Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously, we describe a unique binding site for the Fc region of IgG in human intestinal goblet cells, but regulation of the intestinal IgG Fc binding site (Fc gamma IBS) has not been clarified. In this work, we examined the effects of tumour necrosis-alpha (TNF-alpha) and interferon gamma (IFN-gamma) on expression of the Fc gamma IBS in HT29-N2 colonic cancer cells, which differentiate readily into goblet cells containing the binding site when grown in galactose-containing medium. Expression of the site was monitored immunocytochemically and by ELISA on homogenates of the cells. TNF-alpha in doses of 0.1-100 ng/ml caused a reduction in expression of the Fc gamma IBS and the proportion of cells positive for mucin (as demonstrated by Alcian blue stain), without affecting the viability of the cells. The effects of TNF-alpha on the FC gamma IBS and mucin production could not be attributed to a decreased proliferative rate of the cells, as the cells' incorporation of 5-bromo-2'-deoxyuridine was unaffected. By contrast with TNF-alpha, IFN-gamma (i) did not affect the proportion of cells expressing the Fc gamma IBS, (ii) decreased the viability of the cells, and (iii) increased cell proliferation. Additional evidence of specificity of the TNF-alpha effect on the Fc gamma IBS was that TNF-alpha did not affect expression of the polymeric immunoglobulin receptor (secretory component), whereas IFN-gamma increased it. We conclude that TNF-alpha may suppress expression of the Fc gamma IBS by colonocytes and oppose differentiation of the cells towards mucin-producing cells.
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PMID:Tumour necrosis factor-alpha decreases expression of the intestinal IgG Fc binding site by HT29-N2 cells. 174 77

Lectin binding of goblet cell mucin in human colonic mucosa was studied in patients with irritable bowel syndrome, colorectal malignancy and ulcerative colitis using plant lectins, Dolichos biflorus agglutinin (DBA) and peanut agglutinin (PNA). Normal colonic mucosa demonstrated a strong binding with DBA (100%) but did not bind to PNA at all. Colonic carcinomas showed strong PNA binding (7 of 15 biopsies) while DBA binding was absent in 14 of 15 biopsies. The transitional mucosa showed reduced or absent DBA binding in 6 and positive PNA binding in 2 of 15 biopsies. During the active phase of ulcerative colitis, there was a loss of DBA binding in 10 of 15 biopsies, which was restored during remission in all. One biopsy with severe dysplasia showed PNA binding. It is concluded that normal colorectal mucosa binds DBA strongly but not PNA. Malignant tissue and transitional mucosa reveal PNA binding often, with decreased DBA binding. In ulcerative colitis DBA binding decreases during phases of activity.
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PMID:Lectin binding in colorectal mucosa. 291 16

Mucus secreted by colorectal cancer differs in three respects from that produced normally: an overall reduction, a loss of O-acetyl substituents in sialic acid, and an increase in neutral mucin. Similar changes have been reported in apparently normal mucosa bordering colorectal cancer. "Normal" left sided colorectal mucosa from 32 patients with rectal cancer was studied. Each case was matched by age and sex to a patient with diverticular disease and a patient with irritable bowel syndrome. Twenty five patients with right sided cancer were matched to patients with Crohn's disease. Sections were stained with mild periodic acid Schiff (mPAS) (selectively stains N-acetyl sialic acid lacking in O-acetyl group) and other closely related techniques. Reactions were graded negative, weak, and intense. An intense reaction was found in 9% of cases; there was no difference between the various matched groups. Phenylhydrazine interposition failed to block the mPAS effect, indicating that a positive result was due to a deficiency of sialic acid with O-acetyl substituents rather than neutral mucin. Different staining patterns in left and right colon were probably due to differing ratios of total sialic acid:fucose. These findings indicate a hitherto unsuspected colorectal goblet cell sialomucin heterogeneity within the general population, but no association with neoplastic disease is apparent.
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PMID:Colorectal goblet cell sialomucin heterogeneity: its relation to malignant disease. 378 84

