New research in mice and humans suggests that imbalances in gut bacteria could play a key role in promoting the development of colorectal cancer. The finding is helping researchers develop a blood test that may help them diagnose this form of cancer.
In 2019, doctors will have diagnosed an estimated 145,600 new cases of colorectal cancer in the United States alone, according to the National Cancer Institute.
Often, however, this form of cancer has no obvious symptoms in its initial stages, which can make it hard to diagnose early on. This may mean that individuals do not have the opportunity to start the appropriate treatment before the tumors have grown and spread.
Matters become even more complicated in the case of sporadic colorectal cancer, which develops in people with no known risk factors for cancer.
For these reasons, researchers are continually looking for better ways of understanding both what drives colorectal cancer risk, and how to identify its presence early on.
Recently, a team led by Dr. Iradj Sobhani from the Hôpitaux Universitaires Henri Mondor (Assistance Publique – Hôpitaux de Paris) and the University Paris-Est Créteil has shown, thanks to research conducted in a mouse model, that an imbalance in the sensitive gut microbiota, called “dysbiosis,” is tied to the onset of colorectal cancer.
This finding has helped the investigators develop a blood test able to pick up on the epigenetic (gene expression) changes that, in turn, are associated with both dysbiosis and tumor development.
According to the study paper featured in PNAS, this blood test has proven accurate in a small prospective validation trial involving people with sporadic colorectal cancer.
Developing a diagnostic blood test
Following on from previous research suggesting that the gut microbiota may be involved in the development of cancer, the scientists decided to delve deeper into the possible mechanisms at play.
They studied 136 mice into which they transplanted samples of either fresh stools collected from nine people with sporadic colorectal cancer or fresh stool samples from nine healthy individuals.
Then, at 7 and 14 weeks after the transplants, the researchers analyzed the mice’s colons, looking for any changes.
The team found that the mice that had received transplants of stools from cancer patients presented dysbiosis, and what is more, they had developed aberrant crypt foci (precancerous lesions). The researchers also noticed that these mice had an abnormally high number of hypermethylated genes — a feature typically associated with cancer tumors.
When they performed similar analyses for people with sporadic colorectal cancer, the researchers found the same link between dysbiosis and abnormal changes in gene expression.
The team then wondered whether it would be possible to develop a non-invasive blood test to diagnose early stage colorectal cancer in people who did not present symptoms.
So they devised a test assessing the level of hypermethylation of three different genes in the bacterial genome. To do so, they first mapped out the bacterial genomes of 1,000 people who presented no symptoms but were due to receive colonoscopies to check for cancerous tumors.
The researchers called the hypermethylation levels of the three genes the “cumulative methylation index,” and it was this value that the blood test assessed.
Based on the results of this prospective validation study, the team concluded that they could indeed rely on a person’s cumulative methylation index to predict the onset of sporadic colorectal cancer.
The researchers hope to conduct further trials in larger cohorts to make sure that the blood test is reliable on a larger scale.