Eric Wang, Senior Photographer

An article recently published in the scientific journal Cell provides new clues to the mystery behind food allergies by examining the workings of what the authors label as a biological food quality control system — which is intended to regulate the quality of food we consume.

Written by four Yale affiliates, this article delivered a novel perspective on why food allergies exist and suggests why they may exist at higher-than-average rates in industrialized nations. The authors proposed that allergies, like many diseases, are caused by a malfunctioning food quality control system.

“We are trying to … generate a new framework or a new way of thinking about food allergies to help researchers and clinicians,” said William Khoury-Hanold GRD ’16, a postdoctoral fellow in the lab of Ruslan Medzhitov and an author of the article. “Immunologists … are still trying to really break ground on really understanding why people get allergies and what they’re there for.”

According to the article’s authors, allergic reactions are an overly severe immune response triggered by a food quality control system. Assistant professor of life sciences at Arizona State University, Esther Florsheim, explained that the system consists of the immune system and other bodily systems that regulate the quality of the food people ingest.

One example of how the system works as intended is when people avoid foods with unpleasant tastes, such as bitter fruits which contain compounds that would disrupt the body’s ability to digest protein, according to Khoury-Hanold.

 “That’s a big problem for an animal,” Khoury-Hanold said. “So those compounds would disrupt digestion of protein and that would be undesirable in terms of an animal’s lifetime. And in terms of evolutionary history, if a species fails to deal with it and keeps using that thing as a food source, it’s not going to be very successful.”

People’s tendency to find these foods extremely unpleasant to eat causes them to avoid the foods and their harmful effects. Further along the digestive tract, other cells sense the toxicity of digested food and have a low threshold for what they deem worthy of expulsion from the digestive or respiratory tract.

In essence, allergies exist when this powerful system is wired to react to what are normally benign substances, according to the article. Milk, eggs, peanuts, tree nuts, soy, fish and shellfish are cited by the article as the eight food groups which account for the majority of allergies.

Given that this sensitivity to certain foods is specific to different individuals, the article proposes that the allergic reaction that follows is the body’s immune response.

“In certain people, [the immune response] becomes exaggerated,” said Zuri Sullivan, a postdoctoral fellow at Harvard University and the fourth author of the paper. “And that’s sort of the basis of why we experience food allergy.”

It remains unknown why the immune system is wired to react to these certain foods. According to Florsheim, the first possibility is that certain foods are more toxic than we realize. The article cites one example as walnuts, which produce toxins meant to ward away predators — but the toxins may cause minimal damage to human cells.

The other possibility, Florsheim explained, is that the body uses certain foods as proxies for noxious compounds. One example may be oysters, which are known to carry many viruses.

“[Feeling] sick when you eat an oyster,” Florsheim said, “will later cause your senses to tell you, ‘Be careful because when you ate this last time, there was something that triggered this response. … So, maybe don’t eat that.’”

The article’s proposed cause for allergies is vitally important in a time where food allergy rates are on the rise. One theory in the article sought to explain the increased rate of allergies in industrialized nations: the hygiene hypothesis, which links increasing allergy rates to increasingly hygienic living environments.

Essentially, when human environments are more sterile, children are less frequently exposed to the pathogens that the immune system is designed to handle. This limited exposure causes the immune system to function improperly.

“They’re sort of parallel systems,” Sullivan said. “The hygiene hypothesis tries to explain our relationship to microbes from an evolutionary perspective, and this food quality control hypothesis tries to explain our relationship to food in a sort of analogous manner.”

The danger posed by allergies is the “collateral damage” incurred in the process of the immune response through severe allergy-related symptoms, according to Khoury-Hanold. He added that mitigating this collateral damage will be the goal of future researchers and clinicians and that doing so will require a greater understanding of the origins of allergies. This future research is especially important as allergies become more prevalent in human populations, the article states.

Another implication of the article is that to better understand allergies, scientists must work to better understand the gastrointestinal tract and the specific functions of the food quality control system. Florsheim explained how there are some simple questions about the system that scientists are still not able to answer, such as how many cell types exist in the tract and what each of their functions is.

“People, I think, overlook or underestimate how much we actually, indeed, know about [the GI tract],” Florsheim said. “There are lots of things that we don’t know yet. … To integrate neuroscience, animal behavior and immunology and physiology, those things combined, I think, can give us a lot more.”

According to the Asthma and Allergy Foundation of America, over 50 million Americans experience some form of allergy each year.

Amre Proman | amre.proman@yale.edu