Despite some existing limitations in this study that should be noted, we provide, to the best of our knowledge, the first experimental evidence that microbiota depletion protects from systolic dysfunction and adverse cardiac remodeling in response to TAC in a T cell-dependent manner, characterize the microbiota of Tcra−/- mice in response to TAC, and unveil a possible cardioprotective tryptophan/AhR pathway that is predominantly regulated by T cells, and, to a lesser extent, by the microbiota. This evidence concerns the gene AHR and persistent truncus arteriosus.