for cytokine levels of interleukin (IL)-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17A, interferon (IFN)-gamma and tumor necrosis factor (TNF) by MSD MULTI-ARRAY. In total, 109 IBS and 36 healthy sigmoid colon biopsies were analyzed for mRNA expression of IL-8, IL-10, TNF, and FOXP3 by quantitative reverse transcription PCR. Multivariate discrimination analysis evaluated global cytokine profiles. Rectal sensitivity, oroanal transit time, and psychological and gastrointestinal symptom severity were also assessed. RESULTS: Global cytokine profiles of IBS patients and healthy subjects overlapped, but cytokine levels varied more in IBS patients. Serum levels of IL-6 and IL-8 tended to be increased and levels of IFN-gamma tended to be decreased in IBS patients. Mucosal mRNA expression of IL-10 and FOXP3 tended to be decreased in IBS patients. Within both the full study cohort and IBS patients alone, serum level of TNF was associated with looser stool pattern, while subjects with more widespread somatic symptoms had increased serum levels of IL-6. Although neither IBS bowel habit subgroups nor patients with possible post-infectious IBS were associated with distinct cytokine profiles, a small cluster of IBS patients with comparatively elevated immune markers was identified. CONCLUSIONS: Global cytokine profiles did not discriminate IBS patients from healthy subjects, but cytokine profiles were more varied among IBS patients than among healthy subjects, and a small subgroup of patients with enhanced immune activity was identified. Also, association of inflammatory cytokines with some clinical symptoms suggests that immune activation may be of importance in a subset of IBS patients.
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26.
  • Bennet, Sean M. P., et al. (author)
  • Multivariate modelling of faecal bacterial profiles of patients with IBS predicts responsiveness to a diet low in FODMAPs
  • 2018
  • In: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 67:5, s. 872-881
  • Journal article (peer-reviewed)abstract
    • Objective The effects of dietary interventions on gut bacteria are ambiguous. Following a previous intervention study, we aimed to determine how differing diets impact gut bacteria and if bacterial profiles predict intervention response. Design Sixty-seven patients with IBS were randomised to traditional IBS (n=34) or low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) (n=33) diets for 4 weeks. Food intake was recorded for 4 days during screening and intervention. Faecal samples and IBS Symptom Severity Score (IBS-SSS) reports were collected before (baseline) and after intervention. A faecal microbiota dysbiosis test (GA-map Dysbiosis Test) evaluated bacterial composition. Per protocol analysis was performed on 61 patients from whom microbiome data were available. Results Responders (reduced IBS-SSS by >= 50) to low FODMAP, but not traditional, dietary intervention were discriminated from non-responders before and after intervention based on faecal bacterial profiles. Bacterial abundance tended to be higher in non-responders to a low FODMAP diet compared with responders before and after intervention. A low FODMAP intervention was associated with an increase in Dysbiosis Index (DI) scores in 42% of patients; while decreased DI scores were recorded in 33% of patients following a traditional IBS diet. Non-responders to a low FODMAP diet, but not a traditional IBS diet had higher DI scores than responders at baseline. Finally, while a traditional IBS diet was not associated with significant reduction of investigated bacteria, a low FODMAP diet was associated with reduced Bifidobacterium and Actinobacteria in patients, correlating with lactose consumption. Conclusions A low FODMAP, but not a traditional IBS diet may have significant impact on faecal bacteria. Responsiveness to a low FODMAP diet intervention may be predicted by faecal bacterial profiles.
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27.
