Intestinal mucus

Precellular solute ionization dictates membrane permeability dependence on mucosal pH. Therefore, lumenal or cellular events that affect mucosal microclimate pH may alter the membrane transport of ionizable solutes. The mucosal microclimate pH is defined by a region in the neighborhood of the mucosal membrane in which pH is lower than in the lumenal fluid. This is the result of proton secretion by the enterocytes, for which outward diffusion is slowed by intestinal mucus. (In fact, mucosal secretion of any ion coupled with mucus-restricted diffusion will provide an ionic microclimate.) Important differences in solute transport between experimental systems may be due to differences in intestinal ions and mucus secretion. It might be anticipated that microclimate pH effects would be less pronounced in epithelial cell culture (devoid of goblet cells) transport studies than in whole intestinal tissue. 

NA Peppas, PJ Hansen, PA Buri. A theory of molecular diffusion in the intestinal mucus. Int J Pharm 20 107-118, 1984. 

Bell, R.G., Adams, L.S. and Ogden, R.W. (1984) Intestinal mucus trapping in the rapid expulsion of Trichinella spiralis by rats induction and expression analyzed by quantitative worm recovery. Infection and Immunity 45, 267-272. 

Carlisle, M.S., McGregor, D.D. and Appleton, J.A. (1991a) Intestinal mucus entrapment of Trichinella spiralis larvae induced by specific antibodies. 

Lee, G.B. and Ogilvie, B.M. (1982) The intestinal mucus layer in Trichinella spiralis infected rats. In Strober, W., Hanson, L.A. and Sell, K.W. (eds) Recent Advances in Mucosal Immunity. Raven Press, New York, p. 319. 

Khan, W.I., Abe, T., Ishikawa, N., Nawa, Y. and Yoshimura, K. (1995) Reduced amount of intestinal mucus after treatment with anti-CD4 antibody interferes with the spontaneous cure of Nippostrongylus brasiliensis infection in mice. Parasite Immunology 17, 485-491. 

Schultsz C, van den Berg FM, ten Kate FW, Tytgat GN, Dankert J The intestinal mucus layer from patients with inflammatory bowel disease harbours numbers of bacteria compared with controls. Gastroenterology 1999 117 1089-1097. 

Guth, D. and van Engelhardt, W. (1989). Is gastro-intestinal mucus an ion-selective barrier In Mucus and Related Topics, eds. Chantler, E. and Ratcliffe, N. A., The Company of Biologists, Cambridge, pp. 117-121. 

For this reason, a further experiment was performed on the hydrolysis of PCP-glucuronide contained in bile on incubation with intestinal mucus of goldfish. 

As shown in Table IV (12), a considerable amount of the PCP-glucuronide in bile was hydrolyzed by the intestinal mucus. This indicates that the glucuronide conjugation plays an important role in reduction of the concentration of free-PCP in the fish body, but not in elimination of PCP from the fish body as compared with the sulfate conjugation, because the PCP released from the glucuronide in the intestine must be reabsorbed there. 

McCormick, B. A., Stocker, B. A., Laux, D. C., and Cohen, P. S. (1988). Roles of motility, chemotaxis, and penetration through and growth in intestinal mucus in the ability of an avirulent strain of Salmonella typhimurium to colonize the large intestine of streptomycin-treated mice. Infect. Immun. 56, 2209-2217. 

The free iron in the food enters the intestinal mucus from which it is absorbed by the epithelial cells via a transporter protein. This absorption is decreased by tea, coffee and phytate (inositol hexaphosphate) present in cereal fibre. Iron combined in haem is absorbed directly by epithehal cells after being released from haem-containing protein. The free iron is released in these cells by the enzyme haem oxidase. The free Fe is then bound to paraferritin and released into the blood where it is bound by ferritin. The three reactions are as follows. 

The chemical barriers are also important but are sometimes neglected in discussions of defence. To some extent they are specific for each tissue or organ and examples are as follows. Enzymes, such as lysozyme, which digests part of the bacterial coat, are present in many secretions (e.g. tears, milk) acid in the stomach, in the vagina, on the surface of the skin alkali in the small intestine mucus in the intestine, respiratory tract and vagina. 

