How Gut Bacteria May Cause Cancer in Obese Individuals

For reasons that have remained unclear, obese people are at a much higher risk for developing cancer compared to their thinner friends. The National Cancer Institute (NCI) estimates that around 85,000 new cancer cases each year are a direct result of obesity. While not yet up to the 171,000 or so new cases of lung cancer caused by smoking, obesity-related cancers are catching up. And as the number of smokers go down and the number of obese people go up, there may come a time in the future when obesity-related cancers are the most preventable ones.

Ideally, we would want to prevent these cancers by having obese people lose weight (but we’ve seen how successful this has been so far.)

Another way to reduce these numbers might be to figure out how obesity causes cancer. If we can do that, then maybe we can block the process and keep these cancers from forming in the first place. People can have their cake and eat it too!

A new study out in Nature is a first step on this path (at least in mice). In this study, Yoshimoto and coworkers show that obesity by itself does not cause cancer in mice. Instead, bacteria specific to the gut of obese mice make certain cells more susceptible to getting cancer when exposed to carcinogens. Obesity makes the mice less able to deal with environmental insults.

The researchers first showed that in a protected environment, mice fed a high-fat diet were not at a higher risk for cancer compared to mice fed a low-fat diet. Both had about the same rates of cancer. So obesity itself does not directly cause cancer in these mice.

The situation is very different if these two groups of mice are exposed to a carcinogen (DMBA) while still in the womb. In that case, only around 5% of the mice fed the low-fat diet ended up with cancer while 100% of the mice fed the high-fat diet did. And the two groups ended up with different cancers—the thinner mice got lung cancer while the obese ones got liver cancer. Clearly something about obesity was making the livers of obese mice much more susceptible to the effects of the carcinogen.

That something turned out to be bacteria specific to the guts of the obese mice. When the mice that were fed the high-fat diet were also given a cocktail of antibiotics, their number of liver tumors was reduced around fourfold. These mice were less likely to get cancer because the bacteria in their gut were changed.

A little more investigative work pointed to a chemical that a subset of these bacteria made called DCA. This chemical caused parts of the liver to look and behave older than they were—the cells had become senescent. When the researchers gave DCA to mice fed a low-fat diet, these mice developed liver cancer. And when the researchers decreased the number of older cells in the livers of obese mice, they developed less cancer.

Taken together, these data strongly suggest that one way that obesity causes cancer in mice is through some obese-specific gut bacteria. And if we get a similar result in people, then there may be some relatively simple ways to reduce cancers in obese people.

Maybe obese people could be given a set of antibiotics that prunes away harmful gut bacteria. Or what might be even better is if obese people underwent a fecal transplant from thinner people. This might swap out the bacteria of the thin with the bacteria of the obese and so decrease obese people’s cancer risk.

While gross, this last idea has the advantage of not increasing antibiotic use (which is already a big problem.) It also wouldn’t make it so we had to fine tune the cocktail of antibiotics. We wouldn’t need to know all the beneficial or harmful bacteria–we’d simply swap thin for obese. This last idea also has the advantage that it is just creepy enough that it might spur people to lose weight. Better a bit of exercise and the occasional salad as opposed to a fecal transplant!