title: The influence of small intestinal mucus structure on particle transport ex vivo.
abstract: Mucus provides a barrier to bacteria and toxins while allowing nutrient absorption and waste transport. Unlike colonic mucus, small intestinal mucus structure is poorly understood. This study aimed to provide evidence for a continuous, structured mucus layer and assess the diffusion of different sized particles through it. Mucus structure was assessed by histology and immunohistochemistry. Ultra-structure was assessed by scanning electron microscopy. Tracking of 100 nm and 500 nm latex beads was conducted using ex vivo porcine mucus. The porcine jejunum and ileum were filled with mucus. Layered MUC2 staining was visible throughout the small intestine, covering villus tips. Scanning electron microscopy showed net-like mucin sheets covering villi (211 ± 7 nm pore diameter). Particle tracking of 100 nm latex beads, showed no inhibition of diffusion through mucus while 500 nm beads displayed limited diffusion. These results suggest a continuous mucus layer exists throughout the small intestine, which is highly stratified adjacent to the epithelium. The network observed is consistent with previous observations and correlates with stratified MUC2 staining. Mucin pore size is consistent with free diffusion of 100 nm and limited diffusion of 500 nm particles. Small Intestinal mucus structure has important implications for drug delivery systems and prevention and treatment of conditions like mucositis and inflammatory bowel disease.
authors.affiliation: Institute of Food Research, Norwich, Norfolk, UK. Electronic address: Balazs.Bajka@ifr.ac.uk.
authors.forename: Balázs H
authors.initials: BH
authors.lastname: Bajka
authors.affiliation: Institute of Food Research, Norwich, Norfolk, UK.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Rigby
authors.affiliation: Institute of Food Research, Norwich, Norfolk, UK.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Cross
authors.affiliation: Institute of Food Research, Norwich, Norfolk, UK; Department of Fats and Detergents Technology, Faculty of Chemistry, Gdansk University of Technology, Narutowicza 11/12, 80-952 Gdansk, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Macierzanka
authors.affiliation: Institute of Food Research, Norwich, Norfolk, UK.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Mackie
mesh_terms: D000818:Animals; D007082:Ileum / Q000378:metabolism; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D007421:Intestine, Small / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D007583:Jejunum / Q000378:metabolism; D051379:Mice; D008863:Microspheres; D055262:Mucin-2 / Q000378:metabolism; D009093:Mucus / Q000737:chemistry / Q000378:metabolism*; D053758:Nanoparticles / Q000378:metabolism*; D010316:Particle Size; D013552:Swine
chemical_list: C524626:Muc2 protein, mouse; D055262:Mucin-2
keywords: MUC2; Mucus; Particle transport; Small intestine; Structure