The microbiome's influence on the neurobiology of opioid addiction and brain connectivity

Abstract

Background: Opioids are the most effective and potent analgesics available for acute pain management. With no viable alternative for treating chronic or post operative pain, it is not surprising that over 10 million people misuse opioids. This study explores the developmental influence of the microbiome on resistance to opioid addictive behavior and functional connectivity.

Methods: Female germ free reared (GFR) mice were compared to wild-type (WT) mice, before and after conventionalization using conditioned place preference (CPP) with oxycodone (OXY) exposure. Functional connectivity data were collected providing site-specific analysis for over 140 different brain areas.

Results: GFR mice showed significant reduction in CPP after OXY exposure. When GFR mice are conventionalized CPP reward behavior mirrors WT mice. Functional connectivity data shows significant differences across several brain regions e.g., thalamus, hippocampus, and sensory cortices between GFR and WT before and after conventionalization. Prior to conventionalization GFR mice showed hyperconnectivity that became less organized and more global after conventionalization. Sequencing of the fecal microbiome of the GFR mice before conventionalization showed an absence of normal murine gut microbiome members, but the presence of Corynebacterium, Staphylococcus, Paenibacillus, and Turicibacter.

Conclusion: The implications suggest the microbiome has a direct impact on the development of reward seeking behavior. With the widespread number of opioid receptors found in the gut, studying the interaction between the microbiota and substance use disorder may lead to a better understanding of the mechanisms that lead to the development of addiction as well as potential treatments.

Keywords: Germ free; Gut brain axis; MRI; Microbiome; Opioids; Resting state functional connectivity; Substance use disorder.