| 1. |
- Dicksved, Johan, et al.
(author)
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Lactobacillus reuteri Maintains a Functional Mucosal Barrier during DSS Treatment Despite Mucus Layer Dysfunction
- 2012
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:9
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Journal article (peer-reviewed)abstract
- Treatment with the probiotic bacterium Lactobacillus reuteri has been shown to prevent dextran sodium sulfate (DSS)-induced colitis in rats. This is partly due to reduced P-selectin-dependent leukocyte-and platelet-endothelial cell interactions, however, the mechanism behind this protective effect is still unknown. In the present study a combination of culture dependent and molecular based T-RFLP profiling was used to investigate the influence of L. reuteri on the colonic mucosal barrier of DSS treated rats. It was first demonstrated that the two colonic mucus layers of control animals had different bacterial community composition and that fewer bacteria resided in the firmly adherent layer. During DSS induced colitis, the number of bacteria in the inner firmly adherent mucus layer increased and bacterial composition of the two layers no longer differed. In addition, induction of colitis dramatically altered the microbial composition in both firmly and loosely adherent mucus layers. Despite protecting against colitis, treatment with L. reuteri did not improve the integrity of the mucus layer or prevent distortion of the mucus microbiota caused by DSS. However, L. reuteri decreased the bacterial translocation from the intestine to mesenteric lymph nodes during DSS treatment, which might be an important part of the mechanisms by which L. reuteri ameliorates DSS induced colitis.
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| 2. |
- Jansson, Janet, et al.
(author)
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Metabolomics reveals metabolic biomarkers of Crohn's disease
- 2009
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:7, s. e6386-
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Journal article (peer-reviewed)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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| 3. |
- Schreiber, Olof, 1980-, et al.
(author)
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Influence of Lactobacillus reuteri on the colonic microbiota in health and DSS-induced colitis
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Other publication (other academic/artistic)abstract
- Aim: To investigate the impact of Lactobacillus reuteri and Dextran Sulphate Sodium (DSS) on the colonic microbiota by investigating bacterial content and composition in the individual colonic mucus layers and mesenteric lymph nodes. Methods: Rats were divided into 4 groups: control, L. reuteri, DSS and L. reuteri+DSS. L. reuteri was given as a cocktail containing 109 cfu of four different strains of L. reuteri by gavage daily for 16 days. Colitis was induced by 5% DSS in the drinking water for 9 days. The firmly and loosely mucus layers and mesenteric lymph nodes were collected, homogenized and its bacterial content was monitored using both culturing as well as the molecular method terminal restriction fragment length polymorphism (TRFLP). Results: In controls, the number of bacteria was significantly lower in the inner firmly adherent mucus layer than the outer loosely adherent layer, indicating a barrier function of the inner mucus layer. The composition of the microbiota was also different between layers. L. reuteri prevented colitis but did not alter the microbiota. DSS obliterated the differences between mucus layers both in terms of number of bacteria, and bacterial composition, indicating that DSS destroys the mucus regardless of the addition of L. reuteri. L. reuteri did however significantly decrease bacterial translocation in the DSS-model. Conclusion: The firmly adherent mucus layer serves as a barrier towards luminal bacteria. DSS alters the colonic microbiota and destroys the mucus barrier. L. reuteri ameliorates DSS-colitis by decreasing bacterial translocation.
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| 4. |
- Willing, Ben P., et al.
(author)
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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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In: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 139:6, s. 1844-U105
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Journal article (peer-reviewed)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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| 5. |
- Willing, Ben, et al.
(author)
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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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In: Inflammatory Bowel Diseases. - New York : John Wiley & Sons. - 1078-0998 .- 1536-4844. ; 15:5, s. 653-660
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Journal article (peer-reviewed)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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