Jose Clemente, PhD, associate professor of Genetics and Genomics and Immunology at the Icahn School of Medicine at Mount Sinai

Jose Clemente, PhD

The Early-Life Window: Can Food Allergy Be Prevented Before It Begins?

 in early life was the standard advice. However, new research shows this is not always the case.

A growing body of research now suggests that early exposure, rather than avoidance, may reduce the risk of food allergy and promote immune tolerance during a critical developmental period.

The change began with the Learning Early About Peanut Allergy (LEAP) trial, which showed that by 5 years old, 3.2% of the consumption group and 17.2% of the avoidance group had developed a peanut allergy.

 This represented an approximately 80% relative risk reduction in peanut-exposed children.

Follow-up studies demonstrated that this protection persisted even after a period of peanut avoidance, suggesting durable immune tolerance. A study published in October 2025 analyzed data from > 85,000 children across nearly 50 pediatric practices and found a 27% drop in peanut allergies following the 2015 early introduction guidelines (

 <.001) and a 43% drop after the 2017 addendum (

Building on this dietary prevention model, newer research is expanding attention to early-life immune programming. One area of focus is the infant microbiome, which begins forming at birth and may influence downstream immune responses.

Investigators studying cesarean-delivered infants have examined vaginal microbial transfer as a strategy to partially restore maternal microbial exposure.

 In the ACTIVATE trial, vaginal seeding altered early microbiome composition, shifting bacterial profiles toward those seen after vaginal delivery. Infants who received the intervention also showed differences in food sensitization during infancy, suggesting early microbial exposure may influence allergic risk, although long-term outcomes remain under study.

Mechanistic work has linked microbial activity to immune regulation. Certain bifidobacteria produce aromatic lactate metabolites associated with reduced development of food allergen–specific immunoglobulin E, providing a potential biological pathway connecting microbiome composition to tolerance.

Moreover, translational research examining dietary antigens has identified discrete food-derived proteins recognized by intestinal regulatory T cells; these proteins were found in corn, wheat, and soybean.

 These antigen-specific populations emerge around the time of weaning, when infants first encounter solid foods, and early consumption has been associated with tolerance responses.

These data suggest multiple early-life pathways may influence allergy risk. Microbial colonization, bacteria-derived metabolites, and exposure to dietary antigens each appear to contribute to immune training. This suggests that prevention strategies may extend beyond feeding practices alone to broader early immune development.

: Associate professor of Genetics and Genomics and Immunology at the Icahn School of Medicine at Mount Sinai

An allergist/immunologist at St. Paul Allergy & Asthma and associate professor of medicine at the University of Minnesota Medical School

Clemente J. Vaginal Seeding Partially Modifies Infant Microbiome in ACTIVATE, With Jose Clemente, PhD. HCPLive. Published on March 1, 2026. Accessed on April 13, 2026. 

https://www.hcplive.com/view/vaginal-seeding-partially-modifies-infant-microbiome-activate-jose-clemente-phd

Brix-Pedersen S. Early-Life Bifidobacteria Linked to Lower Food Allergy Risk, With Susanne Brix Pedersen. 

Published on February 4, 2026. Accessed on April 13, 2026. 

https://join.hcplive.com/view/early-life-bifidobacteria-linked-lower-food-allergy-risk-susanne-brix-pedersen

Blum, J. Dietary Epitopes Drive Oral Tolerance, With Jamie Blum, PhD. HCPLive. Published on March 26, 2026. Accessed on April 13, 2026. 

https://www.hcplive.com/view/dietary-epitopes-drive-oral-tolerance-jamie-blum-phd

Gabryszewski S, Gupta R, and Hernandez-Trujillo V. Peanut Allergy Rates Plummet 10 Years After AAP Early Introduction Guidelines. 

 Published October 30, 2025. Accessed on April 13, 2026. 

https://www.hcplive.com/view/peanut-allergy-rates-plummet-10-years-aap-early-introduction-guidelines

Videos

Early allergen introduction, microbiome research, and immune programming studies suggest food allergy prevention may begin during infancy.

 The Early-Life Window: Can Food Allergy Be Prevented Before It Begins?

HCPLive Five: AAAAI 2026

2026 American Academy of Allergy, Asthma & Immunology (AAAAI)

 annual meeting in Philadelphia from February 27 – March 2, investigators presented new data spanning drug hypersensitivity, food 

 treatment, microbiome science, and biologic therapies for chronic inflammatory disease.

In this installment of HCPLive Five, the editorial team highlights 5 key expert interviews conducted on site, featuring insights from leading clinicians and investigators on emerging data. Topics include pharmacogenomic risk for lamotrigine-induced DRESS, adjunct biologic strategies for multi-allergen oral immunotherapy (OIT), microbiome modulation in infants born via cesarean delivery, and long-acting biologic therapies for chronic rhinosinusitis with nasal polyps (CRSwNP) and hereditary angioedema (HAE).

