The bidirectional relationship between opioids and the gut microbiome: Implications for opioid tolerance and clinical interventions

Opioids are widely used in treating patients with acute and chronic pain; however, this class of drugs is also commonly abused. Opioid use disorder and associated overdoses are becoming more prevalent as the opioid crisis continues. Chronic opioid use is associated with tolerance, which decreases the efficacy of opioids over time, but also puts individuals at risk of fatal overdoses. Therefore, it is essential to identify strategies to reduce opioid tolerance in those that use these agents. The gut microbiome has been found to play a critical role in opioid tolerance, with opioids causing dysbiosis of the gut, and changes in the gut microbiome impacting opioid tolerance. These changes in turn have a detrimental effect on the gut microbiome, creating a positive feedback cycle. We review the bidirectional relationship between the gut microbiome and opioid tolerance, discuss the role of modulation of the gut microbiome as a potential therapeutic option in opioid-induced gut dysbiosis, and suggest opportunities for further research and clinical interventions.