2010-07-06 15:55:28 UTC

Do the Colonic Microbial Flora Serve to Trigger Colon Cancer?

July 6, 2010

Cynthia L. Sears, MD

Cynthia L. Sears, MD

Professor, Divisions of Infectious Diseases and Gastroenterology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD  

Hassan Ashktorab, PhD

Hassan Ashktorab, PhD

Professor, Department of Medicine and Cancer Center, College of Medicine, Howard University, Washington, DC  

Hassan Brim, PhD

Hassan Brim, PhD

PAssistant Professor, Pathology Department, Howard University, Washington, DC  


There are several cancers that are now considered to be triggered by microbes and are of concern to gastroenterologists. Such is the case for human papilloma virus (HPV), which is the main cause of cervical cancer, anal cancer, as well as some oropharnygeal tumors, and hepatitis B and C viruses that are strongly associated with hepatocellular cancer. Helicobacter pylori (H. pylori) was designated as a carcinogen by the World Health Organization in 1995, and Marshall and Warren were awarded the Nobel Prize in medicine in 2005 for their seminal discovery linking H. pylori to gastritis and peptic ulcer disease. This discovery led to the linkage between H. pylori and gastric cancer. Given that the colon mucosa is continuously in contact with ~1012 bacteria/gm feces representing at least 500 different bacterial species, the concept that this bacterial mass may contribute to colon oncogenesis has long been of interest. Through elegant murine investigations, we now believe that the colonic microbiota is essential to health, contributing to epithelial, mucosal and possibly systemic immune development, and to nutrition. But, is there a potential downside to some of us as a result of the colonic flora we carry?

The colonic flora adapts to a changing environment. Both laboratory and epidemiologic data support the concept that diet alters the composition and likely function of the colonic microbiota. Changes in diet and hence, colonic flora, are associated with changing risk in developing colon cancer, best illustrated by studies in which individuals move from low to high colon cancer prevalence regions and then begin to develop colon cancer at rates associated with their new locale. A key example is African Americans who are well known to have a high incidence of colorectal cancer (CRC).1 African Americans share the same genetic background with people of African descent that have a very low rate of colon cancer. Studies of genetic and/or epigenetic changes have not yet led to an explanation of the higher incidence of CRC in African Americans. Such observations point to a major role of diet, colonic flora and their interactions on colon homeostasis, and potentially oncogenesis in this population.

However, the mechanisms by which the colonic flora may contribute to colon oncogenesis remain largely unknown. Over time, extensive effort has been devoted to identifying what ingested carcinogens and/or carcinogenic metabolites generated by the colonic flora may precipitate oncogenic epithelial changes in the colon.2 No clear detectable “biomarkers” for clinical use to identify those at increased risk for colon cancer have yet emerged from these studies. The suggestion that inflammation is pivotal to oncogenesis dates to initial observations by Virchow in 1863 and the increased incidence of bowel tumors in IBD — both Crohn’s disease and ulcerative colitis — serve as clear examples supporting the role of chronic inflammation in bowel oncogenesis. Many, if not most, common colonic enteric infections induce inflammation that, in some, persists for an ill-defined time post-infection with, in some cases, ongoing colonization by the microbe. Whether ongoing colonization and low-level colonic inflammation induced by specific microbes, usually bacteria, contribute to colon oncogenesis is unknown. Certain members of bacterial species typically classified as commensals (i.e., doing no harm to the host) have been proposed to possess the ability to trigger oncogenic events in the colon. Candidate oncogenic colonic bacteria include Streptococcus gallolyticus (also known as S. bovis), Escherichia coli, superoxide-producing Enterococcus fecalis and, most recently, enterotoxigenic Bacteroides fragilis.3-7 What could be critical is not only the specific virulence properties of strains of these bacterial species, but the makeup of the rest of the colonic microbiome combined with the character of induced, low-level mucosal inflammation over time.

High-throughput technologies are emerging to analyze not only the composition of the bacterial communities (i.e., which microbes are present) within populations at high risk for developing colon cancer, but their expressed genes (transcriptome) and metabolic function (metabolome). Whether these tools will enable us to discern an easily detected, affordable “fecal signature” aligned with colon malignancies or other clinical problems central to the practice of gastroenterology, such as IBD, IBS and malnutrition, remains the challenge. Conversely, perhaps we will identify what constitutes the core members of a microbiota associated with health. We will learn a great deal over the next few years through the Human Microbiome Project and associated projects and, hopefully, we will harness this new knowledge towards improved approaches to disease prevention and population health.


1. Nouraie M, Hosseinkhah F, Brim H, Zamanifekri B, Smoot DT, Ashktorab H. Clinicopathological Features of Colon Polyps from African-Americans. Dig Dis Sci 2010.
2. Rowland IR. The role of the gastrointestinal microbiota in colorectal cancer. Curr Pharm Des 2009;15:1524-1527.
3. Herrera P, Kwon YM, Ricke SC. Ecology and pathogenicity of gastrointestinal Streptococcus bovis. Anaerobe 2009;15:44-54.
4. Swidsinski A, Khilkin M, Kerjaschki D, Schreiber S, Ortner M, Weber J, Lochs H. Association between intraepithelial Escherichia coli and colorectal cancer. Gastroenterology 1998;115:281-286.
5. Martin HM, Campbell BJ, Hart CA, Mpofu C, Nayar M, Singh R, Englyst H, Williams HF, Rhodes JM. Enhanced Escherichia coli adherence and invasion in Crohn's disease and colon cancer. Gastroenterology 2004;127:80-93.
6. Huycke MM, Abrams V, Moore DR. Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis 2002;23:529-536.
7. Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, Huso DL, Brancati FL, Wick E, McAllister F, Housseau F, Pardoll DM, Sears CL. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med 2009;15:1016-1022.

More on Colorectal Cancer

Principles of GI for the NP and PA

Aug. 10, 2018

Hear from the experts as they provide you with critical updates on treating and managing patients with a variety of GI disorders.

2018 AGA Postgraduate Course

June 2, 2018

Secure your spot for this clinically focused, multi-topic course that offers immediately applicable information. Held in conjunction with DDW®. Save $75 when you register by April 18.

Choose from 30 breakout sessions at the 2018 AGA Postgraduate Course

March 22, 2018

Delve deeper into specific clinical topics that interest you and get concrete action items that can be immediately implemented into your practice.