Can Food Allergy Be Prevented Before It Begins? A Look At 3 Recent Studies

Food allergy care has long focused on management after sensitization, with efforts on desensitization and forms of epinephrine for anaphylaxis. The ultimate question is: can we prevent allergy before it begins?

Currently, food allergy management relies on 3 approaches: avoidance, medications, and immunotherapy. For emergencies, patients can carry epinephrine. Until recently, allergies could only be managed, not prevented altogether, but now new research shows the possibility of preventing food allergies in the critical early-life window.1

“If a child is either sensitized to a food allergen or…theoretically allergic to a food allergen… we can actually get small amounts of the food into their diet without actually stimulating their immune allergic response,” Nicole Chase, MD, an allergist/immunologist at St. Paul Allergy & Asthma, told HCPLive. “We actually can sometimes reverse this process.”

She referenced a study led by Julie E. M. Upton, MD, MPH, from the Food Allergy and Anaphylaxis Program at the Hospital for Sick Children in Toronto, which showed that if you can get 30 mg of peanut protein into a kid’s diet, it can help promote tolerance.2 The data indicate that early food introduction can be safe in children under 35 months of age, but Chase suspects 18 months is probably the right number. The study found that very low-dose oral immunotherapy (VLOIT), with a goal to slowly escalate to a 30 mg per nut maintenance dose, led to significant gains in reaction threshold by 18 months, with mean tolerated doses reaching 1000 mg.

“This is why for parents and families where there's been some type of reaction to foods, it's so important to get those kids in to see an allergist right away,” she added.

However, Upton and colleagues’ study included children already allergic to 2 – 5 nuts, so this research did not provide insight into food allergy prevention before sensitization.

Previously, the landmark Learning Early About Peanut Allergy (LEAP) trial showed early peanut introduction can protect high-risk infants from developing peanut allergies.3 By 5 years old, 3.2% of the peanut consumption group vs 17.2% of the avoidance group developed a peanut allergy, representing an approximately 80% relative risk reduction in peanut-exposed children.

The LEAP study informed early food introduction guidelines in 2015 for high-risk infants and the 2017 addendum guidelines which extended the recommendations to moderate-to-high-risk infants.4 A study published October 2025 reported a 27% decline in peanut allergy rates following the 2015 early introduction guidelines (0.67% vs 0.92%; P <.0001).4

New data continue to drive momentum in food allergy prevention before sensitization, suggesting risk may be modified at the microbiota level.

Vaginal Seeding Linked to Early Microbiome Changes and Food Sensitization

Late-breaking data from the ACTIVATE trial, presented at the 2026 American Academy of Allergy, Asthma, & Immunology (AAAAI) meeting in Philadelphia, suggest vaginal seeding in cesarean-delivered infants can partially modify early gut microbiome development and may influence food allergen sensitization at 12 months.5 The double-blind, placebo-controlled randomized study evaluated whether exposure to maternal vaginal microbiota at birth could alter allergy risk among infants at high risk for allergic disease.

The trial included 39 vaginally delivered infants, 37 cesarean-delivered infants assigned to placebo seeding, and 37 cesarean-delivered infants who underwent vaginal microbial transfer. Seeding involved swabbing newborns with gauze incubated in the maternal vagina before delivery. Shotgun metagenomic sequencing confirmed microbial transfer, with enrichment of Lactobacillus immediately after birth in seeded infants (P =.002).

At 3 months, microbiome similarity to vaginally delivered infants was greater among seeded infants, although the effect was partial (similarity indices 0.876 ± 0.07 vs 0.9 ± 0.06; P =.169) and diminished over time. By 12 months, global microbiome composition differences were no longer apparent.

Maternal vaginal microbiome composition was not associated with food sensitization at 12 months (P =.86). However, specific infant gut microbes were linked to sensitization, including Rothia mucilaginosa with egg (P =.036), Bifidobacterium breve with milk (P =.028), and Ruminococcus gnavus with egg, milk, and peanut sensitization (P =.013, .032, and .006, respectively). Seeded infants exhibited lower levels of R. gnavus and, when microbial transfer was effective, lower sensitization rates than placebo.

“It's important to remember that the ACTIVATE trial is a pilot trial,” Jose Clemente, PhD, associate professor of genetics and genomics and immunology at the Icahn School of Medicine at Mount Sinai, told HCPLive. “One of the ideas behind the trial is to determine whether the procedure is safe, and that is the case; the procedure is not associated with increased adverse events. There is a measurable benefit, but it's not yet ready to be [developed] in [the] clinic.”

Early-Life Bifidobacteria Linked to Lower Food Allergy Risk

A study published in Nature Microbiology in February 2026 reported that early colonization with aromatic lactate–producing bifidobacteria was associated with lower risk of food allergen sensitization and atopic dermatitis.6

“There's no causal link at this moment,” investigator Susanne Brix-Pedersen, professor at DTU Bioengineering told HCPLive. “As I see it, we have this prospective study where we see associations, but we don't have any studies that have been designed to actually look at the causal interaction at this moment. We are undertaking a bigger study in 1000 Danish infants, where we are trying to…investigate this in detail.”

