| 1. |
- Klingberg, Eva, et al.
(författare)
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A distinct gut microbiota composition in patients with ankylosing spondylitis is associated with increased levels of fecal calprotectin
- 2019
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Ankylosing spondylitis (AS) shares many characteristics with inflammatory bowel disease (IBD). Intestinal microbiota most likely plays an important role in the development of IBDs and may also be involved in the pathogenesis of AS. We aimed to define and compare the fecal microbiota composition in patients with AS, ulcerative colitis (UC), and healthy controls (HC) and to determine relationships between fecal microbiota, fecal calprotectin, and disease-related variables in AS. Methods Fecal microbiota composition was assessed with GA-map (TM) Dysbiosis Test (Genetic Analysis, Oslo, Norway), which also reports the degree of deviation of the microbiota composition compared with a healthy control population, a Dysbiosis Index (DI) score 1-5. The AS patients were assessed with questionnaires, back mobility tests, fecal calprotectin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Results Totally, 150 patients with AS (55% men, median age 55.5 years, median BASDAI 3.2), 18 patients with UC (56% men, median age 30.5 years), and 17 HC (65% men, median age 22 years) were included. Principal component analysis showed highly separate clustering of fecal microbiota from the patients with AS, UC, and HC. Compared with HC, fecal microbiota in AS was characterized by a higher abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcus species, and Actinobacteria, but lower abundance of Bacteroides and Lachnospiraceae. Further, fecal microbiota composition differed between patients with normal (<= 50 mg/kg, n = 57) and increased (>= 200 mg/kg, n = 36) fecal calprotectin. Patients with increased fecal calprotectin had lower abundance of bacteria with anti-inflammatory properties such as Faecalibacterium prausnitzii and Clostridium and higher abundance of the genus Streptococcus. No association was found between the fecal microbiota composition and HLAB27 status, disease activity, function, or medication. Dysbiosis (defined as DI >= 3) was found in 87% of AS patients. Conclusions Patients with AS have a distinct fecal microbiota signature, which is linked to fecal calprotectin levels, a marker of intestinal inflammation, but not to other clinical parameters. These findings suggest a local interplay between intestinal microbiota and gut inflammation in AS.
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| 2. |
- Klingberg, Eva, et al.
(författare)
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A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis
- 2017
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with ankylosing spondylitis (AS) are at increased risk of developing inflammatory bowel disease (IBD). We aimed to determine the variation in fecal calprotectin in AS over 5 years in relation to disease activity and medication and also to study the incidence of and predictors for development of IBD. Methods: Fecal calprotectin was assessed at baseline (n = 204) and at 5-year follow-up (n = 164). The patients answered questionnaires and underwent clinical evaluations. At baseline and at 5-year follow-up, ileocolonoscopy was performed in patients with fecal calprotectin = 500 mg/kg and = 200 mg/kg, respectively. The medical records were checked for diagnoses of IBD during the follow-up period. Results: Fecal calprotectin > 50 mg/kg was found in two-thirds of the patients at both study visits. In 80% of the patients, fecal calprotectin changed by < 200 mg/kg between the two measuring points. Baseline fecal calprotectin was positively correlated with Ankylosing Spondylitis Disease Activity Score based on C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin at 5-year follow-up. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with higher fecal calprotectin, and 3-week cessation of NSAIDs resulted in a drop of a median 116 mg/kg in fecal calprotectin. The use of tumor necrosis factor (TNF) blockers was associated with lower fecal calprotectin at both visits, but the users of TNF receptor fusion proteins had significantly higher fecal calprotectin than users of anti-TNF antibodies at 5-year follow-up. The 5-year incidence of Crohn's disease (CD) was 1.5% and was predicted by high fecal calprotectin. Conclusions: Fecal calprotectin was elevated in a majority of the patients and was associated with disease activity and medication at both visits. CD developed in 1.5% of the patients with AS, and a high fecal calprotectin was the main predictor thereof. The results support a link between inflammation in the gut and the musculoskeletal system in AS. We propose that fecal calprotectin may be a potential biomarker to identify patients with AS at risk of developing IBD
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| 3. |
- Moraes Holst, Luiza, et al.
(författare)
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Downregulated Mucosal Autophagy, Alpha Kinase-1 and IL-17 Signaling Pathways in Active and Quiescent Ulcerative Colitis
- 2022
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Ingår i: Clinical and Experimental Gastroenterology. - : DOVE MEDICAL PRESS LTD. - 1178-7023. ; 15, s. 129-144
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Moraes, Luiza, et al.
(författare)
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Systemic Inflammatory Protein Profiles Distinguish Irritable Bowel Syndrome (IBS) and Ulcerative Colitis, Irrespective of Inflammation or IBS-Like Symptoms.
- 2020
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Ingår i: Inflammatory bowel diseases. - : Oxford University Press (OUP). - 1536-4844 .- 1078-0998. ; 26:6, s. 874-884
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Tidskriftsartikel (refereegranskat)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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| 5. |
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| 6. |
- Cardeno, A., et al.
(författare)
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The unsaponifiable fraction of extra virgin olive oil promotes apoptosis and attenuates activation and homing properties of T cells from patients with inflammatory bowel disease
- 2014
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Ingår i: Food Chemistry. - : Elsevier BV. - 0308-8146. ; 161, s. 353-360
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Tidskriftsartikel (refereegranskat)abstract
- The unsaponifiable fraction (UF) of extra virgin olive oil (EV00) possesses anti-inflammatory properties and exerts preventative effects in murine models of inflammatory bowel disease (IBD). The present study was designed to determine the in vitro effects of UF on blood and intestinal T cells from IBD patients and healthy subjects. The T cell phenotype was investigated by flow cytometry and cytokine secretion was determined by ELISA. The presence of UF of EVO0 promoted apoptosis and attenuated activation of intestinal and blood T cells isolated from IBD patients, decreasing the frequency of CD69(+) and CD25(+) T cells and, also, the secretion of IFN-gamma. Moreover, UF reduced the expression of the gut homing receptor integrin beta 7 on blood T cells from IBD patients. In conclusion, UF modulates the activity and the gut homing capacity of T cells, and might therefore be considered as a dietary complement with an anti-inflammatory role in IBD patients. (C) 2014 Published by Elsevier Ltd.
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| 7. |
- Dahlén, Rahil, et al.
(författare)
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Global mucosal and serum cytokine profile in patients with ulcerative colitis undergoing anti-TNF therapy
- 2015
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 50:9, s. 1118-1126
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective. The knowledge of the effects of anti-tumour necrosis factor (TNF) treatment on the global cytokine profile in patients with ulcerative colitis (UC) is limited. A better understanding of these mechanisms could improve the ability to select patients that should undergo the therapy. Therefore, the aim was to determine the global mucosal and serum cytokine profile before and during induction therapy with anti-TNF in UC patients. Materials and methods. In total, mucosal biopsies (n = 28) and serum samples (n = 42) were collected from UC patients (total n = 48) before anti-TNF therapy. At week 14 response to the therapy was evaluated and again mucosal biopsies (n = 14) and serum samples (n = 42) were collected. Quantitative real-time PCR was used to determine mucosal cytokine mRNA expression and the MSD MULTI-ARRAY assay system platform was used for analysis of cytokines in serum. The global cytokine profile was evaluated by multivariate factor analysis. Results. At baseline, the global profile of mucosal cytokine mRNA expression and serum cytokines discriminated therapy responders from non-responders. Responders had lower mucosal mRNA expression of interleukin 1 beta (IL-1 beta), IL-17A, IL-6 and interferon gamma (IFN-gamma) than non-responders. Fourteen weeks after therapy start mucosal IL-1 beta and IL-6 were down-regulated in therapy responders but not in non-responders. At week 14, serum levels of IL-6 were decreased in therapy responders whereas IFN-gamma and IL-12p70 were increased in non-responders. Conclusions. Our data suggest that patients with a therapy failure have a more severe pro-inflammatory cytokine profile before start of anti-TNF treatment, which is less well suppressed by the treatment as compared to therapy responders.
