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| 2. |
- Willing, Ben, et al.
(författare)
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Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease
- 2009
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Ingår i: Inflammatory Bowel Diseases. - New York : John Wiley & Sons. - 1078-0998 .- 1536-4844. ; 15:5, s. 653-660
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Large interindividual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease (CD).METHODS: To reduce variations in exposure during establishment of the gut flora and the influence of genotype, we studied the mucosa-associated microbiota of monozygotic twin pairs that were discordant (n = 6) or concordant (n = 4) for CD. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing, and quantitative real-time polymerase chain reaction (PCR).RESULTS: The microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal CD had a dramatically lower abundance (P < 0.001) of Faecalibacterium prausnitzii and increased abundance (P < 0.03) of Escherichia coli compared to healthy co-twins and those with CD localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype.CONCLUSIONS: The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal CD phenotype, distinct from colonic CD, and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of CD and eventually customized treatment.
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| 3. |
- Dicksved, Johan, et al.
(författare)
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Molecular analysis of the gut microbiota of identical twins with Crohn's disease
- 2008
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Ingår i: The ISME Journal. - : Nature Publishing Group. - 1751-7362 .- 1751-7370. ; 2:7, s. 716-727
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence suggests that a combination of host genetics and the composition of the gut microbiota are important for development of Crohn's disease (CD). Our aim was to study identical twins with CD to determine microbial factors independent of host genetics. Fecal samples were studied from 10 monozygotic twin pairs with CD (discordant n=6 and concordant n=4) and 8 healthy twin pairs. DNA was extracted, 16S rRNA genes were PCR amplified and T-RFLP fingerprints generated using general bacterial and Bacteroides group-specific primers. The microbial communities were also profiled based on their percentage G+C contents. Bacteroides 16S rRNA genes were cloned and sequenced from a subset of the samples. The bacterial diversity in each sample and similarity indices between samples were estimated based on the T-RFLP data using a combination of statistical approaches. Healthy individuals had a significantly higher bacterial diversity compared to individuals with CD. The fecal microbial communities were more similar between healthy twins than between twins with CD, especially when these were discordant for the disease. The microbial community profiles of individuals with ileal CD were significantly different from healthy individuals and those with colonic CD. Also, CD individuals had a lower relative abundance of B. uniformis and higher relative abundances of B. ovatus and B. vulgatus. Our results suggest that genetics and/or environmental exposure during childhood, in part, determine the gut microbial composition. However, CD is associated with dramatic changes in the gut microbiota and this was particularly evident for individuals with ileal CD.
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| 7. |
- Jansson, Janet, et al.
(författare)
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Metabolomics reveals metabolic biomarkers of Crohn's disease
- 2009
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:7, s. e6386-
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Tidskriftsartikel (refereegranskat)abstract
- The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.
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| 8. |
- Gustavsson, Anders, et al.
(författare)
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Clinical trial : colectomy after rescue therapy in ulcerative colitis-3-year follow-up of the Swedish-Danish controlled infliximab study
- 2010
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 32:8, s. 984-989
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Tidskriftsartikel (refereegranskat)abstract
- Background The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described. Aim To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis. Method In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up. Results Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P = 0.02). There was no mortality. Conclusion The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy.
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| 9. |
- Gustavsson, Anders, et al.
(författare)
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Long-term colectomy rate after intensive intravenous corticosteroid therapy for ulcerative colitis prior to the immunosuppressive treatment era
- 2007
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Ingår i: American Journal of Gastroenterology. - New York : American College of Gastroenterology. - 0002-9270 .- 1572-0241. ; 102:11, s. 2513-2519
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Corticosteroids are a cornerstone in the treatment of a severe attack of ulcerative colitis (UC). The long-term prognosis in this patient group is not well described. We studied the long-term colectomy and relapse rates in patients given intensive intravenous corticosteroid treatment (IIVT) for acute UC. METHODS: A retrospective clinical study of 158 patients with UC treated in 1975-1982 with IIVT. Patients were followed-up to death, colectomy or last visit. RESULTS: A total of 11 patients were excluded due to change of diagnosis (N = 10) or lost to follow-up (N = 1). The indication for index IIVT in the remaining 147 patients was a severe attack (N = 61), a moderately severe attack (N = 45), a mild attack (N = 29) or chronic continuous disease (N = 12). The median (range) duration of follow-up was 173 (4-271) months in patients escaping colectomy during the first 3 months. Three months after IIVT, the colectomy rates were 28/61 (46%) in a severe attack, 4/45 (9%) in a moderately severe, and 1/29 (3%) in a mild attack. After 10 yr, the colectomy rates were 39/61 (64%), 22/45 (49%), and 8/29 (28%), respectively. During follow-up, neither colectomy incidence beyond 3 months, time to first relapse nor relapse incidence was influenced by severity of initial attack, except for a lower relapse incidence after a severe attack. CONCLUSIONS: In patients escaping colectomy during the first 3 months after IIVT, the future prognosis was similar irrespective of initial disease severity.
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| 10. |
- Halfvarson, Jonas, 1970-, et al.
(författare)
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Longitudinal concordance for clinical characteristics in a Swedish-Danish twin population with inflammatory bowel disease
- 2007
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Ingår i: Inflammatory Bowel Diseases. - New York, NY : Raven Press. - 1078-0998 .- 1536-4844. ; 13:12, s. 1536-1544
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The genetic influence on disease course in inflammatory bowel disease (IBD) remains unknown. We therefore aimed to study longitudinal concordance for clinical characteristics and longitudinal stability using the Montreal Classification in an IBD twin population. METHODS: A total of 158 twins with ulcerative colitis (UC) (18 belonging to 9 concordant monozygotic pairs) and 141 twins with Crohn's disease (CD) (34 belonging to 17 concordant monozygotic pairs) were enrolled. Medical notes were scrutinized for clinical characteristics at diagnosis and after 10 years. Using the binominal distribution, we tested the hypothesis that clinical characteristics were independent within individuals in disease concordant monozygotic pairs. RESULTS: In CD, location was identical in 11/17 monozygotic concordant pairs at diagnosis (P = 0.008) and in 11/16 pairs after 10 years (P = 0.02). Behavior at diagnosis was identical in 13/17 pairs (P = 0.03) and in 11/16 pairs after 10 years (P = 0.01). Monozygotic UC twins were concordant (within 5 years) for age at diagnosis (6/9 pairs; P < 0.001) and symptomatic onset (4/9 pairs; P = 0.02) but not for extent of disease at diagnosis or after 10 years. The Montreal Classification did not demonstrate longitudinal stability, either regarding location or behavior of CD or extent of UC. CONCLUSIONS: The high phenotypic concordance, both at diagnosis and longitudinally, in monozygotic twins with CD supports a genetic influence not only on disease occurrence but also on disease course. This contrasts with UC, where the genetic impact appears less. Montreal Classification characteristics changed over time and should be used cautiously.
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