HLA-A*32:01 Linked to Lamotrigine DRESS Risk, With Matthew Krantz, MD

New research highlights a strong genetic association between the antiseizure medication lamotrigine and drug reaction with eosinophilia and systemic symptoms (Drug Reaction with Eosinophilia and Systemic Symptoms) among carriers of the HLA-A*32:01 allele. In an interview, Matthew Krantz, MD, of Vanderbilt University Medical Center, discussed prospective case-control findings conducted with Mass General Brigham showing 12-fold increased odds of lamotrigine-induced DRESS among HLA-A*32:01 carriers.

The multi-institutional analysis included 30 confirmed DRESS cases and 300 lamotrigine-tolerant controls from the BioVU biobank. Findings show the potential role of HLA genotyping in clarifying causality when multiple medications are involved and may inform future pharmacogenomic strategies to identify patients at elevated risk for severe lamotrigine hypersensitivity.

Dupilumab Reduces GI Symptoms During Multi-Allergen OIT, With Sayantani Sindher, MD

Findings from the COMBINE trial suggest the biologic dupilumab may improve tolerability and desensitization during omalizumab-facilitated multi-allergen OIT. In an interview, Sayantani Sindher, MD, from Stanford University, discussed results from the randomized study of 108 patients with multiple food allergies undergoing OIT. Although adding dupilumab did not significantly improve sustained unresponsiveness, it increased tolerance to higher allergen doses and reduced gastrointestinal adverse events.

Participants receiving dupilumab tolerated larger allergen exposures and experienced fewer GI symptoms per dose. Findings suggest dupilumab may serve as a targeted adjunct therapy to improve safety and patient experience during multi-allergen OIT.

Vaginal Seeding Partially Modifies Infant Microbiome in ACTIVATE, With Jose Clemente, PhD

Results from the ACTIVATE trial suggest vaginal microbial transfer may partially modify the infant gut microbiome in cesarean-delivered infants and influence early allergy risk. In an interview, Jose Clemente, PhD, from Icahn School of Medicine at Mount Sina, discussed findings showing that vaginal seeding increased colonization with beneficial microbes such as 

 shortly after birth and temporarily shifted microbiome profiles toward those seen in vaginally delivered infants. Although global microbiome differences diminished by 12 months, infants with successful microbial transfer showed lower levels of microbes associated with food sensitization.

Twice-Yearly Depemokimab Reduces Rescue Use in Recurrent CRSwNP, With Josesph Han, MD

A pooled post hoc analysis of ANCHOR-1 and ANCHOR-2 suggests the anti–IL-5 biologic depemokimab may improve disease control in patients with CRSwNP and prior surgery. In an interview, Joseph K. Han, MD, from Old Dominion University, discussed findings showing twice-yearly depemokimab improved nasal obstruction, sense of smell, and health-related quality of life compared with placebo in patients with type 2 inflammation. Depemokimab significantly reduced the need for rescue interventions such as systemic corticosteroids or additional surgery.

Navenibart at 3- and 6-Month Dosing Reduces HAE Attacks, With Adil Adatia, MD

Interim phase 2 ALPHA-SOLAR data suggest the investigational monoclonal antibody navenibart may provide durable prophylaxis for HAE types 1 and 2. In an interview, Adil Adatia, MD, from University of Alberta, reported that both 3-month and 6-month subcutaneous dosing schedules produced substantial reductions in HAE attacks, with median reductions exceeding 95%. The long-acting plasma kallikrein–targeting antibody demonstrated a favorable safety profile, with mostly mild treatment-emergent adverse events and few injection-site reactions.

Investigators also noted improvements in patient quality of life as attack frequency declined. Findings support continued evaluation of navenibart in the ongoing phase 3 ALPHA-ORBIT trial.

This HCPLive Five captures 5 interviews conducted on-site at AAAAI 2026.

HCPLive Five at AAAAI 2026

Early Microbiome Shifts May Define a Critical Window for Allergy Risk, With Jose Clemente, PhD

New ACTIVATE data found that vaginal seeding in cesarean-delivered infants was associated with altered early gut microbiome patterns and differences in 

Jose Clemente, PhD, associate professor of genetics and genomics and immunology at the Icahn School of Medicine at Mount Sinai, presented these late-breaking findings at the 2026 American Academy of Allergy, Asthma, & Immunology (AAAAI) in Philadelphia from February 27 to March 2. ACTIVATE, a double-blind, randomized trial, evaluated whether exposure to maternal vaginal microbiota at birth can influence food allergen sensitization in cesarean-delivered infants at high risk for allergic disease.

The study enrolled 39 vaginally delivered infants, 37 cesarean-delivered infants who received placebo seeding, and 37 cesarean-delivered infants who underwent vaginal seeding, along with their mothers. Vaginal seeding in the study involved placing sterile gauze in the maternal vagina approximately 1 hour before cesarean delivery, and then immediately after birth, using the gauze to swab the infant’s mouth, face, and body.

, abundant in maternal vaginal samples, was enriched in the stool of infants who received vaginal microbial transfer compared with placebo immediately after birth (

 =.002). At 3 months, infants who underwent vaginal seeding had stool microbiomes more similar to vaginally delivered infants than placebo-treated infants (similarity 0.876 ± 0.07 vs 0.9 ± 0.06;

 =.169); this effect was partial and waned over time. The analysis also showed that maternal vaginal microbiome composition itself was not associated with food sensitization at 12 months (

 =.86), but specific infant gut microbes identified at 12 months were associated with allergen sensitization (

during AAAAI, Clemente emphasized that even temporary microbial shifts may influence long-term immune trajectories.