  • Bennet, Sean, et al. (author)
  • Systemic cytokines are elevated in a subset of patients with irritable bowel syndrome but largely unrelated to symptom characteristics
  • 2018
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 30:10
  • Journal article (peer-reviewed)abstract
    • BackgroundSerum levels of pro-inflammatory cytokines tend to be increased in irritable bowel syndrome (IBS) patients, or subgroups thereof. Still, the link between cytokine levels and IBS symptoms is unclear. We aim to determine systemic cytokine levels in IBS patients and healthy subjects (HS), confirm the presence of a subset of patients with an increased immune activity and to establish if cytokines are linked to IBS symptoms and pathophysiological factors. MethodsSerum levels of interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF), and IL-10 were measured. All subjects reported IBS symptoms using validated questionnaires and underwent colonic sensorimotor testing. Multivariate supervised orthogonal partial least squares-discriminant analysis (OPLS-DA) and unsupervised principal component analysis (PCA) and hierarchical cluster analysis (HCA) were implemented. Key ResultsIrritable bowel syndrome patients (n=246) had higher serum levels of IL-1, IL-6, IL-8, TNF, and IL-10 compared to HS (n=21); however, serum cytokine profiles could not discriminate patients from HS. Moreover, cytokine levels were not correlated with symptoms among patients. Supervised OPLS-DA identified 104 patients (40% of patients) and unsupervised HCA analysis identified 49 patients (20%) with an increased immune activity indicated by elevated levels of serum cytokines compared to HS and the other patients. However, irrespective of how patients with increased immune activity were identified they were symptomatically similar to patients with no indication of increased immune activity. Conclusions & InferencesSerum cytokines are elevated in IBS patients compared to HS. Immune activation characterizes a subset of patients, but modest associations between cytokine profile and symptoms suggest immune activity does not directly influence symptoms in IBS.
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28.
  • Björkman, Ida, et al. (author)
  • More similarities than differences between men and women with irritable bowel syndrome
  • 2015
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 27:6, s. 796-804
  • Journal article (peer-reviewed)abstract
    • Background: Differences regarding symptoms, coping abilities, and quality of life (QOL) between men and women with irritable bowel syndrome (IBS) have been reported but data are sparse and sometimes conflicting. The aim of present study was to investigate gender differences in gastrointestinal, extra-intestinal, and psychological symptoms, and sense of coherence (SOC) and QOL in a large group of patients diagnosed with IBS. Methods: We analyzed questionnaire data from 557 patients (152 men) diagnosed with IBS consecutively included in studies at an outpatient clinic for functional bowel disorders between 2002 and 2010. Following questionnaires were included: IBS severity scoring system (IBS-SSS), Hospital Anxiety and Depression Scale (HAD), IBSQOL Scale, Visceral Sensitivity Index (VSI), SOC Scale, Bristol Stool Form Scale (BSFS), and Patient Health Questionnaire (PHQ-15). Key Results: Women had harder stools (FDR-adjusted p-value: q = 0.033), more severe bloating (q = 0.020), higher symptom severity (q = 0.042), higher total somatic symptom burden (q = 0.035), lower SOC (q = 0.042), and lower QOL. Women rated more general anxiety (q = 0.017) and gastrointestinal-specific anxiety (q = 0.042), but there were no group differences in depression, pain, stool frequency, impact on daily life, dissatisfaction with bowel habit, or extra-colonic symptoms. The differences found were small (effect sizes: r < 0.3). Conclusions & Inferences: In this study, we demonstrated more similarities than differences between men and women with IBS. The largest difference were seen for QOL which might reflect certain structural stressors to which women in general are more exposed than men. © 2015 John Wiley & Sons Ltd.
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29.
  • Bonfiglio, F., et al. (author)
  • A meta-analysis of reflux genome-wide association studies in 6750 Northern Europeans from the general population
  • 2017
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 29:2
  • Journal article (peer-reviewed)abstract
    • BackgroundGastroesophageal reflux disease (GERD), the regurgitation of gastric acids often accompanied by heartburn, affects up to 20% of the general population. Genetic predisposition is suspected from twin and family studies but gene-hunting efforts have so far been scarce and no conclusive genome-wide study has been reported. We exploited data available from general population samples, and studied self-reported reflux symptoms in relation to genome-wide single nucleotide polymorphism (SNP) genotypes. MethodsWe performed a GWAS meta-analysis of three independent population-based cohorts from Sweden, Finland, and UK. GERD cases (n=2247) and asymptomatic controls (n=4503) were identified using questionnaire-derived symptom data. Upon stringent quality controls, genotype data for more than 2.5M markers were used for association testing. Bioinformatic characterization of genomic regions associated with GERD included gene-set enrichment analysis (GSEA), in silico prediction of genetic risk effects on gene expression, and computational analysis of drug-induced gene expression signatures using Connectivity Map (cMap). Key resultsWe identified 30 GERD suggestive risk loci (P5x10(-5)), with concordant risk effects in all cohorts, and predicted functional effects on gene expression in relevant tissues. GSEA revealed involvement of GERD risk genes in biological processes associated with the regulation of ion channel and cell adhesion. From cMap analysis, omeprazole had significant effects on GERD risk gene expression, while antituberculosis and anti-inflammatory drugs scored highest among the repurposed compounds. ConclusionsWe report a large-scale genetic study of GERD, and highlight genes and pathways that contribute to further our understanding of its pathogenesis and therapeutic opportunities.
