What is the association between Clostridium perfringens and colorectal cancer?

  Two studies published in Genome Research in October show a mysterious link between bacteria and colon cancer, according to Time magazine’s list of the top 10 medical breakthroughs of 2011. When scientists compared healthy colon tissue with cancerous tissue, they noticed that a bacterium called Clostridium difficile, which is rarely found in the normal human intestine, was significantly concentrated and active in the cancerous tissue, and in some samples, the difference was hundreds of times greater. Thus, for the first time, people began to think: are changes in intestinal flora a cause or an end of human disease?  Research Introduction The microenvironment of colorectal tumors is a complex system that includes genomically altered cancer cells, non-tumor cells, and many different microorganisms.  Meyerson et al. performed whole-genome sequencing of colon cancer colonies in 9 tumor/normal control pairs and found that Clostridium perfringens sequences were abundant, a result confirmed by quantitative polymerase chain reaction (PCR) and 16S rDNA sequencing of 95 tumor/normal control pairs. The investigators also saw Clostridium perfringens in colorectal tumors by fluorescence in situ hybridization (FISH).  In a study by Canadian scholar Holt et al. that included 99 colon cancer samples, quantitative PCR analysis was performed to compare the enrichment of Clostridium perfringens fragments in tumor tissue and adjacent normal tissue, and a positive correlation was observed with lymph node metastasis.  Clostridium nucleolyticum is often treated as an oral pathogen, and the apparent overexpression of Clostridium in colorectal cancer tissues surprised the researchers. The enrichment of Clostridium difficile in colorectal cancer may suggest that these microorganisms contribute to tumorigenesis, or it is possible that Clostridium simply accumulates in the tumor microenvironment and is not involved in tumor development. Alterations in specific bacterial flora in colorectal cancer flora may provide a basis for future prevention, diagnosis, treatment and prognostic strategies. If Clostridium difficile infection is associated with early cancer, it may provide a suitable target for vaccines and antimicrobial therapy, and further studies of Clostridium difficile-associated biomarkers could be used to monitor the emergence or risk of colorectal cancer.  In an interview with this reporter, Dr. Meyerson noted that the next step in the study is to explore in animal models whether Clostridium induces or promotes colon cancer, and then to determine whether the presence of Clostridium is a cause, a consequence, or both of colon cancer.  UEGW Related Reports In October of 2009, at the 19th European Digestive Disease Week (UEGW), French scholars reported the first finding that colon cancer may be associated with significant alterations in intestinal bacteria, and the study became one of the studies specifically recommended by the UEGW President.  The composition of the fecal flora of colon cancer patients is significantly different from that of healthy individuals, and when these bacteria are transferred to healthy mice, they may stimulate small intestinal cell proliferation and differentiation, as well as increase precancerous colon lesions in the presence of chemical carcinogens, suggesting that the flora of colorectal cancer patients may promote the development of colorectal cancer.  This study provides strong evidence for the presence of oncogenic factors in the stool of colon cancer patients, suggesting that abnormal intestinal flora is one of the key factors in the development of colorectal cancer.  Chronic inflammation is the “root of all evils” and pathogenic infection is an important cause. In the case of gastrointestinal tumors, the relationship between hepatitis B virus and liver cancer, and between Helicobacter pylori and gastric cancer has been well established, and the discoverers of these pathogens, Bloomberg, and Barry Marshall and Robin Warren, were awarded the Nobel Prize in Medicine, respectively.  The increasing number of colon cancers may also be related to chronic inflammation, as the non-specific anti-inflammatory drug aspirin, which has a preventive effect on gastric cancer, may also reduce the incidence of colon cancer, but traditional intestinal pathogenic infections do not seem to be related to colon cancer, and with improved food hygiene, infectious intestinal diseases are decreasing. Yet this has not stopped humans from exploring the relationship between chronic infections, inflammation and colon cancer. The altered intestinal microecology that accompanies dietary changes is strongly associated with obesity and diabetes, but is intestinal flora also associated with colon cancer in the same dietary context?  Two research groups in the United States and Canada have published nearly identical reports indicating that Fusobacterium, a bacterium rarely found in the human gut, is unusually active in colon cancer cells and appears to correlate with the malignancy of the tumor. French scholars, who won the best abstract award at this year’s European Digestive Diseases Week in October, found that colon pre-cancerous lesions may occur in colon cancer patients when fecal flora from colon cancer patients are transferred to healthy mice. These studies open a new chapter in the study of the relationship between specific bacteria and colon cancer, and thus may provide a basis for future prevention, treatment and prognostic strategies for colon cancer.