To investigate the expression patterns of fecal iron metabolism-related proteins at the early stage of food allergy (FA) onset in infants, and to explore the association between imbalance of local intestinal iron homeostasis and infant FA.

A nested case-control design within a prospective clinical cohort was used. From October 2024 to June 2025, 162 infants with suspected FA were recruited from outpatient clinics, the child health department, and community settings, and classified into an FA group (n=88) and a non-FA group (n=74) according to standardized oral food challenge results. Baseline fecal samples collected prior to diagnosis were tested by enzymelinked immunosorbent assay for iron metabolism-related proteins, and fecal non-heme iron content was measured. Group differences were compared.

FA onset peaked at 4-6 months of age, coinciding with the period of physiological depletion of fetal iron stores. Gastrointestinal symptoms predominated. Compared with the non-FA group, the FA group had significantly higher fecal transferrin receptor 1 concentrations (P<0.001) and significantly lower ferritin heavy chain, ferritin light chain, and non-heme iron content (all P<0.05). No significant between-group differences were observed in lactoferrin or hephaestin concentrations (P>0.05).

Infants with FA exhibit an imbalance of local intestinal iron homeostasis at the early stage of disease onset, characterized by enhanced iron uptake signaling alongside reduced iron storage, indicative of a functional iron deficiency state. This imbalance appears associated with the early occurrence of infant FA.