The cohort followed 147 children from birth to age 5, with serial fecal sampling at 8 time points alongside maternal samples, blood draws, and clinical assessments. Investigators identified a microbiota–metabolite–immune axis in which infants with higher abundance of specific bifidobacteria, particularly within the first 6 months of life, had elevated levels of aromatic lactates and reduced food allergen–specific immunoglobulin E (IgE) through age 5. The protective association appeared mediated by 4-hydroxy-phenyllactate (4-OH-PLA), a bacterial metabolite that selectively inhibited IgE production in ex vivo human immune cell cultures without affecting IgG.

Infants with higher levels of these bacteria also had reduced rates of atopic dermatitis at age 2. Early-life exposures influenced colonization, with vaginal delivery, exclusive breastfeeding during the first 2 months, and exposure to older siblings associated with greater acquisition. Vaginally delivered infants were up to 14 times more likely to acquire the strains from their mothers.

Dietary Epitopes Identified as Drivers of Oral Tolerance

New translational research has identified discrete dietary epitopes that drive oral tolerance. The research, published in Science Immunology in March 2026, offers mechanistic insight into how the immune system classifies foods as safe.7

Investigators isolated intestinal regulatory T (Treg) cells in murine models fed standard chow and mapped their T cell receptor (TCR) specificity, identifying 3 dominant epitopes derived from seed storage proteins in corn, wheat, and soybean. One of the strongest responses targeted α-zein, a digestion-resistant maize storage protein.

Investigators observed convergence on a limited number of antigens, suggesting a small set of dietary proteins may disproportionately shape immune tolerance. Antigen-specific Treg populations emerged around weaning, coinciding with introduction of solid foods and aligning with clinical evidence supporting early allergen exposure to promote tolerance.

The identified Treg cells demonstrated canonical immunosuppressive functions, including anti-inflammatory cytokine secretion and inhibition of effector T cell proliferation. The study also identified cross-reactivity, with TCRs recognizing a soybean-derived epitope responding to structurally similar proteins in sesame and quinoa.

“What this could suggest, and my lab is working on this a bit now, is perhaps if we could map cross-reactivity for things like a peanut, you could become tolerant to peanut by eating something that has those shared proteins without actually having the peanut exposure,” said Jamie Blum, PhD, from the Salk Institute, in an interview with HCPLive.

What The Studies Mean for Food Allergy Prevention

Food allergy prevention before sensitization has not yet become a reality. These studies are still in the early stages, with more research needed to confirm whether these strategies will work.

For now, the guidelines recommend food introduction beginning at 4-6 months of age. The addendum guidelines suggest first consulting an allergy specialist who can perform peanut allergy testing, followed by trying peanut for the first time at a doctor’s office.

“I'm going to steal it from the Australians… eat early and eat often,” Chase said. “We don't want children to be exposed to foods that might be choking hazards, but really to otherwise go ahead and try and expose them to everything they're eating. I have a lot of families where they are nervous for whatever reason, because maybe another child has a food allergy…those parents need to be offered an evaluation by an allergist because they may not be willing to do it at home to introduce foods early. Putting the food directly into the baby's mouth and…exposing them to it on a semi-regular basis [is] what's been shown to reduce your food allergy risk.”

Watch the dynamic video on food allergy prevention, featuring Chase, Clemente, Brix-Pedersen, and Blum, here.

References

1. Clemente J, Brix-Pedersen S, Blum J, et al. The Early-Life Window: Can Food Allergy Be Prevented Before It Begins? HCPLive. Published on April 13, 2026. Accessed on April 15, 2026. https://www.hcplive.com/view/early-life-window-can-food-allergy-prevented-before-begins-

2. Upton J. VLOIT Boosts Multi-Nut Tolerance in Children, With Julia E. M. Upton, MD, MPH. HCPLive. Published on January 17, 2026. Accessed on April 15, 2026. https://www.hcplive.com/view/vloit-boosts-multi-nut-tolerance-in-children-julia-upton-md-mph

3. Du Toit G, Sampson HA, Plaut M, Burks AW, Akdis CA, Lack G. Food allergy: Update on prevention and tolerance. J Allergy Clin Immunol. 2018 Jan;141(1):30-40. doi: 10.1016/j.jaci.2017.11.010. Epub 2017 Nov 27. PMID: 29191680; PMCID: PMC12548800.

4. Derman C. Early Peanut Introduction Guidelines Linked to Drop in Food Allergy Rates. HCPLive. Published October 20, 2025. Accessed April 15, 2026. https://www.hcplive.com/view/early-peanut-introduction-guidelines-linked-drop-food-allergy-rates

5. Clemente J. Vaginal Seeding Partially Modifies Infant Microbiome in ACTIVATE, With Jose Clemente, PhD. HCPLive. Published on March 1, 2026. Accessed on April 15, 2026. https://www.hcplive.com/view/vaginal-seeding-partially-modifies-infant-microbiome-activate-jose-clemente-phd

6. Brix-Pedersen S. Early-Life Bifidobacteria Linked to Lower Food Allergy Risk, With Susanne Brix Pedersen. HCPLive. Published on February 4, 2026. Accessed on April 15, 2026. https://join.hcplive.com/view/early-life-bifidobacteria-linked-lower-food-allergy-risk-susanne-brix-pedersen

7. Blum, J. Dietary Epitopes Drive Oral Tolerance, With Jamie Blum, PhD. HCPLive. Published on March 26, 2026. Accessed on April 15, 2026. https://www.hcplive.com/view/dietary-epitopes-drive-oral-tolerance-jamie-blum-phd