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30.
  • 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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31.
  • Böhn, Lena, et al. (author)
  • Diet Low in FODMAPs Reduces Symptoms of Irritable Bowel Syndrome as Well as Traditional Dietary Advice: A Randomized Controlled Trial.
  • 2015
  • In: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 149:6
  • Journal article (peer-reviewed)abstract
    • A diet with reduced content of fermentable short-chain carbohydrates (fermentable oligo-, di-, monosaccharides, and polyols [FODMAPs]) has been reported to be effective in the treatment of patients with irritable bowel syndrome (IBS). However, there is no evidence of its superiority to traditional dietary advice for these patients. We compared the effects of a diet low in FODMAPs with traditional dietary advice in a randomized controlled trial of patients with IBS.
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32.
  • Böhn, Lena, et al. (author)
  • Self-Reported Food-Related Gastrointestinal Symptoms in IBS Are Common and Associated With More Severe Symptoms and Reduced Quality of Life
  • 2013
  • In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270. ; 108:5, s. 634-641
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: Despite the fact that food and diet are central issues, that concern patients with irritable bowel syndrome (IBS), the current understanding about the association between the intake of certain foods/food groups and the gastrointestinal (GI) symptom pattern, psychological symptoms, and quality of life is poor. The aim of this study was to determine which food groups and specific food items IBS patients report causing GI symptoms, and to investigate the association with GI and psychological symptoms and quality of life. METHODS: We included 197 IBS patients (mean age 35 (18–72) years; 142 female subjects) who completed a food questionnaire in which they specified symptoms from 56 different food items or food groups relevant to food intolerance/allergy. The patients also completed questionnaires to assess depression and general anxiety (Hospital Anxiety and Depression), GI-specific anxiety (Visceral Sensitivity Index), IBS symptoms (IBS-Severity Scoring System), somatic symptoms (Patient Health Questionnaire-15), and quality of life (Irritable Bowel Syndrome Quality of Life Questionnaire). RESULTS: In all, 84% of the studied population reported symptoms related to at least one of the food items surveyed. Symptoms related to intake of food items with incompletely absorbed carbohydrates were noted in 138 (70%) patients; the most common were dairy products (49%), beans/lentils (36%), apple (28%), flour (24%), and plum (23%). Of these, 58% experienced GI symptoms from foods rich in biogenic amines, such as wine/beer (31%), salami (22%), and cheese (20%). Histamine-releasing foods, such as milk (43%), wine/beer (31%), and pork (21%), were also considered causes of symptoms in IBS patients. GI symptoms were also frequently reported after intake of fried and fatty foods (52%). With increasing IBS symptom severity, patients reported more food items responsible for their GI symptoms (P=0.004), and this was also found in patients with more severe somatic symptoms (P<0.0001). Women tended to report more food items causing symptoms than men (P=0.06). A high number of food items causing GI symptoms was also associated with reduced quality of life and this was significant for the following domains: sleep (r=−0.25; P=0.001), energy (r=−0.21; P=0.005), food (r=−0.29; P<0.001), social functioning (r=−0.23; P=0.001), and physical status (r=−0.16; P<0.05). However, the number of food items reported to provoke GI symptoms was unrelated to body mass index, age, IBS subtype, anxiety, depression, or GI-specific anxiety. CONCLUSIONS: The majority of IBS patients believe that certain food items are important triggers of their GI symptoms. This is especially true for foods containing carbohydrates and fat, and also may be relevant for histamine-releasing food items and foods rich in biogenic amines. Self-reported food intolerance is associated with high symptom burden and reduced quality of life.
