Vertebrate intestinal surfaces are in constant contact with a vast consortium of commensal bacteria. To preserve mutually beneficial host-microbial relationships, gut epithelia have evolved strategies to limit the proinflammatory potential of resident gut microbes. In this issue of Cell Host & Microbe, Bates and colleagues report that intestinal alkaline phosphatase, whose expression is induced during establishment of the microbiota, dephosphorylates lipopolysaccharide and promotes mucosal tolerance to commensal bacteria in zebrafish.