Combined Intervention with Human Milk Oligosaccharides and Lacticaseibacillus paracasei 1 Alleviates Ovalbumin-induced Food Allergy by Modulating the Gut Microbiota

Food allergy represents a group of disorders driven by abnormal immune responses, with a prevalence that has been rising steadily in recent years. Research indicates that human milk oligosaccharides and gut probiotics play an essential role in early-life immune regulation and the establishment of allergic tolerance. This study preliminarily explored the alleviating effects of a combined intervention with HMOs and Lc. paracasei 1 in OVA-induced food-allergic mice. The results demonstrated that the combined intervention markedly relieved allergic symptoms, reduced symptom scores, lowered serum IgE levels, rebalanced Th1/Th2 cytokines, and enhanced intestinal barrier integrity. 16S rRNA sequencing revealed that the HMOs and Lc. paracasei 1 combination significantly increased gut microbiota α-diversity and promoted the enrichment of beneficial bacteria, including Lactobacillus and Bifidobacterium . Concurrently, levels of key microbial metabolite, particularly short-chain fatty acids, rose substantially. Further untargeted Metabolomics analysis identified significant alterations in multiple differential metabolites across treatment groups, such as indole-3-acetic acid, indole-3-propionic acid, tryptophan, taurocholic acid, deoxycholic acid, and arachidonic acid. KEGG pathway enrichment analysis showed these metabolites were primarily involved in tryptophan metabolism, fatty acid metabolism, bile acid metabolism, and amino acid biosynthesis. Microbiome-metabolite correlation analysis further indicated that the abundances of Lactobacillus and Bifidobacterium were strongly positively correlated with indole metabolites and SCFAs. These findings suggest that the combined intervention of HMOs and Lc. paracasei 1 may alleviate food allergy symptoms by modulating gut microbiota composition and the metabolic profile, thereby influencing the body’s immune response.