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      The Interaction of the Gut Microbiota with the Mucus Barrier in Health and Disease in Human

      review-article
      Microorganisms
      MDPI
      gastrointestinal, glycoprotein, glycosylation, glycan, glycocode, microbiota, mucus, mucin, mucosal

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          Abstract

          Glycoproteins are major players in the mucus protective barrier in the gastrointestinal and other mucosal surfaces. In particular the mucus glycoproteins, or mucins, are responsible for the protective gel barrier. They are characterized by their high carbohydrate content, present in their variable number, tandem repeat domains. Throughout evolution the mucins have been maintained as integral components of the mucosal barrier, emphasizing their essential biological status. The glycosylation of the mucins is achieved through a series of biosynthetic pathways processes, which generate the wide range of glycans found in these molecules. Thus mucins are decorated with molecules having information in the form of a glycocode. The enteric microbiota interacts with the mucosal mucus barrier in a variety of ways in order to fulfill its many normal processes. How bacteria read the glycocode and link to normal and pathological processes is outlined in the review.

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          Most cited references472

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          The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions.

          The normal intestinal microbiota inhabits the colon mucus without triggering an inflammatory response. The reason for this and how the intestinal mucus of the colon is organized have begun to be unraveled. The mucus is organized in two layers: an inner, stratified mucus layer that is firmly adherent to the epithelial cells and approximately 50 μm thick; and an outer, nonattached layer that is usually approximately 100 μm thick as measured in mouse. These mucus layers are organized around the highly glycosylated MUC2 mucin, forming a large, net-like polymer that is secreted by the goblet cells. The inner mucus layer is dense and does not allow bacteria to penetrate, thus keeping the epithelial cell surface free from bacteria. The inner mucus layer is converted into the outer layer, which is the habitat of the commensal flora. The outer mucus layer has an expanded volume due to proteolytic activities provided by the host but probably also caused by commensal bacterial proteases and glycosidases. The numerous O-glycans on the MUC2 mucin not only serve as nutrients for the bacteria but also as attachment sites and, as such, probably contribute to the selection of the species-specific colon flora. This observation that normal human individuals carry a uniform MUC2 mucin glycan array in colon may indicate such a specific selection.
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            The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences.

            Campylobacter jejuni, from the delta-epsilon group of proteobacteria, is a microaerophilic, Gram-negative, flagellate, spiral bacterium-properties it shares with the related gastric pathogen Helicobacter pylori. It is the leading cause of bacterial food-borne diarrhoeal disease throughout the world. In addition, infection with C. jejuni is the most frequent antecedent to a form of neuromuscular paralysis known as Guillain-Barré syndrome. Here we report the genome sequence of C. jejuni NCTC11168. C. jejuni has a circular chromosome of 1,641,481 base pairs (30.6% G+C) which is predicted to encode 1,654 proteins and 54 stable RNA species. The genome is unusual in that there are virtually no insertion sequences or phage-associated sequences and very few repeat sequences. One of the most striking findings in the genome was the presence of hypervariable sequences. These short homopolymeric runs of nucleotides were commonly found in genes encoding the biosynthesis or modification of surface structures, or in closely linked genes of unknown function. The apparently high rate of variation of these homopolymeric tracts may be important in the survival strategy of C. jejuni.
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              Mucins in cancer: protection and control of the cell surface.

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                Author and article information

                Journal
                Microorganisms
                Microorganisms
                microorganisms
                Microorganisms
                MDPI
                2076-2607
                02 August 2018
                September 2018
                : 6
                : 3
                : 78
                Affiliations
                Mucin Research Group, School of Clinical Sciences, Bristol Royal Infirmary, Level 7, Marlborough Street, Bristol BS2 8HW, UK; mdapc@ 123456bristol.ac.uk
                Author information
                https://orcid.org/0000-0003-3380-0242
                Article
                microorganisms-06-00078
                10.3390/microorganisms6030078
                6163557
                30072673
                719bb8fd-59ed-44bf-8ce5-744763400564
                © 2018 by the author.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 June 2018
                : 30 July 2018
                Categories
                Review

                gastrointestinal,glycoprotein,glycosylation,glycan,glycocode,microbiota,mucus,mucin,mucosal

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