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33.
  • Cajander, Per, 1976- (author)
  • Risk of pulmonary aspiration during anesthesia and sedation
  • 2023
  • Doctoral thesis (other academic/artistic)abstract
    • Pulmonary aspiration is a feared complication in anesthesia practice. Even if it is a rare event it is the most common cause of anesthesia related death. There are two different types of pulmonary aspiration, macroaspirationwhere large amounts of gastric content are inhaled to the lungs, and the silent, often unnoticed, microaspiration, where small amounts of gastric or oropharyngeal contents are aspirated. Micro aspirations is much more common and can occur at any time during the perioperative period, presenting as postoperative pulmonary complications, often several days after the anesthesia procedure. Human physiology features multiple mechanisms of protection against pulmonary aspiration, including the esophageal sphincters that prevent gastric regurgitation and complex laryngeal reflex systems protecting the airway. An additional vital defense against pulmonary aspiration is an intact swallowing function, with dysphagia being the primary cause of aspiration pneumonia. Anesthetic agents affect these protective mechanisms to various extent.The aim of this thesis was to study the effects of sedative agents on swallowing function, and different ventilatory techniques during anesthesia induction in healthy volunteers. In study I, the use of positive end expiratory pressure during mask ventilation after anesthesia induction was studied in regard of risk of gastric insufflation. In study II and IV the pharmacological effects of the opioid remifentanil on swallowing function were studied. Study III was the first study on effects of dexmedetomidine on human swallowing physiology. The experiments in this thesis has led to a deeper understanding in how different anesthetic agents affects the physiological protective mechanisms against pulmonary aspiration, both during anesthesia induction and sedation. The findings may facilitate clinical decisions, leading to better risk management in terms of macroaspiration during anesthesia and sedation, and postoperative pulmonary complications related to microaspirations.
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34.
  • 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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35.
  • Clevers, Egbert, et al. (author)
  • Development of Irritable Bowel Syndrome Features Over a 5-year Period
  • 2018
  • In: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 16:8
  • Journal article (peer-reviewed)abstract
    • BACKGROUND & AIMS: There are few data from longitudinal studies of the gastrointestinal and psychologic features of irritable bowel syndrome (IBS). We studied within-person correlations among features of IBS, along with progression of gastrointestinal (GI) symptoms and quality of life, and factors associated with changes over time. METHODS: We performed a longitudinal study of 276 patients with IBS in Sweden (70% female; ages, 19-76 years) who completed questionnaires, each year for 5 years, about their GI symptom severity, quality of life, GI-specific anxiety, general anxiety, depression, and coping resources. We performed within-person correlation analyses, latent class growth analysis, and random-intercept cross-lagged panel analysis. RESULTS: Within-person correlations with GI symptom severity were strongest for quality of life (r = -0.56) and GI-specific anxiety (r = 0.47). Progression of GI symptom severity was defined based on 3 classes; the class with the highest mean levels of GI, depression, and (GI-specific) anxiety symptoms at baseline did not improve over the 5-year period, contrary to the other classes. GI-specific anxiety was associated with an increase in GI symptom severity and decrease in quality of life 1 year later (P < .05) but other features of IBS were not. CONCLUSIONS: In a 5-year study of patients with IBS in Sweden, we found 3 classes of GI symptom development. We found levels of GI-specific anxiety to associate with GI symptom severity and quality of life 1 year later. Clinicians should be aware of GI-specific anxiety in patients with IBS, to identify patients at risk for lack of long-term symptom improvement with standard medical treatment.
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36.
