Identification of a Quorum Sensing-Dependent Communication Pathway Mediating Bacteria-Gut-Brain Cross Talk

Despite recently established contributions of the intestinal microbiome to human health and disease, our understanding of bacteria-host communication pathways with regard to the gut-brain axis remains limited. Here we provide evidence that intestinal neurons are able to sense'' bacteria independently of the host immune system. Using supernatants from cultures of the opportunistic pathogen Staphylococcus aureus (S. aureus) we demonstrate the release of mediators with neuromodulatory properties at high population density. These mediators induced a biphasic response in extrinsic sensory afferent nerves, increased membrane permeability in cultured sensory neurons, and altered intestinal motility and secretion. Genetic manipulation of S. aureus revealed two key quorum sensing-regulated classes of pore forming toxins that mediate excitation and inhibition of extrinsic sensory nerves, respectively. As such, bacterial mediators have the potential to directly modulate gut-brain communication to influence intestinal symptoms and reflex function in vivo, contributing to homeostatic, behavioral, and sensory consequences of infection.