Long access heroin self-administration significantly alters gut microbiome composition and structure

Area of Science:

• Microbiology
• Neuroscience
• Pharmacology

Background:

• Chronic opioid use disorder is linked to gastrointestinal (GI) dysfunction, including constipation and reduced motility.
• Opioid-induced GI issues may stem from compromised gut barrier function and altered gut microbiome composition.
• The specific impact of long-access opioid self-administration on the gut microbiome remains largely unknown.

Purpose of the Study:

• To investigate the effects of long-access heroin self-administration on the gut microbiome structure and function in a rat model.
• To identify microbial and functional pathway alterations associated with heroin self-administration and extinction.

Main Methods:

• Utilized 16S rRNA gene sequencing to analyze gut microbiome composition in three independent rat cohorts.
• Assessed microbial alpha- and beta-diversity across different phases: naïve, self-administration, and post-extinction reinstatement.
• Employed MaAsLin2 for high-dimensional class comparisons and PICRUSt2 for predicting functional pathways.

Main Results:

• Heroin self-administration did not alter overall microbial alpha-diversity compared to saline controls.
• Significant differences in beta-diversity (community structure) were observed between heroin and saline-yoked groups.
• Heroin exposure led to alterations in specific bacterial taxa (e.g., increased Firmicutes, decreased Deferribacteres, increased Patescibacteria) and impacted metabolic pathways, including increased degradation of carbohydrates and decreased biosynthesis of vitamins and lipids.

Conclusions:

• Long-access heroin self-administration significantly alters gut microbiome structure in rats.
• Inferred metabolic pathway changes suggest a microbial imbalance that may favor gut inflammation and altered energy expenditure.
• Identified potential microbial biomarkers and functional pathways that could serve as targets for therapeutic interventions in opioid use disorder.