The gut microbiota plays crucial roles in the development and functions of the central nervous system (CNS) as well as in modulation of neurobehavior in heath and disease. The gut brush border enzyme intestinal alkaline phosphatase (IAP) is an important positive regulator of gut microbial homeostasis. In mice, IAP is encoded by Akp3 gene, which is specifically expressed in the duodenum of the small intestine. IAP deficiency alters gut bacterial composition and gut barrier function. Decreased IAP activity has been observed in aging, gut inflammatory diseases, and metabolic disorders. We hypothesized that this enzyme could also play an important role in modulating neurobehavior. We performed deep sequencing of gut bacterial 16S rRNA and found that IAP deficiency changed gut microbiota composition at various taxonomic levels. Using targeted metabolomic analysis, we also found that IAP deficiency resulted in changes of gut bacteria-derived metabolites in serum and brain metabolism. Neurobehavioral analyses revealed that Akp3