Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor

Significance The gut microbiome comprises trillions of microorganisms that inhabit the mammalian intestines. These microbes regulate many aspects of host physiology, including defense mechanisms against factors that contribute to inflammatory bowel diseases (IBDs). Despite the abundance of the gut microbiota, little is known regarding how these microbes modulate these host processes, including the barrier function of the intestinal epithelium, which controls intestinal permeability associated with IBDs. Here, we discover that three gut microbially produced, small-molecule metabolites, which derive from dietary tryptophan, improve intestinal barrier integrity and protect against inflammation caused by IBDs. Our studies identify a host receptor and downstream targets of the metabolites, which could serve as potential pathways for prophylactic and therapeutic treatments for ameliorating morbidity in IBDs.