Food antigens help to suppress gut tumours

Researchers at the RIKEN Center for Integrative Medical Sciences have discovered that food antigens like milk proteins help keep tumours from growing in the small intestines, with experiments revealing how these proteins trigger the intestinal immune system. The study has been published in the journal Frontiers in Immunology.

Food antigens get a lot of negative press because they are the source of allergic reactions to foods such as peanuts, shellfish, bread, eggs and milk. Even when they don’t lead to allergic reactions, these antigens — along with the many others found in plants and beans — are still considered foreign objects that need to be checked out by the immune system.

RIKEN’s Hiroshi Ohno and his team have previously reported that food antigens activate immune cells in the small intestines, but not the large intestines. At the same time, some immune cells activated by gut bacteria are known to suppress tumours in the gut. In the new study, the researchers brought these two lines of thought together and tested whether food antigens suppress tumours in the small intestines.

The team began with a special kind of mouse with a mutation in a tumour-suppression gene. Like people with familial adenomatous polyposis, when this gene malfunctions, the mice develop tumours throughout the small and large intestines. The researchers fed these mice normal or antigen-free food and found that the mice that got normal food had fewer tumours in the small intestines, but the same amount in the large intestines.

Next, the researchers added a common representative antigen called albumin — which can be found in meat and was not in the normal food — to the antigen-free diet, making sure that the total amount of the protein equalled the amount of protein in the normal diet. When the mice were given this diet, tumours in the small intestine were suppressed just as they had been with normal food. This means that tumour suppression was directly related to the presence of antigen, not the nutritional value of the food or any specific antigen.

The three diets also affected immune cells, specifically T cells, in the small intestines. Mice that got the plain antigen-free diet had many fewer T cells than those that got the normal food or the antigen-free food with milk protein. Further experiments revealed the biological process that makes this possible.

These findings have clinical implications. Similar to antigen-free diets, clinical elemental diets include simple amino acids but not proteins, which reduces digestive work. These diets can help people with severe gastrointestinal conditions, such as Crohn’s disease or irritable bowel syndrome, but they are also sometimes adopted by people without such conditions as a healthy way to lose weight or reduce bloating and inflammation. The new findings suggest that this could be risky.

“Small intestinal tumours are much rarer than those in the colon, but the risk is higher in cases of familial adenomatous polyposis, and therefore the clinical use of elemental diets to treat inflammatory bowel disease or other gastrointestinal conditions in these patients should be considered very carefully,” Ohno concluded.

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