Bifidobacterium breve M‐16V Alleviates Cow's Milk Allergy in a Mouse Model via Gut Microbiota‐Derived Indole‐3‐Propionic Acid‐Aryl Hydrocarbon Receptor Signaling Axis

ABSTRACT Background Gut microbiota plays a crucial role in the development of food allergy (FA), and probiotic intervention is a promising therapeutic strategy targeting the gut microbiota. Previous investigations have reported that some Bifidobacterium species mitigate FA by regulating the microbial composition and metabolic functions. However, the key metabolites and potential mechanisms remain poorly understood. We aim to investigate the alleviating effect of Bifidobacterium breve ( B. breve ) M‐16V on cow's milk allergy (CMA) and elucidate the underlying molecular mechanism. Methods We evaluated the mitigation effect of B. breve M‐16V on CMA using a BALB/c mouse model, combined with 16S rRNA sequencing, transcriptome sequencing, and metabolomics to determine the key metabolites and explore their molecular mechanisms. Results B. breve M‐16V supplementation was found to alleviate CMA symptoms, reverse Th2‐biased immune response, and enhance intestinal barrier function. It was demonstrated that these positive effects of B. breve M‐16V depended upon its cooperation with the original gut microbes. This contributed to promoting the expansion of tryptophan‐metabolizing bacteria, regulating the tryptophan metabolism function of the host and the indole derivatives production by intestinal microbiota, especially increasing indole‐3‐propionic acid (IPA) level. Moreover, the results further indicated that IPA improved CMA through activating the aryl hydrocarbon receptor (AhR) signaling pathway, and consistently, the AhR activation was necessary for B. breve M‐16V to alleviate CMA. Conclusions B. breve M‐16V ameliorates CMA depending on the activation of AhR signaling by an increase in microbiota‐derived IPA, presenting a potential approach for the management of FA.