Abstract 4901: Clostridium cluster XIVa species an early biomarker in radiation injury

Abstract

Abstract Radiation therapy is being used in the treatment of nearly 60% of the current cancer patients. In spite of the best efforts to provide special care in minimizing radiation exposure, significant radiation injury remains a common side-effect particularly to the gastro intestinal tract. Severe injury to GI tract may lead to multiple organ dysfunction syndrome. The status of fecal microbiota has been proposed as a rapid diagnostic platform in radiation injury. Gut microbes play a role in immunity, health, and disease. Imbalances in gut microbiota are related to numerous disorders, such as inflammatory bowel disease, colorectal cancer (CRC), and atopy. In patients with immune suppression due to high-dose chemotherapy or that undergoing radiation therapy, disruption of the microbiota through antibiotics and impairment of host immunity gives rise to perturbations favoring intestinal domination by pathogenic species, resulting in increased bacterial translocation and susceptibility to systemic infection. Here, using real-time PCR assays, we assessed the immediate changes and quantitative alterations to fecal microbiota in response to radiation injury. Swiss-albino Mice were subjected to 10 Gy X-ray whole body irradiation doses using commercially available X-RAD 320 irradiator (1Gy/min; F2 beam hardening filter 1.5mm Al, 0.25mm Cu, 0.75mm Sn; Precision X-ray inc, USA). Fecal samples collected immediately after the radiation exposure were analyzed. We show that Clostridium cluster XIVa that accounts for almost 60% of the mucin-adhered microbiota is significantly increased (11.71 +/- 0.29 fold n=6) in the fecal samples, compared to the total bacteria and other bacteria that tend to enrich in the luminal region. Along with the Bacteroidetes and Proteobacteria from the luminal region, minimal changes in the levels of Firmicutes that colonize the mucin layer were observed. Further, these changes varied considerably between the subjects and were inconsistent compared to the Clostridium cluster species. Clostridium cluster XIVa has been proposed to be the mucosal butyrate producers producing butyrate close to the epithelium. This enhances butyrate bioavailability required in treating diseases such as inflammatory bowel disease. These findings provide opportunities to evaluate the potential use of intestinal microbiota as biomarkers in radiation injury. Also, provides insights into the microbial changes tantamount to the radiation induced GI injury. Citation Format: Ishfaq Ahmed, William McLauglin, Shrikant Anant, Shahid Umar, Rao V. Papineni. Clostridium cluster XIVa species an early biomarker in radiation injury. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4901. doi:10.1158/1538-7445.AM2014-4901