Abnormal Mucosal Glycoprotein Synthesis in Inflammatory Bowel Is Not Related to Cigarette Smoking

Ryder, Stephen; Raouf, Ahmed A.; Parker, N.; Walker, Robert J.; Rhodes, JM

doi:10.1159/000201261

Cited by 17 publications

(10 citation statements)

References 17 publications

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“…The thickness of mucus layer is determined by the dynamic equilibrium between secretion of mucins and its removal into the lumen [44]. 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.…”

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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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%

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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“…Mucus synthesis has been shown to be normal in non-inflamed colonic mucosal explants from UC patients but is likely to be reduced in active colitis [32]. An alternative explanation for the striking lack of the mucus layer in active colitis could be increased enzymatic breakdown of the secreted mucus.…”

Section: Alterations In the Mucosal Barrier In Inflammatory Bowel Dismentioning

confidence: 99%

Mucosal Barrier, Bacteria and Inflammatory Bowel Disease: Possibilities for Therapy

Merga

Campbell

Rhodes

2014

Dig Dis

157

113

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The mucosal barrier has three major components, the mucus layer, the epithelial glycocalyx and the surface epithelium itself, whose integrity largely depends on tight junction function. In health, there is relatively little direct interaction between the luminal microbiota and the epithelium - the continuous mucus layer in the colon keeps the surface epithelium out of contact with bacteria and the ileo-caecal valve ensures that the distal small intestine is relatively microbe free. Most interaction takes place at the Peyer's patches in the distal ileum and their smaller colonic equivalents, the lymphoid follicles. Peyer's patches are overlain by a ‘dome' epithelium, 5% of whose cells are specialised M (microfold) epithelial cells, which act as the major portal of entry for bacteria. There are no goblet cells in the dome epithelium and M cells have a very sparse glycocalyx allowing easy microbial interaction. It is intriguing that the typical age range for the onset of Crohn's disease (CD) is similar to the age at which the number of Peyer's patches is greatest. Peyer's patches are commonly the sites of the initial lesions in CD and the ‘anti-pancreatic' antibody associated with CD has been shown to have as its epitope the glycoprotein 2 that is the receptor for type-1 bacterial fimbrial protein (fimH) on M cells. There are many reasons to believe that the mucosal barrier is critically important in the pathogenesis of inflammatory bowel disease (IBD). These include (i) associations between both CD and ulcerative colitis (UC) with genes that are relevant to the mucosal barrier; (ii) increased intestinal permeability in unaffected relatives of CD patients; (iii) increased immune reactivity against bacterial antigens, and (iv) animal models in which altered mucosal barrier, e.g. denudation of the mucus layer associated with oral dextran sulphate in rodents, induces colitis. Whilst some IBD patients may have genetic factors leading to weakening of the mucosal barrier, it is likely that environmental factors may be even more important. Some may be subtle and indirect, e.g. the effects of stress on the mucosa barrier, whilst others may be more obvious, e.g. the effect of pathogen-related gastroenteritis, known often to act as trigger for IBD relapse. We have also been very interested in the potentially harmful effects of ingested detergents - either by contamination of cutlery by inadequate rinsing or via ingestion of processed foods containing permitted emulsifiers. In vitro and ex vivo studies show that even very small trace amounts of these surfactants can greatly increase bacterial translocation. Implications for therapy are not yet so obvious. We advise our IBD patients to avoid processed foods containing emulsifiers and to rinse their dishes well - whilst accepting that there is no direct evidence yet to support this. Therapies that aim to enhance the mucosal barrier have yet to come to market, but trials of enteric-delivered phosphatidylcholine in UC are promising. The faecal concentration of mucus-degrading bact...

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“…It has been speculated that some of the protective effect of smoking may be related to nicotine, and nicotine patches have been used, with some benefit, to treat UC [25,261. Previous work has suggested that mucosal biopsies from smokers with UC have higher rates of mucin synthesis when cultured in uitro than biopsies from non-smokers [27], although studies on mucosal biopsies in uitro from smoking and non-smoking control subjects have failed to show any such effect [28]. Furthermore, nicotine infusions in rabbits have an unusual effect on mucus thickness in the colon; causing a reduction in the thickness at very low concentrations, and an increase at higher concentrations [29].…”

Section: Disc U Sslo Nmentioning

confidence: 99%

Stimulation of Colonic Mucin Synthesis by Corticosteroids and Nicotine

et al. 1996

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1. We speculated that corticosteroids might cause beneficial stimulation of mucus synthesis, since this is a known action of carbenoxolone, itself a corticosteroid, and has also been proposed as a possible mechanism for the protective effect of smoking on ulcerative colitis. We have therefore compared the effects of corticosteroids including carbenoxolone, and nicotine on mucin synthesis, assessed by incorporation of N-[3H]acetylglucosamine into mucin by colonic epithelial biopsies in culture. 2. In histologically normal biopsies from the left colon, hydrocortisone and prednisolone caused a very marked concentration-dependent increase in mucin synthesis, with maximal effect (580 and 300% of control values respectively) at 6 mumol/l [P < 0.001, n = 35 biopsies (seven patients)] and 1.5 mumol/l [P < 0.001, n = 35 (seven patients)] respectively. The maximal effect of hydrocortisone was significantly greater than that of prednisolone (P < 0.05). Carbenoxolone, 0.17 mmol/l, also increased mucin synthesis in the left colon by 242% [P < 0.05, n = 15 (three patients)]. In contrast, these corticosteroids caused only a small, non-significant increase in mucin synthesis in the histologically normal right colon; fludrocortisone, 2 and 20 mumol/l, and aldosterone, 0.1-10 mumol/l, had no effect. Nicotine significantly increased mucin synthesis (180-220% of control values) between 62.5 nmol/l and 6.25 mumol/l (P < 0.05 at all concentrations) in both the right and left colon. In biopsies from the relatively uninvolved right colon of patients with ulcerative colitis, corticosteroids and nicotine caused relatively smaller increases in mucin synthesis. 3. The marked stimulation of mucin synthesis by corticosteroids suggests that this may account, at least in part, for their therapeutic effect in ulcerative colitis.

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Abnormal Mucosal Glycoprotein Synthesis in Inflammatory Bowel Is Not Related to Cigarette Smoking

Cited by 17 publications

References 17 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

Mucosal Barrier, Bacteria and Inflammatory Bowel Disease: Possibilities for Therapy

Stimulation of Colonic Mucin Synthesis by Corticosteroids and Nicotine

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