A key to gut health in a few microns of mucus

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Science Translational Medicine  21 Oct 2015:
Vol. 7, Issue 310, pp. 310ec180
DOI: 10.1126/scitranslmed.aad4449

The trillions of gut microbes inhabiting our intestines live only a few microns away from our own cells. Mucosal immune cells and a physical barrier, the gut epithelium, keep these microbes at bay while allowing them to thrive in the intestinal lumen. A critical element in this balance is the mucus layer that lines the intestinal epithelium and provides a semisolid barrier that separates the gut microbes from our epithelium by a few dozen microns. Gut mucus is not static—rather, it dynamically changes, particularly in response to environmental perturbations such as diet. Quantifying these dynamics, however, is a challenge, as the mucus layer varies across the irregularly shaped intestinal epithelium. Working in mice, Earle et.al. have developed quantitative imaging software to foster a more rigorous and systematic approach to teasing apart the factors that regulate this layer of mucus that lines the intestines.

In order to obtain sufficient magnification (20x) to quantify mucus layer thickness in an entire colonic section surrounding a fecal pellet, the authors collected and stitched together approximately 40 fields of view. They used specific dyes, antibodies, and FISH probes to visually differentiate the host epithelium, the mucus, and the microbes, respectively. With edge detection and computational straightening of the image along the length of the epithelial and mucus interface, the authors systematically determined the mucus thickness along the surface of the intestine. Using these quantitative imaging tools, Earle et al. showed that the elimination of microbiota-accessible carbohydrates from the host diet reduced the intestinal mucus layer thickness by approximately one-half. This reduced mucus layer brought the intestinal microbiota closer to the host tissue, which then expressed more of the inflammatory marker Reg3β. This suite of tools enables a more quantitative assessment of this dynamic mucus interface, furthering the identification of environmental and host factors that regulate this important barrier.

K. A. Earle et al., Quantitative imaging of gut microbiota spatial organization. Cell Host Microbe 18, 478–488 (2015). [Full Text]

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