by Brittany Phillips, University of North Carolina at Chapel Hill School of Medicine

Conclusions. Credit: Pediatric Allergy and Immunology (2024). DOI: 10.1111/pai.14267

Metabolites—small molecules within cells, biofluids, tissues or organisms—play an integral role in various diseases, and studying the many metabolites (metabolomics) can teach us how the body works in ways that help researchers develop new treatments, especially for food allergens.

As the prevalence of potentially life-threatening immunoglobulin E (IgE)-mediated food allergies continues to rise, the development of therapies requires a comprehensive understanding of immune tolerance to allergens. This includes how tolerance differs between individuals with and without food allergies, and how this is modified by treatment.

One study, led by Yamini Virkud, MD, MPH, associate professor of pediatrics and director of Bioinformatics at the UNC FAI in the Department of Pediatrics at the UNC School of Medicine, is now identifying key metabolite pathways associated with food allergy and differential responses to one of the treatments for food allergy, OIT (oral immunotherapy).

“Understanding how food allergies and their therapies (of which there are only two) work is key to discovering new treatments for food allergy,” said Virkud. “We hope that using metabolomics as a tool to explore the immune system will help us learn more about immune tolerance to foods to help treat our patients with food allergies.”

Published in the journal Pediatric Allergy and Immunology, Virkud’s research studied children with food allergies compared to participants without food allergies, and demonstrated that bile acids were higher in children with food allergies and lower in children without food allergies. Researchers then looked at metabolite profiles in children receiving OIT, and compared participants who were able to maintain the protection of OIT even after stopping OIT for a month (remission) to those who lost protection soon after stopping.

They found that those who lost protection also had generally higher levels of bile acids. However, those with remission had higher levels of two specific bile acids, known as lithocholates. Virkud explained that while the main job of bile acids is to help with digestion in the gut, it turns out that bile acids are also important for controlling immune cells.

“In particular, other studies demonstrated that lithocholates control the same immune cells, T cells, which have been shown to be important for remission,” said Virkud. “Connecting our data with these other studies suggests that certain bile acid profiles may be important for determining whether someone with food allergies has a better or worse outcome on OIT.

“We also found differences in other metabolites (histidines and poly-unsaturated fatty acids) that have known roles in the immune system, and we look forward to studying all of these connections further in the future.”

The study examined metabolomic profiles of children with food allergies in multiethnic cohorts, including Genetics of Asthma in Costa Rica [GACRS], the Vitamin D Antenatal Asthma Reduction Trial [VDAART] infant cohort, and the Peanut Oral Immunotherapy (PNOIT) trial. Researchers aimed to determine key pathways of interest, ascertain how metabolomics evolve with OIT, and associate the metabolomic profiles with therapeutic OIT outcomes.

Researchers also used repeated sampling on the same participants to define pathophysiologic differences between those who had transient protection versus sustained unresponsiveness while on OIT. Virkud said her team was surprised by the findings.

“Clinical allergists and immunologists don’t generally spend a lot of time thinking about bile acids, and many of the associations between the specific bile acids and immune cells we are interested in weren’t discovered until 2019–2020,” said Virkud. “It was quite exciting to come across those papers that finally gave some biological significance to our findings.”

The study concludes that further functional validation of these metabolic pathways in the context of allergic tolerance may both help identify patients most likely to benefit from OIT and guide the development of new pathways and potential therapies that can improve outcomes for patients with food allergies.

More information: Yamini V. Virkud et al, Immunomodulatory metabolites in IgE‐mediated food allergy and oral immunotherapy outcomes based on metabolomic profiling, Pediatric Allergy and Immunology (2024). DOI: 10.1111/pai.14267

Provided by University of North Carolina at Chapel Hill School of Medicine

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