  • Clevers, Egbert, et al. (author)
  • Factor Analysis Defines Distinct Upper and Lower Gastrointestinal Symptom Groups Compatible With Rome IV Criteria in a Population-based Study
  • 2018
  • In: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565. ; 16:8
  • Journal article (peer-reviewed)abstract
    • BACKGROUND & AIMS: The Rome IV criteria define functional gastrointestinal (GI) disorders by specific combinations of symptoms. It is possible to empirically evaluate these symptom combinations by factor analysis (a statistical procedure that groups variables that correlate). However, this analysis has not been performed for the Rome IV criteria, and factor analyses based on the previous versions of the Rome criteria did not use population-based data. We therefore investigated symptom grouping by the Rome IV questionnaire using factor analysis of a population-based sample. METHODS: The Rome IV questionnaire was completed online in English by 5931 respondents from the United Kingdom, United States, and Canada (49% female, age range, 18-92 years). We performed an exploratory factor analysis on the Rome IV questions. Next, we performed a confirmatory factor analysis to compare the exploratory factor result to that of the Rome IV criteria. RESULTS: The exploratory factor analysis identified 8 factors that accounted for 45% of the variance in response: constipation, diarrhea, irritable bowel syndrome, abdominal pain, heartburn, nausea or vomiting, globus, and other upper GI symptoms. Most factors corresponded to distinct functional GI disorders defined by the Rome IV criteria-exceptions included abdominal pain and upper GI symptoms. In confirmatory factor analysis, the exploratory model fitted slightly better than that based on the Rome IV criteria (root mean square error of approximation, 0.063 vs 0.077). CONCLUSIONS: We used factor analysis to identify distinct upper and lower GI symptom groups that are compatible with the Rome IV criteria. Our findings support the use of the Rome IV criteria in research and clinical practice as a basis for development of diagnostics and management of patients.
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37.
  • 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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38.
  • Clevers, Egbert, et al. (author)
  • Health problems associated with irritable bowel syndrome: analysis of a primary care registry
  • 2018
  • In: Alimentary Pharmacology & Therapeutics. - : Wiley. - 0269-2813. ; 47:10, s. 1349-1357
  • Journal article (peer-reviewed)abstract
    • Background: Associations between irritable bowel syndrome and other health problems have been described, but comprehensive reports are missing, especially in primary care. Aims: To investigate which health problems are associated with irritable bowel syndrome, how they cluster together and when they are typically diagnosed relative to irritable bowel syndrome. Methods: We used Intego, a general practice registry in Flanders, Belgium. Patients with an irritable bowel syndrome diagnosis (n=13701) were matched with controls without gastrointestinal diagnosis and controls with organic gastrointestinal disease. Long-term prevalences of 680 symptoms and diagnoses were compared between patients and controls. Results were summarised using functional enrichment analysis and visualised in a network and we calculated incidence rate ratios in the 10 years before and after the irritable bowel syndrome diagnosis for the network's key components. Results: Various symptoms and infections, but not neoplasms, were enriched in irritable bowel syndrome patients compared to both control groups. We characterised the comorbidities of irritable bowel syndrome as psychosocial health problems, urogenital symptoms and infections, musculoskeletal symptoms and other somatic symptoms. These had a uniform incidence in the years around the irritable bowel syndrome diagnosis, and did not structurally precede or follow irritable bowel syndrome. Conclusions: Irritable bowel syndrome shares long-term associations with psychosocial health problems, urogenital symptoms and infections, musculoskeletal symptoms and other somatic symptoms in primary care. Clinicians are encouraged to take comorbidities into account when diagnosing and managing irritable bowel syndrome, as this may have important treatment implications.
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39.