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| 8. |
- Dahlén, Rahil, et al.
(författare)
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Infliximab Inhibits Activation and Effector Functions of Peripheral Blood T Cells in vitro from Patients with Clinically Active Ulcerative Colitis
- 2013
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475. ; 78:3, s. 275-284
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Tidskriftsartikel (refereegranskat)abstract
- Many patients with inflammatory bowel disease (IBD) are undergoing therapy with infliximab, an antibody specific for TNF. However, the exact mechanisms of action of infliximab are not completely understood. The aim of this study was to determine the in vitro effects of infliximab on blood T cells derived from anti-TNF therapy-naive ulcerative colitis (UC) patients with clinically active disease. Peripheral blood mononuclear cells were stimulated polyclonally or by antigen in the presence or absence of infliximab. The T cell phenotype was investigated by flow cytometry, cytokine secretion was determined by ELISA, and cell proliferation was determined by thymidine assay or CFSE dye. Presence of infliximab resulted in reduced expression of CD25 in CD4(+) and CD8(+) T cell populations and inhibited secretion of IFN-, IL-13, IL-17A, TNF as well as granzyme A. Infliximab also suppressed CD4(+) and CD8(+) T cell proliferation. These effects of infliximab were recorded both in T cells activated by polyclonal and antigen-specific stimulation. The effects of infliximab on T cell apoptosis and induction of FOXP3(+)CD4(+) T regulatory cells were ambiguous and depended on the originating cellular source and/or the stimulation mode and strength. In conclusion, infliximab is able to reduce T cell activation as measured by CD25, proliferation and cytokine secretion in vitro from UC patients with clinically active disease. These data suggest that suppression of T cell activity may be important for infliximab-mediated disease remission in patients with UC.
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| 9. |
- Forshammar, Johan, et al.
(författare)
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A pilot study of colonic B cell pattern in irritable bowel syndrome
- 2008
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 43:12, s. 1461-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Low-grade gastrointestinal inflammation has been reported in patients with irritable bowel syndrome (IBS). However, the colonic B-cell pattern has not been investigated in these patients. Therefore, the aim of this pilot study was to investigate the distribution and isotype of immunoglobulin-producing B cells in the colonic mucosa of IBS patients. MATERIAL AND METHODS: Patients with IBS (n=12) fulfilling the Rome II criteria were compared with controls (n=11). Immunohistochemical staining of biopsies from the sigmoid and ascending colon was performed. RESULTS: The number of IgA(+) B cells in the ascending colon was lower in IBS patients than in controls (p=0.039). Furthermore, unlike controls, IBS patients had a reduction of IgA(+) B cells in the ascending colon relative to the sigmoid colon (p=0.04). Neither the IgG(+), nor the IgM(+) colonic B-cell numbers differed between IBS patients and controls. Very few colonic IgE(+) cells were detected and there was no difference between the two subject groups. CONCLUSIONS: The reduced number of colonic IgA(+) B cells in IBS patients suggests that the disorder may be associated with a modified gut immune defence. Whether this phenomenon is causally related to symptoms remains unknown and merits further investigation in a larger group of patients.
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| 10. |
- Gunterberg, Veronica, et al.
(författare)
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Autonomic nervous system function predicts the inflammatory response over three years in newly diagnosed ulcerative colitis patients
- 2016
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 28:11, s. 1655-1662
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe autonomic nervous system (ANS) modulates intestinal inflammation in animal models. Human evidence confirming such modulating influence is limited. We aimed to investigate whether ANS function is associated with inflammatory parameters at disease onset, and whether it predicts the evolution of inflammation in patients with ulcerative colitis (UC). MethodsWe prospectively monitored 51 patients from onset of UC for 3 years. Upon remission of the onset flare, ANS activity was assessed by heart rate variability analysis and compared with healthy controls. Inflammatory parameters in blood, stool, and colonic biopsies obtained at onset and during follow-up visits were analyzed. Generalized linear models were used to test cross-sectional associations between ANS activity and inflammatory parameters at onset; linear mixed models were used to test whether ANS function at onset predicted the evolution of inflammation over the following 3 years. Key ResultsSympathovagal balance was different in UC patients compared to healthy controls, and cross-sectional associated with higher levels of systemic (erythrocyte sedimentation rate [ESR], CRP, TNF-, IFN-) and mucosal inflammation (interleukin-8, IFN-) at onset. Conversely, a negative cross-sectional association with parasympathetic activity was found for ESR & TNF-. Longitudinally, parasympathetic activity at onset predicted systemic (ESR, WBC), but not mucosal inflammation during follow-up. Conclusions & InferencesThis study further strengthens the association between the ANS system and intestinal inflammation previously found in animal models and recently in patients with inflammatory bowel disease. These results may have important implications for the pathogenesis and treatment of UC.
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| 11. |
- Jakobsson, G. L., et al.
(författare)
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Validating inflammatory bowel disease (IBD) in the Swedish National Patient Register and the Swedish Quality Register for IBD (SWIBREG)
- 2017
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 52:2, s. 216-221
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Tidskriftsartikel (refereegranskat)abstract
- Background: Both the Swedish National Patient Register (NPR) and the Swedish Quality Register for inflammatory bowel disease (IBD, SWIBREG) are important sources of research data and information. However, the validity of a diagnosis of IBD in these registers is unknown. Methods: Medical charts of 129 randomly selected patients from the NPR and 165 patients registered both in SWIBREG and the NPR were reviewed. Patients were classified according to standardized criteria for ulcerative colitis (UC), Crohn's disease (CD), or IBD unclassified (IBD-U). Positive predictive values (PPVs) for UC, CD, IBD-U (only SWIBREG), or having any form of IBD were then calculated. Results: For cases with >= 2 diagnoses of IBD in the NPR (hospitalizations or non-primary care outpatient visits), the PPV was 93% (95% CI: 87-97) for any IBD, 79% (66-88) for UC and 72% (60-82) for CD. In UC patients with >= 2 UC diagnoses but never a CD diagnosis, the PPV increased to 90% (77-97). The PPV for CD in patients with >= 2 CD diagnoses but never a UC diagnosis was 81% (67-91)). Combining data from SWIBREG (>= 1 record) and the NPR (>= 1 record), the PPV was 99% for any IBD (97-100), 96% (89-99) for UC, and 90% (82-96) for CD. Conclusion: The validity of the UC, CD, and IBD diagnoses is high in the NPR but even higher when cases were identified both in SWIBREG and the NPR. These results underline the need for a well-functioning Swedish Quality Register for IBD as a complement to the NPR.
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| 12. |
- Johannesson, Elisabet, et al.
(författare)
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Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial.
- 2011
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Ingår i: The American journal of gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 1572-0241 .- 0002-9270. ; 106:5, s. 915-22
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity has been shown to be effective in the treatment of conditions, such as fibromyalgia and depression. Although these conditions are associated with irritable bowel syndrome (IBS), no study has assessed the effect of physical activity on gastrointestinal (GI) symptoms in IBS. The aim was to study the effect of physical activity on symptoms in IBS.
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| 13. |
- Jonefjäll, Börje, et al.
