By Kristina Campbell
Scientists are starting to develop an idea of how colorectal carcinoma (CRC) arises. It all starts with bacteria in the digestive tract: possibly a strain of Bacteroides fragilis or the infamous Escherichia coli. Whether the bacteria are new to the body, or resided there all along, doesn't matter. The bacteria somehow get a green light to start producing chemical agents that damage the genetic information in the body's cells. The damaged cells rapidly divide. Soon enough, polyps (also called adenomas) appear in the colon. These polyps can become cancerous.
Currently, there's a gap in CRC detection methods. This is a problem that's directly connected with patient mortality: if CRC is detected at an early stage, survival rate is more than 80%. But if it's left until a late stage, it's less than 10%.
The two standard ways to detect this cancer are a fecal occult blood test (FOBT) and a colonoscopy. FOBT – which tests for traces of blood in the stool – has limited sensitivity for CRC. It's only a rough guide, since it misses many cases. Colonoscopy is the most effective method of diagnosis, but it's far from perfect because it's invasive and costly.
New research shows that the microbiota might lead to better CRC detection. Iradj Sobhani and colleagues recently published an intriguing paper in Molecular Systems Biology called ‘Potential of fecal microbiota for early-stage detection of colorectal carcinoma'. They took fecal samples from healthy people and those with confirmed CRC, and used metagenomic sequencing to find out how they differed.
They found that the fecal samples held clues that were missing from FOBT. Using both methods together, they increased the sensitivity of colon cancer detection 45% (as compared with FOBT alone). Used effectively in the clinic, this could save thousands of lives each year.
Sobhani said he and his colleagues are working on a clinical tool to help patients make use of this information. In a recent interview, he said, "Now we know a panel of some 18-20 [relevant] bacteria and we are trying to make an easy and simple tool to identify these bacteria. We can, I hope, in a very short future time, make low-cost tools to identify the bacterial phenotype usually found in patients with colon cancer."
A smaller study from the Schloss lab found a similar result: enhanced CRC detection using information from FOBT and a fecal sample, as well as body mass index, age, and race (which are known risk factors for colon cancer).
Schloss said that one kind of bacteria in particular piqued his interest. "We’re trying to better understand [why] Fusobacterium seems to be popping up in a lot of these stories. How does Fusobacterium get from the mouth to the gut? Everybody has it in their mouth. But not everybody has it in the gut. So what’s breaking down there? Does it have a role in disease?"
The Sobhani study went beyond CRC detection to factors that might be involved in prevention. The researchers looked at the bacterial genes in the guts of those with CRC and asked, "What can these bacteria do well?" In other words, they looked at the bacterial functions as indicated by their genes.
This analysis showed some interesting links to diet. Sobhani explained, "Those with colon cancer had largely more meat-metabolizing bacteria] compared to those who have no colon cancer, who have bacteria that show more functions to metabolize vegetables." He added, "Then there are functions involved in the transfer and capture of… minerals."
Whatever made the meat metabolizers more abundant in the colon could turn out to be what caused the cancer in the first place. But it's not clear whether red meat consumption itself accounts for the disease-associated condition of the microbiota, or whether other components of the diet play a role. (Fiber is a prime preventative candidate under investigation.)
A whopping 95% of CRC could be attributable to environmental factors. More research related to the gut microbiota and CRC might one day reveal exactly what those environmental factors are, so we can kick colon cancer to the curb.
Zackular J, Rogers M, Ruffin M and Schloss P. (2014) The Human Gut Microbiome as a Screening Tool for Colorectal Cancer. Cancer Prevention Research doi: 10.1158/1940-6207.CAPR-14-0129
Zeller G, Tap J, Voigt AY, et al. (2014) Potential of fecal microbiota for early-stage detection of colorectal cancer. Molecular Systems Biology doi: 10.15252/msb.20145645