  • Clevers, Egbert, et al. (author)
  • Relations between food intake, psychological distress, and gastrointestinal symptoms: A diary study
  • 2019
  • In: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 7:7, s. 965-973
  • Journal article (peer-reviewed)abstract
    • Background: Gastrointestinal symptoms can be triggered by food intake and psychological distress, but individual-level research on food-symptom and stress-symptom associations is scarce. Objective: We aimed to identify associations between food intake, psychological distress and gastrointestinal symptoms, and their implications for personalised clinical management. Methods: Through the mobile phone application mySymptoms, 163 users kept, for a median of five weeks, a diary of food intake, psychological distress and gastrointestinal symptoms. We quantified associations between these on the individual level. The presence of individual-level associations was compared over latent classes of daily symptom patterns. Results: Various gastrointestinal symptoms had demonstrable food-symptom associations (heartburn: 73%, discomfort: 67%, diarrhoea: 57%, bloating: 53%, and gas: 48%). Food-symptom associations for pain in the abdomen (33%) were concentrated in the latent class of individuals with pain in the morning (68%), rather than those with pain in the evening and night (27% and 10%, respectively, p < 0.001). Stress-symptom relations were also found, although only 18% of individuals reported psychological distress. Conclusion: Personal food-symptom and stress-symptom relations can be detected, and may translate into specific daily symptom patterns. A next step will be to let personal food-symptom and stress-symptom relations serve as the basis for personalised clinical management.
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40.
  • 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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41.
  • 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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42.
  • Derrien, M., et al. (author)
  • Fasting breath H-2 and gut microbiota metabolic potential are associated with the response to a fermented milk product in irritable bowel syndrome
  • 2019
  • In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 14:4
  • Journal article (peer-reviewed)abstract
    • Objectives Aim of this study was to assess the effect of a fermented milk product containing Bifidobacterium lactis CNCM I-2494 (FMP) on gastrointestinal (GI) symptoms and exhaled H-2 and CH4 during a nutrient and lactulose challenge in patients with irritable bowel syndrome (IBS). We included 125 patients with IBS (Rome III). Fasted subjects were served a 400ml liquid test meal containing 25g lactulose. The intensity of eight GI symptoms and the amount of exhaled H-2 and CH4 were assessed before and during 4h after meal intake. The challenge was repeated after 14 days consumption of FMP or a control product in a double-blind, randomized, parallel design. The metabolic potential of fecal microbiota was profiled using 16S MiSeq analysis of samples obtained before and after the intervention. 106 patients with IBS were randomized. No difference between FMP or control groups was found on GI symptoms or breath H-2 and CH4 in the whole cohort. A post-hoc analysis in patients stratified according to their fasting H-2 levels showed that in high H-2 producers (fasting H-2 level >= 10ppm, n = 35), FMP consumption reduced fasting H-2 levels (p = 0.003) and H-2 production during the challenge (p = 0.002) and tended to decrease GI discomfort (p = 0.05) vs. control product. The Prevotella /Bacteroides metabolic potential at baseline was higher in high H-2 producers (p<0.05) vs. low H-2 producers and FMP consumption reduced this ratio (p<0.05) vs. control product. The response to a fermented milk product containing Bifidobacterium lactis CNCM I-2494 (FMP) in patients with IBS seems to be associated with the metabolic potential of the gut microbiota.
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43.
  • Drossman, D. A., et al. (author)
  • Neuromodulators for Functional Gastrointestinal Disorders (Disorders of Gut−Brain Interaction): A Rome Foundation Working Team Report
  • 2018
  • In: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 154:4
  • Journal article (peer-reviewed)abstract
    • Background & Aims: Central neuromodulators (antidepressants, antipsychotics, and other central nervous system−targeted medications) are increasingly used for treatment of functional gastrointestinal disorders (FGIDs), now recognized as disorders of gut−brain interaction. However, the available evidence and guidance for the use of central neuromodulators in these conditions is scanty and incomplete. In this Rome Foundation Working Team report, a multidisciplinary team summarized available research evidence and clinical experience to provide guidance and treatment recommendations. Methods: The working team summarized the literature on the pharmacology of central neuromodulators and their effects on gastrointestinal sensorimotor function and conducted an evidence-based review on their use for treating FGID syndromes. Because of the paucity of data for FGIDs, we included data for non-gastrointestinal painful disorders and specific symptoms of pain, nausea, and vomiting. This information was combined into a final document comprising a synthesis of available evidence and recommendations for clinical use guided by the research and clinical experience of the experts on the committee. Results: The evidence-based review on neuromodulators in FGID, restricted by the limited available controlled trials, was integrated with open-label studies and case series, along with the experience of experts to create recommendations using a consensus (Delphi) approach. Due to the diversity of conditions and complexity of treatment options, specific recommendations were generated for different FGIDs. However, some general recommendations include: (1) low to modest dosages of tricyclic antidepressants provide the most convincing evidence of benefit for treating chronic gastrointestinal pain and painful FGIDs and serotonin noradrenergic reuptake inhibitors can also be recommended, though further studies are needed; (2) augmentation, that is, adding a second treatment (adding quetiapine, aripiprazole, buspirone α2δ ligand agents) is recommended when a single medication is unsuccessful or produces side effects at higher dosages; (3) treatment should be continued for 6−12 months to potentially prevent relapse; and (4) implementation of successful treatment requires effective communication skills to improve patient acceptance and adherence, and to optimize the patient−provider relationship. Conclusions: Based on systematic and selectively focused review and the consensus of a multidisciplinary panel, we have provided summary information and guidelines for the use of central neuromodulators in the treatment of chronic gastrointestinal symptoms and FGIDs. Further studies are needed to confirm and refine these recommendations.