(författare)
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Characterization of IBS-like symptoms in patients with ulcerative colitis in clinical remission
- 2013
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 25:9
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Tidskriftsartikel (refereegranskat)abstract
- Background Gastrointestinal symptoms compatible with Irritable Bowel Syndrome (IBS) are common in patients with inflammatory bowel disease. It has been suggested that these symptoms are a reflection of occult inflammation rather than coexisting IBS. The aim of this study was to characterize IBS-like symptoms in patients with Ulcerative Colitis (UC) in clinical remission by assessing inflammatory markers, psychological symptoms, and quality of life. Methods Ninety-four patients with new onset of UC were followed prospectively during 3 years with yearly follow-up visits. The patients completed self-administrated questionnaires. Fecal calprotectin was used as an inflammatory biomarker. Remission was defined as a total Mayo-score <= 2 and an endoscopic subscore <= 1, with no relapse during the 3-month period prior to visit. Key Results The prevalence of patients that fulfilled Rome II criteria for IBS among UC patients in remission was 11% at visit 1, 23% at visit 2, and 17% at visit 3. When comparing UC patients in remission with and without IBS-like symptom, patients with IBS-like symptoms had more severe gastrointestinal symptoms, tendencies toward more severe psychological symptoms and reduced levels of quality of life, but the calprotectin levels did not differ between the two groups. Conclusions & Inferences IBS-like symptoms are common in patients with UC in clinical remission and these fluctuate over time. The symptoms are associated with poor psychological wellbeing and reduced quality of life, and do not seem to be a reflection of low-grade inflammatory activity.
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| 14. |
- Jonefjäll, Börje, et al.
(författare)
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IBS-like Symptoms in Patients with Ulcerative Colitis in Deep Remission Are Associated with Increased Levels of Serum Cytokines and Poor Psychological Well-being
- 2016
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998. ; 22:11, s. 2630-2640
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Tidskriftsartikel (refereegranskat)abstract
- Background:Gastrointestinal symptoms (GI) compatible with irritable bowel syndrome (IBS) are common in patients with ulcerative colitis (UC) in remission. The causes of these symptoms remain to be clarified. Our aim was to investigate prevalence and factors associated with IBS-like symptoms in patients with UC in deep remission.Methods:We included 298 patients with UC and used Mayo score, sigmoidoscopy, and fecal calprotectin to define deep remission versus active disease. Presence of IBS-like symptoms according to the Rome III criteria, severity of GI, extraintestinal and psychological symptoms, stress levels, and quality of life were measured with validated questionnaires. Serum cytokines and high-sensitive C-reactive peptide were determined.Results:The criteria for deep remission was fulfilled by 132 patients (44%) and 24 of these fulfilled the Rome III criteria for IBS (18%). Patients with UC in deep remission with IBS-like symptoms had comparable levels of GI symptoms, non-GI somatic symptoms, and quality of life as patients with active UC. The patients with UC in deep remission with IBS-like symptoms had similar levels of fecal calprotectin as patients in deep remission without IBS-like symptoms (18 versus 31 g/g, P = 0.11), but higher levels of serum cytokines (interleukin [IL]-1, IL-6, IL-13, IL-10 and IL-8, P < 0.05) and higher levels of anxiety (P < 0.001), depression (P = 0.02) and perceived stress (P = 0.03).Conclusions:IBS-like symptoms in patients with UC in deep remission are common, but not as prevalent as previously reported. Poor psychological well-being and increased serum cytokine levels, but not colonic low-grade inflammation, were associated with IBS-like symptoms.
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| 15. |
- Jonefjäll, Börje, et al.
(författare)
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Psychological distress, iron deficiency, active disease and female gender are independent risk factors for fatigue in patients with ulcerative colitis
- 2018
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Ingår i: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 6:1, s. 148-158
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with ulcerative colitis often report fatigue. Objectives: To investigate prevalence of and risk factors for fatigue in patients with ulcerative colitis with active disease and during deep remission. Methods: In this cross-sectional study, disease activity was evaluated with endoscopy and calprotectin, and patients were classified as having active disease (n=133) or being in deep remission (n=155). Blood samples were analysed to assess anaemia, iron deficiency and systemic immune activity. Patients completed questionnaires to assess fatigue, psychological distress, gastrointestinal symptoms and quality of life. Results: The prevalence of high fatigue (general fatigue >= 13, Multidimensional Fatigue Inventory) was 40% in the full study population. Among patients with high fatigue, female gender and iron deficiency were more prevalent, and these patients had more severe disease activity and reported higher levels of anxiety, depression and decreased quality of life compared with patients with no/mild fatigue. A logistic regression analysis identified probable psychiatric disorder (odds ratio (OR) (confidence interval) 6.1 (3.1-12.2)), iron deficiency (OR 2.5 (1.2-5.1)), active disease (OR 2.2 (1.2-3.9)) and female gender (OR 2.1 (1.1-3.7)) as independent risk factors for high fatigue. Similar results were found concerning psychological distress, gender and quality of life, but immune markers did not differ in patients in deep remission with high vs. no/mild fatigue. Conclusions: Probable psychiatric disorder, iron deficiency, active disease and female gender are independent risk factors for high fatigue in patients with ulcerative colitis. Low-grade immune activity does not seem to be the cause of fatigue among patients in deep remission.
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| 16. |
- Jonefjäll, Börje, et al.
(författare)
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The severity of inflammation at onset of ulcerative colitis is not associated with IBS-like symptoms during clinical remission
- 2015
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press (OUP). - 1873-9946 .- 1876-4479. ; 9:9, s. 776-783
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Symptoms compatible with Irritable bowel syndrome (IBS) are common in patients with ulcerative colitis (UC) in clinical remission. It has been suggested that these symptoms might arise due to post-inflammatory changes comparable with post-infectious IBS. The aim was to study factors at new onset of UC that predict development of IBS-like symptoms during clinical remission. METHODS: In total, 98 patients with new onset of UC were followed prospectively during three years with yearly follow up visits. Data from the first visit at the onset of UC were compared between the group of patients that fulfilled the criteria for IBS while in remission (UCR+IBS) during follow-up and the group that did not (UCR-IBS). RESULTS: Among the UC patients, 87 met the criteria for clinical remission, and 25 (29%) of these reported IBS-like symptoms in remission during follow-up. There was no difference in inflammatory disease activity at the initial flare or prevalence of previous IBS symptoms comparing UCR+IBS and UCR-IBS patients. The UCR+IBS patients reported more severe GI symptoms including abdominal pain during their primary flare. CONCLUSION: The severity and extension of inflammation at onset of UC do not seem to affect the development of IBS-like symptoms in UC patients during clinical remission. The high prevalence of IBS-like symptoms is not explained by pre-existing IBS. UCR+IBS patients reported more severe GI symptoms at disease onset, which might indicate a more sensitive GI tract in this category of patients.
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| 17. |
- Lasson, Anders, et al.
(författare)
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Fecal Calprotectin Levels Predict the Clinical Course in Patients With New Onset of Ulcerative Colitis
- 2013
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Ingår i: Inflammatory Bowel Diseases. - 1078-0998. ; 19:3, s. 576-581
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The clinical course of ulcerative colitis (UC) is unpredictable. During recent years, the ability of fecal biomarkers to predict relapse in inflammatory bowel disease has been evaluated. The objective of this study was to assess fecal calprotectin (FC) as a predictor of disease recurrence in patients with new onset of UC. METHODS: Sixty-nine patients were included. After the initial treatment, patients were followed up after 3 months and then yearly for 3 years. The prognostic role of FC 3 months after the initial therapy was evaluated. RESULTS: The FC levels 3 months after the diagnosis were higher in patients experiencing a relapsing disease course compared with those with a mild disease course during 1 year (median, 263; interquartile range [IQR], 100-634 μg/g versus median, 102; IQR, 38-225 μg/g; P = 0.009) and 3 years of follow-up (median, 280; IQR, 102-622 μg/g versus median, 118; IQR, 39-219 μg/g; P = 0.01). The area under the receiver operating characteristic curves using calprotectin to predict a relapsing disease course during 1 year and 3 years were 0.69 (95% confidence interval, 0.56-0.82) and 0.70 (95% confidence interval, 0.57-0.83), respectively. In the Kaplan-Meier survival analysis, a FC level >262 μg/g was associated with an increased risk of a relapsing disease course during the study period (P = 0.003). In logistic regression analysis, only FC and age were found to be independent predictors of having a relapsing disease course. CONCLUSIONS: Levels of FC 3 months after the initial therapy in patients with new onset of UC predict the disease course over the following years, and they are of value in the clinical management of these patients.
