Longitudinal Analyses of Gut Mucosal Microbiotas in Ulcerative Colitis in Relation to Patient Age and Disease Severity and Duration

Fite, Alemu; Macfarlane, Sandra; Furrie, Elizabeth; Bahrami, Bahram; Cummings, John H.; Steinke, Douglas; Macfarlane, G.T.

doi:10.1128/jcm.02574-12

Cited by 87 publications

(58 citation statements)

References 58 publications

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“…38,39 Our results showed that the numbers of bacteria within Lachnospiraceae and Coriobacteriaceae were lower in both UC and CD patients as compared with the control children [p < 0.05], which are in agreement with previous studies. 9,12,40,41,42,43,44,45 In addition, the temporal stability of the Lachnospiraceae population was lower in the UC patients of our study than in the control children [p < 0.05]. The diversity of bacteria within Ruminococcaceae was higher in the control children than in UC and CD patients [p < 0.05 for all control vs disease groups] of our study.…”

Section: Discussionmentioning

confidence: 50%

Altered Fecal Microbiota in Paediatric Inflammatory Bowel Disease

Maukonen

Kolho

Paasela

et al. 2015

ECCOJC

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Background and Aims: Several factors support the view of inflammatory bowel disease [IBD] origin in the host responsiveness to intestinal bacteria, although no single bacterial species has been shown as a causative agent in the pathogenesis. Our aim was to analyse the fecal microbiota of paediatric IBD patients at different stages of the disease. In addition, the characteristics of immune response to the bacterial isolates showing very low abundance in IBD were studied. Methods: Fecal samples [1-3 samples/child] were collected from 10 paediatric patients with crohn's disease [CD],] and 12 with ulcerative colitis [UC] and from 8 healthy children, for polyphasic microbiological analysis (culture, real-time polymerase chain reaction [PCR], and denaturing gradient gel electrophoresis). In addition, in vitro cytokine responses of peripheral blood mononuclear cells to the bacterial isolates, which showed very low abundance in IBD, were studied. Results: Although predominant bacterial diversity was higher in IBD, the numbers of Lachnospiraceae and Coriobacteriaceae bacteria were lower in IBD patients as compared with control children [p < 0.05]. In addition, Ruminococcaceae population diversity was lower in IBD [p < 0.05] and correlated negatively with fecal calprotectin levels. Both abundance and diversity of bifidobacterial populations were lower in children with IBD [p < 0.05], and particularly low numbers of certain bifidobacterial isolates were detected. In CD, we found enhanced up-regulation of interleukin-6 transcripts and impaired RAR-related orphan receptor C response to bifidobacteria, whereas decreased interferon-gamma response was observed in both CD and UC. Conclusion: We demonstrate altered fecal microbiota in paediatric IBD, particularly low numbers and diversity of bifidobacterial populations. Interestingly, immunological response to bifidobacteria differed between paediatric CD patients and control children.

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Section: Discussionmentioning

confidence: 50%

Altered Fecal Microbiota in Paediatric Inflammatory Bowel Disease

Maukonen

Kolho

Paasela

et al. 2015

ECCOJC

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“…The genus Enterococcus encompasses protease-secreting species and is reported to be enriched in patients with IBD (47). Additionally, the mucosal densities of E. faecalis, a species within this genus, have been shown to correlate positively with clinical activity indices and sigmoidoscopy scores in UC patients (48). The enteric microbe E. faecalis has been shown previously to circumvent the defense of the intestinal epithelial barrier directly through proteolytic degradation of an adherence junction protein (E-cadherin) and to contribute to intestinal inflammation in the IL-10-deficient mouse model of colitis (27).…”

Section: Discussionmentioning

confidence: 99%

Enterococcus faecalis Gelatinase Mediates Intestinal Permeability via Protease-Activated Receptor 2

