Grant: CIHR Fellowship

Pain is a critical sensation that protects organisms from internal and external sources of danger. Nociceptor neurons that mediate pain hypersensitivity express specific molecular transducers at their nerve terminals that detect heat, cold, and other noxious stimuli. The gastrointestinal (GI) tract is densely innervated by dorsal root ganglia nociceptors, and visceral pain accompanies many gut disorders. Recent studies have established these neurons not only mediate pain, but regulate other GI functions including epithelial barrier function, mucus production, host defense, and gut motility. Despite increasing interest in the "gut-brain-axis" and observations that the gut microbiota affects brain function and behavior, the molecular and cellular mechanisms that mediate crosstalk between neurons and specific bacteria to modulate pain are not clear. Thus, there is a need to better define the exact molecular mechanisms by which neuron-bacteria communication occurs. In this proposal, I will analyze the bidirectional relationship between nociceptor neurons and specific gut commensal bacterial species. This project will produce new insights into host neuron-microbe interactions that impact our understanding of health and disease. Future analysis will extend to human population neuron-microbiota interactions and clinical settings. We will also determine if microflora from people with capsaicin-laden diets that constantly activate nociceptors differ from the microflora of people with milder diets. By defining human neuron-microbe molecular interactions, this work has the potential to develop targeted therapies for the modulation of chronic pain and microbial dysbiosis.