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Fibrosis in ulcerative colitis is directly linked to severity and chronicity of mucosal inflammation.

ABSTRACT: BACKGROUND:Fibrosis in ulcerative colitis has remained largely unexplored despite its clinical implications. AIMS:This cross-sectional study was aimed at characterising the presence, anatomical location and degree of ulcerative colitis-associated fibrosis and its possible link to clinical parameters. METHODS:Seven hundred and six individual tissue cross-sections derived every 10 cm along the length of 89 consecutive Ulcerative colitis colectomy specimens were examined and compared to Crohn's disease colitis, diverticular disease and uninvolved areas from colorectal cancer patients. Degree of inflammation, fibrosis and morphometric measurements of all layers of the intestinal wall were evaluated. Three gastrointestinal pathologists independently assessed colon sections stained with haematoxylin and eosin, Masson trichrome and Sirius red. Clinical data were collected prospectively. RESULTS:Submucosal fibrosis was detected in 100% of ulcerative colitis colectomy specimens, but only in areas affected by inflammation. Submucosal fibrosis was associated with the severity of intestinal inflammation (Spearman correlations rho (95% confidence interval): 0.58 (P < 0.001) and histopathological changes of chronic mucosal injury, but not active inflammation. Colectomy for refractory disease rather than presence of dysplasia was associated with increased fibrosis and a thicker muscularis mucosae, whereas a thinner muscularis mucosae was associated with anti-tumour necrosis factor therapy. No feature on endoscopic mucosal biopsies could predict the underlying amount of fibrosis or the thickness of the muscularis mucosae. CONCLUSIONS:A significant degree of fibrosis and muscularis mucosae thickening should be considered as common complications of chronic progressive ulcerative colitis. These features may have clinical consequences such as motility abnormalities and increased wall stiffness.

SUBMITTER: Gordon IO

PROVIDER: S-EPMC5842117 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Fibrosis in ulcerative colitis is directly linked to severity and chronicity of mucosal inflammation.

Gordon I O IO Agrawal N N Willis E E Goldblum J R JR Lopez R R Allende D D Liu X X Patil D Y DY Yerian L L El-Khider F F Fiocchi C C Rieder F F

Alimentary pharmacology & therapeutics 20180206 7

<h4>Background</h4>Fibrosis in ulcerative colitis has remained largely unexplored despite its clinical implications.<h4>Aims</h4>This cross-sectional study was aimed at characterising the presence, anatomical location and degree of ulcerative colitis-associated fibrosis and its possible link to clinical parameters.<h4>Methods</h4>Seven hundred and six individual tissue cross-sections derived every 10 cm along the length of 89 consecutive Ulcerative colitis colectomy specimens were examined and c ...[more]

PMID: 29411405

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Project description:ObjectiveThe pathogenesis of UC relates to gut microbiota dysbiosis. We postulate that alterations in the viral community populating the intestinal mucosa play an important role in UC pathogenesis. This study aims to characterise the mucosal virome and their functions in health and UC.DesignDeep metagenomics sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on the rectal mucosa of 167 subjects from three different geographical regions in China (UC=91; healthy controls=76). Virome and bacteriome alterations in UC mucosa were assessed and correlated with patient metadata. We applied partition around medoids clustering algorithm and classified mucosa viral communities into two clusters, referred to as mucosal virome metacommunities 1 and 2.ResultsIn UC, there was an expansion of mucosa viruses, particularly Caudovirales bacteriophages, and a decrease in mucosa Caudovirales diversity, richness and evenness compared with healthy controls. Altered mucosal virome correlated with intestinal inflammation. Interindividual dissimilarity between mucosal viromes was higher in UC than controls. Escherichia phage and Enterobacteria phage were more abundant in the mucosa of UC than controls. Compared with metacommunity 1, metacommunity 2 was predominated by UC subjects and displayed a significant loss of various viral species. Patients with UC showed substantial abrogation of diverse viral functions, whereas multiple viral functions, particularly functions of bacteriophages associated with host bacteria fitness and pathogenicity, were markedly enriched in UC mucosa. Intensive transkingdom correlations between mucosa viruses and bacteria were significantly depleted in UC.ConclusionWe demonstrated for the first time that UC is characterised by substantial alterations of the mucosa virobiota with functional distortion. Enrichment of Caudovirales bacteriophages, increased phage/bacteria virulence functions and loss of viral-bacterial correlations in the UC mucosa highlight that mucosal virome may play an important role in UC pathogenesis.

Project description:BackgroundThe significance of endoscopic evaluation in the diagnosis and management of ulcerative colitis (UC) has been widely recognized. Over the years, scholars have established several endoscopic scores. Herein, we assessed the clinical application value of the Mayo Endoscopic Subscore (Mayo ES), the Degree of Ulcerative Colitis Burden of Luminal Inflammation (DUBLIN) score, and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score in UC patients, by comparing their correlation with disease activity and their predictive potential for treatment response and clinical outcomes.MethodsUC patients hospitalized from September 2015 to September 2019 were retrospectively analysed. We employed Spearman's rank correlation coefficient to assess the linear association of the assessed endoscopic scores with the clinical parameters. The receiver-operating characteristic curve was applied to evaluate the predictive capabilities of the endoscopic scores for treatment escalation and 1-year readmission.ResultsA total of 178 patients were enrolled; most of them (82%) suffered moderate or severe colitis. Among them, 48 (27%) patients received treatment escalation and 59 (33%) were readmitted within 1 year. The DUBLIN and UCEIS scores demonstrated higher correlations with clinical parameters than the Mayo ES. The DUBLIN scores significantly differed between patients with mild, moderate, and severe colitis (all P < 0.001). The UCEIS scores demonstrated the best predictabilities for treatment escalation and 1-year readmission with an area under the curve of 0.88 and 0.75, respectively. Compared to the UCEIS and DUBLIN scores, the predictive capabilities of the Mayo ES for treatment escalation (both P < 0.001) and 1-year readmission (P < 0.001 and P = 0.002, respectively) were lower. The UCEIS scores exhibited a significant difference between the steroid-responsive group and the steroid-dependent or steroid-refractory group (both P < 0.001), while no significant differences in the Mayo ES and DUBLIN scores were found among the three groups (both P > 0.05).ConclusionThis study demonstrates that both the DUBLIN and UCEIS scores outperform the Mayo ES in assessing disease severity and predicting treatment response and clinical outcomes in UC patients.

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Fibrosis in ulcerative colitis is directly linked to severity and chronicity of mucosal inflammation.

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Fibrosis in ulcerative colitis is directly linked to severity and chronicity of mucosal inflammation.

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