Microbiome Depletion Increases Fentanyl Self-Administration and Alters the Striatal Proteome Through Short-Chain Fatty Acids

• DOI: 10.1523/eneuro.0388-23.2023
• Publication Date: 2023-12-21T18:50:40Z
• Authors: Rebecca S. Hofford; Katherine R. Meckel; Elizabeth J. Wiser; Weiwei Wang; Jonathon P. Sens; Michelle Kim; Arthur Godino; TuKiet T. Lam; Drew D. Kiraly
• Keywords: Gut microbiome

Opioid use disorder (OUD) is a public health crisis currently being exacerbated by increased rates of and overdose synthetic opioids, primarily fentanyl. Therefore, the identification novel biomarkers treatment strategies to reduce problematic fentanyl relapse taking critical. In recent years, there has been growing body work demonstrating that gut microbiome can serve as potent modulator behavioral transcriptional responses both stimulants opioids. Here, we advance this define how manipulations drive intake fentanyl-seeking in translationally relevant drug self-administration model. Depletion male rats with broad spectrum antibiotics leads administration on fixed ratio, progressive seeking after abstinence. Utilizing 16S sequencing contents from these animals, specific populations bacteria correlate closely levels taking. Additionally, global proteomic analysis nucleus accumbens following manipulation status alters functional landscape key limbic substructure. These data demonstrate an altered marked changes synaptic proteome response repeated treatment. Finally, effects depletion are reversible upplementation derived short-chain fatty acid metabolites. Taken together, findings establish clear relevance for gut-brain signaling models OUD lay foundations further translational space.