UCI Researchers Discover Diverse Gut Microbiome is Necessary to Decrease the Desire to Use Fentanyl

In a study published in the International Journal of Molecular Sciences, UCI researchers Michelle Ren, pharmacological sciences PhD student graduating on February 14, 2023, from the UC Irvine School of Pharmacy & Pharmaceutical Sciences, and Shahrdad Lotfipour, assistant professor of pharmaceutical sciences, emergency medicine, pathology & laboratory medicine from the UCI School of Medicine, discovered that gut bacterial depletion increased the desire to use fentanyl, while a healthy, diverse gut microbiome decreased the desire to use fentanyl.

Fentanyl is a powerful synthetic opioid (80 times more potent than morphine) that has driven the steep rise in opioid overdoses. According to the Centers for Disease Control and Prevention, rates of overdose deaths involving synthetic opioids other than methadone (which includes fentanyl and fentanyl analogs) increased over 56% from 2019 to 2020. More than 56,000 people died from overdoses involving synthetic opioids in 2020.

“Our research focused on the role of gut bacteria in an animal model of fentanyl intravenous self-administration,” says Ren. “Our findings provide valuable insight into opioid addiction, which is an unrelenting public health crisis, as the number of opioid-related deaths continues to rise.”

The research team depleted rats’ gut bacteria using an oral antibiotic cocktail. When the antibiotic cocktail was administered, the gut bacterial depletion enhanced fentanyl self-administration. When the researchers restored the gut microbial metabolites, they found fentanyl self-administration decreased in the gut bacteria-depleted rats.

 “Future work could identify further mechanisms driving this gut-brain communication and to determine the specific bacterial strains that are involved in fentanyl abuse,” says Lotfipour. “The studies could translate into a clinical setting to develop targeted therapeutics in opioid-related disorders.”

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Michelle Ren will defend her dissertation on Tuesday, February 14. Click here for more information.