Tryptophan metabolites at the service of neuroimmune sensing of microbes

Hosts have evolved multifaceted, intricate mechanisms to sense and respond to the microbes they coexist with, and these mechanisms play an important role in health and disease. The co-metabolism of dietary components by hosts and their microbiomes produces a myriad of signaling molecules, which are increasingly recognized in pathophysiology regulation via their engagement with the neuro-immune network. In this review, we focus on the emerging role of tryptophan (Trp) metabolites in host-microbe crosstalk through the lens of neuroimmune sensing in the gut and beyond. We highlight how Trp metabolites orchestrate the immune and neural networks to mediate the local and trans-organ effects of the microbiome. We also consider how a neuroimmunometabolic perspective could offer valuable insights into the pathogenesis of, and treatment strategies for, chronic diseases.