Polymers in the gut compress the colonic mucus hydrogel
Polymers in the gut compress the colonic mucus hydrogel
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DOI：
10.1073/pnas.1602789113
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发表时间：
2016-06-28
影响因子：
11.1
通讯作者：
Ismagilov, Rustem F.
中科院分区：
文献类型：
--
作者：
Datta, Sujit S.;Steinberg, Asher Preska;Ismagilov, Rustem F.
结肠粘液是一种重要的生物水凝胶，可保护肠道免受感染和物理损伤，并介导宿主-微生物相互作用和药物传递。然而，人们对它的结构如何受到它经常接触的材料的影响知之甚少。例如，肠道中含有大量聚合物，如膳食纤维或药物，但这些聚合物是否与粘液水凝胶相互作用，如果是，如何相互作用，仍不清楚。虽然一些生物过程已被确定为粘液结构的潜在调节因子，但肠道环境的聚合物组成却被忽视了。在这里，我们证明肠道聚合物确实调节黏液水凝胶结构，并且聚合物-黏液相互作用可以用基于Flory-Huggins溶液理论的热力学模型来描述。我们发现饮食和治疗聚合物在体内和体外都能显著压缩小鼠结肠粘液。这种行为强烈依赖于聚合物浓度和分子量，与我们的热力学模型的预测一致。此外，暴露于无菌小鼠的富含聚合物的管腔液会强烈压缩黏液水凝胶，而暴露于无特定病原体小鼠的管腔液（其微生物群会降解肠道聚合物）则不会；这表明肠道微生物通过降解聚合物来调节粘液结构。这些发现强调了黏液作为一种反应性生物材料的作用，并揭示了黏液重组的机制，必须将其整合到涉及治疗性聚合物、膳食纤维和纤维降解肠道微生物的研究的设计和解释中。
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.