The major saccharidase of the small intestine is amylase that digests starch to the disaccharide maltose and the trisaccharide maltotriose. Intestinal mucus is secreted by goblet cells, which either ooze (constitutive basal secretion) or burst as a result of stimuli. In the last mode of secretion condensed mucus gel granules can expand 500-fold within 20 ms [20]. 

Apart from being a diffusional barrier, mucin can also interact with drugs to decrease their bioavailability, as has been shown with tetracycline [106], phenylbutazone, and warfarin [107]. On the other hand, studies in rats showed that binding of some water-soluble drugs to intestinal mucus was essential for their absorption and that damage to the mucus significantly reduced absorption [108], The acidic mucus is essential for lipid absorption and could be important for the diffusion of lipophilic drugs (see below). 

Nakamura, J., et al. 1978. Role of intestinal mucus in the absorption of quinine and water soluble dyes from rat small intestine. Chem Pharm Bull Tokyo) 26 857. 

Poly(vinyl alcohol)-gel spheres with chitosan (PVA-GS/Ch) or without chitosan (PVA-GS) were prepared to control the GI transit time of drugs, and their particles were 5-10 pm [26]. PVA-GS/Ch displayed a longer small-intestinal transit time than PVA-GS. The transit rate was considered to decrease by the adhesion of chitosan to the intestinal mucus layer. PVA-GS/Ch and PVA-GS were loaded with theophylline and ampicillin. These released the drugs in a similar manner. The drugs were released almost completely at 4 h after the start of the release test. Both the gel spheres containing theophylline exhibited a bioavailability similar to that of the theophylline solution. Also, the bioavailability of ampicillin was greater in PVA-GS/Ch than in the PVA-GS and ampicillin solution the bioavailability of PVA-GS/Ch was approximately 150% of that of ampicillin solution (Table 3.2). As theophylline is rapidly absorbed in... 

Bernkop-Schniirch, A., and R. Fragner. 1996. Investigations into the diffusion behaviour of polypeptides in native intestinal mucus with regard to their peroral administration. Pharm Sci 2 361. 

O Toole, R., Lundberg, S., Fredriksson, S. A., Jansson, A., Nilsson, B., and Wolf-Watz, H., The chemotactic response of Vibrio anguillarum to fish intestinal mucus is mediated by a combination of multiple mucus components, J. Bacteriol., 181, 4308, 1999. 

The columnar epithelial cells of the intestinal mucosa actively absorb and secrete extracellular ions, nutrients, and water. The active secretion of ions by these cells with an accompanying fluid flux acts to dilute and purge microorganisms or toxins in the bowel promotes the transfer of secretory immunoglobulin A, antimicrobial defensin peptides, and mucin into intestinal mucus and the gut lumen and, by affecting intraluminal pH, may alter the growth characteristics of enteric microflora [121]. Mucosal secretion is modulated by several enteric neurotransmitters, as well as inflammatory mediators released by mucosal mast cells that may affect transport indirectly through their ability to stimulate enteric neurons [122],... 

It is important to note that hatching in H. nana is somewhat different from that of H. diminuta (204) and this may be related to the fact that hatching not only takes place in the insect intermediate host but also in the intestine of the definitive rodent host. It has been pointed out earlier (p. 183) that the embryophore in H. nana (in contrast to that of H. diminuta) is thin and discontinuous (Fig. 7.11) and this may make it more readily vulnerable to the host s enzyme action and hence facilitates intestinal hatching. The presence of polar filaments in this species may serve to delay expulsion of the hatched oncosphere from the rodent intestine by becoming entangled in the intestinal mucus and villi. This process would also serve to bring the oncosphere into close contact with the gut wall and hence facilitate successful penetration (204). 

Collado, M. C., Isolauri, E., and Salminen, S. (2008). Specific probiotic strains and their combinations counteract adhesion of Enterobacter sakazakii to intestinal mucus. FEMS Microbiol. Lett. [Epub ahead of print]. 

Larhed AW, Artursson P, Bjork E (1998) The influence of intestinal mucus components on the diffusion of drugs. Pharm Res 15 66-71... 

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