Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis

Johansson, Malin; Gustafsson, Jenny; Holmén-Larsson, Jessica; Jabbar, Karolina S.; Xia, Lijun; Xu, Hua; Ghishan, Fayez K.; Carvalho, Frédéric A.; Gewirtz, Andrew T.; Sjövall, Henrik; Hansson, Gunnar C.

doi:10.1136/gutjnl-2012-303207

Cited by 737 publications

(733 citation statements)

References 38 publications

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“…The inner mucus layer of the colon is not penetrable by bacteria or fluorescent beads the size of small bacteria (0.5 to 1 μm), in contrast to the outer colon mucus layer and the WT small intestine ( Fig. 1M) (3,16). As observed previously, the small intestinal mucus of CF mice was not penetrable to these fluorescent beads (Fig.…”

Section: Resultssupporting

confidence: 49%

Microbial-induced meprin β cleavage in MUC2 mucin and a functional CFTR channel are required to release anchored small intestinal mucus

Schutte¹,

Ermund²,

Becker‐Pauly

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

165

164

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The mucus that covers and protects the epithelium of the intestine is built around its major structural component, the gel-forming MUC2 mucin. The gel-forming mucins have traditionally been assumed to be secreted as nonattached. The colon has a twolayered mucus system where the inner mucus is attached to the epithelium, whereas the small intestine normally has a nonattached mucus. However, the mucus of the small intestine of meprin β-deficient mice was now found to be attached. Meprin β is an endogenous zinc-dependent metalloprotease now shown to cleave the N-terminal region of the MUC2 mucin at two specific sites. When recombinant meprin β was added to the attached mucus of meprin β-deficient mice, the mucus was detached from the epithelium. Similar to meprin β-deficient mice, germ-free mice have attached mucus as they did not shed the membraneanchored meprin β into the luminal mucus. The ileal mucus of cystic fibrosis (CF) mice with a nonfunctional cystic fibrosis transmembrane conductance regulator (CFTR) channel was recently shown to be attached to the epithelium. Addition of recombinant meprin β to CF mucus did not release the mucus, but further addition of bicarbonate rendered the CF mucus normal, suggesting that MUC2 unfolding exposed the meprin β cleavage sites. Mucus is thus secreted attached to the goblet cells and requires an enzyme, meprin β in the small intestine, to be detached and released into the intestinal lumen. This process regulates mucus properties, can be triggered by bacterial contact, and is nonfunctional in CF due to poor mucin unfolding.protease | von Willebrand factor | gastrointestinal tract

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Section: Resultssupporting

confidence: 49%

Microbial-induced meprin β cleavage in MUC2 mucin and a functional CFTR channel are required to release anchored small intestinal mucus

Schutte¹,

Ermund²,

Becker‐Pauly

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

165

164

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“…If we will use multiple probe labeled with different fluorescent dyes, we can find an abnormality of bacteria's location and changes of bacterial composition. Intestinal bacteria was perfectly separated from epithelium by secreted mucus in the healthy condition, but penetration of bacteria into the mucus layer have been observed in experimental models and in patients with inflammatory bowel diseases (23,24).…”

Section: Culture-independent Methodsmentioning

confidence: 99%

The intestinal microbiota and its role in human health and disease

Kataoka

2016

J. Med. Invest.

120

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: The role of the intestinal microbiota in human health is gaining more attention since clear changes in the composition of the intestinal bacteria or environment are seen in patients with inflammatory bowel disease, allergy, autoimmune disease, and some lifestyle-related illnesses. A healthy gut environment is regulated by the exquisite balance of intestinal microbiota, metabolites, and the host's immune system. Imbalance of these factors in genetically susceptible persons may promote a disease state. Manipulation of the intestinal microbiota with prebiotics, which can selectively stimulate growth of beneficial bacteria, might help to maintain a healthy intestinal environment or improve diseased one. In this review, analytical methods for identification of intestinal bacteria and an update on the correlation of the intestinal microbiota with human health and disease were discussed by introducing our recent studies to determine the prebiotic effects of a fiber-rich food in animal model and on healthy people and patients with ulcerative colitis (UC).

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“…The substance is a sucrose and sulfate-aluminum complex which, when in contact with gastrointestinal secretions, forms a viscous gel that adheres to the mucosa creating a physical barrier that protects the mucosa [15][16][17][18] . The complex formed, in addition to preventing the degradation of the mucus that covers the gastrointestinal epithelium has antimicrobial properties 31,36 . Studies have shown that SCF also has a bactericidal effect, effective against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus 37 .…”

Section: Evaluation Of the Application Of Enemas Containing Sucralfatmentioning

confidence: 99%

Evaluation of the application of enemas containing sucralfate in tissue content of neutral and acid mucins in experimental model of diversion colitis

et al. 2014

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PURPOSE:To evaluate the effects of sucralfate on tissue content of neutral and acids mucins in rats with diversion colitis. METHODS:Thirty-six rats were submitted to a proximal right colostomy and a distal mucous fistula. They were divided into two groups according to sacrifice to be performed two or four weeks after intervention. Each group was divided into three subgroups according daily application of enemas containing saline, sucralfate at 1.0 g/kg/day or 2.0 g/kg/day. Colitis was diagnosed by histological analysis and neutral and acid mucins by Periodic Acid Schiff and Alcian Blue techniques, respectively. The contents of mucins were quantified by computer-assisted image analysis. Student's t paired and ANOVA test were used to compare the contents of both types of mucins among groups, and to verify the variance with time, establishing level of signification of 5% for both (p<0.05). RESULTS:Enemas containing sucralfate improves the inflammation and increases the tissue contents of neutral and acid mucins.The content of neutral mucins does not change with the time or concentration of sucralfate used, while acid mucins increases with concentration and time of intervention. CONCLUSIONS:Sucralfate enemas improve the inflammatory process and increase the tissue content of neutral and acid mucins in colon without fecal stream.

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Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis

Cited by 737 publications

References 38 publications

Microbial-induced meprin β cleavage in MUC2 mucin and a functional CFTR channel are required to release anchored small intestinal mucus

Microbial-induced meprin β cleavage in MUC2 mucin and a functional CFTR channel are required to release anchored small intestinal mucus

The intestinal microbiota and its role in human health and disease

Evaluation of the application of enemas containing sucralfate in tissue content of neutral and acid mucins in experimental model of diversion colitis

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