Bugging the intestinal response to radiation

An article by Crawford and Gordon (1) in a recent issue of PNAS describes a new relationship between the gut microbial flora and the host that has importance for understanding how radiation damage is processed by the small intestine. Trillions of diverse microbes colonize the intestine that provide essential functions for host survival (2). In addition to digestion, the gut microbia regulate caloric storage, metabolize xenobiotics, modify the immune system, and regulate postnatal gut development including a network of capillaries in the mesenchyme of the small intestinal villi (3-8). Understanding of the microbehost relationship has been increased by studies on germ-free (GF) mice compared with animals that acquire a microbiota from birth [conventionally raised (CONV-R)] or are initially germ-free and then colonized at various stages of postnatal development or during adult-hood with microflora from CONV-R donors (designated as CONV-D, or “conventionalized”) (3, 5). Crawford and Gordon apply these models to investigate whether the intestinal flora modifies the tissue response of the small bowel to ionizing radiation (IR). IR has been used in cancer therapy for >100 years. Approximately 50% of all cancer patients receive radiotherapy. However, radiation therapy is limited by effects of IR on normal tissues as well as the resistance of tumors to this treatment. Radiation effects on the small intestine limit potentially curative radiation doses from being delivered in whole-abdomen radiotherapy for ovarian cancer and also limit the target volume and dose that can be delivered for other abdominal malignancies such as pancreatic, stomach, and colon cancer (9).