Transport of particles in intestinal mucus under simulated infant and adult physiological conditions: impact of mucus structure and extracellular DNA.

Adam Macierzanka,Neil M Rigby,Didier Dupont,Françoise Nau,Balazs H Bajka,Alan R Mackie,Adam J Munn

doi:10.1371/journal.pone.0095274

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.

Highlights

The last boundary between ingested food and the gastrointestinal (GI) tract mucosa is the mucus layer
Mucus Organization in the Proximal Small Intestine Prior to investigating the transport of particles in the intestinal mucus, confocal microscopy was used to visualize the architecture of the mucus in the jejunal part of pig and piglet small intestines that had been fresh-frozen after collection
The mucus layer covering the tips of villi (Figure 1D, I) and the mucus released to the lumen in the form of aggregates (Figure 1E, J) contained both mucin and DNA, the latter most likely originating from degrading nuclei of the epithelial cells shed from the tips of villi as a result of the continuous turnover of the intestinal epithelium [10]

Summary

Introduction

The last boundary between ingested food and the gastrointestinal (GI) tract mucosa is the mucus layer This highly complex viscoelastic medium has evolved to provide a robust barrier that can trap and immobilize potentially hazardous particulates such as bacteria but still allow the passage of nutrients to the epithelial surfaces [1,2,3,4]. These conflicting properties are important in the small intestine where the mucus layer is thinnest [5] and the majority of nutrient absorption takes place. In our previous work [7,8], we showed that adsorption of bile salts to the surface of model microparticles and partially digested emulsion droplets significantly enhanced their diffusion in the small intestinal mucus

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