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| 18. |
- Lasson, Anders, et al.
(författare)
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Fecal calprotectin one year after ileocaecal resection for Crohn's disease - A comparison with findings at ileocolonoscopy.
- 2014
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Ingår i: Journal of Crohn's & colitis. - : Oxford University Press (OUP). - 1876-4479 .- 1873-9946. ; 8:8, s. 789-795
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Tidskriftsartikel (refereegranskat)abstract
- Ileocaecal resection for Crohn's disease is commonly performed. The severity of endoscopic lesions in the anastomotic area one year postoperatively is considered to reflect the subsequent clinical course. Fecal calprotectin (FC) has been shown to correlate with the findings at ileocolonoscopy in Crohn's disease. The objectives of this study were to assess whether the concentration of FC reflects the endoscopic findings one year after ileocaecal resection and to evaluate the variation of FC in individual patients during 6months prior to the ileocolonoscopy.
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| 19. |
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| 20. |
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| 21. |
- Lebrero-Fernandez, Cristina, et al.
(författare)
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Altered expression of Butyrophilin (BTN) and BTN-like (BTNL) genes in intestinal inflammation and colon cancer
- 2016
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Ingår i: Immunity Inflammation and Disease. - : Wiley. - 2050-4527. ; 4:2, s. 191-200
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Tidskriftsartikel (refereegranskat)abstract
- Several Butyrophilin (BTN) and Btn-like (BTNL) molecules control T lymphocyte responses, and are genetically associated with inflammatory disorders and cancer. In this study, we present a comprehensive expression analysis of human and murine BTN and BTNL genes in conditions associated with intestinal inflammation and cancer. Using real-time PCR, expression of human BTN and BTNL genes was analyzed in samples from patients with ulcerative colitis, irritable bowel syndrome, and colon tumors. Expression of murine Btn and Btnl genes was examined in mouse models of spontaneous colitis (Muc2(-/-)) and intestinal tumorigenesis (Apc(Min/+)). Our analysis indicates a strong association of several of the human genes with ulcerative colitis and colon cancer; while especially BTN1A1, BTN2A2, BTN3A3, and BTNL8 were significantly altered in inflammation, colonic tumors exhibited significantly decreased levels of BTNL2, BTNL3, BTNL8, and BTNL9 as compared to unaffected tissue. Colonic inflammation in Muc2(-/-) mice significantly down-regulated the expression of particularly Btnl1, Btnl4, and Btnl6 mRNA, and intestinal polyps derived from Apc(Min/+) mice displayed altered levels of Btn1a1, Btn2a2, and Btnl1 transcripts. Thus, our data present an association of BTN and BTNL genes with intestinal inflammation and cancer and represent a valuable resource for further studies of this gene family.
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| 22. |
- Ling Lundström, Maria, et al.
(författare)
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Fecal Biomarkers of Neutrophil and Eosinophil Origin Reflect the Response to Biological Therapy and Corticosteroids in Patients With Inflammatory Bowel Disease
- 2023
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Ingår i: Clinical and Translational Gastroenterology. - : Nature Publishing Group. - 2155-384X. ; 14:8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Fecal calprotectin (FC) is anoninvasive tool for examining response to biologics in inflammatory boweldisease (IBD), but its performance in relation to other novel fecal markers of various cellular origins is unknown.Methods: We performed a prospective multicenter cohort study and included patients with active IBD who provided a fecal sample at initiation of biological therapy. Levels of FC, myeloperoxidase (MPO), human neutrophil lipocalin (HNL), and eosinophil-derived neurotoxin (EDN) were analyzed and related to clinical remission status at 3 months. Changes in levels of markers at 3 months were calculated, and the impact of concomitant use of corticosteroids at baseline was estimated.Results: In patients achieving clinical remission (n = 27), a decrease in levels of FC (P = 0.005), MPO (P < 0.001), HNL (P < 0.001), and EDN (P < 0.001) was observed, whereas no significant decrease was seen in patients not achieving remission (n = 39). There was a significant difference in the change in the level of MPO (P = 0.01) and HNL (P = 0.02) between patients achieving clinical remission and those who did not, but changes in FC and EDN could not differentiate between these groups. Patients with concomitant systemic corticosteroids at inclusion had lower levels of HNL (P = 0.01) and EDN (P < 0.001) at baseline, compared with patients without corticosteroids.Discussion: Fecal MPO, HNL, and EDN are all promising biomarkers for assessing the treatment outcome of biologics in patients with IBD. Fecal levels of EDN and HNL are significantly affected by corticosteroids indicating a greater sensitivity to the effects of corticosteroids compared with levels of FC and MPO.
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| 23. |
- Magnusson, Maria K, 1972, et al.
(författare)
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Anti-TNF Therapy Response in Patients with Ulcerative Colitis Is Associated with Colonic Antimicrobial Peptide Expression and Microbiota Composition
- 2016
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 10:8, s. 943-952
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Anti-tumour necrosis factor [TNF] therapy is used in patients with ulcerative colitis [UC], but not all patients respond to treatment. Antimicrobial peptides [AMPs] and the gut microbiota are essential for gut homeostasis and may be important for treatment outcome. The aim of this study was to determine AMP and microbiota profiles in patients with UC before anti-TNF therapy start and correlate these data to treatment outcome.METHODS: Serum and biopsies were obtained from UC patients naïve to biological therapy [n = 56] before anti-TNF therapy start [baseline]. Fecal samples were taken at baseline and Weeks 2 and 6. Quantitative proteomic analysis was performed in mucosal biopsies. Expression of AMPs and cytokines was determined in biopsies and serum. Microbiota analysis of fecal samples was performed using GA-map™ Dysbiosis Test and real-time quantitative polymerase chain reaction [rtPCR]. Treatment response was evaluated 12-14 weeks after baseline.RESULTS: At baseline, proteomic analysis of biopsies showed that treatment responders and non-responders had differential expression of AMPs. Eleven AMP and AMP-related genes were analysed by rtPCR in mucosal biopsies and could together discriminate responders from non-responders at baseline. The most important nominators for response were increased expression of defensin 5 and eosinophilic cationic protein. Microbiota analysis revealed lower dysbiosis indexes and higher abundance of Faecalibacterium prausnitzii in responders compared with non-responders at baseline. Also, abundance of F. prausnitzii increased during induction therapy in responders.CONCLUSIONS: Anti-TNF therapy responders and non-responders display distinctly separate patterns of mucosal AMP expression and gut microbiota before treatment start. This indicates that intestinal antimicrobial/microbial composition can influence treatment outcome.
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| 24. |
- Magnusson, Maria K, 1972, et al.
(författare)
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CD25 and TNF receptor II reflect early primary response to infliximab therapy in patients with ulcerative colitis
- 2013
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Ingår i: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 1:6, s. 467-476
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Tidskriftsartikel (refereegranskat)abstract
- Background Although infliximab treatment is an option for patients with ulcerative colitis (UC), not all patients do respond to therapy, and cellular mechanisms leading to therapy response are incompletely known. Objective The objective of this article is to determine early effects of infliximab therapy on T cells in the blood of UC patients and if effects differed in therapy responders and nonresponders. Methods: Blood samples were obtained before and two weeks post-treatment start from 34 anti-tumor necrosis factor (TNF) therapy-naïve UC patients undergoing infliximab therapy. Response to therapy was evaluated prior to the fourth treatment dose. Expression of T cell surface markers and levels of soluble receptors and cytokines in serum were determined. Results At baseline, there were no differences in cellular, biochemical or clinical parameters between therapy responders and nonresponders. Infliximab therapy reduced frequencies of CD25+ T cells and increased frequencies of annexin V+ T cells in patients responding to infliximab, but not in nonresponding patients, two weeks after therapy start. Only therapy responders had decreased serum levels of sCD25 and sTNFRII two weeks after treatment start. In contrast, clinical parameters did not reflect therapy outcome already two weeks after therapy start. Conclusion Soluble and membrane-bound T cell receptors may be early indicators of infliximab therapy response in UC, which can be of clinical importance for the decision when to continue or to stop the treatment.