“We see differences for the first few months, but then after a while, those differences, at least looking at the microbes…disappear,” Clemente said. “It doesn't matter if you've been exposed to the microbes or not when the babies are 1 year of age. We don't see differences anymore, but we think it's really those first few months when it’s critical to intervene if we want to lower [allergy] risk. I think a harder problem that comes out of it is, well, what happens if you have a child that already has an allergy? That's a much harder problem to tackle because we know that it's during these first few months when we can modulate the microbiome and modulate the immune development based on those interventions.”

Clemente J, Bu K, Cantor A, et al. Microbiome Associations with Food Sensitization in the ACTIVATE Trial: Exposure to Vaginal Microbiome in C-section Infants at High-risk for Allergies. 

Journal of Allergy and Clinical Immunology

doi:https://doi.org/10.1016/j.jaci.2025.12.935

Early gut microbiome changes in c-section infants linked to food sensitization at 12 months, highlighting a potential critical intervention window.

Vaginal seeding in cesarean-delivered infants was associated with altered early gut microbiome patterns and differences in 

 at 12 months, according to late-breaking ACTIVATE trial data presented at the 2026 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in Philadelphia.

The Journal of Allergy and Clinical Immunology had published a report on the link between delivery mode and allergy risk had been reported > 2 decades ago. However, as cesarean delivery rates continue to rise in the United States and globally, rising from 7% in 1990 to 21% in 2025, interest has intensified around how birth mode influences early immune development and allergy risk.

 spoke with Jose Clemente, PhD, associate professor of Genetics and Genomics and Immunology at the Icahn School of Medicine at Mount Sinai, who discussed the biologic rationale behind the trial and what the findings may mean for clinicians.

“A few years ago, we thought, okay… c-section is associated with different type of colonization with microbes. Maybe if we restore microbes in this c-section babies, we can hopefully modulate the risk for allergies,” Clemente said. “That's the whole idea behind…this particular trial.”

ACTIVATE is a double-blind, placebo-controlled, randomized clinical trial evaluating whether exposure to maternal vaginal microbiota at birth can influence food allergen sensitization in cesarean-delivered infants at high risk for allergic disease.

The study enrolled 39 vaginally delivered infants, 37 cesarean-delivered infants who received placebo seeding, and 37 cesarean-delivered infants who underwent vaginal seeding, along with their mothers.

Vaginal seeding in ACTIVATE involved placing sterile gauze in the maternal vagina approximately 1 hour prior to cesarean delivery. Immediately after birth, the gauze was used to swab the infant’s mouth, face, and body in an effort to approximate microbial exposure during vaginal birth.

Shotgun metagenomic sequencing confirmed microbial transfer. Lactobacillus, abundant in maternal vaginal samples, was enriched in the stool of infants who received vaginal microbial transfer compared with placebo immediately after birth (

At 3 months, the stool microbiome of infants who underwent vaginal seeding more closely resembled that of vaginally delivered infants than infants who underwent placebo seeding (similarity indices 0.876 ± 0.07 vs 0.9 ± 0.06;

 =.169), though the effect was partial and diminished over time. By 12 months, global microbiome composition differences between groups were no longer apparent.

Clemente emphasized that this partial modification is biologically meaningful. Vaginal seeding does not replicate the full microbial exposure of vaginal delivery, but even limited early colonization may act as a developmental primer, influencing downstream microbial succession and immune programming.

“When you're born, you're essentially born with no microbes,” Clemente said. “We think that this first exposure is important because it sets the baby on the correct developmental pathway. It sets the baby to acquire microbes then are going to lead to a transition to other microbes that might also be eventually beneficial, in terms of risk against risk of allergies.”

Maternal vaginal microbiome composition itself was not associated with food sensitization at 12 months (P =.86). Instead, specific infant gut microbes identified at 12 months were associated with allergen sensitization, including 

 = 0.013, 0.032, and 0.006, respectively). Infants with vagina seeding exhibited lower levels of R. gnavus, a microbe previously implicated in inflammatory pathways.

The investigators demonstrated that among infants who underwent vaginal seeding and in whom microbial transfer was effective, rates of sensitization were lower compared with placebo-seeded counterparts, although Clemente characterized the trial as exploratory and not yet practice-changing.

“It's important to remember that the activate trial is a pilot trial,” Clemente said. “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. Two, whether we see a measurable benefit, and that's what we have shown that there is a measurable benefit, but it's not quite yet ready to be developing in clinic.”

McKeever TM, Lewis SA, Smith C, Hubbard R. Mode of delivery and risk of developing allergic disease. 

. 2002;109(5):800-802. doi:https://doi.org/10.1067/mai.2002.124046

Trial data show early microbiome shifts after vaginal microbial transfer in cesarean-delivered infants, with differences in food sensitization at 12 months.

Jose Clemente, PhD

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