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Mucus Keeps Gut Bacteria at Bay to Prevent Inflammation

Research using a mouse model has provided a new understanding of how mucus coating the inner colon isolates bacteria from the gut wall, potentially offering new ways to diagnose and treat intestinal inflammation. A thriving community of bacteria (microbiome) lives in the human gut, helping with digestion and receiving nourishment from the food we eat. However, bacterial contact with the intestinal lining can trigger an inflammatory response (colitis), leading to chronic pain, bleeding, and diarrhea. One important way the body keeps inflammation in check is through a layer of mucus coating the inside of the colon, physically separating gut bacteria from the intestinal lining. A breakdown of this mucus layer has been implicated in several gastrointestinal diseases, but developing treatments to restore it has been challenging because of an unclear understanding of how it is produced.

To gain a better understanding of how the colon builds and maintains the mucus barrier, researchers conducted studies in male and female mice to develop a new way to visualize the mucus layer along the entire length of the colon. They found that the proximal area of the colon—where the colon joins with the small intestine—produces a thick layer of mucus that not only coats the intestinal lining, but also encapsulates fecal material and its associated bacteria. As the intestinal contents move further along the GI tract, they encounter a second, thinner, chemically distinct layer of mucus that is produced by the distal colon (the latter portion of the colon). The researchers generated mouse models with disrupted mucus production in either one or both areas of the colon and showed that both of the mucus layers were important for keeping bacteria sequestered in fecal pellets and separated from the intestinal lining. They also showed that both layers were critical for preventing spontaneous inflammation, with the most severe inflammation occurring when mucus production was turned off in both areas. The researchers also uncovered an intimate interaction between gut bacteria and the mucus layer: the presence of bacteria drove up mucus production in the proximal colon, while turning off mucus production changed the makeup of the bacterial community. This suggests that the proximal colon mucus provides an environment that favors growth of healthy bacteria, and a defective mucus layer could be a sign of an unhealthy microbiome.

These results in mice present a new model for intestinal mucus function, whereby the mucus layer dynamically insulates bacteria from the intestinal lining. Further research would be needed to confirm whether human colonic mucus functions in a similar way. If so, the fecal mucus coating could serve as a diagnostic tool to detect gastrointestinal disease, and, ultimately, as a target for new approaches to restore the gut to a healthy state.

Bergstrom K, Shan X, Casero D,…Xia L. Proximal colon-derived O-glycosylated mucus encapsulates and modulates the microbiota. Science 370: 467-472, 2020.

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