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| 25. |
- Magnusson, Maria K, 1972, et al.
(författare)
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Cultured blood T-cell responses predict anti-TNF therapy response in patients with ulcerative colitis
- 2015
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Ingår i: Alimentary Pharmacology & Therapeutics. - : Wiley. - 0269-2813. ; 41:11, s. 1149-1161
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAnti-tumour necrosis factor (TNF) therapy is used for treatment of ulcerative colitis (UC). As approximately 30% of patients with UC do not benefit from the treatment, it is of clinical interest to identify biomarkers of response before therapy is initiated. AimTo identify prognostic biomarkers of anti-TNF therapy response in anti-TNF therapy-naive patients with UC. MethodsPeripheral blood cells were obtained from 56 patients with UC before therapy started. Thirty-four patients were included in an exploratory cohort and 22 patients in a validation cohort. Blood cells were stimulated in vitro with influenza vaccine with and without anti-TNF. T-cell surface receptor expression and cytokine release were determined (in total 17 variables). Treatment response was evaluated using the Mayo score 12-14weeks after the first infusion. ResultsIn the exploratory cohort, blood cells from the patients showed stronger anti-TNF-dependent suppression of T-cell surface receptor expression and cytokine secretion among therapy responders than nonresponders. In particular, anti-TNF suppressed the expression of CD25 on T cells and secretion of interleukin 5, to a higher degree in responders than in nonresponders. These variables were used to a create model to predict therapy outcome, which was confirmed in the validation cohort. Correct classification of future therapy response was achieved in 91% of the cases in the validation cohort. ConclusionThe effects of anti-TNF on cultured blood T cells, obtained before therapy started, predict treatment outcome in patients with UC.
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| 26. |
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| 27. |
- Magnusson, Maria K, 1972, et al.
(författare)
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The Mucosal Antibacterial Response Profile and Fecal Microbiota Composition Are Linked to the Disease Course in Patients with Newly Diagnosed Ulcerative Colitis
- 2017
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Ingår i: Inflammatory Bowel Diseases. - : Oxford University Press (OUP). - 1078-0998. ; 23:6, s. 956-966
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Tidskriftsartikel (refereegranskat)abstract
- Background: The clinical disease course of ulcerative colitis (UC) varies substantially between individuals and can currently not be reliably predicted. The gut microbiota and the host's immune defense are key players for gut homeostasis and may be linked to disease outcome. The aim of this study was to determine fecal microbiota composition and mucosal antibacterial response profile in untreated patients with newly diagnosed UC and the impact of these factors on disease course. Methods: Stool samples and intestinal biopsies were obtained from therapy-naive newly diagnosed patients with UC. Patients were defined to have mild or moderate/severe disease course assessed by disease activity during the 3 years follow-up. Fecal microbiota was analyzed by the GA-map Dysbiosis test (n = 18), and gene expression in intestinal biopsies was analyzed by RT2 Profiler polymerase chain reaction array (n = 13) and real-time polymerase chain reaction (n = 44). Results: At the time of diagnosis of UC, the fecal microbiota composition discriminated between patients with mild versus moderate/severe disease course. Also, the mucosal antibacterial gene expression response profile differed between patients with mild versus moderate/severe disease course with bactericidal/permeability-increasing protein (BPI) being most important for the discrimination. Mucosal bactericidal/permeability-increasing protein gene expression at diagnosis was higher in patients with mild versus moderate/severe disease course when confirmed in a larger patient cohort (P = 0.0004, n = 44) and was a good predictor for the number of flares during the 3 years follow-up (R-2 = 0.395, P < 0.0001). Conclusions: In patients with newly diagnosed UC, fecal microbiota composition and mucosal antibacterial response profile, especially bactericidal/permeability-increasing protein, are linked to disease course.
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| 28. |
- Mavroudis, Georgios, et al.
(författare)
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Health-related quality of life in patients with long-standing ulcerative colitis in remission
- 2022
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Ingår i: Therapeutic Advances in Gastroenterology. - : SAGE Publications. - 1756-283X .- 1756-2848. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Ulcerative colitis (UC) contributes to impaired health-related quality of life (HRQoL). Although disease activity is the most important factor, reduced HRQoL has been reported even in quiescent UC. We aimed to determine HRQoL, and identify predictors thereof, in patients with long-standing UC in remission. Methods: In total, 66 patients with inactive UC were included 10 years after the disease onset. Clinical assessment including rigid sigmoidoscopy was performed to ensure remission. Data on demographic, clinical, treatment-related, and psychological determinants of HRQoL were obtained with a structured interview and self-assessment questionnaires measuring gastrointestinal (GI) and psychological symptoms and fatigue. HRQoL was measured with the Short Form Health Survey (SF-36). Results: The SF-36 domains were comparable to the general Swedish population, except for Vitality, where UC patients scored lower. Gender, smoking, comorbidity, or disease phenotype had no impact on HRQoL. In contrast, corticosteroid use and sick leave during the previous year were independently associated with Physical Functioning and Bodily Pain domains of SF-36; persisting GI symptoms during remission with Bodily Pain; and fatigue with Role Physical, General Health and Vitality. For all other SF-36 domains reflecting mental HRQoL (Social Function, Role Emotional, Mental Health), only psychological distress contributed uniquely. Conclusions: Although overall HRQoL in long-standing UC in remission is comparable to the general population, previous disease activity as well as persisting GI symptoms, fatigue, and psychological distress are associated with a lower HRQoL among these patients. Improved HRQoL may allow for better UC patient health and reduced costs for health care. © The Author(s), 2021.
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| 29. |
- Mavroudis, Georgios, et al.
(författare)
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Mucosal and Systemic Immune Profiles Differ During Early and Late Phases of the Disease in Patients With Active Ulcerative Colitis
- 2019
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Ingår i: Journal of Crohns & Colitis. - : Oxford University Press (OUP). - 1873-9946. ; 13:11, s. 1450-1458
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Alterations in the immunopathogenesis in ulcerative colitis [UC] during the disease course have been proposed. We therefore aimed to determine mucosal and systemic immune profiles in individual patients at the time of diagnosis [early disease] and after 10 years [late disease]. Methods: Patients with UC provided serum and mucosal biopsies during a flare in early and in late disease. Serum samples were analysed using the Olink Proseek Inflammation panel. mRNA gene expression of biopsies was analysed using the Qiagen RT2 Profiler PCR Arrays Antibacterial response and T Helper Cell Differentiation. Results: Orthogonal projections to latent structures discriminant analyses [OPLS-DA] demonstrated that the profile of 15 serum proteins discriminated in early and late disease [R2 = 0.84, Q2 = 0.65] in 15 UC patients. Eight of these proteins were differently expressed between the groups [Q <0.05]. Further, OPLS-DA of the mRNA profiles in biopsies strongly discriminated early and late disease with high predictability [R2 = 0.96, Q2 = 0.89]; 42 genes were differently expressed at the two time points [Q <0.05]. Finally, principal component analysis showed that T helper [Th] 1- and Th2-related genes were associated with early disease and late disease, respectively, and hierarchical cluster analysis was able to cluster patients with early from late disease with only minor overlap. Conclusions: Mucosal and systemic immune profiles differ between early and late disease in patients with active UC, with a transition from a Th1- to a Th2-driven disease in the intestine. Improved understanding of the variation in immunopathogenesis during the disease course in UC is important to guide individualised treatment decision making.
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| 30. |
- Mavroudis, Georgios, et al.