When exposed to prolonged stress, rats develop gastric ulceration, enhanced colon motility with depletion of its mucin content and signs of physiological and behavioral arousal. In this model, we tested whether antidepressants (fluoxetine and bupropion), anxiolytics (diazepam and buspirone) or the novel nonpeptide corticotropin-releasing hormone (CRH) type-1 receptor (CRH-R1) antagonist, antalarmin, modify these responses. Fluoxetine, bupropion, diazepam and antalarmin all suppressed stress-induced gastric ulceration in male Sprague-Dawley rats exposed to four hours of plain immobilization. Antalarmin produced the most pronounced anti-ulcer effect and additionally suppressed the stress-induced colonic hypermotility, mucin depletion, autonomic hyperarousal and struggling behavior. Intraperitoneal CRH administration reproduced the intestinal but not the gastric responses to stress while vagotomy antagonized the stress-induced gastric ulceration but not the intestinal responses. We conclude that brain CRH-R1 and vagal pathways are essential for gastric ulceration to occur in response to stress and that peripheral CRH-R1 mediates colonic hypermotility and mucin depletion in this model. Nonpeptide CRH-R1 antagonists may therefore be prophylactic against stress ulcer in the critically ill and therapeutic for other pathogenetically related gastrointestinal disorders such as peptic ulcer disease and irritable bowel syndrome.
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PMID:Marked suppression of gastric ulcerogenesis and intestinal responses to stress by a novel class of drugs. 1208 65

HLA-B27 transgenic rats spontaneously developing a chronic inflammation mainly involving the colon are recognized as a powerful animal model for IBD. We investigated the mucin production in 6-month-old HLA-B27 rats by measuring in vivo fractional synthesis rate (FSR) and expression of mucins. In the inflamed colon of HLA-B27 rats, the mucin FSR was stimulated by 75% compared to F-344 controls, while MUC2,3 mRNA expression was unchanged. A local depletion in mucus-containing goblet cells was observed, suggesting a rapid mucin production/release and/or a real global decrease in goblet cell number. In the noninflamed jejunum of HLA-B27 rats, the mucin FSR was reduced by 35% compared to controls, while MUC2,3 mRNA expression was unchanged. Different alterations in mucin metabolism and expression are observed between HLA-B27 rats and a model of chemically induced chronic colitis (DSS-treated rats), suggesting that mucin alterations may be dependent on the animal model and colitis underlying mechanism.
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PMID:The chronic colitis developed by HLA-B27 transgenic rats is associated with altered in vivo mucin synthesis. 1510 81

The irritable bowel syndrome (IBS) follows an acute, presumably infectious diarrheal illness in approximately 15% of patients. There may be a persistent, mild inflammatory state with changes in mucosal function or structure. Changes in the colonic bacterial flora reported in IBS seem related to predominant bowel. Colonic bacteria normally metabolize nutrients with the formation of gas and short chain fatty acids. The latter may induce propulsive contractions and accelerate colonic transit or they may enhance fluid and sodium absorption in the colon. This review addresses the mechanisms, rationale and current evidence for the efficacy of probiotics, including Lactobacilli, Bifidobacteria, and VSL#3, in the treatment of IBS. The mechanisms influenced by probiotics include immune function, motility, and the intraluminal milieu. Probiotics may suppress the low-grade inflammation associated with IBS or restore normal local immune function. Lactobacilli and Bifidobacteria subspecies are able to deconjugate and absorb bile acids, potentially reducing the colonic mucosal secretion of mucin and fluids that may contribute to functional diarrhea or IBS with diarrhea. Therapeutic trials show the potential benefit of Bifidobacteria or Lactobacilli species alone or in the specific probiotic combination, VSL#3, on symptoms in IBS. Colonic transit was retarded in IBS patients treated with VSL#3 without induction of significant changes in bowel function. In summary, probiotics are promising therapies in IBS.
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PMID:Probiotics and irritable bowel syndrome: rationale, putative mechanisms, and evidence of clinical efficacy. 1663 34

There is an upsurge of interest in gastro-intestinal microbiology to improve the balance between positive and negative commensals. Mucosal bacteria make closer contact with the host than luminal ones and can therefore have a stronger health impact. An in vitro adhesion assay was developed to study the mucin colonization of bacteria from the mixed microbial communities of the Simulator of the Human Intestinal Microbial Ecosystem. Adhesion capacity differed substantially between bacteria and decreased from lactobacilli over fecal coliforms, bifidobacteria, and clostridia to total anaerobes. Lactobacillus rhamnosus GG adhered most selectively. Further, intestinal water lowered adhesion compared to phosphate-buffered saline. By processing the data to an Adhesion-Related Prebiotic Index, it was found that intestinal water stimulated adherence of positive commensals. Arabinoxylans decreased the adhesion capacity matrix independently, whereas inulin had less or no influence. Measurements of bacterial surface tension, surface hydrophobicity, liquid surface tension, and viscosity showed that bacterial adhesion to mucin agar is a matter of both non-specific and specific interactions. The developed methodology can be useful for the characterization of the relevant but barely investigated mucin-associated bacterial community in health and disease (e.g., IBD) as well as for its modulation with functional foods like prebiotics.
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PMID:In vitro model to study the modulation of the mucin-adhered bacterial community. 1930 5