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44.
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45.
  • Ek, Weronica E, et al. (author)
  • Germline genetic contributions to risk for esophageal adenocarcinoma, barrett's esophagus, and gastroesophageal reflux
  • 2013
  • In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 105:22, s. 1711-1718
  • Journal article (peer-reviewed)abstract
    • Background Esophageal adenocarcinoma (EA) is an increasingly common cancer with poor survival. Barrett's esophagus (BE) is the main precursor to EA, and every year 0.12% to 0.5% of BE patients progress to EA. BE typically arises on a background of chronic gastroesophageal reflux (GERD), one of the risk factors for EA. Methods We used genome-wide association data to investigate the genetic architecture underlying GERD, BE, and EA. We applied a method to estimate the variance explained (array heritability, h2 g) and the genetic correlation (rg) between GERD, BE, and EA by considering all single nucleotide polymorphisms (SNPs) simultaneously. We also estimated the polygenic overlap between GERD, BE, and EA using a prediction approach. All tests were twosided, except in the case of variance-explained estimation where one-sided tests were used. Results We estimated a statistically significant genetic variance explained for BE (h2 g = 35%; standard error [SE] = 6%; one-sided P = 1 × 10-9) and for EA (h2 g = 25 %; SE = 5%; one-sided P = 2 × 10-7). The genetic correlation between BE and EA was found to be high (rg = 1.0; SE = 0.37). We also estimated a statistically significant polygenic overlap between BE and EA (one-sided P = 1 × 10-6), which suggests, together with the high genetic correlation, that shared genes underlie the development of BE and EA. Conversely, no statistically significant results were obtained for GERD. Conclusions We have demonstrated that risk to BE and EA is influenced by many germline genetic variants of small effect and that shared polygenic effects contribute to risk of these two diseases. © The Author 2013.
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46.
  • Emmanuel, A., et al. (author)
  • Impact of symptom severity in patients with diarrhoea-predominant irritable bowel syndrome (IBS-D): results from two separate surveys of HCPs and patients with IBS-D
  • 2020
  • In: BMC Gastroenterology. - : Springer Science and Business Media LLC. - 1471-230X. ; 20:1
  • Journal article (peer-reviewed)abstract
    • Background Management of diarrhoea-predominant irritable bowel syndrome (IBS-D) is generally based on patient-reported symptoms; however, limited information on symptom severity exists. The objective of the study was to assess the impact of IBS-D severity on patient burden and patient and healthcare professional attitudes towards IBS. Methods We conducted two web-based surveys of healthcare professionals and patients from Australia, Canada and Europe. We analysed patient characteristics and attitudes by IBS-D severity, which was assessed retrospectively using a composite of four variables: worst abdominal pain, IBS symptom frequency, Bristol Stool Form Scale and quality of life. Results Of 679 healthcare professional respondents, one-third routinely classified patients by severity. The patient survey was completed by 513 patients with mild (26%), moderate (33%) and severe (41%) IBS-D, classified using the composite scale. Age, sex and treatment satisfaction did not change with severity; however, 19% of patients classified with severe IBS-D agreed with the statement: 'When my IBS is bad, I wish I was dead' versus 4 and 7% of patients with mild and moderate IBS-D, respectively (p < 0.05). Significantly more patients classified with severe IBS-D reported medication use versus mild IBS-D. Conclusion Compared with milder symptoms, severe IBS-D was associated with increased medication use and a negative perspective of IBS-D. This highlights the need for a validated severity scale to inform treatment decisions.
