Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor

Significance While the effects of gut microbes on brain development and function have been described, the mechanisms remain largely unknown. Here, we report that tryptophan-metabolizing gut microbes secrete indoles that regulate neurogenesis in the adult hippocampus. This stimulatory effect on adult neurogenesis is mediated by the metabolic- and immune-linked aryl hydrocarbon receptor (AhR). Another AhR ligand, the tryptophan metabolite kynurenine, failed to induce neurogenesis, suggesting ligand specificity of AhR-mediated regulation of adult neurogenesis. The indole-AhR signaling pathway elevates transcription factors and signaling proteins that promote adult neurogenesis, as well as key markers of synaptic maturation. Our data demonstrate a symbiotic gut–brain coregulatory axis that connects the metabolic status of gut microbes to the control of neurogenesis in the adult hippocampus.