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      Mucus and mucins in diseases of the intestinal and respiratory tracts

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      1 ,
      Journal of Internal Medicine
      John Wiley and Sons Inc.
      COPD, cystic fibrosis, mucin, mucus, ulcerative colitis

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          Abstract

          This review describes the organization and importance of mucus in the intestine and lungs in relation to the diseases cystic fibrosis ( CF), ulcerative colitis and chronic obstructive pulmonary disease (COPD). The inner surfaces of the body are protected by mucus built around polymeric glycoproteins called mucins. In the disease CF, the small intestinal mucus is in contrast the normal attached to the epithelium, explaining the intestinal problems at this disease. The inner of the two mucus layers of colon is normally impenetrable to bacteria, keeping the commensals away from and protecting the epithelium. This impenetrable property is dependent on the bacterial composition and the host diet, observations that can explain the increased incidence of inflammatory bowel diseases in the western world as bacteria reach the epithelial cells in active ulcerative colitis. The respiratory tract is normally cleared by thick mucus bundles that moved by the cilia sweep the epithelial surface. In CF, the bundles are nonmoving already at birth. Cholinergic stimulations stop the bundle movement explaining some of the beneficial effect of anticholinergic treatment in COPD. In this disease as well as in more developed CF, an attached mucus layer is formed. This mucus has features similar to the protective inner colon mucus and is by this able to separate bacteria from the epithelial surface. When formed in healthy individuals this mucus can be coughed up, but in chronically diseased lungs, bacteria colonizing the mucus will remain in the lungs and the resulting inflammation contribute to the destruction of the lungs.

          Abstract

          Content List ‐ 15th Key symposium ‐ “Innate immunity”.

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          Most cited references33

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          Energy contributions of volatile fatty acids from the gastrointestinal tract in various species.

          E BERGMAN (1990)
          The VFA, also known as short-chain fatty acids, are produced in the gastrointestinal tract by microbial fermentation of carbohydrates and endogenous substrates, such as mucus. This can be of great advantage to the animal, since no digestive enzymes exist for breaking down cellulose or other complex carbohydrates. The VFA are produced in the largest amounts in herbivorous animal species and especially in the forestomach of ruminants. The VFA, however, also are produced in the lower digestive tract of humans and all animal species, and intestinal fermentation resembles that occurring in the rumen. The principal VFA in either the rumen or large intestine are acetate, propionate, and butyrate and are produced in a ratio varying from approximately 75:15:10 to 40:40:20. Absorption of VFA at their site of production is rapid, and large quantities are metabolized by the ruminal or large intestinal epithelium before reaching the portal blood. Most of the butyrate is converted to ketone bodies or CO2 by the epithelial cells, and nearly all of the remainder is removed by the liver. Propionate is similarly removed by the liver but is largely converted to glucose. Although species differences exist, acetate is used principally by peripheral tissues, especially fat and muscle. Considerable energy is obtained from VFA in herbivorous species, and far more research has been conducted on ruminants than on other species. Significant VFA, however, are now known to be produced in omnivorous species, such as pigs and humans. Current estimates are that VFA contribute approximately 70% to the caloric requirements of ruminants, such as sheep and cattle, approximately 10% for humans, and approximately 20-30% for several other omnivorous or herbivorous animals. The amount of fiber in the diet undoubtedly affects the amount of VFA produced, and thus the contribution of VFA to the energy needs of the body could become considerably greater as the dietary fiber increases. Pigs and some species of monkey most closely resemble humans, and current research should be directed toward examining the fermentation processes and VFA metabolism in those species. In addition to the energetic or nutritional contributions of VFA to the body, the VFA may indirectly influence cholesterol synthesis and even help regulate insulin or glucagon secretion. In addition, VFA production and absorption have a very significant effect on epithelial cell growth, blood flow, and the normal secretory and absorptive functions of the large intestine, cecum, and rumen. The absorption of VFA and sodium, for example, seem to be interdependent, and release of bicarbonate usually occurs during VFA absorption.(ABSTRACT TRUNCATED AT 400 WORDS)
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            Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters.

