Protein-Free Diet Aggravates Food Allergy Response via the Consumption of Glycochenodeoxycholic Acid in a Murine Model

Amino acid–based formulas (AAFs) are increasingly consumed in infants with food allergy (FA), while the effects of their long-term consumption on FA remain poorly known. This study investigated the effects of the long-term consumption of AAFs on FA by subjecting neonatal mice to an amino acid–based diet (AAD). Long-term consumption of AAD exacerbated allergic symptoms, Th2 responses, and mast cell activation and concurrently suppressed the differentiation of CD103 + DCs and Tregs in the MLN. Furthermore, integrated metabolomics and metagenomics analysis revealed that AAD induced intestinal microbiota dysbiosis and altered the systemic metabolome, characterized by a marked depletion of Bacteroides and glycochenodeoxycholic acid (GCDCA). Critically, oral supplementation with GCDCA effectively attenuated the FA response in AAD-fed mice. In summary, our findings suggest that long-term consumption of AAD aggravates FA via GCDCA depletion, which highlights the necessity to avoid the excessive use of AAFs and positions GCDCA supplementation as a promising therapeutic strategy for FA.