Abstract B31: Sulfidogenic bacteria are an important diet-driven exposure promoting colorectal cancer in African Americans

Abstract

Objectives. Colorectal cancer (CRC) incidence is higher in post-industrial cultures, and the incidences varies among different populations. In the US, there is a higher incidence of CRC in African Americans (AAs) compared to non-Hispanic whites (NHWs). Recent evidence links consumption of a diet high in animal protein and fat as an environmental risk factor for the development of CRC. The intestinal microbiota is postulated to modulate the effects of diet in promoting or preventing CRC development. Hydrogen sulfide, which is produced by normal members of the colonic microenvironment (sulfidogenic bacteria), triggers pro-inflammatory and hyper-proliferative pathways, and it is genotoxic. We hypothesized that the production of hydrogen sulfide by sulfidogenic bacteria is a key environmental carcinogen contributing to CRC risk. Design. The abundance of sulfidogenic bacteria via quantitative PCR (qPCR) was compared in non-involved colonic mucosa of 97 AA and 56 NHW CRC patients and in 100 AA and 76 NHW healthy controls. In addition, we performed 16S rDNA sequencing in 61 AA cases and 94 AA controls. Additionally, we tested correlations among race, dietary intake, disease status, and sulfidogenic bacterial abundance. Results. Overall, the functional gene for hydrogen sulfide production in sulfate-reducing bacteria, dissimilatory sulfate reductase (dsrA), was more abundant in AAs than in NHWs, in both cases and controls. In addition, AA CRC cases exhibited a significantly higher abundance of Bilophila wadsworthia-specific dsrA. Linear discriminant analysis of 16S rDNA sequencing results revealed several taxa that differed between AA cases and controls, including the known butyrate producer Faecalibacterium that was more abundant in AA controls, and the sulfidogenic Pyramidobacter that was more abundant in AA CRC cases. Importantly, we found that dietary intake of protein and fat was higher in AAs compared to NHWs, and these dietary components correlated with a higher abundance of sulfidogenic bacteria. Conclusion. There were significant differences in sulfidogenic bacterial abundance between AAs and NHWs, in both cases and controls, and implicate sulfidogenic bacteria as an important diet-driven environmental exposure that contributes to the increased risk of CRC in AAs. Replication studies are needed to test that effectiveness of using B. wadsworthia as a biomarker for increased CRC risk. Citation Format: Cemal Yazici, Patricia G. Wolf, Tzu-Wen Liu, Karin Vermillion, Timothy Carroll, Ece Mutlu, Lisa Tussing-Humphreys, Carol Braunschweig, Rosa M. Xicola, Barbara Jung, Xavier Llor, Nathan A. Ellis, H. Rex Gaskins. Sulfidogenic bacteria are an important diet-driven exposure promoting colorectal cancer in African Americans. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B31.