Occurence of initiation and progression of colorectal cancer in the changed intestinal environment.

Abstract

416 Background: Use of new molecular biology–based methods of bacterial identification is expected to help elucidate the relationship between colorectal cancer (CRC) and intestinal microbiota. However, it remains unclear whether microbial dysbiosis is the cause or the result of CRC onset. We analyzed the intestinal environments to determine whether the changes differed with the stage of CRC or adenoma. Methods: We analyzed fecal microbiota, organic acid concentrations, and pH in CRC patients (n=93), individuals with adenoma (n=23), and individuals with normal intestinal tracts (n=27). After patient hospitalization, the feces of all subjects were collected before any administration of laxatives or antibiotics to prepare the bowel.Thirteen bacterial groups were enumerated in the fecal microbiota by using reverse transcription–quantitative PCR (RT-qPCR). Eight kinds of organic acid were quantified using high-performance liquid chromatography, and fecal pH was measured by pH meter. Results: The counts of total bacteria (10.3 ± 0.7 vs. 10.8 ± 0.3 log10 cells/g of feces; p<0.001), 5 groups of obligate anaerobe (Clostridium coccoides group, C. leptum subgroup, Bacteroides fragilis group, Bifidobacterium, and Atopobium cluster), and 2 groups of facultative anaerobes (Enterobacteriaceae and Staphylococcus) were significantly lower in the CRC group than in the healthy individuals. While the concentrations of organic acids—particularly short chain fatty acids (SCFAs) such as acetic acid, propionic acid, and butyric acid—were significantly decreased in the CRC group, the pH was increased in the CRC group (7.4 ± 0.8 vs. 6.9 ± 0.6; p<0.001). Comparison among the CRC, adenoma, and non-adenoma groups revealed that fecal SCFAs concentrations and pH in the adenoma group were intermediate to the CRC group and the non-adenoma group. Within the CRC group, no differences in microbiota or organic acids were observed among T-stages or Dukes stages. Conclusions: CRC patients showed significant differences in the intestinal environment, including alterations of microbiota, decreased SCFAs, and elevated pH. These changes are not a result of CRC progression but are involved in CRC onset.