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Science 307 (5717): 1895-

Copyright © 2005 by the American Association for the Advancement of Science

Contents
News
The Dynamic Gut
What’s Eating You?
A Mouthful of Microbes
Viewpoint
No Organ Left Behind: Tales of Gut Development and Evolution
D. Y. R. Stainier
Reviews
Self-Renewal and Cancer of the Gut: Two Sides of a Coin
F. Radtke and H. Clevers
The Gut and Energy Balance: Visceral Allies in the Obesity Wars
M. K. Badman and J. S. Flier
Foldout: The Inner Tube of Life
Host-Bacterial Mutualism in the Human Intestine
F. Bäckhed, R. E. Ley, J. L. Sonnenburg, D. A. Peterson, J. I. Gordon
Immunity, Inflammation, and Allergy in the Gut
T. T. MacDonald and G. Monteleone
See related SAGE KE and STKE material and Editorial.

The Gut: Inside Out

Stephen Simpson, Caroline Ash, Elizabeth Pennisi, John Travis

The average adult human is, in essence, a 10-meter-long tube. The inner lining of this tube--the gut--absorbs nutrients and defends against would-be pathogens, yet the number of microorganisms it accepts and even embraces is higher than the number of cells making up our entire body. Its tissues are wreathed in sensory cells and awash in hormones relaying information back and forth. What goes on within the gut is still largely mysterious, and in this issue we explore some of its most interesting secrets.

The development and evolution of the gut, as Stainier (p. 1902) points out, is one of the earliest consequences of multicellularity. As a tube, the gut is not straight, nor is it smooth: Radtke and Clevers (p. 1904) reveal how the gut's topology of villi and crypts, combined with its amazing rate of self-renewal, make it particularly vulnerable to malignancy but also valuable for studying stem cell biology. A Report by Sakatani et al. (p. 1976) describes how epigenetic changes in the intestinal epithelium may also affect the risk of cancer. On Science's Signal Transduction Knowledge Environment (STKE), Hollande et al. (www.sciencemag.org/sciext/gut) throw light on the role of local signaling in maintaining the integrity of this thin lining of cells, even as they face high rates of renewal and the shear forces of the flow of the gut's liquid contents. A News story by Pennisi (p. 1896) explores how such features facilitate adaptive changes in gut size as an energy-saving device for fasting animals.

Figure 1

CREDIT: JUSTIN SONNENBURG, JAIME DANT, AND JEFFREY GORDON

Colonization of the gut by bacterial cells starts at birth, and they develop into an unusually diverse adult microbial community. One such niche is the mouth, and in a second News piece, Pennisi describes how both beneficial and harmful oral microorganisms jockey for supremacy (p. 1899). Bäckhed and colleagues (p. 1915) review strategies for investigating the interaction between the gut flora and human biology, and in an example of such a study, Sonnenburg et al. (p. 1955) describe new results on bacterial polysaccharide foraging within the gut. The gut epithelium and the associated mucosal immune system act as the mediators between the host and its symbiotic flora, and as MacDonald and Monteleone (p. 1920) discuss, different factors that interrupt this interplay can lead to inflammatory disorders of the gut. Despite the gut's extensive surveillance system, intestinal pathogens can wreak havoc, and on STKE, Peek explains how the notorious bacterium Helicobacter pylori disrupts stomach function to cause gastritis and possible cancer.

Information flow is as vital as transit times for proper gut function. Badman and Flier (p. 1909) review humoral and neural signals that regulate energy balance and food intake, as well as their potential for therapies in treating obesity. On STKE, Sharkey and Pittman explain how part of the pleasure of eating relates to cannabinoid receptors in the brain, whereas Emeson and Morabito reveal how "food fights" arise through the hormonal link between aggression circuits and the feeding pathway. Finally, Wade and Hornby describe how age-related neurodegenerative changes affect gastrointestinal function.

There are enormous amounts of information about the gut still to digest, but it is hoped that this journey through our inner tube will leave readers with an appetite to learn more.



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Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882