(författare)
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Symptoms compatible with functional bowel disorders are common in patients with quiescent ulcerative colitis and influence the quality of life but not the course of the disease
- 2019
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Ingår i: Therapeutic Advances in Gastroenterology. - : SAGE Publications. - 1756-2848. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Whether patients with inactive ulcerative colitis (UC) have symptoms compatible with functional bowel disorders (FBDs) other than irritable bowel syndrome (IBS) is unclear. Our aim was to investigate the prevalence and burden of these symptoms and determine impact on the UC course. Methods: We used Mayo score, sigmoidoscopy and calprotectin (f-cal) to define remission in 293 UC patients. Presence of symptoms compatible with FBD, severity of gastrointestinal, extraintestinal and psychological symptoms, stress levels and quality of life (QoL) were measured with validated questionnaires. At 1 year later, remission was determined by modified Mayo score and f-cal in 171 of these patients. They completed the same questionnaires again. Results: A total of 18% of remission patients had symptoms compatible with FBD other than IBS, and 45% subthreshold symptoms compatible with FBD. The total burden of gastrointestinal symptoms in patients with symptoms compatible with FBD was higher than in patients without FBD (p < 0.001), which had negative impact on QoL (p = 0.02). These symptoms were not correlated with psychological distress, systemic immune activity or subclinical colonic inflammation and were not a risk factor for UC relapse during follow up. Conclusion: Symptoms compatible with FBD other than IBS are common during UC remission influencing patients' QoL but not the UC course.
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| 31. |
- Mavroudis, Georgios, et al.
(författare)
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Visceral hypersensitivity is together with psychological distress and female gender associated with severity of IBS-like symptoms in quiescent ulcerative colitis
- 2021
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 33:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: A subset of ulcerative colitis (UC) patients in remission demonstrate IBSlike symptoms. Visceral hypersensitivity is a key pathophysiological mechanism in IBS, but its relevance to IBS-like symptoms in inactive UC remains unclear. Methods: UC patients in remission (UCR) were screened for IBS-like symptoms. Rectal sensitivity was assessed with rectal balloon distensions, with determination of sensory thresholds and unpleasantness/pain intensity ratings. Patients completed questionnaires evaluating gastrointestinal (GI) and psychological symptoms. Age- and gendermatched IBS subjects and healthy controls (HC) also underwent a rectal sensitivity test. Key Results: We included 36 UCR patients (18 with IBS-like symptoms (UCR + IBS) and 18 without (UCR - IBS)), 36 IBS subjects, and 14 HC. UCR and IBS patients were more sensitive to rectal balloon distensions than HC, but no differences between UCR and IBS patients were observed. UCR + IBS patients had lower sensory thresholds and higher unpleasantness ratings than UCR - IBS. In UCR patients, the overall GI symptom severity, pain, and bloating, but not diarrhea, constipation or satiety, were associated with rectal sensitivity. In multivariate analyses, rectal sensitivity, psychological distress, and female gender were identified as factors independently associated with GI symptom severity. 61% of UCR patients demonstrated rectal hypersensitivity, and these patients more commonly reported at least mild bloating and pain, and overall GI symptoms, compared to those with normal rectal sensitivity. Conclusion & Inferences: Visceral hypersensitivity was associated with IBS-like symptoms, in particular pain and bloating, in inactive UC. Together with psychological factors and female gender, visceral hypersensitivity seems to be involved in GI symptom generation in quiescent UC.
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| 32. |
- Moraes Holst, Luiza, et al.
(författare)
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Fecal Luminal Factors from Patients with Gastrointestinal Diseases Alter Gene Expression Profiles in Caco-2 Cells and Colonoids
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067 .- 1661-6596. ; 23:24
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Tidskriftsartikel (refereegranskat)abstract
- Previous in vitro studies have shown that the intestinal luminal content, including metabolites, possibly regulates epithelial layer responses to harmful stimuli and promotes disease. Therefore, we aimed to test the hypothesis that fecal supernatants from patients with colon cancer (CC), ulcerative colitis (UC) and irritable bowel syndrome (IBS) contain distinct metabolite profiles and establish their effects on Caco-2 cells and human-derived colon organoids (colonoids). The metabolite profiles of fecal supernatants were analyzed by liquid chromatography-mass spectrometry and distinguished patients with CC (n = 6), UC (n = 6), IBS (n = 6) and healthy subjects (n = 6). Caco-2 monolayers and human apical-out colonoids underwent stimulation with fecal supernatants from different patient groups and healthy subjects. Their addition did not impair monolayer integrity, as measured by transepithelial electrical resistance; however, fecal supernatants from different patient groups and healthy subjects altered the gene expression of Caco-2 monolayers, as well as colonoid cultures. In conclusion, the stimulation of Caco-2 cells and colonoids with fecal supernatants derived from CC, UC and IBS patients altered gene expression profiles, potentially reflecting the luminal microenvironment of the fecal sample donor. This experimental approach allows for investigating the crosstalk at the gut barrier and the effects of the gut microenvironment in the pathogenesis of intestinal diseases.
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| 33. |
- Niklasson, Anna, 1977, et al.
(författare)
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Prevalence of gastrointestinal symptoms in patients with chronic obstructive pulmonary disease.
- 2008
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Ingår i: European journal of gastroenterology & hepatology. - 0954-691X. ; 20:4, s. 335-41
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Symptoms of gastro-oesophageal reflux disease (GERD) have previously been shown to be of importance in patients with asthma. Limited data, however, exist on the prevalence of GERD in patients with chronic obstructive pulmonary disease (COPD), and information about the occurrence of the total burden of gastrointestinal (GI) symptoms in these patients is lacking. METHODS: A total of 113 patients with COPD completed four self-administered questionnaires: the Gastrointestinal Symptom-Rating Scale (GSRS), ROME II modular questionnaires (criteria for irritable bowel syndrome), the Psychological General Well-Being index (PGWB), and the Hospital Anxiety and Depression scale. Eighty-two patients with chronic renal failure (CRF) and 2000 healthy individuals from the general Swedish population served as controls. RESULTS: The total GSRS score in patients with COPD was 2.12 (1.92-2.28) which was significantly higher than the score from the general population of 1.96 (1.81-2.12). No significant difference between COPD and CRF patients was, however, observed, in any of the GSRS dimensions. Patients in the COPD group had lower total PGWB scores compared both with CRF patients 90 (78-104) vs. 98 (83-113) (P<0.05) and with the general population 103 (102-104) (P<0.001). A negative correlation between the GSRS and PGWB scores (r=-0.49; P<0.001) was observed in patients with COPD. Sixteen (14%) of the patients with COPD fulfilled the Rome II criteria for irritable bowel syndrome. CONCLUSION: The prevalence of GI symptoms is higher in patients with COPD than in healthy individuals, but not higher than in CRF patients. The GI symptoms are associated with impairments in psychological well-being, and they require diagnostic workups to explore different treatment options in these patients.
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| 34. |
- Peyrin-Biroulet, L, et al.
(författare)
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Results from the 2nd Scientific Workshop of the ECCO (I): Impact of mucosal healing on the course of inflammatory bowel disease
- 2011
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Ingår i: Journal of Crohn's and Colitis. - 1873-9946. ; 5:5, s. 477-483
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Tidskriftsartikel (refereegranskat)abstract
- Over the past years, mucosal healing has emerged as a major therapeutic goal in clinical trials in inflammatory bowel diseases. Accumulating evidence indicates that mucosal healing may change the natural course of the disease by decreasing the need for surgery and reducing hospitalization rates in both ulcerative colitis and Crohn's disease. Mucosal healing may also prevent the development of long-term disease complications, such as bowel damage in Crohn's disease and colorectal cancer in ulcerative colitis. Histologic healing may be the ultimate therapeutic goal in ulcerative colitis, whereas its impact on the course of Crohn's disease is unknown. Complete mucosal healing may be required before considering drug withdrawal. Targeting early Crohn's disease is more effective than approaches aimed at healing mucosa in longstanding disease. Several questions remain to be answered: should mucosal healing be systematically used in clinical practice? Should we optimize therapies to achieve mucosal healing? What is the degree of intestinal healing that is required to change the disease course? Large prospective studies addressing these issues are needed.