The colonic ecosystem differs from that in the proximal gut in several important respects. The colonic microbiota represents the largest population of microbes colonizing humans from birth. Constraints on bacterial numbers, composition, and interaction with the host involve not only the innate and acquired immune system, but also the colonic mucin structure. While the microbiota provides beneficial protective, trophic, nutritional, and metabolic signals for the host, it may become a risk factor for disease depending on context and host susceptibility. Technological advances including DNA-based high-throughput compositional analysis have linked changes in the indigenous microbiota with several human diseases. In some instances, these findings have the potential to serve as new biomarkers of risk of disease. In this overview, recent advances are focused upon in relation to irritable bowel syndrome, inflammatory bowel disease, and colon cancer. The possibility that the therapeutic solution to some of these disorders may reside within the microbiota will also be addressed.
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PMID:The colonic microbiota and colonic disease. 2294 33

There is extensive evidence implicating the intestinal microbiota in inflammatory bowel disease [IBD], but no microbial agent has been identified as a sole causative agent. Bacteroidales are numerically dominant intestinal organisms that associate with the mucosal surface and have properties that both positively and negatively affect the host. To determine precise numbers and species of Bacteroidales adherent to the mucosal surface in IBD patients, we performed a comprehensive culture based analysis of intestinal biopsies from pediatric Crohn's disease [CD], ulcerative colitis [UC], and control subjects. We obtained biopsies from 94 patients and used multiplex PCR or 16S rDNA sequencing of Bacteroidales isolates for species identification. Eighteen different Bacteroidales species were identified in the study group, with up to ten different species per biopsy, a number higher than demonstrated using 16S rRNA gene sequencing methods. Species diversity was decreased in IBD compared to controls and with increasingly inflamed tissue. There were significant differences in predominant Bacteroidales species between biopsies from the three groups and from inflamed and uninflamed sites. Parabacteroides distasonis significantly decreased in inflamed tissue. All 373 Bacteroidales isolates collected in this study grew with mucin as the only utilizable carbon source suggesting this is a non-pathogenic feature of this bacterial order. Bacteroides fragilis isolates with the enterotoxin gene [bft], previously associated with flares of colitis, were not found more often at inflamed colonic sites or within IBD subjects. B. fragilis isolates with the ability to synthesize the immunomodulatory polysaccharide A [PSA], previously shown to be protective in murine models of colitis, were not detected more often from healthy versus inflamed tissue.
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PMID:Characterization of adherent bacteroidales from intestinal biopsies of children and young adults with inflammatory bowel disease. 2377 34

Despite well-known intestinal epithelial barrier impairment and visceral hypersensitivity in irritable bowel syndrome (IBS) patients and IBS-like models, structural and physical changes in the mucus layer remain poorly understood. Using a water avoidance stress (WAS) model, we aimed at evaluating whether 1) WAS modified gut permeability, visceral sensitivity, mucin expression, biochemical structure of O-glycans, and related mucus physical properties, and 2) whether Lactobacillus farciminis treatment prevented these alterations. Wistar rats received orally L. farciminis or vehicle for 14 days; at day 10, they were submitted to either sham or 4-day WAS. Intestinal paracellular permeability and visceral sensitivity were measured in vivo. The number of goblet cells and Muc2 expression were evaluated by histology and immunohistochemistry, respectively. Mucosal adhesion of L. farciminis was determined ex situ. The mucin O-glycosylation profile was obtained by mass spectrometry. Surface imaging of intestinal mucus was performed at nanoscale by atomic force microscopy. WAS induced gut hyperpermeability and visceral hypersensitivity but did not modify either the number of intestinal goblet cells or Muc2 expression. In contrast, O-glycosylation of mucins was strongly affected, with the appearance of elongated polylactosaminic chain containing O-glycan structures, associated with flattening and loss of the mucus layer cohesive properties. L. farciminis bound to intestinal Muc2 and prevented WAS-induced functional alterations and changes in mucin O-glycosylation and mucus physical properties. WAS-induced functional changes were associated with mucus alterations resulting from a shift in O-glycosylation rather than from changes in mucin expression. L. farciminis treatment prevented these alterations, conferring epithelial and mucus barrier strengthening.
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PMID:Stress disrupts intestinal mucus barrier in rats via mucin O-glycosylation shift: prevention by a probiotic treatment. 2497 Jul 79


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