Diverse Biology of the Gut Featured in Science

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Beginning with a cover photo of a colored barium x-ray image of the colon in the early stages of Crohn’s disease, the March 25 issue of the journal Science contains an editorial and special section that features the diverse biology of the human gut. The section explores the abundant yet largely unknown microorgansisms it harbors, its normal functions of digestion and delivery of nutrients, and the diseases to which it is prone.

In his editorial, “Cancers of the Gut and Western Ills,” Dr. Ian T. Johnson, head of the Gastrointestinal Biology and Health Programme at the Biological Sciences Research Council in the UK, states that despite the huge progress made in understanding the molecular basis of many cancers in recent years, “most of the new knowledge has been deployed in the search for new therapies rather than to understand the role of nutrition in their causation.” Johnson says the mechanisms linking diet to cancer “can be understood and exploited” for both prevention and treatment, and he points to several “scientific and strategic reasons to focus such research on carcinomas of the alimentary tract.” These include evidence in support of “overnutrition” as a factor in an increased risk of bowel cancer within population of the developed world, “where overconsumption of energy, low levels of physical activity, high body mass index, and abdominal obesity are strong independent risk factors for colorectal carcinoma.” He also notes evidence for a link between obesity and esophageal cancer, once rare “but now advancing rapidly throughout North America and Western Europe.”

Johnson sees “little evidence” to support the view that alimentary cancers are tied to the adverse effects in the diet of food-borne carcinogens, despite the presence of mutagens in low concentrations in foods and feces. “It seems more plausible that the Western gut become vulnerable to neoplasia because of adverse metabolic factors, such as pro-inflammatory enzymes in precancerous tissues, and because of low intakes of anti-carcinogens from plant foods.” He asserts that the role of weight, lack of exercise, and inadequate consumption of plant foods in the etiology of gut cancers “needs to be more widely acknowledged and publicized.”

This special section in the journal also contains articles on the pathogenic potential of microbial communities that thrive on and around teeth, gums, and the tongue; gut development and evolution; the gut and energy balance; host-bacterial “mutualism” in the gut; and immunity, inflammation, and allergy in the gut.

Also included in this issue of Science is a report from Johns Hopkins University School of Medicine, the National Institute on Aging, and Keio University School of Medicine in Tokyo, Japan, that suggests a cellular mechansim by which epigenetic alterations in normal cells may affect cancer risk. In the study, loss of imprinting of the insulin-like growth factor II gene (Igf2) is tied to alterations in intestinal maturation and tumorigenesis in mice. According to the authors, such an epigenetic change may serve as a possible marker for cancer screening. They note that a “modest increase in Igf2 expression” resulting from this change is present in the normal colonic mucosa of roughly 30% of patients with colorectal cancer. The study involved a loss of imprinting (LOI) mouse model in which LOI mice developed twice as many intestinal tumors as did control littermates. These mice also showed a shift toward a less differentiated normal intestinal epithelium, as shown by an increase in crypt length and increased staining with progenitor cell markers. “A similar shift in differentiation was seen in the normal colonic mucosa of humans with LOI. Thus, altered maturation of non-neoplastic tissue may be one mechanism by which epigenetic changes affect cancer risk,” the authors state.

For more detail, see Science vol. 307, 25 March 2005.