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| 35. |
- Ringström, Gisela, 1964, et al.
(författare)
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Why do subjects with irritable bowel syndrome seek health care for their symptoms?
- 2007
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Ingår i: Scand J Gastroenterol.. - : Informa UK Limited. - 0036-5521. ; 42:10, s. 1194-1203
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Irritable bowel syndrome (IBS) is common in the population, but not all subjects seek professional health care for their symptoms. The aim of this study was to compare consulters in secondary/tertiary care with those in primary care and non-consulters by using questionnaires to investigate factors of importance for health-care seeking in IBS. Material and methods. The study included 218 subjects with IBS: 70 non-consulters, 53 patients from primary care and 95 from secondary/tertiary care. The subjects completed questionnaires on gastrointestinal (GI) and psychological symptoms, coping resources, health-related quality of life (HRQOL) and reasons for not seeking health care. Results. Consulters (primary and secondary/tertiary care combined) had poorer HRQOL, more severe psychological symptoms, higher levels of GI-specific anxiety and poor coping resources compared with non-consulters, but the GI symptom severity was similar. Mental health and poor social, emotional and physical functioning were independently predictive of being a health-care seeker (r(2)=0.41). Independent predictors for being a consulter in secondary/tertiary care were a high degree of anxiety, low scores on physical functioning, physical role and food (IBSQOL) (r(2)=0.65). Several non-consulters reported mild symptoms and ability to control symptoms as reasons for not seeking health care. Having a close relative with similar symptoms reduced the need to seek health care. Thirty-six non-consulters had sought alternative care or advice from friends and/or relatives about their GI symptoms. Conclusions. GI symptom severity alone cannot explain the illness behavior in IBS. HRQOL and psychological symptoms are important for experience of GI symptoms and the health-care seeking pattern in IBS.
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| 36. |
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| 37. |
- Strid, Hans, 1957, et al.
(författare)
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Delay in gastric emptying in patients with chronic renal failure.
- 2004
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Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 39:6, s. 516-20
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gastrointestinal (GI) symptoms are common in patients with chronic renal failure (CRF). Delayed gastric emptying might be a possible pathophysiological mechanism. The aims of this study were to evaluate gastric emptying in patients with CRF and to correlate the findings with GI symptoms and evaluate the impact of Helicobacter pylori infection in CRF patients on gastric emptying. METHODS: Thirty-nine patients with CRF (17 F, 22 M) were compared with 131 healthy subjects (74 F, 57 M). A standardized breakfast was given with 20 spherical, radiopaque markers (ROMs). The emptying was followed by fluoroscopy after 4, 5 and 6 h. Gastric emptying was assessed by calculating the individual mean percentual gastric retention of markers, 4 to 6 h after the meal. The perceived severity of GI symptoms was assessed with a validated questionnaire. Because of gender differences in gastric emptying, men and women were compared separately and a percentile of 95 was chosen as the upper reference value. H. pylori infection was assessed using a serological method. RESULTS: Delayed gastric emptying was found in 14 out of 39 (36%) of the CRF patients. There was no relationship between delayed gastric emptying and age, GI symptoms, H. pylori infection or underlying renal disease. However, a higher proportion of patients in peritoneal dialysis demonstrated delayed gastric emptying compared with predialytic patients (6 of 9 versus 2 of 13, P = 0.026). Men with CRF had a higher gastric retention compared with healthy men (16.6 (0-63.3)% versus 0 (0-2.1)%, P < 0.0001), and 10 men with CRF had delayed gastric emptying (P < 0.0001). There was no significant difference in mean gastric retention between women with CRF and healthy women (13.3 (0-55.4)% versus 10.8 (0-30.0)%, P = 0.93), but 4 women with CRF had delayed gastric emptying (P = 0.02). Eighteen of the CRF patients had GI symptoms (6 F, 12 M) and 21 were asymptomatic (11 F, 10 M). There was no difference in mean gastric retention in patients with CRF with and without GI symptoms (M: 13.3 (0-55.0)% versus 47.5 (5.0-65.0)%, P = 0.51, F: 16.6 (0-63.3)% versus 13.3 (0-59.2)%, P = 0.96). Gastric emptying in CRF patients with and without H. pylori infection showed no difference. CONCLUSIONS: Delayed gastric emptying is common in patients with chronic renal failure, particularly in men. The delay was not associated with the presence of GI symptoms, underlying renal disease or H. pylori infection. However, the dialytic status might have an impact on gastric emptying in patients with CRF.
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| 38. |
- Strid, Hans, 1957, et al.
(författare)
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Effect of heavy exercise on gastrointestinal transit in endurance athletes.
- 2011
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Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 46:6, s. 673-7
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Tidskriftsartikel (refereegranskat)abstract
- Disturbances in transit of the gastrointestinal (GI) tract have been proposed to be involved in the etiology of the GI symptoms in heavy exercise. However, the results are conflicting. In the present study, we investigated the effect of heavy exercise on GI transit in well-trained athletes.
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| 39. |
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| 40. |
- Strid, Hans, 1957
(författare)
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Gastrointestinal symptoms in chronic renal failure. Prevalence and pathophysiological mechanisms
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic renal failure (CRF) has a varying etiology and is characterised by an increasing accumulation of toxic metabolic waste products in the blood. Malnutrition is a common finding in uraemic patients and is regarded as a marker for morbidity and mortality. Many factors, including gastrointestinal (GI) symptoms, lead to malnutrition in CRF. The aims of the present study were to evaluate the prevalence of GI symptoms in CRF patients and to find possible pathophysiological mechanisms behind these symptoms. Gastrointestinal symptoms and psychological well-being were assessed with the aid of two questionnaires. The use of acid-suppressive therapy was evaluated by interviewing the patients and by reviewing medical records. Motility of the small intestine was measured by means of antroduodenojejunal manometry. Radiopaque markers were used to assess gastric emptying. Aspirate from the jejunum for culture was obtained through the manometry catheter.Gastrointestinal symptoms were more common in CRF compared with reference values from the general population. A relationship between GI symptoms in CRF patients and reduced psychological well-being was observed.There was an overuse of acid-suppressive drugs in dialysis patients and the majority of the indications were inappropriate, with non-specific GI symptoms as a dominating indication. Long-term treatment, more than eight weeks, was predominant. Manometry of the small intestine revealed neuropathic-like motor patterns in 50% of patients. A high proportion of long clusters was observed during phase II as well as a high proportion of retrograde pressure waves in phase II and post-prandially in CRF, both in symptomatic and asymptomatic patients. Accelerated propagation velocity of the activity front of MMC in the duodenum correlated with GI symptoms. Small intestinal bacterial overgrowth (SIBO) was found in 36% of CRF patients irrespective of GI symptoms. A neuropathic-like motor pattern was more commonly observed in CRF patients with SIBO.A delay in gastric emptying was disclosed in patients with CRF, especially in men. Gastric emptying was not correlated to GI symptoms. A delay in emptying was more common in patients on peritoneal dialysis. Helicobacter pylori did not affect gastric emptying.Conclusions: Gastrointestinal symptoms are common in CRF patients and are associated with impaired psychological well-being. Overuse of acid-suppressive therapy is common in CRF patients. Abnormal small bowel motility, delayed gastric emptying and SIBO are common findings in CRF patients. Some abnormal motility findings were related to GI symptoms and may be involved in the pathophysiology of GI symptoms in CRF.
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| 41. |
- Strid, Hans, 1957, et al.
(författare)
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Impact of dialysis on gastroesophageal reflux, dyspepsia, and proton pump inhibitor treatment in patients with chronic renal failure.