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47.
  • Farre, R., et al. (author)
  • In Functional Dyspepsia, Hypersensitivity to Postprandial Distention Correlates With Meal-Related Symptom Severity
  • 2013
  • In: Gastroenterology. - : Elsevier BV. - 0016-5085. ; 145:3, s. 566-573
  • Journal article (peer-reviewed)abstract
    • BACKGROUND & AIMS: Hypersensitivity to gastric distention, an important feature of functional dyspepsia, is assessed by stepwise balloon distention of the proximal stomach in fasting patients. However, symptoms of functional dyspepsia are often worse after a meal, so studies of postprandial balloon distentions might be more relevant. We compared the effects of fasting and postprandial stomach distention in patients with functional dyspepsia. METHODS: Twenty healthy controls and 62 patients with functional dyspepsia participated in a gastric barostat study at Leuven University Hospital with graded isobaric distentions before and after a liquid meal. On a separate day, all patients underwent a gastric emptying breath test with assessment of postprandial severity of 6 different dyspeptic symptoms scored at 15-minute intervals for 4 hours. For each symptom, a meal-related severity score was obtained by adding all scores; the cumulative symptom score (CSS) was obtained by adding individual symptom severity scores. RESULTS: In patients, but not in controls, postprandial sensitivity to balloon distention was significantly greater than fasting sensitivity. The CSS and individual symptom scores did not differ between patients with normal or hypersensitivity to fasting distention, but patients who were hypersensitive to postprandial distention had a significantly higher CSS, along with scores for postprandial fullness, bloating, and nausea (all P < .05). On multivariate analysis, hypersensitivity to postprandial distention was associated with hypersensitivity to fasting distention and with impaired accommodation to a meal. CONCLUSIONS: Postprandial, but not fasting, distention thresholds are related to the severity of meal-related symptoms in patients with functional dyspepsia.
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48.
  • Frändemark, Åsa, 1988, et al. (author)
  • Fatigue: A distressing symptom for patients with irritable bowel syndrome
  • 2017
  • In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 29:1
  • Journal article (peer-reviewed)abstract
    • Background: Fatigue is a frequent symptom in patients with irritable bowel syndrome (IBS), and is associated with poor quality of life. However, few studies have evaluated its impact on daily life or the perceived distress it can cause. Using a multi-methods approach, this study describes the impact and manifestations of fatigue in patients with IBS and investigates the relationship between fatigue severity and illness-related and health-promoting factors. Methods: A total of 160 patients with IBS completed self-reported questionnaires assessing fatigue, gastrointestinal symptoms, psychological distress, and sense of coherence. Fatigue was assessed with the Fatigue Impact Scale, which also includes structured and open-ended questions which were analyzed with a deductive qualitative analysis. Patients were classified as having severe, moderate, or mild fatigue based on frequency, distress and impact on daily life. Key Results: The open-ended questions revealed a multidimensional impact on life. Fatigue mainly interfered with the ability to perform physical activities, work, and domestic work, and the ability to interact socially. Decreased stamina was evident, along with strategies to limit the bodily consequences of tiredness. Severe fatigue was accompanied by more severe IBS symptoms, anxiety and depression and lower sense of coherence. Conclusions & Inferences: Fatigue is a distressing symptom which occurs in a sizeable proportion of patients with IBS. It affects life in a multidimensional way, with poor bodily stamina being the most prominent feature. Fatigue, along with sense of coherence, depression and anxiety, needs to be assessed, confirmed and targeted for interventions.
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49.
  • 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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