            Although biosynthetic gene clusters (BGCs) have been discovered for hundreds of bacterial metabolites, our knowledge of their diversity remains limited. Here, we used a novel algorithm to systematically identify BGCs in the extensive extant microbial sequencing data. Network analysis of the predicted BGCs revealed large gene cluster families, the vast majority uncharacterized. We experimentally characterized the most prominent family, consisting of two subfamilies of hundreds of BGCs distributed throughout the Proteobacteria; their products are aryl polyenes, lipids with an aryl head group conjugated to a polyene tail. We identified a distant relationship to a third subfamily of aryl polyene BGCs, and together the three subfamilies represent the largest known family of biosynthetic gene clusters, with more than 1,000 members. Although these clusters are widely divergent in sequence, their small molecule products are remarkably conserved, indicating for the first time the important roles these compounds play in Gram-negative cell biology. Copyright © 2014 Elsevier Inc. All rights reserved.
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              Immunological aspects of intestinal mucus and mucins.

              A number of mechanisms ensure that the intestine is protected from pathogens and also against our own intestinal microbiota. The outermost of these is the secreted mucus, which entraps bacteria and prevents their translocation into the tissue. Mucus contains many immunomodulatory molecules and is largely produced by the goblet cells. These cells are highly responsive to the signals they receive from the immune system and are also able to deliver antigens from the lumen to dendritic cells in the lamina propria. In this Review, we will give a basic overview of mucus, mucins and goblet cells, and explain how each of these contributes to immune regulation in the intestine.
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                Author and article information

                Contributors
                gunnar.hansson@medkem.gu.se
                Journal
                J Intern Med
                J. Intern. Med
                10.1111/(ISSN)1365-2796
                JOIM
                Journal of Internal Medicine
                John Wiley and Sons Inc. (Hoboken )
                0954-6820
                1365-2796
                22 April 2019
                May 2019
                : 285
                : 5 ( doiID: 10.1111/joim.2019.285.issue-5 )
                : 479-490
                Affiliations
                [ 1 ] Department of Medical Biochemistry University of Gothenburg Gothenburg Sweden
                Author notes
                [*] [* ] Correspondence: Gunnar C. Hansson, Department of Medical Biochemistry, University of Gothenburg, Medicinaregatan 9A, Box 440, 405 30 Gothenburg, Sweden.

                (fax: +46 31 786 3150; e‐mail: gunnar.hansson@ 123456medkem.gu.se ).

                Author information
                https://orcid.org/0000-0002-1900-1869
                Article
                JOIM12910
                10.1111/joim.12910
                6497544
                30963635
                fe607f67-9fe9-4de4-9391-55057fc99301
                © 2019 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 5, Tables: 2, Pages: 12, Words: 7858
                Funding
                Funded by: Vetenskapsrådet
                Award ID: 2017‐00958
                Funded by: Swedish CF Foundation
                Funded by: Swedish State under the agreement between the Swedish Government and the County Council, The ALF agreement
                Award ID: 236501
                Funded by: IngaBritt and Arne Lundberg Foundation
                Funded by: H2020 European Research Council
                Award ID: 694181
                Funded by: The Cystic Fibrosis Foundation
                Funded by: Erica Lederhausen's Foundation
                Funded by: Lederhausen's Center for CF Research at Univ. Gothenburg
                Funded by: Swedish Cancer Foundation
                Funded by: Wilhelm and Martina Lundgren's Foundation
                Funded by: Knut och Alice Wallenbergs Stiftelse
                Award ID: 2017.0028
                Funded by: National Institute of Allergy and Infectious Diseases
                Award ID: U01AI095473
                Categories
                Key Symposium
                15th Key Symposium ‐ Innate Immunity
                Custom metadata
                2.0
                joim12910
                May 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.2.1 mode:remove_FC converted:15.05.2019

                Internal medicine
                copd,cystic fibrosis,mucin,mucus,ulcerative colitis
                Internal medicine
                copd, cystic fibrosis, mucin, mucus, ulcerative colitis

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