Background: Gut microbiota is critical in food allergy (FA) development. While early-life antibiotics increase FA risk, the mechanism is unclear, and current treatments cannot correct underlying immune defects. Objective: To investigate how early-life antibiotics exacerbate FA and whether fructooligosaccharides (FOS) can restore gutimmune balance. Methods: We linked early-life antibiotic use to gut dysbiosis and metabolites in a birth cohor, modeled mechanisms and FOS intervention in antibiotic-exposed FA mice, and validated FOS efficacy in a pediatric trial. Results: Early-life antibiotics caused persistent gut dysbiosis (notably Lactobacillus depletion) and disrupted tryptophan metabolism, ultimately resulting in oxidative stress, barrier damage, and T-cell imbalance. FOS restored Lactobacillus and the tryptophan metabolite indole-3- propionic acid (IPA). IPA alleviates mitochondrial dysfunction and reactive oxygen species accumulation via activation of the aryl hydrocarbon receptor (AhR)-nuclear factor erythroid 2- related factor 2 (Nrf2)-heme oxygenase-1 (HO-1) antioxidant pathway , and enhances intestinal barrier integrity , ultimately rebalancing T-cell homeostasis and attenuating FA. In a pediatric trial, metagenomic sequencing revealed that FOS enriches both Lactobacillus johnsonii and Clostridium sporogenes, synergistically promoting IPA production—which correlates with reduced SCORAD scores and improved weight gain Conclusions: Early-life antibiotics cause lasting disruptions in gut microbiota and metabolism that worsen FA. FOS mitigates FA by boosting microbiota-derived IPA to activate the protective AhR-Nrf2-HO-1 pathway , highlighting its therapeutic potential for FA, particularly in patients with prior antibiotic exposure.