Bile Acids May Impact Who Reaches Food Allergy OIT Remission

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in Food Allergy, Food Allergy News
Published: January 14, 2025
A Mother and her Daughter sit in a medical office across from their Pediatrician during an appointment. The little girl is sitting on her Mothers lap and is smiling as they talk with the doctor.
Photo: Getty Images

Studies show that children with food allergies may have differences in their microbiome – the vast community of bacteria living in the digestive tract – from kids without allergies.

Other research suggests that the intestines of food-allergic children may be more permeable, allowing more or larger food particles through, triggering an immune response. 

New research identifies another gut factor that could be involved – digestive chemicals called bile acids. A recent study reveals that children with food allergies have different bile acid profiles than children without allergies.

These differences likely even influence who achieves a lasting response to oral immunotherapy (OIT) for a food allergy. They appear to impact who stays desensitized – and who loses tolerance quickly if the food is no longer consumed regularly. A lasting response to OIT is called sustained unresponsiveness, or remission. 

People on OIT who can stop eating their allergen yet “maintain that protection are thought to have a different immune state than people who lose the protection as soon as they stop OIT,” says lead study author Dr. Yamini Virkud. She’s director of Bioinformatics at the University of North Carolina School of Medicine Food Allergy Institute. 

According to the study, their “bile acid profiles may be important for determining whether someone with food allergies has a better or worse outcome on OIT.”

Bile Acids and Allergy: Role of Metabolites  

In the study, Virkud and colleagues analyzed children’s metabolite profiles. Metabolites are small molecules produced when the body breaks down food and other substances during metabolism. There are thousands of these metabolite types. 

Study co-author Dr. Yamini Virkud.

The research draws on data from three earlier trials involving kids ranging from toddlers to teens. One study enrolled 384 healthy U.S. infants; 22 of whom developed food allergies. A second included 1,040 children with asthma in Costa Rica; 57 had food allergies. A third was a small peanut OIT trial. 

An analysis was conducted of hundreds of metabolites found in the study subjects’ blood plasma. Researchers found differences in the metabolite profiles of children with and without food allergies. Though they spotted differences in the levels of several metabolites, the most surprising was that children with food allergy had higher overall levels of bile acids. Bile acids are chemicals made by the liver and secreted in the small intestine to break down fat.

Using data from the peanut OIT trial, they also discovered that children with higher levels of bile acids lost tolerance quickly after not eating their allergenic foods for one month. Conversely, children who maintained their level of tolerance to peanut had lower bile acid levels. 

“This sets up the idea that higher levels of bile acids in the blood plasma is not a good thing,” Virkud says.

Bile Acids and the Immune System

However, there were two exceptions among the bile acids. Children who did better on OIT had higher levels of two specific bile acids called lithocholates. 

Intitially, this puzzled researchers because the findings seemed contradictory. But subsequent studies revealed that lithocholates may have a protective effect against allergic reactions through their interactions with T regulatory cells. 

Although bile acids are known mainly for their role in digestion, that’s not all they do, Virkud says. After completing their digestive job in the small intestine, bile acids are reabsorbed into the bloodstream, where they circulate throughout the body and interact with immune cells. 

In the immune system, lithocholates help regulate the differentiation of immature T regulatory cells into mature cells. These T cells blunt the immune system’s reaction to allergens and may be important in maintaining allergen tolerance in OIT. 

“Lithocholates are protective by increasing the production of T regulatory cells. T regulatory cells are thought to be involved in people who outgrow allergies, and in people who develop remission or sustained unresponsiveness on OIT,” Virkud says.

By boosting T regulatory cell production, bile acids could also reduce gut inflammation. This may potentially make the gut less permeable, she says. 

Future Directions with Food Allergy

Though intriguing, much is still to be learned. “Theoretically, we are connecting these dots,” the author says. “But right now, these connections are only observational.” Future studies will apply lithocholates to actual regulatory T cells from individuals with food allergies to see the effect. 

The study of the connections between the metabolic environment and the immune system is called immunometabolomics. It’s an area of growing interest. 

In studying food allergies, there’s a focus on specific immune cell pathways. But Virkud says this may overlook the milieu that immune cells live in, that impacts their production and function. 

“Metabolites can only be produced with the help of the gut bacteria,” she explains. Metabolites, in turn, may impact immune cells that are nowhere near the intestines.

Understanding these interactions may help to explain why some have more success with OIT than others, or even why food allergies develop in the first place. “There is a lot of interplay,” she says. “Looking at these metabolites gives us this unique insight into why bacteria in the gut might be influencing immune cells all throughout the body.”

More also needs to be learned about how treatments such as OIT may change the gut bacteria, and potentially metabolite production, over the long-term. 

Related Reading:
Gut Microbiome Flaws Linked to Allergies from Food to Eczema
FDA Greenlights Palforzia OIT for Toddlers with Peanut Allergy