In a study published in Cancer Prevention Research, Dr. Patrick Schloss (University of Michigan) and his team found that the gut microbiome could enrich current methods of testing for colon cancer.
The group characterized the gut microbiome from stool samples of patients in three stages of colorectal cancer development: healthy, adenoma, and carcinoma. They found distinct features of the bacterial populations in each group.
By taking the gut microbiome data of a patient, along with body mass index, age, and race (which are known clinical risk factors for colon cancer), the team significantly improved their ability to detect the presence of precancerous and cancerous lesions as compared to commonly used methods of detection.
Dr. Patrick Schloss agreed to speak with Gut Microbiota for Health about this work.
Where did you get the idea that the gut microbiota might have something to do with colon cancer, and more specifically, that it might help predict colon cancer?
There have been some mouse-based studies from our lab and others, finding changes in the gut community of mice with colon cancer, as well as some studies in humans. There’s been all these different threads but no one’s done a good job of tying them all together. And so that’s where we came in.
What we wanted to be able to do is say, ‘Well, if you tell me what type of community you have, then I [can] predict your health’. So that’s really where it came from: trying to be more prospective instead of looking back.
Did anything surprise you about your results?
One of the things that really excited us was the ability to complement existing screening procedures with this method, and that our approach does better than things like FOBT [fecal occult blood testing]. But [it] does even better when you combine the methods, and also when you include the subjects’ demographic information. Typically what happens is people say, ‘Well, there are these individual bacterial populations that are associated with colon cancer’. But people rarely look at the full story: look at the subjects’ medical records, [at] other screening procedures, as well as the microbiota.
There’s been a lot of interest in microbiome research over the last number of years, but there’s really not been a deliverable… One of the things we’re excited about was that we’re stepping along that path now. We see that, yes, if we know something about the microbiome we can improve our ability to detect cancer. That it’s not just this cool thing, but that it’s actually useful. And it can improve our ability to make diagnoses.
What’s the next step in order to move this research into clinical practice?
We’re already looking to get larger patient cohorts, because we have 30 normals, 30 adenomas, and 30 carcinomas, and we’d like to get hundreds or thousands. A lot of these companies that make diagnostics, they want thousands, and so the challenge we have is to get paired colonoscopy and stool samples. Preferably stool samples from before the colonoscopy. These are difficulties we face. Often times if you’re looking at tumors, you might have a bio bank somewhere in the hospital of thousands of tumors, whereas we really need a fresh stool sample.
So the next step for us is to validate these with larger cohorts, and then perhaps to generate some type of PCR [polymerase chain reaction]-based panel, so you don’t have to sequence the whole thing, but perhaps quantify individual populations to assess risk. So that’s going down the path of a diagnostic, and we’re also interested in the biology that’s going on, so 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? And similar types of questions with all the other bacterial populations we’ve found.
Is there anything clinicians can put into practice right away?
I think if I sequenced someone’s microbiota and I found Fusobacterium at a high level, I’d be worried. We have limited validation, but if I saw this bug in my stool, or some of these other bacteria, I would want to get a colonoscopy… People don’t want a colonoscopy because it’s invasive, it’s awkward, but if we can do something like take someone’s stool sample and then make more precise suggestions on who should get colonoscopies, hopefully we’ll improve outcomes.
In the future, what might this research thread mean for prevention of colon cancer?
The earlier we can detect it, the better the outcomes. We’re perhaps not as concerned about the conversion between adenomas and carcinomas because at that point we know that the outcomes are not going to be as great, but if we can figure out why normals become adenomas, that’s going to be really powerful. And that’s where a lot of the diagnostics fall apart. Making that detection, that differentiation is really hard.
Can you tell us about your lab’s ongoing research?
We look at cancer, obviously, and then we also look at pathogens like C. difficile and try to understand how something like C. difficile is able to colonize some individuals but not other individuals. A lot of similar types of questions. So if I looked at somebody’s gut microbiota going into the hospital, can I predict their risk of getting C. difficile? And we’re also interested in the general ecology of the bacteria in the gut, that if you lined up 100 people, they would all have different microbiota in their gut. We don’t really know why. And furthermore, it’s really hard to get, say, my microbiota to look like somebody else’s microbiota in a stable, long-term way. I could take antibiotics, but for most people, their gut community’s going to come back for the most part. But if you have somebody that’s got colon cancer, or got a community that looks like they’re going to have colon cancer, we’d like to move them away. We don’t really know how to do that. I don’t know how to take someone that’s got tons of Fusobacterium in their gut but they seem healthy, and… move them to somebody that doesn’t have Fusobacterium inside them.
The other thing that’s interesting is that your gut community might be healthy for certain things but not for other things. There’s tons of different types of bacteria in your gut, and some of them could be associated with diabetes or colon cancer or C. difficile and there’s a lot going on there and it’s very difficult to tease apart.
This interview has been edited for clarity and length.
Source: Cancer Prevention Research
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
News sites that covered this research include…
Daily Mail: Gut Bacteria Help Spot Colon Cancer
Medline Plus: Gut Bacteria May Reveal Colon Cancer, Study Finds
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