| 1. |
- Carstens, Adam, 1975-, et al.
(författare)
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Differential clustering of faecal and mucosa-associated microbiota in healthy individuals
- 2018
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Ingår i: Journal of Digestive Diseases. - : Wiley-Blackwell Publishing Asia. - 1751-2972 .- 1751-2980. ; 19:12, s. 745-752
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Faecal samples are often used to characterise gut microbiota, since they are easily collected. However, whether or not the faecal microbiota differ from the mucosa-associated microbiota remains largely unknown. This may be specifically relevant in conditions that are characterised by complex mucosal microbe-host interactions, such as Crohn's disease. We aimed to determine the degree of agreement between faecal and mucosal microbiota profiles in healthy individuals, using two commonly used collection procedures.MATERIAL AND METHODS: The gut microbiota composition of faecal samples (sent at ambient temperature before storage at -70°C) and of colonic biopsies (obtained at endoscopy and immediately stored at -70°C) was determined by sequencing the 16S rRNA gene. Thirty-one randomly selected healthy individuals from the population-based colonoscopy (Popcol) study were included.RESULTS: Faecal samples were characterised by a reduced degree of richness (p<0.0001) and diversity (p=0.016), and also differences in several phyla, including a lower relative abundance of Proteobacteria (p<0.0001) and Verrucomicrobia (p=0.008) than in biopsies. Only 3 of 30 individuals had a similar faecal and mucosal microbiota profile, based on weighted UniFrac analysis. A difference in Crohn's disease dysbiosis-associated bacteria was observed, including a lower relative abundance of Faecalibacterium (p=0.004) and a higher relative abundance of Ruminococcus (p=0.001) in faeces than in biopsies.CONCLUSIONS: Analysis of faecal samples that have been transported at ambient temperature does not adequately reflect the colonic mucosa-associated microbiota in healthy individuals. These findings have implications for the interpretation of the previous literature, and may be specifically relevant to studies on Crohn's disease.
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| 2. |
- Carstens, Adam, 1975-, et al.
(författare)
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The Gut Microbiota in Collagenous Colitis Shares Characteristics With Inflammatory Bowel Disease-Associated Dysbiosis
- 2019
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Ingår i: Clinical and Translational Gastroenterology. - : Nature Publishing Group. - 2155-384X. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: In inflammatory bowel disease (IBD), an aberrant immune response to gut microbiota is important, but the role of the microbiota in collagenous colitis (CC) is largely unknown. We aimed to characterize the microbiota of patients with CC compared with that of healthy control and patients with IBD.METHODS: Fecal samples were collected from patients with CC (n = 29), age- and sex-matched healthy controls (n = 29), patients with Crohn's disease (n = 32), and patients with ulcerative colitis (n = 32). Sequence data were obtained by 454 sequencing of 16S rRNA gene amplicons, and the obtained sequences were subsequently taxonomically classified.RESULTS: Analysis of similarity statistics showed a segregation between patients with CC and healthy controls with increasing taxonomic resolution, becoming significant comparing operational taxonomic unit data (P = 0.006). CC had a lower abundance of 10 different taxa. Taxa-specific analyses revealed a consistent lower abundance of several operational taxonomic units belonging to the Ruminococcaceae family in patients with CC, q < 0.05 after false discovery rate correction. Loss of these taxa was seen in patients with CC with active disease and/or corticosteroid treatment only and resembled the findings in patients with IBD.DISCUSSION: CC is associated with a specific fecal microbiome seen primarily in patients with active disease or ongoing corticosteroid treatment, whereas the microbiome of CC patients in remission resembled that of healthy controls. Notably, the shift in key taxa, including the Ruminococcaceae family, was also observed in IBD. There may be common mechanisms in the pathogenesis of CC and IBD.
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| 3. |
- Björkqvist, Olle, 1993-, et al.
