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Published June 28, 2016 | Published + Supplemental Material
Journal Article Open

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.

Additional Information

© 2016 National Academy of Sciences. Freely available online through the PNAS open access option. Edited by David A. Weitz, Harvard University, Cambridge, MA, and approved May 6, 2016 (received for review February 18, 2016) Published online before print June 14, 2016, doi: 10.1073/pnas.1602789113 We thank Said Bogatyrev, Andres Collazo, Elaine Hsiao, Julia Kornfield, Octavio Mondragon-Palomino, Ahmad Omar, Alexandre Persat, David Tirrell, Zhen-Gang Wang, and David Weitz for useful discussions; the Beckman Institute Biological Imaging Facility, the Broad Animal Facility, and the Church Animal Facility for experimental resources; the veterinary technicians at the California Institute of Technology for experimental assistance; Jennifer R. Keeffe for assistance with dynamic light scattering measurements; Dorothy Pan for assistance with gel permeation chromatography measurements; and Natasha Shelby for contributions to writing and editing this manuscript. This work was supported in part by Defense Advanced Research Projects Agency Biological Robustness in Complex Settings Contract HR0011-15-C-0093, National Science Foundation (NSF) Emerging Frontiers in Research and Innovation Award Grant 1137089, and NSF Graduate Research Fellowship DGE‐1144469 (to A.P.S.). Author contributions: S.S.D., A.P.S., and R.F.I. designed research; S.S.D. and A.P.S. performed research; S.S.D. and A.P.S. contributed new reagents/analytic tools; S.S.D. and A.P.S. analyzed data; and S.S.D., A.P.S., and R.F.I. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1602789113/-/DCSupplemental.

Attached Files

Published - PNAS-2016-Datta-7041-6.pdf

Supplemental Material - pnas.201602789SI.pdf


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