Dietary tryptophan deficiency promotes gut RORgt plus Treg cells at the expense of Gata3+Treg cells and alters commensal microbiota metabolism

Micronutrient deficiency is a major cause of disease throughout the world. Yet, how perturbations influence the immune-microbiome interface remains poorly understood. Here, we report that loss of dietary tryptophan (Trp) reshapes intestinal microbial communities, including the depletion of probiotic L. reuteri, drives tran-scriptional changes to immune response genes in the intestinal ileum, and reshapes the regulatory T cell (Treg) compartment. Dietary Trp deficiency promotes expansion of RORgt+ Treg cells and the loss of Gata3+ Tregs in a microbiota-dependent manner. In the absence of dietary Trp, provision of the AhR ligand indole-3-carbinol is sufficient to restore the Treg compartment. Together, these data show that dietary Trp deficiency perturbs the interaction between the host and its bacterial symbionts to regulate Treg homeosta-sis via the deprivation of bacterially derived Trp metabolites. Our findings highlight an essential role for im-mune-microbiome crosstalk as a key homeostatic regulator during nutrient deficiency.

Automated summary

Micronutrient deficiency is a leading cause of global diseases. This study reveals that a deficiency in dietary tryptophan (Trp) alters the intestinal microbiome and the immune response, resulting in changes to the Treg cell population. Dietary Trp deficiency leads to the expansion of RORgt+ Treg cells and the loss of Gata3+ Tregs, which can be restored by providing the AhR ligand indole-3-carbinol. These findings emphasize the crucial role of immune-microbiome crosstalk in regulating Treg homeostasis during nutrient deficiency.