Abstract
Mucus constitutes a protective layer which coats the gastrointestinal tract, controlling interactions of both commensal and pathogenic microbes with underlying tissues. Changes to the mucus barrier, for example due to altered mucin expression or external stimuli, may impact interactions with microbes and thus potentially contribute to altered gut homeostasis, onset of inflammation, or pathogen invasion. Food-associated stimuli, including lipids, have been shown to change mucus barrier properties and reduce transport of model drug carriers through mucus. Here, we explore the impact of lipids, specifically triglycerides in a model intestinal medium mimicking a fed state, on Escherichia coli (E. coli) transport through mucus by directly imaging swimming patterns and analyzing associated changes in mucus structure. Lipids in model fed state intestinal contents reduced E. coli speed and track linearity within mucus. These changes may be due in part to changes in molecular interactions within the mucus network as well as crowding of the mucus network by lipid emulsion droplets, which visibly stay intact in the mucus gel. In addition, observed physical interactions between bacteria and lipid structures may impact microbial speed and trajectories. As lipids are normal food components and thus represent safe, mild stimuli, these results support exploration of lipid-based strategies to alter the mucus barrier to control interactions with microbes and potentially prevent microbial invasion of underlying epithelium.
Highlights
Mucus lines the gastrointestinal tract (GIT) and acts as a physical barrier preventing microbial invasion of the underlying epithelium[1]
We have shown that lipids present in fed state medium simulating intestinal lumen contents after eating can significantly impact microbe transport, reducing speed and altering swimming patterns
The lipid microemulsion droplets present in fed state medium visibly maintained integrity upon introduction to buffer and mucus and acted as obstacles altering E. coli swimming patterns, as microbes were observed to associate with microemulsion
Summary
Mucus lines the gastrointestinal tract (GIT) and acts as a physical barrier preventing microbial invasion of the underlying epithelium[1]. Antibodies (i.e. immunoglobulins), antimicrobial peptides, and lysozyme present in the complex, mesh-like mucus gel bind or kill microbes, allowing them to eventually be removed from the GIT as the mucus layer is cleared and replenished[2, 3]. Deficiencies or changes in the mucus layer can expose the epithelium, leading to microbial invasion and inflammation of underlying tissue[4, 5]. Food ingestion results in significant changes in the GIT lumen environment, impacting composition and transit rates of luminal material[6, 7], as well as mucus production[8, 9].
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