High-fat diet may raise cancer risk by changing gut stem cells

Gut stem cells – which last a lifetime – are the cells most likely to accumulate mutations that cause colon cancer.

The study – published in Nature – is the work of researchers from the Whitehead Institute and the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (MIT), both in Cambridge, MA.

Studies published over the last 10 years have shown that being obese and eating a high-fat, high-calorie diet can raise the risk of many types of cancer, including colon cancer.

The new study suggests an underlying mechanism through which this link might operate. It reveals the effect that a high-fat diet has on the biology of stem cells in the lining of the gut of mice and how this might make cancer more likely.

The team discovered that feeding mice on a high-fat diet resulted in a boom in their intestine’s production of stem cells. And it also had an effect on some other cells – it caused them to become more like stem cells and make them more likely to form tumors.

Stem cells are precursor cells that can reproduce indefinitely and have not fully differentiated – they have the potential to become a number of different cells.

Omer Yilmaz, an MIT assistant professor of biology who co-led the investigation, says:

“Not only does the high-fat diet change the biology of stem cells, it also changes the biology of non-stem-cell populations, which collectively leads to an increase in tumor formation.”

Stem cells behaved ‘independently of niche cells’

Recent studies reveal that gut stem cells – which last a lifetime – are the cells most likely to accumulate mutations that cause colon cancer. These stem cells inhabit the epithelium or lining of the gut and differentiate into the many kinds of cell that make up the lining tissue.

For their study, the team fed healthy mice a diet comprising 60% fat for 9 months. This is a much higher proportion of fat than the 20-40% fat content of the average American diet.

The mice gained 30-50% more body mass and developed more intestinal tumors, compared with healthy mice on a normal diet.

When they examined the mice’s gut tissue, the researchers found the ones fed a high-fat diet had many more intestinal stem cells than the mice on a normal diet.

They also noticed that the boosted population of stem cells had another distinctive feature – they could operate independently of the cells around them.

Under normal circumstances, stem cells interact with support or “niche” cells that surround them. These niche cells regulate stem cell activity and signal to them when it is time to differentiate into tissue-specific cells.

However, the researchers found that the stem cells from the intestines of mice on the high-fat diet were so independent of their niche cells that, when cultured outside the body, they could produce “mini-intestines” much more readily than stem cells from normal-fed mice.

Also, when they examined the high-fat diet mouse tissue for another type of cell called progenitor cells – these are a step further along the differentiation process than stem cells – the team found they were behaving more like stem cells.

The stem-like progenitor cells were living much longer (they usually only live for a few days), and they could also produce mini-intestines when cultured on their own.

Prof. Yilmaz says the findings are important because we know that intestinal stem cells are often the cells of the gut that develop and accumulate mutations that give rise to cancer. He adds:

“Not only do you have more of the traditional stem cells (on a high-fat diet), but now you have non-stem-cell populations that have the ability to acquire mutations that give rise to tumors.”

He and his colleagues are investigating some other related findings of the study in an attempt to find possible drug targets for tumors that arise in obesity.

Medical News Today recently learned that stem cells may also be used to fight cancer. Researchers have found a way to transform skin cells into stem cells that target and destroy brain cancer.