Lipids alter microbial transport through intestinal mucus

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.

Mucin CYS domain stiffens the mucus gel hindering bacteria and spermatozoa

“…This natural phenomenon was demonstrated in the endocervix during the periovulatory period of the menstrual cycle preventing spermatozoa passage 5 . Similarly to what has been observed for the delivery of lipids in mucus, direct interactions between the transgene rCYSx12 and motile cells can not be ruled out 57 .…”

Milk exosomes with enhanced mucus penetrability for oral delivery of siRNA

“…The mucus transport properties of unmodified and PEGylated mExo were evaluated using an in vitro transwell model as previously described. [30][31][32][33][34] Native porcine intestinal mucus was harvested as previously described 30 and frozen at −80°C until use. The transwell setup was as follows: 0.4 μm polycarbonate membrane transwell inserts (0.33 cm 2 surface area) were used to separate the donor and acceptor compartments.…”

Impact of diet and the bacterial microbiome on the mucous barrier and immune disorders

“…95 In a mucus gel in vitro with media containing lipids and bile acids designed to reflect GI contents after consumption of a normal meal, the generation of a lipid microemulsion formed a physical barrier to E coli migration. 123 However, this study did not assess the impact of media containing a higher abundance of lipids to reflect digestion of a high-fat diet (HFD), nor did it assess whether other microbiota may influence this relationship in vivo.…”