Research links food antigens from proteins to reduced gut tumor development

20 Sep 2024 --- Scientists reveal that food antigens trigger the intestinal immune system to stop new tumors from forming, specifically in the small intestines. The study sheds new light on these food antigens — substances that cause the body to make an immune response against them — which are the source of allergic reactions to food like peanuts, shellfish, bread, eggs and milk. 

The research builds on an earlier study by the same team, reporting that food antigens activate immune cells in the small but not in the large intestines. Meanwhile, gut bacteria are known to trigger some immune cells that can suppress tumors in the gut. 

The team investigated the impact of tumor development in mice after feeding them three different diets — regular food, antigen-free food and an antigen-free diet with added albumin. The regular food did not include this food antigen. Protein sources such as meat and poultry, fish, dairy, eggs, legumes and nuts can help the body produce albumin. 

Lead researcher Hiroshi Ohno, Ph.D., of the RIKEN Center for Integrative Medical Sciences in Japan, tells Nutrition Insight that the study dealt with “elementary diets,” utterly devoid of food antigens. These liquid meal replacement diets offer a complete nutritional profile broken down into elemental forms. For example, proteins, fats and carbohydrates are broken down into amino acids, short-chain triglycerides and maltodextrins. 

“Therefore, it is different from other studies on nutrition,” Ohno underscores. “The latter is basically about the role of food ingredients in the host metabolic diseases, not related to immunological aspects, including the role of antigens.” 

He explains that the study’s outcomes “can be important for patients who suffer from familial adenomatous polyposis or Crohn’s disease. They are sometimes treated with an elemental diet, but at the same time, they have a higher risk of small intestinal tumors, and special caution should be taken in those cases.”

Antigen-free diets

The study, published in Frontiers in Immunology, uses mice with a mutation in a tumor-suppressor gene. When this gene malfunctions, the animals develop tumors throughout the small and large intestines, similar to people with familial adenomatous polyposis. This disease is an inherited condition that affects the gastrointestinal tract, where patients develop polyps inside the colon or rectum. 

In the first experiment, the researchers fed mice either regular or antigen-free food. Mice eating a typical diet had fewer tumors in their small intestines but the same amount in their large intestines. 

Tumor suppression was directly related to the presence of albumin, not food’s nutritional value or other antigens.In a third diet fed to the mice, the researchers added albumin to the antigen-free diet while ensuring that the total amount of protein was equal to that of the normal food. The team used bovine serum albumin, derived from cows, or ovalbumin, the main protein found in egg whites. 

On this diet, the researchers discovered that tumors in the small intestines of mice were suppressed, much like when they consumed a regular diet. According to the team, tumor suppression was directly related to the presence of albumin, not the food’s nutritional value or other antigens. 

Immunity system

In addition, mice that consumed the plain antigen-free diet had fewer T cells — white blood cells essential in the immune system — than mice eating regular or antigen-free diets with albumen. In further experiments, the researchers discovered the biological process that enables this development. They propose that the number of T cells infiltrating tumors is essential for the anti-tumor response. 

Ohno notes, “additional research should be needed to further elucidate the underlying mechanisms.” 

For example, the researchers detail that it is unclear whether other tissue in the abdomen plays a role in inducing small intestinal immune cells. They expect that future “clarification of this mechanism” will help explain how food antigens suppress the creation of tumors through the immune system.

Elementary diets offer a complete nutritional profile broken down into elemental forms, which can be taken orally or enterally.Enteral nutrition

The study’s findings have clinical significance, concludes the report. Ingredients in the antigen-free diet in the study are similar to those used for enteral nutrition, also known as tube feeding, where nutrition is sent right to the stomach or small intestine. 

For example, clinical elemental diets, which can be taken orally or enterally, include simple amino acids but not protein to reduce digestive work and help people with severe gastrointestinal conditions, such as Crohn’s disease or irritable bowel disease (IBD). In addition, IBD is a risk factor for small intestinal cancer and tumor development. 

The researchers illustrate that enteral feeding is commonly used to support therapy in gastrointestinal health issues, such as patients suffering from familial adenomatous polyposis, who often suffer from small intestinal tumors. 

Ohno cautions: “Small intestinal tumors 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 IBD or other gastrointestinal conditions in these patients should be considered very carefully.”

The study concludes that more studies in humans are required before definitive conclusions can be reached on using enteral nutrition in these patients. 

By Jolanda van Hal