Polymers in the gut compress the colonic mucus hydrogel

Abstract

Colonic mucus is a key biological hydrogel that protects the gut from infection and physical damage and mediates host-microbe interactions and drug delivery. However, little is known about how its structure is influenced by materials it comes into contact with regularly. For example, the gut abounds in polymers such as dietary fibers or administered therapeutics, yet whether such polymers interact with the mucus hydrogel, and if so, how, remains unclear. Although several biological processes have been identified as potential regulators of mucus structure, the polymeric composition of the gut environment has been ignored. Here, we demonstrate that gut polymers do in fact regulate mucus hydrogel structure, and that polymer-mucus interactions can be described using a thermodynamic model based on Flory-Huggins solution theory. We found that both dietary and therapeutic polymers dramatically compressed murine colonic mucus ex vivo and in vivo. This behavior depended strongly on both polymer concentration and molecular weight, in agreement with the predictions of our thermodynamic model. Moreover, exposure to polymer-rich luminal fluid from germ-free mice strongly compressed the mucus hydrogel, whereas exposure to luminal fluid from specific-pathogen-free mice-whose microbiota degrade gut polymers-did not; this suggests that gut microbes modulate mucus structure by degrading polymers. These findings highlight the role of mucus as a responsive biomaterial, and reveal a mechanism of mucus restructuring that must be integrated into the design and interpretation of studies involving therapeutic polymers, dietary fibers, and fiber-degrading gut microbes.hydrogel | biophysics | biomaterials | polymers | mucus B iological hydrogels (including mucus, blood clots, and the extracellular matrix) provide critical functions, yet little is known about how their structure is influenced by materials they come into contact with regularly. For example, the environments of many hydrogels abound in polymers, such as dietary fibers (1, 2) or administered therapeutics (3-5) in the gut and soluble glycoproteins in tissues. Whether such polymers interact with these hydrogels, and if so, how, remains unclear. An important example is the case of colonic mucus, which protects the gut from infection and physical damage (6-8), mediates drug delivery (9), and mediates host-microbe interactions (10) in a structure-dependent manner; for example, a "tighter" mesh could impede the infiltration of microorganisms from the intestinal lumen (6, 11-13). Mucus restructuring is typically attributed solely to changes in secretion (14-16), or to the activity of specific enzymes (8, 17), detergents (18), or dextran sulfate sodium-induced inflammation (19). However, the physicochemical properties of the gut environment itself-particularly its polymeric composition-have not been considered as a potential regulator of mucus structure. We therefore sought to characterize the structure of the colonic mucus hydrogel in the absence and in the presence of polymers. Res...

Osmotaxis in Escherichia coli through changes in motor speed

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High-molecular-weight polymers from dietary fiber drive aggregation of particulates in the murine small intestine

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Mucus models to evaluate the diffusion of drugs and particles

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