Antioxidants in diet could raise risk of bowel cancer, new study reveals

By Dr. Ananya Mandal, MDJul 30 2020

Health benefits of antioxidants in food have been proven across a considerable body of scientific literature. Now, a new study shows that too much of a good thing may not be that good! Typically antioxidants in food, including polyphenols, flavonoids, and other plant compounds, could raise the risk of bowel cancer finds a new study from Israeli researchers. The study titled, "The gut microbiome switches mutant p53 from tumour-suppressive to oncogenic," was published this week in the journal Nature.

Study: The gut microbiome switches mutant p53 from tumour-suppressive to oncogenic. Intestinal bacteria, Gut microbiome, 3d illustration Credit: nobeastsofierce / Shutterstock

What was this study about?

Researchers from the Hebrew University of Jerusalem studied the effects of food and gut bacteria on health and cancer-causing genes. The team explained that an important gene called the p53 is responsible for the suppression of tumors in the gut. They explained that certain mutations of this gene had been known to raise the risk of cancers. The mutation causes oncogenic changes in the cells, they wrote.

A gene called the Tp53 is found in all cells of the body. This gene produces an essential protein called p53. Protein p53  protects cells from harmful mutations that could cause cancer. When the Tp53 gene is itself mutated, it produces altered or mutated p53 proteins. The altered p53 cannot protect cells from mutations and now actually helps tumors to grow and spread.

What was done in this study?

The gene that codes for p53 in mice is called the Trp53. For this study special genetically modified mice were used. These mice were missing an important gene called the "Csnk1a1 deletion," and they had "Apc^Min mutation." Studies have shown these mutations to contribute to cancers due to the loss of p53.

What was found?

P53 mutation – protection and cancer risk

Results of the experiment showed that as the mutations of p53 took place in these experimental mice, several changes were seen in different parts of the gastrointestinal tract of the mice. The prominent cancer-causing effect was seen in the distal end of the gut due to mutated p53 protein, they wrote. In the upper part of the gut, this mutated protein, however, played a protective role against cancer, promoting healthy growth and development they noted. Here these proteins were called "super suppressors." This, they explained saying, "mutant p53 was more effective than wild-type p53 at inhibiting tumor formation".

Role of the gut microbiome

Next, they found that this tumor protective effect of the p53 mutation was removed entirely due to altered gut microbial flora. They noted that gut microflora that released a metabolite called gallic acid could influence the effects of the whole gut microbiome. They took experimental mice that had no gut flora and p53 mutations and supplemented their gut with gallic acid. This resulted in the mice having TCF4–chromatin interaction and led to the activation of the cancer-causing risk throughout the gut. They explained that mice that had been fed antioxidant-rich foods such as black tea, nuts, chocolate, and berries developed gut flora that produced more gallic acid and raised the risk of large intestine cancer.

Implications of these findings

This study shows that both food and gut microbes play a role in cancer risk. They noted that small intestines are relatively protected from cancer while the large intestines are more at risk of bowel cancer. Experts say that only 2 percent of bowel cancers affect small intestines, and 98 percent are seen in the large intestine - colon.

The authors wrote in conclusions, "Our study demonstrates the substantial plasticity of a cancer mutation and highlights the role of the microenvironment in determining its functional outcome."

Explaining the role of antioxidants in the diet that raised risk of bowel cancers, lead researcher Professor Yinon Ben-Neriah from Hebrew University of Jerusalem (HU)'s Lautenberg Center for Immunology and Cancer Research, said, "We were riveted by what we saw. The gut bacteria had a Jekyll and Hyde effect on the mutated p53 proteins. In the small bowel, they totally switched course and attacked the cancerous cells, whereas in the colon, they promoted the cancerous growth."

Ben-Neriah added, "Scientifically speaking, this is new territory. We were astonished to see the extent to which microbiomes affect cancer mutations–in some cases, entirely changing their nature."

Neriah said, "Scientists are beginning to pay more and more attention to the role gut microbiomes play in our health: both their positive effects and, in this case, their sometimes pernicious role in aiding and abetting disease." Speaking about the implication of this study, the team said those who are at a higher risk of colorectal cancer might benefit from the screening of their gut microbiome from time to time. Foods these individuals take are also to be considered say experts given that they may play a role in altering the gut microbes and, in turn, alter the tumor causing capacity of the mutated proteins within the intestines.