(författare)
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Alterations in the relative abundance of Faecalibacterium prausnitzii correlate with changes in fecal calprotectin in patients with ileal Crohn's disease : a longitudinal study
- 2019
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 54:4, s. 577-585
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Crohn's disease is characterized by a gut dysbiosis with decreased abundance of butyrate producers such as Faecalibacterium prausnitzii. Although F. prausnitzii secretes anti-inflammatory molecules, few studies have addressed the importance of F. prausnitzii in a longitudinal setting. We aimed to examine the relationship between temporal profiles of F. prausnitzii, the C. leptum group, overall butyrate production, and inflammatory activity.Material and methods: Fecal samples (n = 59) were collected every third month from nine patients with ileal Crohn's disease. The abundance of F. prausnitzii and C. leptum was quantified relative to the total amount of bacteria using quantitative-PCR. To assess butyrate production of gut microbiota, gene copy numbers of the butyryl-CoA:acetate-CoA transferase (BCoAT) gene were quantified by qPCR. The inflammatory activity was defined by fecal (f)-calprotectin.Results: No correlation between the relative abundance of F. prausnitzii, the C. leptum group, or copy numbers of the BCoAT gene, and f-calprotectin was observed in the total sample set. By analyzing alterations between consecutive samples, a negative correlation between changes in the relative abundance of F. prausnitzii and f-calprotectin was observed (R = -0.39; p = .009). Changes in C. leptum (R = -0.18, p = .23) and number of copies of the BCoAT gene (R = -0.12; p = .42) did not correlate with f-calprotectin.Conclusions: There was an inverse correlation between temporal changes in the relative abundance of F. prausnitzii, but not overall butyrate producing capacity, and changes in inflammatory activity in ileal Crohn's disease. These findings indicate that F. prausnitzii may play a role in gut homeostasis, even though causality is still to be demonstrated.
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| 4. |
- Carstens, Adam, 1975-
(författare)
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Chronic inflammatory bowel diseases : studies of microbiota and its influence
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Inflammatory bowel diseases are becoming increasingly common. The underlying mechanisms are not entirely known but the gut microbiota seem to be involved in the pathogenesis. Aim: The aim of this thesis was to characterise gut microbiota related to diagnosis, disease course and response to biological treatment, taking aspects of the source of biological material into account. Materials and methods: Patients and healthy individuals from several different cohorts in Sweden and Europe were invited. Faecal samples and mucosal biopsies were analysed using different sequencing platforms to investigate the gut microbiota. In Study I the faecal microbiota was correlated to different inflammatory bowel diseases. In Study II we compared the microbiota in faeces to the microbiota in mucosal biopsies. In StudyIII we related the faecal microbiota to the outcome of biological treatment. In Study IV we investigated the diagnostic and prognostic properties of the GAmapTM Dysbiosis Test.Results: The faecal microbiota in collagenous colitis resembles the faecalmicrobiota in inflammatory bowel disease. The faecal microbiota differs from the mucosal microbiota. Faecal microbiota at initiation of biological treatment among patients with Crohn’s disease differ between responders and non-responders. The GAmapTM Dysbiosis Test discriminates patients with inflammatory bowel disease from healthy individuals.Conclusion: Collagenous colitis may share microbial underpinnings with other inflammatory bowel diseases. Conclusions about mucosal interactions with the gut microbiota should be made with caution when usingfaecal samples to characterise the microbiota. In Crohn’s disease, the faecal microbiota may be included in a model to predict the outcome of biological treatment. The GAmap Dysbiosis Test does not seem to be superior to other current diagnostic tools in clinical decision-making.
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| 5. |
- 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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| 6. |
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| 7. |
- Nyström, Niklas, et al.
