Abstract
The intestinal mucus layer is a physical barrier separating the tremendous number of gut bacteria from the host epithelium. Defects in the mucus layer have been linked to metabolic diseases, but previous studies predominantly investigated mucus function during high-caloric/low-fiber dietary interventions, thus making it difficult to separate effects mediated directly through diet quality from potential obesity-dependent effects. As such, we decided to examine mucus function in mouse models with metabolic disease to distinguish these factors. Here we show that, in contrast to their lean littermates, genetically obese (ob/ob) mice have a defective inner colonic mucus layer that is characterized by increased penetrability and a reduced mucus growth rate. Exploiting the coprophagic behavior of mice, we next co-housed ob/ob and lean mice to investigate if the gut microbiota contributed to these phenotypes. Co-housing rescued the defect of the mucus growth rate, whereas mucus penetrability displayed an intermediate phenotype in both mouse groups. Of note, non-obese diabetic mice with high blood glucose levels displayed a healthy colonic mucus barrier, indicating that the mucus defect is obesity- rather than glucose-mediated. Thus, our data suggest that the gut microbiota community of obesity-prone mice may regulate obesity-associated defects in the colonic mucosal barrier, even in the presence of dietary fiber.
Highlights
The intestinal mucus layer is a physical barrier separating the tremendous number of gut bacteria from the host epithelium
To investigate mucus function during obesity not confounded by diet, we compared genetically obese leptindeficient mice with their lean, separately housed littermates that were all fed a fiber-containing control chow diet
Intestinal mucus function is mainly studied during dietary interventions, and a defective mucus layer is observed after consumption of high-fat and/or fiber-free diets in mice [4, 5, 7]
Summary
The intestinal mucus layer is a physical barrier separating the tremendous number of gut bacteria from the host epithelium. To prevent the microbiota from directly accessing the mucosal lining, the intestine is covered with a layer of mucus as a first line of defense. This gel-like network, which in the intestine is mainly composed of the highly glycosylated mucin protein MUC2, physically separates the gut bacteria from the intestinal epithelium [2]. When mice are fed a diet devoid of complex microbiota-accessible carbohydrate, microbial glycan degradation can lead to deterioration of the mucus barrier and allow gut bacteria to approach or even translocate the mucosa [4,5,6,7]
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