Approximately 17% of children are diagnosed with NDDs, including ASD, ADHD, and ID, which are highly heterogenous, frequently co-occur, and manifest in early life in sex-dependent fashion. We speculate that some of this heterogeneity is due to interactions between genetic risk factors and environmental exposures (G x E). During neurodevelopment, both the generation of new neurons, termed neurogenesis, and the gut microbiome are exquisitely sensitive to environmental factors, with recent evidence raising concern about childhood antibiotics. To examine this issue, we designed a new G x E model selecting 16p11.2 microdeletion mouse because this human variant increases ASD risk 38-fold, and exposure to the cephalosporin antibiotic, cefdinir. We assess effects on the gut microbiome, hippocampal neurogenesis and structure, gene expression, serum metabolome, and adult behaviors. Our preliminary results suggest that cefdinir exposure alters all these parameters, supporting a possible role of antibiotic-induced changes of the microbiome in autism pathogenesis.