Human Milk Oligosaccharide Synbiotic Alleviates Food Allergy in Mice by Modulating Gut Microbiota and Increasing Indole-3-lactic Acid Levels

While synbiotic interventions show promise in alleviating food allergy (FA), targeted optimization of probiotic–prebiotic combinations for enhanced immunomodulatory metabolite production remains insufficiently explored. This study constructed a novel synbiotic containing five human milk oligosaccharides (5-HMOs), Bifidobacterium bifidum R0071, bovine whey protein hydrolysate, and tryptophan, which demonstrated efficient production of indole-3-lactic acid (ILA) in vitro. In an ovalbumin (OVA)-induced FA mouse model, the synbiotic significantly alleviated allergic symptoms, reduced OVA-sIgE levels, restored Th2/Th17 immune balance, improved intestinal barrier integrity, and activated the aryl hydrocarbon receptor. 16S rRNA sequencing revealed that this synbiotic treatment enriched beneficial gut bacteria, including Bifidobacterium, Akkermansia, and Lactobacillus johnsonii. Targeted metabolomics confirmed elevated intestinal ILA levels, which were closely correlated with the alleviation of FA. Collectively, these findings demonstrate that the 5-HMOs synbiotic alleviates FA by modulating the gut microbiota and enhancing ILA production, offering novel insights into the targeted development of synbiotic-based interventions against FA.