Grant: Doctoral Research Award: Canada Graduate Scholarships

Canada is currently facing an opioid crisis, with approximately 20 Canadians dying every day due to opioid overdose. Relapse following treatment for opioid addiction is common, and novel strategies are needed to reduce the likelihood of relapse. This project aims to explore the gut microbiome as a possible target for treatment during opioid withdrawal. The development of a pronounced neuroinflammatory state during withdrawal has been associated with the emergence of centrally-mediated aversive symptoms, including hyperalgesia and dysphoria. Given the ability of the gut microbiome to interact with the immune system and generate neuroinflammation via a gut-brain signalling axis, the withdrawal symptomology, neuroinflammatory state, and composition of the gut microbiome in opioid-dependent mice will be characterized in both acute and protracted opioid withdrawal. The causal role of the gut microbiome in withdrawal will be assessed via examination of the withdrawal phenotype in germ-free mice, as well as following fecal transfer experiments from opioid-dependent conventional mice to opioid-naïve germ-free mice. Furthermore, given the withdrawal-associated microbial shift, the contribution of withdrawal-induced changes in GI motility as a driver of these symptoms will be investigated by assessing the efficacy of multiple pharmacological manipulations of gut motility in either eliciting or normalizing this withdrawal phenotype. If the relationship between the gut microbiome and symptoms of withdrawal persists, interventions that aim to restore the composition of the gut microbiome could prove to be an attractive target in alleviating the withdrawal symptoms associated with chronic opioid use.