Sporadic colorectal cancer (CRC) is the second leading cause of death for men and women in the United States and, hence, is a major public health problem for which available preventive measures currently falter. The role of infectious and inflammatory processes in colon carcinogenesis is of intense interest since the colon is colonized with ~1012-13 commensal bacteria with the potential to induce inflammatory processes if colonic epithelial homeostasis is disrupted. Herein, we seek support to test the hypothesis that human CRC is associated with an oncogenic microbiota that induces specific procarcinogenic immune and metabolic pathways that directly affect tumor development. We propose that specific microbiota, metabolic and/or immunologic mechanisms will provide a new basis for detection and prevention of CRC. This project represents a consortium among three principal investigators and institutions, Johns Hopkins (Sears), J. Craig Venter Institute (JCVI, Peterson) and the Scripps Institute (Siuzdak) to address our hypothesis using a robust human sample accrual program at Johns Hopkins combined with microbiome (JCVI) and metabolome (Scripps) expertise. Through our specific aims, we will identify the microbial populations associated with CRC, define the metagenomic composition of human CRC and define early metabolites and the biochemical association(s) between the microbiome and CRC. Bioinformatic approaches will be applied and integrated with clinical data to identify candidate microbial, immunologic and/or metabolic biomarkers associated with CRC. Identification of CRC biomarkers has the potential for application to the early detection of CRC as well as to development of interventions for high risk individuals through approaches such as vaccination and/or metabolic regulation via diet, probiotic administration or drugs.
Colon cancer is the second leading cause of cancer death for women and men in the United States. Current approaches to prevention of colon cancer are underutilized due to their expense and inconvenience leading to excessive morbidity and mortality. This project will integrate microbiota, immunologic and metabolomic data to identify novel biomarkers with potential to enhance the prevention and detection of human colon cancer.
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| Chen, L A; Van Meerbeke, S; Albesiano, E et al. (2015) Fecal detection of enterotoxigenic Bacteroides fragilis. Eur J Clin Microbiol Infect Dis 34:1871-7 |
| Sears, Cynthia L; Geis, Abby L; Housseau, Franck (2014) Bacteroides fragilis subverts mucosal biology: from symbiont to colon carcinogenesis. J Clin Invest 124:4166-72 |
| Dejea, Christine M; Wick, Elizabeth C; Hechenbleikner, Elizabeth M et al. (2014) Microbiota organization is a distinct feature of proximal colorectal cancers. Proc Natl Acad Sci U S A 111:18321-6 |
| McAllister, Florencia; Housseau, Franck; Sears, Cynthia L (2014) Microbiota and immune responses in colon cancer: more to learn. Cancer J 20:232-6 |
| Johnson, Caroline H; Fisher, Timothy S; Hoang, Linh T et al. (2014) Luciferase does not Alter Metabolism in Cancer Cells. Metabolomics 10:354-360 |
| Sears, Cynthia L; Garrett, Wendy S (2014) Microbes, microbiota, and colon cancer. Cell Host Microbe 15:317-28 |
