Polymers in the gut compress the colonic mucus hydrogel.
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.
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125;
Sujit S
SS
Datta
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125;
Asher
A
Preska Steinberg
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125 rustem.admin@caltech.edu.
Rustem F
0000-0002-3680-4399
RF
Ismagilov
D000818:Animals; D001696:Biomechanical Phenomena; D003106:Colon / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D000069196:Gastrointestinal Microbiome; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000737:chemistry* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism
D011108:Polymers; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
biomaterials; biophysics; hydrogel; mucus; polymers