title: Transport of particles in intestinal mucus under simulated infant and adult physiological conditions: impact of mucus structure and extracellular DNA.
abstract: The final boundary between digested food and the cells that take up nutrients in the small intestine is a protective layer of mucus. In this work, the microstructural organization and permeability of the intestinal mucus have been determined under conditions simulating those of infant and adult human small intestines. As a model, we used the mucus from the proximal (jejunal) small intestines of piglets and adult pigs. Confocal microscopy of both unfixed and fixed mucosal tissue showed mucus lining the entire jejunal epithelium. The mucus contained DNA from shed epithelial cells at different stages of degradation, with higher amounts of DNA found in the adult pig. The pig mucus comprised a coherent network of mucin and DNA with higher viscosity than the more heterogeneous piglet mucus, which resulted in increased permeability of the latter to 500-nm and 1-µm latex beads. Multiple-particle tracking experiments revealed that diffusion of the probe particles was considerably enhanced after treating mucus with DNase. The fraction of diffusive 500-nm probe particles increased in the pig mucus from 0.6% to 64% and in the piglet mucus from ca. 30% to 77% after the treatment. This suggests that extracellular DNA can significantly contribute to the microrheology and barrier properties of the intestinal mucus layer. To our knowledge, this is the first time that the structure and permeability of the small intestinal mucus have been compared between different age groups and the contribution of extracellular DNA highlighted. The results help to define rules governing colloidal transport in the developing small intestine. These are required for engineering orally administered pharmaceutical preparations with improved delivery, as well as for fabricating novel foods with enhanced nutritional quality or for controlled calorie uptake.
authors.affiliation: Institute of Food Research, Norwich Research Park, Norwich, United Kingdom; Agrocampus Ouest, UMR 1253, Rennes, France; Institut National de la Recherche Agronomique, STLO, UMR 1253, Rennes, France.
authors.forename: Adam
authors.initials: A
authors.lastname: Macierzanka
authors.affiliation: Institute of Food Research, Norwich Research Park, Norwich, United Kingdom.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Mackie
authors.affiliation: Institute of Food Research, Norwich Research Park, Norwich, United Kingdom.
authors.forename: Balazs H
authors.initials: BH
authors.lastname: Bajka
authors.affiliation: Institute of Food Research, Norwich Research Park, Norwich, United Kingdom.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Rigby
authors.affiliation: Agrocampus Ouest, UMR 1253, Rennes, France; Institut National de la Recherche Agronomique, STLO, UMR 1253, Rennes, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Nau
authors.affiliation: Agrocampus Ouest, UMR 1253, Rennes, France; Institut National de la Recherche Agronomique, STLO, UMR 1253, Rennes, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Dupont
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001692:Biological Transport; D004247:DNA / Q000378:metabolism*; D004058:Diffusion; D005110:Extracellular Space / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology; D007421:Intestine, Small / Q000166:cytology / Q000502:physiology*; D009093:Mucus / Q000378:metabolism*; D012212:Rheology; D055672:Static Electricity; D034421:Sus scrofa; D014783:Viscosity
chemical_list: D004247:DNA
references.citation: Biopolymers. 2014 Apr;101(4):366-77
references.pmid: 23955640
references.citation: J Anat. 1972 May;112(Pt 1):27-33
references.pmid: 5086211
references.citation: Nat Chem Biol. 2011 Dec 15;8(1):36-45
references.pmid: 22173358
references.citation: Biophys J. 2001 Jun;80(6):2954-67
references.pmid: 11371468
references.citation: Development. 1990 Dec;110(4):1001-20
references.pmid: 2100251
references.citation: Dig Dis Sci. 1997 Nov;42(11):2384-93
references.pmid: 9398821
references.citation: Proc Soc Exp Biol Med. 1971 May;137(1):151-4
references.pmid: 5581653
references.citation: J Cell Sci. 1994 Dec;107 ( Pt 12):3569-77
references.pmid: 7706406
references.citation: Am J Physiol Gastrointest Liver Physiol. 2012 Feb 15;302(4):G430-8
references.pmid: 22159279
references.citation: J Anat. 1971 Jan;108(Pt 1):63-77
references.pmid: 5543214
references.citation: Adv Drug Deliv Rev. 2005 Jan 2;57(1):63-78
references.pmid: 15518921
references.citation: Adv Drug Deliv Rev. 2009 Feb 27;61(2):75-85
references.pmid: 19135107
references.citation: Gastroenterology. 2005 Sep;129(3):902-12
references.pmid: 16143130
references.citation: Development. 1988 Aug;103(4):785-90
references.pmid: 3248525
references.citation: Eur Respir J. 1995 Mar;8(3):381-6
references.pmid: 7789481
references.citation: Am J Clin Nutr. 2001 Jun;73(6):1131S-1141S
references.pmid: 11393191
references.citation: Biol Neonate. 1972;20(1):51-7
references.pmid: 4554816
references.citation: Dev Biol. 1968 Nov;18(5):501-4
references.pmid: 5704422
references.citation: Virchows Arch B Cell Pathol Incl Mol Pathol. 1982;40(1):51-62
references.pmid: 6126954
references.citation: Cell Tissue Kinet. 1982 Nov;15(6):595-609
references.pmid: 7172197
references.citation: Curr Opin Microbiol. 2012 Feb;15(1):57-62
references.pmid: 22177113
references.citation: Pediatr Res. 1993 Jun;33(6):564-7
references.pmid: 8378112
references.citation: Am J Vet Res. 1991 Oct;52(10):1743-6
references.pmid: 1768000
references.citation: Annu Rev Physiol. 2009;71:241-60
references.pmid: 18808327
references.citation: Nat Rev Gastroenterol Hepatol. 2013 Jun;10(6):352-61
references.pmid: 23478383
references.citation: PLoS One. 2008;3(12):e3952
references.pmid: 19088856
references.citation: Proc Natl Acad Sci U S A. 1990 Dec;87(23):9188-92
references.pmid: 2251263
references.citation: Langmuir. 2012 Dec 18;28(50):17349-62
references.pmid: 23171215
references.citation: Mucosal Immunol. 2008 May;1(3):183-97
references.pmid: 19079178
references.citation: Am J Physiol Gastrointest Liver Physiol. 2001 May;280(5):G922-9
references.pmid: 11292601
references.citation: Appl Environ Microbiol. 2000 May;66(5):2166-74
references.pmid: 10788396
references.citation: Adv Colloid Interface Sci. 2004 May 20;108-109:227-58
references.pmid: 15072944
references.citation: Crit Rev Food Sci Nutr. 2014;54(11):1427-57
references.pmid: 24580539
references.citation: Gut. 1997 Jun;40(6):782-9
references.pmid: 9245933
references.citation: Pediatrics. 1959 Nov;24:739-45
references.pmid: 13809672
references.citation: Pediatrics. 1961 Apr;27:589-96
references.pmid: 13692850
references.citation: J Biol Chem. 2003 Dec 12;278(50):50393-401
references.pmid: 13679362
references.citation: Macromol Biosci. 2010 Dec 8;10(12):1473-83
references.pmid: 20857389
references.citation: J Cell Mol Med. 2005 Jan-Mar;9(1):11-24
references.pmid: 15784161
references.citation: Histochem J. 1990 Feb;22(2):102-5
references.pmid: 2329051