ANN ARBOR, Mich.—In pursuit of answers regarding the connection between the gut microbiome and colorectal cancer, a team of researchers from the University of Michigan, led by Patrick Schloss, Ph.D., have published new results revealing the role that the microbiome plays in tumorigenesis. Their results, “The gut microbiome modulates colon tumorigenesis,” appeared in mBio November 5.
The team tested their work in mouse models of inflammation-associated colorectal cancer similar to what is seen in humans, studying the development of the microbial community in the face of inflammation and tumorigenesis. They then introduced microbiota from the tumor-bearing mice to a population of germfree mice, a move that “significantly increased tumorigenesis in the colon compared to that for animals colonized with a healthy gut microbiome from untreated mice,” as noted in the abstract. In addition, those mice that received the microbiota from the tumor-bearing models presented with a higher number of bacterial populations linked to tumor formation.
The researchers then tested what would happen if the mice were administered antibiotics, and discovered that such a move resulted in “a dramatic decrease in both the number and size of tumors,” the paper notes.
“What struck us was that there are very few examples out there where people see a difference in the microbiome in humans and then are able to go in and directly modify the community and see an effect in mice,” says Schloss, associate professor of Microbiology and Immunology at the University of Michigan. “So treating the mice with antibiotics and getting rid of tumors, transferring the microbiota to germ-free mice and getting more tumors, those are both results that did a very nice job of pinning down the fact that it was the microbiome that was driving tumorigenesis.”
On Schloss’ page on the University of Michigan website, he notes that “The human microbiome is more than 10-times larger than the number of human cells, and represents a collective genome that is at least 100-times more complex than our genome … Numerous lines of evidence indicate that our genetics, diet, behavior and life experiences affect the structure of our microbiome and make us each unique. Yet, because of this daunting intra- and interpersonal complexity, it is difficult to make statements about the precise interactions between specific bacterial groups within our microbiome and their interaction with overall human health.”
As for whether gut community changes are the cause or result of cancer, Schloss says it’s not yet known. And given the relative scarcity of colorectal cancer, he adds, it would be difficult to find a large enough population to track microbiome changes.
“We don’t know if the community we see in people with colon cancer is the community of someone with colon cancer, or the community that causes colon cancer,” he explains. “At least in the mouse model, our study goes a long ways to saying it’s both, actually, the microbiome and the host’s immune system that’s driving this progression of tumorigenesis.
“There’s two sides of this,” Schloss continues. “The angle that we took in this paper was getting more towards causation and towards mechanism, but the microbiome could also be very useful as a diagnostic. As a diagnostic, we could perhaps look at the community, the microbiome people have, and say ‘yeah, that’s the microbiome of someone associated with colon cancer.’ And I know there’s also interest in saying ‘well, can we look at stool samples, the gut community, and predict whether or not somebody has breast cancer or pancreatic cancer or other cancers?’ It’s kind of thought that the gut is in a way a representation of overall health, and so if we can detect changes there, then it can be used as a diagnostic, even if we don’t understand the mechanisms of what’s going on.”
In terms of whether the microbiome affects tumorigenesis in other types of cancer, Schloss says it definitely plays a role in stomach cancer, noting that work is also being done in other labs to explore its role in esophageal cancer.
The researchers will next be working with the mouse models to determine whether antibiotics and diet changes can affect the rates of tumorigenesis, according to Schloss, who notes that they will also move forward into examining this research in humans, particularly to determine the potential of using the microbiome as a biomarker for tumorigenesis.
“We’re trying to take both the animal model as well as the human angle to better understand the role of the microbiome in colorectal cancer,” he concludes.
