The mechanistic role of gut microbes and their microbial metabolites underlying human infections and diseases remains unknown. Fungal commensals coexist in a complex milieu of bacteria within the human body. Severe and recurrent infections tend to manifest more frequently within immunocompromised hosts and microbial dysbiosis, suggesting that the host/microbe environment could significantly influence the infection, the generation of colonization resistance and protective tolerance and the efficacy of therapy. Expanding on these studies will provide insights into how microbial and host metabolism can influence human infections, potentially leading to personalized infection control strategies based on a patient’s metabolic state. We have deciphered the contribution of the microbiota at the host/fungus interface and captured the dialogue between the mammalian host and its microbiota via metabolomics. A functional metabolic node by which certain bacteria species contribute to host-fungal symbiosis and mucosal homeostasis in the gut has been discovered in mice and confirmed in humans. A microbial tryptophan metabolic pathway activated through the indoleamine 2, 3-dioxygenase 1 enzyme proved to be capable of correcting dysfunctional host-pathogen interaction. Working through the aryl hydrocarbon receptor (AhR), the indole-3-aldehyde (3-IAld), produced by Lactobacillus reuteri upon tryptophan feeding, regulated IL-22 expression and helped maintaining epithelial barrier and intraepithelial lymphocytes function. These activities ensured that commensal bacteria outcompete potential pathogenic fungi, allowing AhR to mediate host-microbe homeostasis through indole sensing. It seems therefore that elucidating the function of microbial metabolites and bacterial chemical signaling systems may contribute to the development of host- and microbiota-directed therapeutics and vaccine efficacy in fungal infections.
This study was supported by the European Research Council (ERC-2011-AdG-293714).