et al. 2015

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e Microbial protease-mediated disruption of the intestinal epithelium is a potential mechanism whereby a dysbiotic enteric microbiota can lead to disease. This mechanism was investigated using the colitogenic, protease-secreting enteric microbe Enterococcus faecalis. Caco-2 and T-84 epithelial cell monolayers and the mouse colonic epithelium were exposed to concentrated conditioned media (CCM) from E. faecalis V583 and E. faecalis lacking the gelatinase gene (gelE). The flux of fluorescein isothiocyanate (FITC)-labeled dextran across monolayers or the mouse epithelium following exposure to CCM from parental or mutant E. faecalis strains indicated paracellular permeability. A protease-activated receptor 2 (PAR2) antagonist and PAR2-deficient (PAR2 ؊/؊ ) mice were used to investigate the role of this receptor in E. faecalis-induced permeability. Gelatinase (GelE) purified from E. faecalis V583 was used to confirm the ability of this protease to induce epithelial cell permeability and activate PAR2. The protease-mediated permeability of colonic epithelia from wild-type (WT) and PAR2 ؊/؊ mice by fecal supernatants from ulcerative colitis patients was assessed. Secreted E. faecalis proteins induced permeability in epithelial cell monolayers, which was reduced in the absence of gelE or by blocking PAR2 activity. Secreted E. faecalis proteins induced permeability in the colonic epithelia of WT mice that was absent in tissues from PAR2 ؊/؊ mice. Purified GelE confirmed the ability of this protease to induce epithelial cell permeability via PAR2 activation. Fecal supernatants from ulcerative colitis patients induced permeability in the colonic epithelia of WT mice that was reduced in tissues from PAR2 ؊/؊ mice. Our investigations demonstrate that GelE from E. faecalis can regulate enteric epithelial permeability via PAR2.A potential mechanism for the pathogenesis of inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS) involves disruption of the intestinal epithelial barrier and exposure of a genetically defective immune system to enteric microbial antigens. Indeed, IBD and IBS patients exhibit a higher level of intestinal permeability than healthy controls (1-7). Additionally, first-degree relatives of IBD patients display elevated levels of enteric permeability (8-10), suggesting that this abnormality is independent of inflammation. Consistent with this hypothesis are animal models of colitis that use chemical disruption of the epithelial barrier with trinitrobenzene sulfonic acid, dextran sodium sulfate, or nonsteroidal anti-inflammatory drugs (NSAIDs) to elicit inflammation (11). Further, disruption of the intestinal epithelial barrier by exposure of susceptible patients to NSAIDs (blockers of prostaglandin synthesis) is a risk factor for intestinal inflammation (12).Enteric proteases can act broadly as catalysts of protein degradation or specifically as selective agents that control physiological processes (13). Additionally, these enzymes can disrupt mucosal barriers and modulate the host immune resp...

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“…Only E. rectale and Clostridium clostridioforme had high age dependence. These findings demonstrated that longitudinal variations in mucosal bacterial populations occur in ulcerative colitis and that bacterial community structure was related to disease severity [52].…”

Section: Commentmentioning

confidence: 71%

“…Fite and coauthors (2013) have shown that the bacteria belonging to the normal colonic microbiota were associated with the etiology of ulcerative colitis. Although several mucosal species have been implicated in the disease process, the organisms and mechanisms involved are unknown [52]. These authors have also characterized mucosal biofilm communities over time and determined the relationship of these bacteria to patient age and disease severity and duration.…”

Section: Commentmentioning

confidence: 99%

Etiological Role of Sulfate-Reducing Bacteria in the Development of Inflammatory Bowel Diseases and Ulcerative Colitis

Kushkevych¹

2014

AJIDM

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Inflammatory bowel disease and ulcerative colitis are complex multifactorial diseases of unknown etiology. The etiological role of the sulfate-reducing bacteria Desulfovibrio piger Vib-7 and Desulfomicrobium sp. Rod-9 in the development of these inflammatory diseases in rats was studied. Applying sulfate-reducing bacteria, ulcerative colitis in the animals was experimentally induced at the fist time. In total 45 animals in three groups were separated and used in this experiment. Animals in the first group received the standard diet containing a special certified feed for rats and were used as a control. The second group received the standard feed and a dose (1 ml per each day) of modified Kravtsov-Sorokin's liquid medium for the initiation of own potential animal intestinal microflora of sulfate-reducing bacteria. The third group of the animals received the standard feed and dose of a suspension with D. piger Vib-7 and Desulfomicrobium sp. Rod-9 (at a ratio of 1 to 1) in the medium. The changes in the colonic microbiota under these conditions were studied. The bacteria belonging to the normal colonic microbiota were associated with the etiology of inflammatory bowel disease and ulcerative colitis. The concentration of sulfide and acetate in feces from different sections of the large intestine of the rats was determined. The level of ulcerations in the second and third groups of sick animals under the specific conditions was demonstrated. The described experimental results could be particularly useful for the study of inflammatory bowel disease and ulcerative colitis and its therapeutic strategy. These data are also indispensable to apply into mechanistic details that will facilitate better preclinical drug/therapy design to target specific components involved in the disease pathogenesis. Keywords

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Longitudinal Analyses of Gut Mucosal Microbiotas in Ulcerative Colitis in Relation to Patient Age and Disease Severity and Duration

Cited by 87 publications

References 58 publications

Altered Fecal Microbiota in Paediatric Inflammatory Bowel Disease

Altered Fecal Microbiota in Paediatric Inflammatory Bowel Disease

Enterococcus faecalis Gelatinase Mediates Intestinal Permeability via Protease-Activated Receptor 2

Etiological Role of Sulfate-Reducing Bacteria in the Development of Inflammatory Bowel Diseases and Ulcerative Colitis

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