- 2009
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Ingår i: European journal of gastroenterology & hepatology. - 1473-5687. ; 21:2, s. 137-42
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Gastrointestinal (GI) symptoms are common in patients with chronic renal failure. Patients with chronic renal failure on dialysis have a high consumption of proton pump inhibitors (PPIs) and long-term treatment is very common. The aim of the study was to investigate the prevalence of gastroesophageal reflux symptoms (GORS), dyspeptic symptoms, and PPI treatment in patients with chronic renal failure on dialysis and to compare the impact of the different types of dialysis on these upper GI symptoms and PPI treatment. METHODS: One hundred and twelve peritoneal dialysis (PD) patients and 157 hemodialysis (HD) patients participated in the study. The patients were asked to complete two questionnaires: Gastrointestinal Symptom Rating Scale measuring GI symptoms in general and a GI symptom questionnaire evaluating upper GI tract symptoms specifically. Information about the use of and indication for PPI treatment and onset of GI symptoms was obtained by interviewing the patients and/or reviewing the medical records. RESULTS: Dyspepsia was more common among PD patients compared with HD patients (55 vs. 38%, P=0.003). The start of dialysis tended to have a greater impact on dyspepsia (P=0.09) and GORS (P=0.09) in PD patients than in HD patients. The proportion of patients who started PPI treatment after onset of dialysis was high but did not differ between PD and HD patients (51 vs. 44%, P=0.43). A higher proportion of women with chronic renal failure started PPI treatment after the onset of dialysis than men with chronic renal failure (P=0.002). CONCLUSION: Dyspepsia and GORS leading to PPI treatment are common in CRF patients on dialysis. Dialysis in general and the type of dialysis seem to affect the presence of upper GI symptoms.
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| 42. |
- Van Den Houte, Maaike, et al.
(författare)
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Predictors of symptom trajectory in newly diagnosed ulcerative colitis: a 3-year follow-up cohort study.
- 2024
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Ingår i: Journal of Crohn's & colitis. - 1876-4479.
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Tidskriftsartikel (refereegranskat)abstract
- Psychological symptoms are associated with poorer ulcerative colitis (UC)-related outcomes. However, the majority of research is cross-sectional. We aimed to identify subgroups based on the longitudinal evolution of GI symptom levels and health-related quality of life (HRQoL), and to disentangle the directionality of effects between GI symptom levels and psychological distress.Self-reported GI symptom severity, HRQoL, inflammatory biomarkers and psychological distress were assessed in 98 newly diagnosed UC patients at disease onset and yearly for 3 consecutive years. Latent class growth analysis was used to determine subgroups based on longitudinal trajectories of symptom severity and HRQoL, and baseline predictors of trajectory group membership were determined. Cross-lagged structural equation models were used to disentangle temporal relationships between psychological functioning and symptom severity.Patients with higher initial psychological distress had increased probability of maintaining higher levels of diarrhea and abdominal pain. Conversely, patients with lower initial levels of diarrhea and abdominal pain had higher chances of maintaining lower levels of psychological distress. Higher levels of C-reactive protein at baseline predicted greater improvements in mental health after anti-inflammatory treatment. Reductions in diarrhea and abdominal pain preceded reductions in psychological symptoms over time.Baseline psychological distress is predictive of increased GI symptom severity and reduced mental HRQoL over time, suggesting early assessment of psychological symptoms may identify patients who may have worse disease trajectories. Abdominal pain predicted increased psychological distress, but not the other way around. Intervening on abdominal pain may help prevent or reduce future psychological distress.
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| 43. |
- Wenzel, Ulf Alexander, 1975, et al.
(författare)
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Spontaneous colitis in Muc2-deficient mice reflects clinical and cellular features of active ulcerative colitis.
- 2014
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- The colonic mucus layer plays a critical role in intestinal homeostasis by limiting contact between luminal bacteria and the mucosal immune system. A defective mucus barrier in animal models allows bacterial contact with the intestinal epithelium and results in spontaneous colitis. A defective mucus barrier is also a key feature of active ulcerative colitis (UC). Alterations in the immune compartment due to intestinal bacterial breach in mice lacking the colon mucus barrier have not been characterized and correlated to active UC.
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| 44. |
- Öhman, Lena, 1967, et al.
(författare)
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B-cell activation in patients with irritable bowel syndrome (IBS).
- 2009
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Ingår i: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 21:6
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Tidskriftsartikel (refereegranskat)abstract
- Patients with irritable bowel syndrome (IBS) may have a low grade immune activation. However, little is known about the properties of B cells of IBS patients. We therefore investigated activation level and antigen presenting phenotype of blood B cells of IBS patients. We also examined B-cell responses to lipopolysaccharide (LPS) and probiotic bacteria. Blood samples were obtained from 74 IBS patients and 30 healthy subjects. Peripheral blood mononuclear cells were isolated and stimulated with LPS or an UV-light inactivated bacterial cocktail consisting of the probiotic Gram-positive strains; Lactobacillus paracasei ssp. paracasei 19, Lactobacillus acidophilus La5, Bifidobacterium lactis B612. The phenotype of CD19(+) B cells was investigated by flow cytometry before and after 72 h cell culture. Furthermore, IBS symptom severity was assessed. B cells isolated from blood of IBS patients displayed an amplified activation level as demonstrated by increased cell surface expression of IgG, and also the costimulatory molecules CD80 and CD86. Expression of antigen presenting HLA-DR and costimulatory molecule CD40 on B cells was, however comparable in IBS patients and controls. B cells of IBS patients displayed an impaired ability to increase expression of CD80, but not CD86, in response to both LPS as well as probiotic bacteria stimulations. To conclude, blood B cells of IBS patients have an increased activation level. Bacterial component induced expression of the costimulatory molecule CD80, regarded as important for tolerance induction, is impaired. These data suggest that B-cell antigen presentation in IBS patients is associated with altered capacity of providing costimulation to T cells.
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| 45. |
- Öhman, Lena, 1967, et al.
(författare)
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Increased TLR2 expression on blood monocytes in irritable bowel syndrome patients.
- 2012
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Ingår i: European journal of gastroenterology & hepatology. - 1473-5687. ; 24:4, s. 398-405
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Tidskriftsartikel (refereegranskat)abstract
- The understanding of the mechanisms for increased immune activation in subgroups of patients with irritable bowel syndrome (IBS) is incomplete. We hypothesized that monocytes are more activated in patients with IBS than in the healthy population. We therefore examined activation phenotype and cytokine secretion of blood monocytes.
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| 46. |
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| 47. |
- Öhman, Lena, 1967, et al.
(författare)
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T-cell activation in patients with irritable bowel syndrome.
- 2009
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Ingår i: The American journal of gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 1572-0241 .- 0002-9270. ; 104:5, s. 1205-12
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Irritable bowel syndrome (IBS) has been found to be associated with low-grade immune activation in a subset of patients. We therefore investigated blood and colonic T-cell activity in IBS patients. METHODS: Blood samples were initially obtained from 74 IBS patients and 30 controls. Supplementary blood samples, to confirm data, were taken from another cohort (26 patients and 14 controls). In addition, colonic biopsies were taken from a third cohort (11 patients and 10 controls). Peripheral blood and colonic mononuclear cells were stimulated with anti-CD3/CD28 antibodies. Proliferation, cytokine secretion, and T-cell phenotype were investigated. IBS symptom severity was assessed. RESULTS: IBS patients displayed an activated phenotype with increased frequencies of blood T cells expressing CD69 and integrin beta7/HLA-DR. Anti-CD3/CD28-stimulated blood and colonic T cells from IBS patients proliferated less than T cells from controls. IBS patients had an increased polyclonally stimulated T-cell secretion of IL-1beta, which also weakly correlated with increased bowel habit dissatisfaction. Furthermore, despite normal frequencies of CD25high T cells in the blood of IBS patients, lower blood CD25high T-cell frequencies were modestly correlated with more bowel habit dissatisfaction and increased total IBS symptom severity. CONCLUSIONS: IBS patients have an increased frequency of activated T cells, demonstrated by the expression of activation markers and reduced proliferation in response to restimulation in vitro. The increased level of T-cell activation is consistent with the hypothesis of low-grade immune activation in IBS and may also be involved in symptom generation in IBS.
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