Thickness and continuity of the adherent colonic mucus barrier in active and quiescent ulcerative colitis and Crohn’s disease

Strugala, Vicki; Dettmar, PW; Pearson, Jeffrey P.

doi:10.1111/j.1742-1241.2007.01665.x

Cited by 166 publications

(122 citation statements)

References 25 publications

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“…For mild and moderate UC, the synthesis of secretory mucins in UC was controversially reported, showing all directions -no change [45,46], increase [47] or decrease [48] -in the cultures of tissue biopsies when compared to healthy controls. However, the thickness of the adherent mucus gel was found generally lower or unchanged [44,49], possibly due to excessive removal. In severe UC, both synthesis of mucins and the thickness of mucus barrier substantially declined [48][49][50].…”

Section: Discussionmentioning

confidence: 99%

“…However, the thickness of the adherent mucus gel was found generally lower or unchanged [44,49], possibly due to excessive removal. In severe UC, both synthesis of mucins and the thickness of mucus barrier substantially declined [48][49][50]. The decreased mucin levels confirmed that the lower lipid/protein ratio in UC is due to an even larger scale of reduction in lipids.…”

Section: Discussionmentioning

confidence: 99%

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In vivo analysis of mucosal lipids reveals histological disease activity in ulcerative colitis using endoscope-coupled Raman spectroscopy

Ding

Dupont

Singhal

et al. 2017

Biomed. Opt. Express

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Abstract:The goal of this study is to evaluate endoscopic Raman spectroscopy as a noninvasive technique to determine histological inflammatory status of colitis. Colon mucosal composition was investigated in vivo from patients with ulcerative colitis (UC) and from ageand body mass index (BMI) matched controls using endoscope-coupled Raman spectroscopy. The results were co-registered with histological assessment of inflammatory status at the same locations. Substantial decreases (50-60%) in the content of phosphotidylcholines (PCs) and total lipids were observed in inflamed colon tissue (histology grade 1, 2 and 3) compared to those from the quiescent (histology grade 0) and from the controls. No significant difference was observed in lipids or PC contents between control and grade 0, or among grades 1 -3. The degree of lipid unsaturation increased in the inflamed tissue regardless of disease severity. The inflammation-associated alterations in lipids and PC are observed independent of BMI or the anatomical locations for data collection. Multivariate analysis using support vector machine (SVM) algorithm classified the spectra of the controls or the inactive colitis from those of inflamed tissue with a sensitivity of 83.5% and 97.1% respectively. Our results showed that mucosal lipid content is related to the microscopic disease activity, and thus could serve as a valuable spectral marker to differentiate active colitis from the quiescent. References and links1. E. V. Loftus, Jr., "Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences," Gastroenterology 126(6), 1504-1517 (2004). 2. J. Misiewicz, J. Lennard-Jones, A. Connell, J. Baron, and F. A. Jones, "Controlled trial of sulphasalazine in maintenance therapy for ulcerative colitis," Lancet 285(7378), 185-188 (1965

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

In vivo analysis of mucosal lipids reveals histological disease activity in ulcerative colitis using endoscope-coupled Raman spectroscopy

Ding

Dupont

Singhal

et al. 2017

Biomed. Opt. Express

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“…Besides the selective degradation of prebiotics by specific butyrate producers Schwiertz et al, 2002), stimulating mucus secretion may be a mechanism by which prebiotics increase butyrate levels. A second example is IBD, a disease in which the mucus layer becomes thinner and more discontinuous (Strugala et al, 2008). Recent in vivo (Swidsinski et al, 2005;Sokol et al, 2008;Walker et al, 2011) and in vitro (Vermeiren et al, 2012) studies revealed that this disease correlates with lower levels of mucosal butyrate producers, including Roseburia and Faecalibacterium, indicating that a damaged mucus layer may lower the ecological fitness of specific butyrate producers.…”

Section: Discussionmentioning

confidence: 99%

Butyrate-producing Clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model

et al. 2012

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The human gut is colonized by a complex microbiota with multiple benefits. Although the surfaceattached, mucosal microbiota has a unique composition and potential to influence human health, it remains difficult to study in vivo. Therefore, we performed an in-depth microbial characterization (human intestinal tract chip (HITChip)) of a recently developed dynamic in vitro gut model, which simulates both luminal and mucosal gut microbes (mucosal-simulator of human intestinal microbial ecosystem (M-SHIME)). Inter-individual differences among human subjects were confirmed and microbial patterns unique for each individual were preserved in vitro. Furthermore, in correspondence with in vivo studies, Bacteroidetes and Proteobacteria were enriched in the luminal content while Firmicutes rather colonized the mucin layer, with Clostridium cluster XIVa accounting for almost 60% of the mucin-adhered microbiota. Of the many acetate and/or lactate-converting butyrate producers within this cluster, Roseburia intestinalis and Eubacterium rectale most specifically colonized mucins. These 16S rRNA gene-based results were confirmed at a functional level as butyryl-CoA:acetate-CoA transferase gene sequences belonged to different species in the luminal as opposed to the mucin-adhered microbiota, with Roseburia species governing the mucosal butyrate production. Correspondingly, the simulated mucosal environment induced a shift from acetate towards butyrate. As not only inter-individual differences were preserved but also because compared with conventional models, washout of relevant mucin-adhered microbes was avoided, simulating the mucosal gut microbiota represents a breakthrough in modeling and mechanistically studying the human intestinal microbiome in health and disease. Finally, as mucosal butyrate producers produce butyrate close to the epithelium, they may enhance butyrate bioavailability, which could be useful in treating diseases, such as inflammatory bowel disease.

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“…Interestingly, MUB 70 is not toxic for living cells as it has no cell penetration property, allowing its specific localization in the mucus layer located on the epithelium surface. In addition to the colonic mucinous carcinoma (30), Muc2 expression is up-regulated in mucinous carcinomas affecting various organs (31), including the lung (32), the stomach (33,34), the breast (35), the prostate (36), and the bile ducts (37). Hence, targeting Muc2 with MUB 70 , as observed on human colonic mucinous carcinomas, is anticipated to provide promising innovative approaches to develop new prognosis and diagnostic tools on various mucinous carcinomas.…”

Section: Discussionmentioning

confidence: 99%

Design of a Specific Colonic Mucus Marker Using a Human Commensal Bacterium Cell Surface Domain

Coïc

Baleux

Poyraz

et al. 2012

Journal of Biological Chemistry

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Background: Imaging colonic mucus on living cells, tissues, and organs is required for live microscopy. Results: We have identified, synthesized, and validated a new human colonic mucus bacterial marker (MUB 70 ). Conclusion: This non-toxic marker is used to image the secreted colonic mucus. Significance: Beyond imaging applications, Cy5-MUB 70 might be used for diagnostic and prognosis applications on colonic mucinous carcinoma.

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Thickness and continuity of the adherent colonic mucus barrier in active and quiescent ulcerative colitis and Crohn’s disease

Abstract: It is not until severe UC that there is a global change in mucosal protection as a consequence of large regions lacking mucus, a decrease in secretory potential caused by a loss of goblet cells and a thinner, less effective mucus layer even when it is present.

Cited by 166 publications

References 25 publications

In vivo analysis of mucosal lipids reveals histological disease activity in ulcerative colitis using endoscope-coupled Raman spectroscopy

In vivo analysis of mucosal lipids reveals histological disease activity in ulcerative colitis using endoscope-coupled Raman spectroscopy

Butyrate-producing Clostridium cluster XIVa species specifically colonize mucins in an in vitro gut model

Design of a Specific Colonic Mucus Marker Using a Human Commensal Bacterium Cell Surface Domain

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