How Gut Microbes Can Help Us Detect Cancer

Behavioral changes in our gut ecosystems will likely become key to spotting cancer—but can the new diagnostic methods help scientists treat it?
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Behavioral changes in our gut ecosystems will likely become key to spotting cancer—but can the new diagnostic methods help scientists treat it?
(Photo: pnnl/Flickr)

(Photo: pnnl/Flickr)

There is a factoid often recited by the scientists who study the symbiotic bacteria that live in the human body: Our microbes outnumber our own cells 10 to one. As my colleague Jeffrey Gordon puts it, each of us is "an amalgamation of human and microbial parts." While this is not a new idea—we've long known that our guts are filled with bacteria—scientists have only recently developed the tools to systematically study the ecosystem inside our guts. Their results suggest that thinking about ourselves as a human-microbe amalgamation could become increasingly important in medicine. Researchers are trying to figure out how we can use our microbial parts to detect, prevent, and even treat disease.

People have tried to improve human health by manipulating our gut microbes for more than a century. But, the shelves of probiotics at your local GNC notwithstanding, these efforts haven't been particularly effective. That's because most of the bacteria inside us have been practically invisible. Since many gut bacteria can't be cultured outside the body in a test tube, scientists had no way to identify or measure them. The development of new DNA analysis tools has changed that. By measuring the bacterial DNA in our excrement, researchers now have the capability to track what's going on in our guts.

What they’ve found is a rich ecosystem: We carry anywhere from hundreds to thousands of different species of bacteria in our intestines. Taken together, these bacteria have more than 100 times the number of genes in the human genome. Many of these genes encode specialized enzymes that enable our gut bacteria to metabolize our food in ways that our own enzymes can't, making them an influential component of our digestive system. These bacteria also have genes that enable them to co-exist with our immune system—without those genes, our intestinal bacteria would be treated as hostile invaders and targeted for destruction. The potential consequences of this symbiotic relationship for our health could be huge. As some of my Washington University colleagues wrote: "Our growing understanding of the human gut microbiota as an indicator of and contributor to human health suggests that it will play important roles in the diagnosis, treatment, and ultimately prevention of human disease."

Do shifts in our gut ecosystems cause disease? And can we treat disease by shifting those ecosystems back? It's a very tempting idea—as the population of bacteria shifts, so does the metabolism of that population.

How would this work in practice? Fecal transplants, still largely experimental, are one of the more dramatic examples—they are used to fight certain dangerous intestinal infections. But most research is focused on situations that are not so acutely life-threatening. One common approach used by scientists is to take a DNA census of the different bacteria present in people, and ask if this bacterial population is skewed in patients with certain health problems. Researchers are finding that the ecosystem of gut bacteria is altered in patients with inflammatory bowel disease, diabetes, metabolic syndrome, and even in pregnant women. While it's difficult to disentangle cause from effect at this point, it's clear that taking a census of our symbiotic bacteria is a potentially powerful way to read the state of our health.

Last month, an international team of researchers demonstrated the potential of this idea by showing that we can use measurements of our gut bacteria as a screen for colon cancer. A definitive diagnosis of colon cancer involves a colonoscopy and a biopsy, but patients often get those later than they should, missing the chance to catch cancer at its earliest and most treatable stage. To decide whether a patient needs a colonoscopy, physicians turn to a cheaper and less-invasive fecal blood test. The problem is that the fecal blood test isn't particularly sensitive—after the test, some patients who should be advised to get a colonoscopy aren’t.

The researchers wanted to know if they could do better by using a bacterial fingerprint as a test for colon cancer. They recruited roughly 150 French patients who had undergone a fecal blood test and a colonoscopy, slightly fewer than half of whom were diagnosed with colon cancer. The researchers extracted DNA from the patients' fecal samples and tallied up the amount of DNA that came from different species of bacteria. They then used the data to train a computer model to distinguish the cancer patients from the healthy controls. The computer model, by considering the levels of 22 different species of bacteria, was somewhat better than the fecal blood test at picking out the cancer patients. And when the fecal blood test was combined with the computer model into a single diagnostic test, the result was even better: The cancer detection rate improved by 45 percent, without any increase in the rate of healthy people who were misclassified. This was a small pilot study, and the method needs to be systematically tested with more patients. But it's clear that the population of symbiotic bacteria is altered in people with colon cancer.

The study also raises a provocative question that haunts the entire field: Do shifts in our gut ecosystems cause disease? And can we treat disease by shifting those ecosystems back? It's a very tempting idea—as the population of bacteria shifts, so does the metabolism of that population. In colon cancer patients, the researchers found evidence suggesting that the bacteria had shifted away from metabolizing dietary fiber—a healthy function—and were instead producing potentially harmful metabolites. The finding is intriguing, but, at this point, nobody can say whether or how this change contributes to cancer progression. Scientists are now confronting the challenge of doing more than merely observing shifts in our gut microbes by developing new tools to take the next step: sorting out cause from effect.

The study of our internal symbiotic bacteria is still in its early days. Nobody yet knows to what degree we can change our health by changing our microbes. But it's clear that when we think about what it means to be healthy, we shouldn't only consider ourselves as individuals—we also need to think of ourselves as ecosystems.

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