Contributions of neuroimmune and gut-brain signaling to vulnerability of developing substance use disorders

• Published in: Neuropharmacology Vol. 192; p. 108598
• Main Authors: Lucerne, Kelsey E., Osman, Aya, Meckel, Katherine R., Kiraly, Drew D.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2021
• Subjects: Behavior, Addictive - immunology; Behavior, Addictive - metabolism; Behavior, Addictive - psychology; Brain - immunology; Brain - metabolism; Brain-Gut Axis - physiology; Cytokine; Dysbiosis - immunology; Dysbiosis - psychology; Gastrointestinal Microbiome - physiology; Humans; Microbiome; Neuroimmune; Neuroimmunomodulation - physiology; Opioid; Stimulant; Substance use disorder; Substance-Related Disorders - immunology; Substance-Related Disorders - metabolism; Substance-Related Disorders - psychology; Substance use disorder; Opioid; Stimulant; Neuroimmune; Cytokine; Microbiome
• ISSN: 0028-3908; 1873-7064; 1873-7064
• DOI: 10.1016/j.neuropharm.2021.108598

Epidemiology and clinical research indicate that only a subset of people who are exposed to drugs of abuse will go on to develop a substance use disorder. Numerous factors impact individual susceptibility to developing a substance use disorder, including intrinsic biological factors, environmental factors, and interpersonal/social factors. Given the extensive morbidity and mortality that is wrought as a consequence of substance use disorders, a substantial body of research has focused on understanding the risk factors that mediate the shift from initial drug use to pathological drug use. Understanding these risk factors provides a clear path for the development of risk mitigation strategies to help reduce the burden of substance use disorders in the population. Here we will review the rapidly growing body of literature that examines the importance of interactions between the peripheral immune system, the gut microbiome, and the central nervous system (CNS) in mediating the transition to pathological drug use. While these systems had long been viewed as distinct, there is growing evidence that there is bidirectional communication between both the immune system and the gut microbiome that drive changes in neural and behavioral plasticity relevant to substance use disorders. Further, both of these systems are highly sensitive to environmental perturbations and are implicated in numerous neuropsychiatric conditions. While the field of study examining these interactions in substance use disorders is in its relative infancy, clarifying the relationship between gut-immune-brain signaling and substance use disorders has potential to improve our understanding of individual propensity to developing addiction and yield important insight into potential treatment options. •Only a subset of individuals exposed to drugs of abuse will go on to develop a substance use disorder.•Individual differences in vulnerability include genetics, inflammatory changes, and alterations in the gut microbiota.•The gut microbiota and immune system form a key interface between genes and environment, and are also affected by drug use.•Identifying how dysregulation of these systems predisposes to substance use disorders will inform treatment development.