Clinical and Preclinical Evidence for Gut Microbiome Mechanisms in Substance Use Disorders

Substance use disorders are a set of recalcitrant neuropsychiatric conditions that cause tremendous morbidity and mortality and are among the leading causes of loss of disability-adjusted life years worldwide. While each specific substance use disorder is driven by problematic use of a different substance, they all share a similar pattern of escalating and out-of-control substance use, continued use despite negative consequences, and a remitting/relapsing pattern over time. Despite significant advances in our understanding of the neurobiology of these conditions, current treatment options remain few and are ineffective for too many individuals. In recent years, there has been a rapidly growing body of literature demonstrating that the resident population of microbes in the gastrointestinal tract, collectively called the gut microbiome, plays an important role in modulating brain and behavior in preclinical and clinical studies of psychiatric disease. While these findings have not yet been translated into clinical practice, this remains an important and exciting avenue for translational research. In this review, we highlight the current state of microbiome-brain research within the substance use field with a focus on both clinical and preclinical studies. We also discuss potential neurobiological mechanisms underlying microbiome effects on models of substance use disorder and propose future directions to bring these findings from bench to bedside.