Abstract
The consumption of generally regarded as safe emulsifiers has increased, and has been associated with an increased prevalence of inflammatory bowel and metabolic diseases, as well as an altered microbiome. The mucus barrier, which selectively controls the transport of particulates and microorganisms to the underlying epithelial layer, has been previously shown to be altered by dietary salts and lipids. However, the potential impact of emulsifiers on the protective mucus barrier, its permeability, and associated structural changes are not clear. In this study, we analyzed changes in the mucus barrier to both passively diffusing nanoparticles and actively swimming E. coli upon exposure to two emulsifiers, carboxymethylcellulose (CMC) and polysorbate 80 (Tween). When exposed to CMC, mucus pore size decreased, which resulted in significantly slower E. coli speed and particle diffusion rates through mucus. Tween exposure minimally impacted mucus microstructure and particle diffusion, but increased E. coli speed in mucus. Moreover, both emulsifiers appeared to alter mucus amount and thickness in rat intestinal tissue and mucus-producing cell cultures. These results indicate that acute exposure to emulsifiers impacts barrier and structural properties of intestinal mucus, modulating interactions between intestinal lumen contents, microbes, and underlying tissue, which may contribute to development of intestinal inflammation.
Highlights
Penetration of commensal and pathogenic bacteria through mucus, associated adherence to and invasion of the epithelium, as well as reduced thickness of the mucus barrier have been associated with mucosal inflammation, such as occurs in inflammatory bowel disease (IBD)[11,12,13], a disease affecting approximately 1.6 million Americans[14]
While certain emulsifiers have been classified by the United States Food and Drug Administration (FDA) as generally regarded as safe (GRAS), it is crucial to understand if and how the increased consumption of emulsifiers may contribute to the rise in obesity and other intestinal inflammatory diseases[13,22]
Results showed that mucus exposed to maleate buffer (MB), CMC, or Tween had similar structure when incubated for 2 hrs (Fig. 1), or mixed overnight (Supplementary Fig. S1)
Summary
Penetration of commensal and pathogenic bacteria through mucus, associated adherence to and invasion of the epithelium, as well as reduced thickness of the mucus barrier have been associated with mucosal inflammation, such as occurs in inflammatory bowel disease (IBD)[11,12,13], a disease affecting approximately 1.6 million Americans[14] These observations suggest that an altered mucus barrier may contribute to the onset of intestinal inflammation and certain disease states[15]. We test the hypothesis that acute exposure to CMC and Tween directly impacts mucus barrier properties, to determine if such changes in this crucial barrier could contribute to the ultimate development of inflammation and metabolic syndrome. To determine particle size and zeta potential, a dynamic light scattering and zeta-sizer instrument (NanoBrook 90Plus PALS, Brookhaven) was utilized
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