(författare)
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Mucosal and Plasma Metabolomes in New-onset Paediatric Inflammatory Bowel Disease : Correlations with Disease Characteristics and Plasma Inflammation Protein Markers
- 2023
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 17:3, s. 418-432
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Tidskriftsartikel (refereegranskat)abstract
- Background and AimsTo advance the understanding of inflammatory bowel disease [IBD] pathophysiology, we compared the mucosal and plasma metabolomes between new-onset paediatric IBD patients and symptomatic non-IBD controls, and correlated plasma inflammation markers and disease characteristics with the altered metabolites.MethodsPaired colonic and ileal biopsies and plasma from 67 treatment-naïve children with incident Crohn’s disease [CD; n = 47], ulcerative colitis [UC; n = 9], and non-IBD controls [n = 11] were analysed using ultra-performance liquid chromatography-mass spectrometry [UPLC-MS/MS]. Inflammatory plasma proteins [n = 92] were assessed.ResultsThe metabolomes in inflamed mucosal biopsies differed between IBD patients and controls. In CD, mucosal levels of several lysophospholipids [lysophosphatidylcholines, lysophosphatidyletanolamines, lysophosphatidylinositols, and lysophosphatidylserines] were decreased, correlating with various plasma metabolites including amino acid analogues and N-acetylated compounds. In both CD and UC, mucosal sphingolipids, including ceramide [d18:2/24:1, d18:1/24:2], lactosyl-N-palmitoyl-sphingosine [d18:1/16:0], behenoyl sphingomyelin [d18:1/22:0], lignoceroyl sphingomyelin [d18:1/24:0], and/or sphingomyelin [d18:1/24:1, d18:2/24:0] were increased, correlating with sphingolipids, bile acids, and/or N-acetylated metabolites in plasma. Among proteins associated with CD, interleukin-24 correlated with plasma metabolites, including lactosyl-N-palmitoyl sphingosine [d18:1/16:0] and phosphatidyletanolamine [18:1/18:1], haemoglobin, and faecal calprotectin. In UC, interleukin-24, interleukin-17A, and C-C motif chemokine 11 correlated with several plasma metabolites, including N-acetyltryptophan, tryptophan, glycerate, and threonate, and with the Paediatric Ulcerative Colitis Activity Index, C-reactive protein, and faecal calprotectin.ConclusionsMucosal perturbations of lysophospholipids and sphingolipids characterised the metabolome in new-onset paediatric IBD and correlated with plasma metabolites. By integrating plasma metabolomics data with inflammatory proteins and clinical data, we identified clinical and inflammatory markers associated with metabolomic signatures for IBD.
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| 8. |
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| 9. |
- Willing, Ben P., et al.
(författare)
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A Pyrosequencing Study in Twins Shows That Gastrointestinal Microbial Profiles Vary With Inflammatory Bowel Disease Phenotypes
- 2010
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 139:6, s. 1844-U105
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: The composition of the gastrointestinal microbiota is thought to have an important role in the etiology of inflammatory bowel diseases (IBDs) such as Crohn's disease (CD) and ulcerative colitis (UC). Interindividual variation and an inability to detect less abundant bacteria have made it difficult to correlate specific bacteria with disease. METHODS: We used 454 pyrotag sequencing to determine the compositions of microbial communities in feces samples collected from a cohort of 40 twin pairs who were concordant or discordant for CD or UC, and in mucosal samples from a subset of the cohort. The cohort primarily comprised patients who were in remission, but also some with active disease. RESULTS: The profiles of the microbial community differed with disease phenotypes; relative amounts of bacterial populations correlated with IBD phenotypes. The microbial compositions of individuals with CD differed from those of healthy individuals, but were similar between healthy individuals and individuals with UC. Profiles from individuals with CD that predominantly involved the ileum differed from those with CD that predominantly involved the colon; several bacterial populations increased or decreased with disease type. Changes specific to patients with ileal CD included the disappearance of core bacteria, such as Faecalibacterium and Roseburia, and increased amounts of Enterobacteriaceae and Ruminococcus gnavus. CONCLUSIONS: Bacterial populations differ in abundance among individuals with different phenotypes of CD. Specific species of bacteria are associated with ileal CD; further studies should investigate their role in pathogenesis.
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| 10. |
- 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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