Prospective birth cohort: Cephalosporins drive gut microbiota and food allergy.

Background: The biological association between early-life antibiotic exposure and the risk of food allergy (FA) remains unclear. Given the widespread use of cephalosporins during the perinatal period and infancy, this relationship and potential mechanisms urgently require clarification. Methods: This study employed a prospective birth cohort design, recruiting 1275 mother-infant pairs, followed until 6 months of age, recorded cephalosporins exposure timing, and collected fecal samples for multi-omics analysis. Results: Nine hundred thirty-nine eligible mother-infant pairs completed the study, and 224 infants were diagnosed with IgE-FA. Multivariate analysis identified intrapartum cephalosporins exposure duration (OR = 1.04) and the first 2 months of life (0-1 months of age: OR = 4.03; 1-2 months of age: OR = 3.13) as critical risk windows for cephalosporins exposure-induced FA. Family allergic history was a synergistic risk factor. This effect exhibited an "all-or-none" pattern, independent of antibiotic dose or treatment course, suggesting it may act as a "switch" triggering allergic susceptibility. Gut microbiota and metabolomic analyses revealed that cephalosporins exposure led to dysbiosis, downregulation of tryptophan metabolism and nitric oxide (NO) production pathways, which were associated with impaired intestinal barrier function and T-helper 2 (Th2) immune imbalance. Conclusions: This study is the first to precisely delineate the critical temporal windows of early-life cephalosporins exposure in the development of IgE-FA, propose the "switch hypothesis", and preliminarily explore its underlying mechanisms. These findings provide a novel rationale for optimizing the precise use of antibiotics during the intrapartum period and infancy, and for FA interventions targeting the microbial metabolic axis. Trial registration number: ChiCTR2300072832.