An increased understanding of the importance of microbiota in shaping the host's immune and metabolic activities has rendered fungal interactions with their hosts more complex than previously appreciated. It is now clear that a three-way interaction between host, fungi, and microbiota dictates the types of host-fungus relationship. Indeed, microbial dysbiosis predisposes to a variety of chronic fungal infections and diseases at local and distant sites. By correlating changes in metabolite profiles with microbiota metagenomic composition, we have defined a functional node whereby certain bacteria species contribute to host-fungal symbiosis and mucosal homeostasis. A tryptophan catabolic pathway is exploited by commensal lactobacilli and the mammalian host to increase fitness in response to Candida albicans by inducing resistance and tolerance mechanisms of antifungal immunity. Much like lactobacilli in the gut, Firmicutes change significantly in the airways during aspergillosis. The aryl hydrocarbon receptor has a pivotal role in connecting tryptophan catabolism by microbial communities and the host's own pathway of tryptophan degradation through the enzyme indoleamine 2,3-dioxygenase 1. These data suggest that the study of the human microbiota in the trans-omics era, with a focus on metagenomics and metabonomics, is providing novel insights into the regulation of host immune responsiveness to fungi.